Cochrane

Interventions for emergency contraception (Review) Cheng L, Che Y, Gülmezoglu AM

This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 8 http://www.thecochranelibrary.com

Interventions for emergency contraception (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 7. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 8. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 9. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Intrauterine contraceptive device versus control, Outcome 1 Observed number of pregnancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.1. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 1 Observed number of pregnancies (all women). Analysis 2.2. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 2 Observed number of pregnancies (by risk status). Analysis 2.3. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 3 Observed number of pregnancies (time from intercourse). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.4. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 4 Need for extra dose. . . . . . . . . . . Analysis 2.5. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 5 Any side effect. . . . . . . . . . . . Analysis 2.6. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 6 Specific side effects. . . . . . . . . . . Analysis 2.7. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 7 Menses. . . . . . . . . . . . . . . Analysis 3.1. Comparison 3 Levonorgestrel split-dose 24 hours versus 12 hours, Outcome 1 Observed number of pregnancy (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.2. Comparison 3 Levonorgestrel split-dose 24 hours versus 12 hours, Outcome 2 Observed number of pregnancy (by risk status). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.6. Comparison 3 Levonorgestrel split-dose 24 hours versus 12 hours, Outcome 6 Specific side effects. . . Analysis 3.7. Comparison 3 Levonorgestrel split-dose 24 hours versus 12 hours, Outcome 7 Menses. . . . . . . Analysis 4.1. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 1 Observed number of pregnancy (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.2. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 2 Observed number of pregnancy (by risk status). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.3. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 3 Observed number of pregnancy (time from intercourse). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 4.6. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 6 Specific side effects. . . . . Analysis 4.7. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 7 Menses. . . . . . . . . . Analysis 5.1. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.2. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 2 Observed number of pregnancies (by risk status). . . . . . . . . . . . . . . . . . . . . . . . . . Interventions for emergency contraception (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

1 1 2 2 5 5 5 8 10 10 11 11 12 13 14 14 15 18 20 21 21 30 90 107 108 109 110 111 111 112 114 115 116 117 119 120 121 122 123 125 126 127 i

Analysis 5.5. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 5 Any side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.6. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 6 Specific side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 5.7. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 7 Menses. . Analysis 5.8. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 8 ITT (all loss follow-up as pregnancy in LNG, and no preg in Mife). . . . . . . . . . . . . . . . . . . . Analysis 5.9. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 9 ITT (all loss follow-up as no pregnancy in LNG, and preg in Mife). . . . . . . . . . . . . . . . . . . . Analysis 6.1. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.2. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 2 Observed number of pregnancies (by risk status). . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.3. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 3 Observed number of pregnancies (time from intercourse). . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.5. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 5 Any side effect. Analysis 6.6. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 6 Specific side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.7. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 7 Menses. . . Analysis 6.8. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 8 ITT (all loss follow-up as pregnancy in LNG, and no preg in Mife). . . . . . . . . . . . . . . . . . . . Analysis 6.9. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 9 ITT (all loss follow-up as no pregnancy in LNG, and preg in Mife). . . . . . . . . . . . . . . . . . . . Analysis 7.1. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 1 Observed number of pregnancy (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.2. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 2 Observed number of pregnancy (by risk status). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.3. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 3 Observed number of pregnancy (time from intercourse). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.4. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 4 Observed number of pregnancy within 0-72 h. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.7. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 7 Specific side effects. . . Analysis 7.8. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 8 Menses. . . . . . . Analysis 8.1. Comparison 8 Levonorgestrel (all doses) versus anordrin (all doses), Outcome 1 Observed number of pregnancy (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.5. Comparison 8 Levonorgestrel (all doses) versus anordrin (all doses), Outcome 5 Any side effect. . . . Analysis 9.1. Comparison 9 mifepristone low dose (10 mg) versus low dose (5 mg), Outcome 1 Observed number of pregnancy (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.6. Comparison 9 mifepristone low dose (10 mg) versus low dose (5 mg), Outcome 6 Specific side effects. . Analysis 10.1. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . Analysis 10.2. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 2 Observed number of pregnancies (by risk status). . . . . . . . . . . . . . . . . . . . . . Analysis 10.3. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 3 Any side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 10.4. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 4 Specific side effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 10.5. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 5 Menses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 11.1. Comparison 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 11.3. Comparison 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg), Outcome 3 Any side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Interventions for emergency contraception (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

128 129 131 132 133 134 135 136 137 138 141 142 143 144 145 146 147 148 150 151 152 152 153 155 156 157 158 162 164 165 ii

Analysis 11.4. Comparison 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg), Outcome 4 Specific side effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 11.5. Comparison 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg), Outcome 5 Delay in menses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.1. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . Analysis 12.2. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 2 Observed number of pregnancies (by risk status). . . . . . . . . . . . . . . . . . . . . . Analysis 12.3. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 3 Any side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.4. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 4 Specific side effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.5. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 5 Menses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.1. Comparison 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . Analysis 13.3. Comparison 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg), Outcome 3 Any side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.4. Comparison 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg), Outcome 4 Specific side effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.5. Comparison 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg), Outcome 5 Menses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.1. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.2. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 2 Observed number of pregnancies (by risk status). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.3. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 3 Observed number of pregnancies (time from intercourse). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.4. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 4 Need for extra dose. . . . . . . Analysis 14.5. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 5 Any side effect. . . . . . . . Analysis 14.6. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 6 Specific side effects. . . . . . . Analysis 14.7. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 7 Menses. . . . . . . . . . . Analysis 15.1. Comparison 15 Mifepristone (all doses) versus danazol (all doses), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 15.2. Comparison 15 Mifepristone (all doses) versus danazol (all doses), Outcome 2 Any side effect. . . . Analysis 15.3. Comparison 15 Mifepristone (all doses) versus danazol (all doses), Outcome 3 Specific side effect. . . Analysis 15.4. Comparison 15 Mifepristone (all doses) versus danazol (all doses), Outcome 4 Menses. . . . . . . Analysis 16.1. Comparison 16 Mifepristone (all doses) versus anordrin (all doses), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 16.3. Comparison 16 Mifepristone (all doses) versus anordrin (all doses), Outcome 3 Any side effect. . . . Analysis 16.4. Comparison 16 Mifepristone (all doses) versus anordrin (all doses), Outcome 4 Specific side effects. . Analysis 16.5. Comparison 16 Mifepristone (all doses) versus anordrin (all doses), Outcome 5 Menses. . . . . . Analysis 17.1. Comparison 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . Analysis 17.3. Comparison 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses), Outcome 3 Any side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 17.4. Comparison 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses), Outcome 4 Specific side effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 17.5. Comparison 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses), Outcome 5 Delay in menses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 18.1. Comparison 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses), Outcome 1 Observed number of pregnancy (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . Interventions for emergency contraception (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

166 168 169 170 171 172 174 175 176 177 179 180 181 182 183 183 184 186 187 187 188 189 190 191 192 193 194 195 196 198 199 iii

Analysis 18.5. Comparison 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses), Outcome 5 Any side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 18.6. Comparison 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses), Outcome 6 Menses. Analysis 19.1. Comparison 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . Analysis 19.3. Comparison 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses), Outcome 3 Observed number of pregnancies (time from intercourse). . . . . . . . . . . . . . . . . . . Analysis 19.6. Comparison 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses), Outcome 6 Specific side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 19.7. Comparison 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses), Outcome 7 Menses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 20.1. Comparison 20 Mifepristone versus mifepristone + misoprostol (all doses), Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 20.6. Comparison 20 Mifepristone versus mifepristone + misoprostol (all doses), Outcome 6 Specific side effect. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 21.1. Comparison 21 Mifepristone (all doses) versus copper intrauterine device, Outcome 1 Observed number of pregnancy (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 21.5. Comparison 21 Mifepristone (all doses) versus copper intrauterine device, Outcome 5 Any side effect. Analysis 21.6. Comparison 21 Mifepristone (all doses) versus copper intrauterine device, Outcome 6 Specific side effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 21.7. Comparison 21 Mifepristone (all doses) versus copper intrauterine device, Outcome 7 Menses. . . . Analysis 22.1. Comparison 22 Mifepristone versus gestrinone, Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 22.2. Comparison 22 Mifepristone versus gestrinone, Outcome 2 Side effects. . . . . . . . . . . . Analysis 22.3. Comparison 22 Mifepristone versus gestrinone, Outcome 3 Menses. . . . . . . . . . . . . Analysis 23.3. Comparison 23 Danazol (all doses) versus Yuzpe, Outcome 3 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 23.4. Comparison 23 Danazol (all doses) versus Yuzpe, Outcome 4 Specific side effects. . . . . . . . Analysis 23.5. Comparison 23 Danazol (all doses) versus Yuzpe, Outcome 5 Menses. . . . . . . . . . . . Analysis 24.1. Comparison 24 High-dose oestrogens versus Yuzpe, Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 25.1. Comparison 25 Half-dose Yuzpe versus standard Yuzpe, Outcome 1 Observed number of pregnancies (all women). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 25.2. Comparison 25 Half-dose Yuzpe versus standard Yuzpe, Outcome 2 Any side effect. . . . . . . . Analysis 25.3. Comparison 25 Half-dose Yuzpe versus standard Yuzpe, Outcome 3 Specific side effects. . . . . . Analysis 26.1. Comparison 26 High-risk women versus low-risk women (all hormonal methods), Outcome 1 Observed number of pregnancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 27.1. Comparison 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone, Outcome 1 ≤ 24 h vs > 24-48 h. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 27.2. Comparison 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone, Outcome 2 ≤ 24 h vs > 48-72 h. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 27.3. Comparison 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone, Outcome 3 > 2448 h vs > 48-72 h. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 27.4. Comparison 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone, Outcome 4 < 72 h vs > 72 h. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 28.1. Comparison 28 Time elapsed since intercourse in levonorgestrel, Outcome 1 ≤ 24 h vs > 24-48 h. . Analysis 28.2. Comparison 28 Time elapsed since intercourse in levonorgestrel, Outcome 2 ≤ 24 h vs > 48-72 h. . Analysis 28.3. Comparison 28 Time elapsed since intercourse in levonorgestrel, Outcome 3 > 24-48 h vs > 48-72 h. . Analysis 28.4. Comparison 28 Time elapsed since intercourse in levonorgestrel, Outcome 4 < 72 h vs > 72 h. . . . Analysis 29.1. Comparison 29 Time elapsed since intercourse in ulipristal acetate, Outcome 1 ≤ 24 h vs > 24-48 h. . Analysis 29.2. Comparison 29 Time elapsed since intercourse in ulipristal acetate, Outcome 2 ≤ 24 h vs > 48-72 h. . Analysis 29.3. Comparison 29 Time elapsed since intercourse in ulipristal acetate, Outcome 3 > 24-48 h vs > 48-72 h. Analysis 29.4. Comparison 29 Time elapsed since intercourse in ulipristal acetate, Outcome 4 < 72 h vs > 72 h. . . Interventions for emergency contraception (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

199 200 201 202 203 205 205 206 208 208 209 211 212 213 215 216 217 218 219 220 220 221 222 223 224 224 225 226 227 228 229 230 230 231 232 iv

Analysis 30.1. Comparison 30 Time elapsed since intercourse in Yuzpe, Outcome 1 ≤ 24 h vs > 24-48 h. . Analysis 30.2. Comparison 30 Time elapsed since intercourse in Yuzpe, Outcome 2 ≤ 24 h vs > 48-72 h. . Analysis 30.3. Comparison 30 Time elapsed since intercourse in Yuzpe, Outcome 3 > 24-48 h vs > 48-72 h. WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .


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[Intervention Review]

Interventions for emergency contraception Linan Cheng1 , Yan Che1 , A Metin Gülmezoglu2 1 Centre

for Clinical Research and Training, Shanghai Institute of Planned Parenthood Research (SIPPR), Shanghai, China. Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland 2 UNDP/UNFPA/WHO/World Bank

Contact address: Linan Cheng, Centre for Clinical Research and Training, Shanghai Institute of Planned Parenthood Research (SIPPR), 2140 Xie Tu Road, Shanghai, 200032, China. [email protected]. Editorial group: Cochrane Fertility Regulation Group. Publication status and date: Edited (conclusions changed), published in Issue 8, 2012. Review content assessed as up-to-date: 18 July 2011. Citation: Cheng L, Che Y, Gülmezoglu AM. Interventions for emergency contraception. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD001324. DOI: 10.1002/14651858.CD001324.pub4. Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. Objectives To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy. Search methods The search included the Cochrane Controlled Trials Register, Popline, MEDLINE, PubMed, Biosis/EMBASE, Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (July 2011). Content experts and pharmaceutical companies were contacted. Selection criteria Randomised controlled trials and controlled clinical trials including women attending services for EC following a single act of unprotected intercourse were eligible. Data collection and analysis Data on outcomes and trial characteristics were extracted in duplicate and independently by two review authors. Quality assessment was also done by two review authors independently. Meta-analysis results are expressed as risk ratio (RR) using a fixed-effect model with 95% confidence interval (CI). In the presence of statistically significant heterogeneity a random-effects model was applied. Main results One hundred trials with 55,666 women were included. Most trials were conducted in China (86/100). Meta-analysis indicated that mid-dose mifepristone (25-50 mg) (20 trials; RR 0.64; 95% CI 0.45 to 0.92) or low-dose mifepristone (< 25 mg) (11 trials; RR 0.70; 95% CI 0.50 to 0.97) were significantly more effective than levonorgestrel (LNG), but the significance was marginal when only high-quality studies were included (4 trials; RR 0.70; 95% CI 0.49 to 1.01). Low-dose mifepristone was less effective than mid-dose mifepristone (25 trials; RR 0.73; 95% CI 0.55 to 0.97). This difference was not statistically significant when only high-quality trials Interventions for emergency contraception (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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were considered (6 trials; RR 0.75; 95% CI 0.50 to 1.10). Ulipristal acetate (UPA) appeared more effective (2 trials; RR 0.63) than LNG at a marginal level (P = 0.09) within 72 hours of intercourse. Regarding effectiveness in relation to the time of administration, women who took LNG within 72 hours of intercourse were significantly less likely to be pregnant than those who took it after 72 hours (4 trials; RR 0.51; 95% CI 0.31 to 0.84). It was not evident that the coitus-treatment time affected the effectiveness of mifepristone and UPA. Single-dose LNG (1.5 mg) showed similar effectiveness as the standard two-dose regimen (0.75 mg 12 h apart) (3 trials; RR 0.84; 95% CI 0.53 to 1.33). This conclusion was not modified by the time elapsed from intercourse to treatment administration. Mifepristone (all doses) (3 trials; RR 0.14; 95% CI 0.05 to 0.41) and LNG (5 trials; RR 0.54; 95% CI 0.36 to 0.80) were more effective than the Yuzpe regimen in preventing pregnancy. One trial compared gestrinone with mifepristone. No significant difference of effectiveness was identified in this trial (996 women; RR 0.75; 95% CI 0.32 to 1.76). All methods of EC were safe. Nausea and vomiting occurred with oestrogen-containing EC methods and progestogen and antiprogestogen methods caused changes in subsequent menses. LNG users were more likely to have a menstrual return before the expected date, but UPA users were more likely to have a menstrual return after the expected date. Menstrual delay was the main adverse effect of mifepristone and seemed to be dose-related. Authors’ conclusions Intermediate-dose mifepristone (25-50 mg) was superior to LNG and Yuzpe regimens. Mifepristone low dose (< 25 mg) may be more effective than LNG (0.75 mg two doses), but this was not conclusive. UPA may be more effective than LNG. LNG proved to be more effective than the Yuzpe regimen. The copper IUD was the most effective EC method and was the only EC method to provide ongoing contraception if left in situ.

PLAIN LANGUAGE SUMMARY Methods of emergency contraception Emergency contraception is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy after unprotected sex. This is a back-up and not a regular contraceptive method. Mifepristone, ulipristal acetate and levonorgestrel are very effective with few adverse effects, and are preferred to an oestrogen and progestogen combined regimen. Levonorgestrel could be used in a single dose (1.5 mg) instead of two split doses (0.75 mg) 12 hours apart. The copper IUD is the most effective emergency contraceptive method and is the only emergency contraceptive method to provide ongoing contraception if left in situ.


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[value] per 1000

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[experimental]

[control]

of Low risk population

Corresponding risk

Assumed risk

Illustrative comparative risks* (95% CI)

No of Participants (studies)

RR [value] ([value] to [value] [value]) ([value])

Relative effect (95% CI)

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moderate

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low

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very low

Quality of the evidence (GRADE)

Comments

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio; [other abbreviations, e.g. OR, etc]

Observed number pregnancies [follow-up]

Outcomes

Patient or population: [participants] with [health problem] Settings: [setting] Intervention: [experimental intervention] Comparison: [control intervention]

[experimental intervention] compared with [control intervention] for [health problem]

S U M M A R Y O F F I N D I N G S F O R T H E M A I N C O M P A R I S O N [Explanation]


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GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx

BACKGROUND Unwanted pregnancy is a common problem. Worldwide, about 44 million pregnancies end in abortion each year (Sedgh 2012). The standard approach to this problem has been primary prevention (contraception), backed up by induced abortion. However, for a long time, contraception in the world has meant only anticipatory contraception. The definition of the primary prevention of unintended pregnancy could and should expand to include post hoc contraception (Grimes 1997). Emergency contraception (EC) is defined as the use of a drug or device as an emergency measure to prevent pregnancy after unprotected intercourse. From this definition it follows that methods of EC are used after coitus but before pregnancy occurs, and that they are intended as a back-up for occasional use rather than a regular form of contraception (Van Look 1993). Although the terms ’morning after pill’ and ’after-sex pill’ are also used to describe the same approach, these can cause confusion regarding the timing and purpose, and are best avoided. EC implies something not to be used routinely (there are far more effective methods for regular contraception) but which can still prevent pregnancy if other options have failed or regular contraception was not used (Webb 1995). To date, no contraceptive method is 100% reliable and few people use their method perfectly each time they have sexual intercourse. Furthermore, EC is useful in cases of sexual assault. EC is especially important for outreach to the 4.6 million women at risk of pregnancy but not using a regular method by providing a bridge to use of an ongoing contraceptive method (Trussell 2012). EC is widely available in Western European and in China. However, use of this method is rising rapidly in developing countries. For example, the 2008-2009 DHS (Demographic and Health Survey) data showed that 22% of unmarried sexually active women in Albania had ever used EC. In Colombia, Kenya, and Nigeria, according to data from DHS, 10% to 16% of unmarried sexually active women ever used EC (ICEC 2012a, ICEC 2012b, ICEC 2012c). This proportion in Peru was 35% in 2010 (INEI 2011). However, EC is largely under-utilised in many other countries. Particularly, in many developing countries, the lack of access to EC may subject women to unsafe abortions, which contribute significantly to maternal mortality and morbidity.

alternative regimens has led to trials of the progestogen LNG, the anti-gonadotropin danazol, and the anti-progestins mifepristone and ulipristal acetate (UPA) (Trussell 2012). Like the Yuzpe regimen, these methods are recommended for use within 72 hours of unprotected intercourse although LNG and mifepristone had been tested up to 120 hours (five days) for research purposes. The postcoital insertion of a copper intrauterine device (Cu-IUD) is an option that can be used up to five days after the estimated time of ovulation and can be left in the uterus as a long-term regular contraceptive method. The main side effects caused by hormonal emergency contraceptives are nausea and vomiting, which seem to be more frequent with oestrogen-containing regimens such as Yuzpe regimen and high-dose oestrogen alone compared to progestogen or anti-progestogen treatment. Mifepristone can cause menstrual delay, while LNG may cause earlier menses. IUD insertion can cause discomfort and requires trained staff and facilities. It is generally recommended that the copper IUD be avoided in women at high risk of sexually transmitted diseases. Information on the comparative effectiveness, safety and convenience of an emergency contraceptive method is crucial for reproductive healthcare providers and the women they serve. The present review aims to search systematically for, and combine, all evidence from randomised controlled trials and controlled clinical trials relating to the effectiveness of different emergency contraceptive methods in order to supply the best evidence currently available on which to base recommendations for clinical practice and further research.

OBJECTIVES To determine, from the best evidence available, which emergency contraceptive method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy.

METHODS Although attempted throughout history, EC methods only started to become effective in the 1960s when hormonal regimens were first introduced. Following the introduction of high-dose oestrogens, the so-called Yuzpe regimen involving the combined use of oestrogen (ethinyl oestradiol 100 µg) and progestogen (levonorgestrel (LNG) 0.5 mg or dl-norgestrel 1 mg) repeated once 12 hours apart with the first dose given within 72 hours of unprotected intercourse, became popular in the late 1970s and early 1980s (Yuzpe 1977). Since the 1990s, there have been several different interventions available for EC (Glasier 1997). Interest in the development of

Criteria for considering studies for this review

Types of studies Randomised controlled trials and controlled clinical trials comparing different EC methods, or comparing one method with expectant management or placebo were considered for inclusion. The unit of randomisation in all these studies was the individual. Only trials reporting clinical outcomes were considered for inclusion.


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Types of participants Women with regular menses requesting EC following unprotected intercourse. Women attending clinics for ’once-a-month’ contraception in the form of luteal phase contraceptives and menstrual regulation using mifepristone and prostaglandin analogues were not eligible for inclusion in this review. Types of interventions To be included, the intervention had to be applied to women seeking EC following unprotected intercourse. Those studies in which similar interventions were used by women as regular postcoital contraception were not eligible. Comparisons of different delivery systems such as advance provision or over-the-counter delivery, and any kind of educational interventions, were not eligible for inclusion in this review. Trials evaluating the following interventions were included in this review: 1. Any regimen versus nothing/placebo; 2. Hormonal emergency contraceptive pills (ECPs): comparison of different regimens: i) LNG versus Yuzpe, ii) Mifepristone versus LNG , iii) mifepristone versus Yuzpe, iv) mifepristone versus anordrin, v) mifepristone versus mifepristone + anordrin, vi) mifepristone versus mifepristone + misoprostol, vii) mifepristone versus mifepristone + tamoxifen, viii) mifepristone versus danazol, ix) Yuzpe versus high-dose oestrogen, x) Yuzpe versus danazol, xi) UPA versus LNG, xii) mifepristone versus gestrinone, xiii) drug/dose comparisons, xiv) others; 3. IUD comparisons to ECPs. Combination treatments and comparison of these with other treatments alone or in combination were considered for inclusion when such data were available, including different doses. Types of outcome measures The review focused on clinical outcome measures. The primary outcome measure was the pregnancy rate in women receiving different regimens (or control). The full list of outcomes included: 1. Observed number of pregnancies (all women); 2. Ectopic pregnancy; 3. Side effects: ◦ any side effect, ◦ nausea, ◦ vomiting, ◦ headache, ◦ dizziness,

◦ fatigue, ◦ breast tenderness, ◦ diarrhoea, ◦ spotting or bleeding, ◦ others; 4. Menses: ◦ early, ◦ late. Several factors may affect the success of EC and the following subgroup analyses were considered when there were sufficient data in an appropriate format to allow such analyses. These factors were: 1. Time elapsed since intercourse (coitus-treatment interval): ◦ ≤ 24 hours, ◦ > 24-48 hours, ◦ > 48-72 hours, ◦ > 72-120 hours, ◦ > 120 hours; 2. Risk status: ◦ high-risk - women who had further acts of intercourse during the same cycle in which EC was used, ◦ low-risk - women without further acts of coitus during that cycle.

Search methods for identification of studies The search strategy for this review included: ELECTRONIC SEARCHES Central/ Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2011)

PubMed: 2003 to July 2011

(contraceptives, postcoital OR contraception, postcoital OR postcoital contracept* OR “emergency contraceptives” OR “emergency contraception” OR “morning after pill” OR “day after pill” OR Yuzpe) AND (advance* OR home OR over the counter OR OTC OR behind the counter OR health services accessibility OR community pharmacy services OR access) limited to human and English “Biosis/EMBASE: 2003 to July 2011

s postcoitus contraceptive agent s emergenc?( )contracept? s morning( )after( )pill s Ru-486 s Yuzpe or post( )coital( )insertion or unprotected( )intercourse or mifepristone or


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danazol or anordrin s s1 or s2 or s3 or s4 or s5 s prenatal( )diagnosis or chromosome( )aberration or menopause or infertility or neoplasm or spontaneous( )abortion or rheumatoid( )arthritis s s6 not s7 s s8 and py=2003:2006 s clinical study s clinical trial or DC=J2.40.10.25 s double blind procedure s crossover procedure s placebo s s10 or s11 or s12 or s13 or s14 s s9 and s15 s s16/human reduce duplicates Popline: to July 2011

(emergency contracept* / postcoital contracept* / morning after pill* / morning after contracept* / morning-after pill* / morningafter contracept* / day after pill* / day after contracept* / dayafter pill* / day-after contracept* / Yuzpe) & (advance* prov* / self administ* / self-administ* / home / over the counter / overthe-counter /otc/ behind the counter / advance prescript*/advance prescib* / pharmac* prov*/ access*) limited to English CINAHL: to July 2011

(contraceptives or emergency contraceptive or morning after pill or Yuzpe or postcoital insertion or unprotected intercourse or mifepristone or danazol or anordrin or Ru-486 or Ru486 or Ru 486) AND (clinical and (article or study or trial or studies or trials) or controlled study or randomised controlled trial or randomised controlled trial or clinical study or single blind or phase 3 clinical study or phase 4 clinical study or crossover or placebo or placebos or allocated or allocation or allocate or assign or assigned or blinded or comparative or comparison or factorial or follow up or prospective or random or randomised or randomised or masked or masking or versus or vs) NOT (prenatal diagnosis or chromosome aberration or menopause or infertility or neoplasm or spontaneous abortion or rheumatoid arthritis) LILACS: to July 2011

contraception, postcoital or anticoncepcion postcoital or anticoncepcao pos-coito or contraceptives, postcoital or anticonceptivos

poscoito or anticoncepcionais pos-coito or contraceptives, postcoital, hormonal or postcoital contraceptives or postcoital contraception or postcoital contraceptive or emergency contraception or emergency contraceptives or emergency contraceptive or morning after pill or Yuzpe or postcoital insertion or unprotected intercourse or mifepristone or danazol or anordrin or Ru-486 or Ru486 or Ru 486 2. World Health Organization (WHO) RESOURCES (July 2011) We contacted HRP/WHO to seek any published or unpublished trials we had missed. 3. Emergency Contraception World Wide Web (July 2011) The Emergency Contraception World Wide Web server operated by the Office of Population Research at Princeton University, US, was checked to identify any relevant publications. 4. Pharmaceutical companies (July 2011) The pharmaceutical companies (Bayer, Beijing Zizhu Pharmaceutical Co., Biopharm Chemical Company, Gador SA, Gedeon Richter, Laboratoire HRA Pharma, Shanghai New Hualian Pharmaceutical Co., Shenyang No. 1 Pharmaceutical Co., Teva, Xianju Pharmaceutical Co.) that are marketing dedicated products for EC were contacted to check if they knew of any unpublished trials that were eligible for inclusion in the review. All Chinese companies, and Bayer, Laboratoire HRA Pharma, and Teva responded but they did not have information on, or knowledge of, other trials. 5. Others (July 2011) The usual steps in the search of a systematic review, such as searching the reference lists and contacting investigators active in this area, were performed.

Data collection and analysis Study selection The trials identified with our search strategy were initially checked for duplicates and relevance for the review by looking at the titles and abstracts. If it was not possible to exclude a publication by looking at the title or the abstract, the full paper was retrieved. Decisions on which trials to include were independently made by two review authors (LC and AMG/CO; LC and QC for the data from 2006 to 2011). Differences were resolved by discussion and consultation of other review authors if needed. Trials were


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excluded if the loss to follow-up was greater than 20%. There were no language preferences in the search or the selection of articles. Data extraction Systematic data extraction was carried out for each trial for the following variables: • intervention and control treatment. Because of the large variation in mifepristone doses, we categorised the doses arbitrarily (before data extraction) as high (> 50 mg), mid (25-50 mg) and low (< 25 mg). We also conducted separate metaanalyses to validate our groupings of the different doses; • clinical outcomes: observed number of pregnancies, ectopic pregnancies, side effects (any, nausea, vomiting, headache, dizziness, fatigue, breast tenderness, spotting/bleeding, diarrhoea, others), timing of menses, coitus-treatment interval, high-/low-risk behaviour; • methodology: random allocation techniques, blinding, post-randomisation exclusions, loss to follow-up; • demographics: type of healthcare setting, city, country, total number of women included, and inclusion and exclusion criteria. For articles written in English, data extraction was independently done by two reviewers (LC and AMG/CO; LC and QC for the data from 2006 to 2011). However, several Chinese trials were published locally in Chinese and data extraction from these trials was performed by one review author (LC), for the data from 2006 to 2011 by LC and QC; and the data entry checked by another review author. Quality assessment Trials were given a quality score for the concealment of allocation as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Study quality was independently assessed by two review authors (LC and AMG/CO). Disagreements were resolved by discussion with other review authors. Statistics Treatment effects were calculated using risk ratio (RR) estimates with 95% confidence intervals (95% CI) with the Review Manager software (RevMan 2011). A fixed-effect model was applied. In case of heterogeneity (P < 0.10), the random-effects model was used to produce summary estimates (except when heterogeneity occurred in subgroup analyses where it was not possible to conduct separate analyses). Treatment effects might be affected by the quality of allocation concealment. Furthermore, more than half of the trials in the first release of the review (in 1999) were from China, and it had been suggested that treatment effects might be different between trials conducted in China and elsewhere (WHO 1990; WHO 1998). Therefore, it was decided that, in the second release of the review (2004) these two potential sources of

heterogeneity should be investigated for the most important outcomes (observed pregnancies; any side effects; specific side effects: nausea, vomiting and breast tenderness), using meta regression in STATA (STATA 2001). Random-effects meta-regression analyses were conducted to take account of both within-trial variances of treatment effects and the residual between-trial heterogeneity (data not shown) (Thompson 2002). In addition, sensitivity analyses were conducted in STATA for all comparisons pooling data from more than two trials (data not shown) (STATA 2001). Interaction tests were conducted using logistic regression with SAS software. Intention-to-treat (ITT) analyses All reports were scrutinised for the presence of ITT analyses. For outcomes with loss to follow-up the number of women with outcome data was taken as the denominator (available case analysis). In the LNG versus Yuzpe comparison and LNG versus mid-dose mifepristone: outcomes for missing patients were imputed under two extreme scenarios (i.e. all missing in one arm had an event and all missing in the other arm did not have an event and vice versa).

RESULTS

Description of studies See: Characteristics of included studies; Characteristics of excluded studies. One hundred trials with 55,666 women were included. Eighty-six trials were conducted in China. All Chinese trials were relatively recent (earliest trial published in 1993) indicating the interest in EC research in this country. Except for the Ellertson 2003, Glasier 2010, Von Hertzen 2002, WHO 1998 and WHO 1999 trials, all had been conducted in a single country, although some were multicentre trials. WHO trials were multinational involving large numbers of diverse populations. Eighty one studies were excluded. Most of these were case-series, reports without a comparison group or meta-analysis. Six studies (Dong 2007; Li F 2005; Liu Y 2002; Tian Q 2000; Turok 2010; Zhang J 1999) compared Cu-IUDs versus mifepristone with or without LNG by informed choice (i.e. not randomly allocated). Only one of the excluded trials was excluded on the basis of high loss to follow-up (20%) (Mo 2004). Two studies compared Cu-IUD either directly with an ECP (LNG, mifepristone) or allocated those women attending clinics between 72-120 hours to IUD and those attending before 72 hours to two alternative ECPs (Su 2001; Wang C 2000) randomly. Eighteen out of 100 trials had more than two treatment arms. The majority of trials used mifepristone, followed by those using LNG and then the Yuzpe regimen. Thirty-six trials involved dose-


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comparison studies of mifepristone in doses from 5 mg to 600 mg. Thirty-one trials compared LNG with mifepristone. Five trials compared LNG with the Yuzpe regimen. Three trials (Arowojolu 2002; Dada 2010; Von Hertzen 2002) compared a split dose with a single dose of LNG and one trial compared a 24-hour with a 12-hour double-dose regimen of LNG. Two trials (Creinin 2006; Glasier 2010) compared UPA, a second-generation progesterone receptor modulator, with LNG. One trial (Wu 2010) compared mifepristone with gestrinone. Other interventions were high-dose oestrogen, danazol and Cu-IUD. Anordrin is a steroid hormone with weak oestrogenic effects and is only used in China as a visitingcontraceptive pill (a type of oral pills that is used for couples who do not cohabit but visit home for a short period. It can start at any day during a menstrual cycle, one pill a day continuing no less than 14 days). In Chinese EC trials, investigators used locally manufactured mifepristone and LNG. Most of the trials report observed number of pregnancies in comparison to expected number of pregnancies according to estimated probability of pregnancy on the day of the menstrual cycle when unprotected intercourse took place. This information is provided in the Characteristics of included studies table without a formal summary analysis. The inclusion and exclusion criteria were similar with some minor differences between trials . In general, women attending after 72 hours (after 120 h in Cu-IUD, some mifepristone and LNG trials), with multiple episodes of unprotected intercourse, with irregular menstrual periods and those using hormonal contraception were excluded. All trials except that of Sang 1999 started the intervention as soon as the women came to the clinic. Sang 1999 included only women who had unprotected intercourse 24 to 96 hours before attending the clinic.

Risk of bias in included studies Chen 2002Twenty-five trials (Arowojolu 2002; Ashok 2002; Creinin 2006; Dada 2010; Ellertson 2003; Glasier 1992; Glasier 2010; Hamoda 2004; He CH 2002; Ho 1993; Liu 2000; Ngai 2005; Qi 2000b; Sang 1999; Van Santen 1985a; Von Hertzen 2002; Wang SZ 2001; Webb 1992; WHO 1998; WHO 1999; Wu 1999a; Wu 2002; Wu 2010; Xiao 2002; Zuo 1999) had adequate concealment of allocation. Most of the remaining trials had insufficient information on randomisation and concealment of allocation, and only used terms such as ’randomly allocated’. Twenty-one trials were reported as double-blinded (Arowojolu 2002; Creinin 2006; Dada 2010; Ellertson 2003; He CH 2002; Lin 2000; Liu 2000; Ngai 2005; Qi 2000b; Van Santen 1985a; Von Hertzen 2002; Wang SZ 2001; Wei RH 2002; WHO 1998; WHO 1999; Wu 1999a; Wu 2002; Wu 2010; Xiao 2002; Zhang

L 2005; Zuo 1999), and two as single-blinded (Glasier 2010; Sang 1999). ITT analysis was available (or possible) for the Creinin 2006, Glasier 2010, Ho 1993, Ngai 2005, WHO 1998 and Xiao 2002 trials and not mentioned in the other studies. Thirty-four trials (Arowojolu 2002; Ashok 2002;Chen 2002; Cheng 1999a; Creinin 2006; Dada 2010; Ding 2005; Ellertson 2003; Fan 2001; Farajkhoda 2009 Glasier 1992; Glasier 2010; Hamoda 2004; He CH 2002; Ho 1993; Lai Z 2004; Liang 2001; Liu L 2001; Ngai 2005; Qi 2000b; Rowlands 1983; Sang 1999; Van Santen 1985a; Von Hertzen 2002; Wang Y 2003; Webb 1992; WHO 1998; WHO 1999; Wu 1999a; Wu 2002; Wu 2010; Xiao 2002; Zhang Y 1998; Zuo 1999) reported the number of lost follow-up or postrandomisation exclusion. The average proportion of loss to follow-up or post-randomisation exclusion was 3.3% (range 0.2% to 16.9%). Although several trials did not mention post-randomisation exclusions, these studies did not explicitly mention ITT analyses either. As there were only a few reported pregnancies, it was possible that some pregnancies could well be excluded after randomisation (Webb 1992). In general, side effects were assessed by women themselves on diary charts. The trial by Askalani 1987 was included in the review because random allocation was explicitly mentioned. Unfortunately, no other methodological details were available for this trial. One trial (Webb 1992) was stopped early for effectiveness reasons. Fifteen trials reported appropriate power calculations for the sample size (Arowojolu 2002; Ashok 2002; Dada 2010; Ellertson 2003; Creinin 2006; Glasier 2010; Hamoda 2004; Ngai 2005; Sang 1999; Von Hertzen 2002; Webb 1992; WHO 1998; WHO 1999; Wu 2010; Xiao 2002). From the 2007 update, the review authors revised the use of the allocation concealment score to be more consistent with Cochrane procedures. This score referred to the concealment of allocation before assignment, and was not an overall quality score. Studies from the initial review were recorded for consistency in the allocation concealment score. The change did not alter the results or conclusions.

Effects of interventions See: Summary of findings for the main comparison 1. IUD versus expectant management Askalani 1987 compared Cu-IUD (Cu-T 200) insertion with expectant management in women requesting EC within four days of unprotected intercourse. Notwithstanding the ethical aspects of this trial, the report was brief and only reported data on number of pregnancies. There was a significantly higher number of pregnancies in the expectant management group (RR 0.09; 95% CI 0.03 to 0.26) (Figure 1; Analysis 1.1).


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Figure 1. Forest plot of comparison: 1 Intrauterine contraceptive device versus control, outcome: 1.1 Observed number of pregnancies.

2. LNG versus Yuzpe regimen Five trials (three Chinese (Ho 1993; Sheng A 2002; Sun MX 2007), one Iranian (Farajkhoda 2009) and one multinational ( WHO 1998)) compared the Yuzpe regimen with LNG 0.75 mg given twice 12 hours apart The five trials provided data on 4221 women. LNG was more effective in preventing pregnancy than the Yuzpe regimen (RR 0.54; 95% CI 0.36 to 0.80) (Figure 2; Analysis 2.1). Additional analysis of the WHO 1998 trial data indicated that the effect was not modified by whether the women abstained from further acts of intercourse or not (P = 0.61 for the interaction test) or by the time elapsed from intercourse to treatment administration (P = 0.58 for the interaction test). Figure 2. Forest plot of comparison: 2 Levonorgestrel versus Yuzpe, outcome: 2.1 Observed number of pregnancies (all women).

The need for repeat dose was less with LNG (WHO 1998; RR 0.53; 95% CI 0.38 to 0.75). LNG was associated with significantly fewer complaints of nausea (RR 0.42; 95% CI 0.38 to 0.46), vomiting (RR 0.23; 95% CI 0.18 to 0.31), dizziness (RR 0.72; 95% CI 0.61 to 0.85) and fatigue (RR 0.63; 95% CI 0.55 to

0.71) than Yuzpe. The difference was marginally significant but nevertheless less in terms of headache (WHO 1998; RR 0.83; 95% CI 0.69 to 1.00), breast tenderness (RR 0.84; 95% CI 0.69 to 1.01) and abdominal pain (WHO 1998; RR 0.84; 95% CI 0.70


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to 1.01) with LNG. The risks of hot flushes (Farajkhoda 2009; RR 0.48; 95% CI 0.09 to 2.54), spotting/bleeding (Ho 1993; Sun MX 2007; RR 0.86; 95% CI 0.64 to 1.15) and the time of menses resumption after treatment (Ho 1993; Sheng A 2002; Sun MX 2007; RR 1.19: 95% CI 0.99 to 1.44) were similar in both groups (Analysis 2.6; Analysis 2.7). 3. LNG split-dose 24 hours versus 12 hours One double-blind randomised multicentre trial conducted in

China (Ngai 2005) compared LNG split-dose in two different regimens (24 h vs 12 h apart). The effectiveness was similar with either regimen (RR 0.98; 95% CI 0.53 to 1.82) (Figure 3; Analysis 3.1). This conclusion was not modified by whether the women abstained from further acts of intercourse or not (Analysis 3.2). Additional analysis of the trial data indicated that, among women who received the 12-hour regimen, the high-risk participants were significantly more likely to have a pregnancy than their low-risk counterparts. This association was not observed among women who received the 24-hour regimen.

Figure 3. Forest plot of comparison: 3 Levonorgestrel split-dose 24 h versus 12 h, outcome: 3.1 Observed number of pregnancy (all women).

4. LNG single dose versus LNG split dose Three trials compared regimens of LNG 1.5 mg single dose with LNG 0.75 mg two doses 12 hours apart. Arowojolu 2002 recruited 1160 women who had a single act of unprotected intercourse within 72 hours, and Von Hertzen 2002 recruited 4136 and Dada 2010 recruited 3022 women who attending the clinics within 120 hours of unprotected intercourse. Meta-analysis showed that there was no statistically significant difference in preventing pregnancy (RR 0.84; 95% CI 0.53 to 1.33) (Figure 4; Analysis 4.1) between the two regimens. Additional analysis of the

Von Hertzen 2002 trial data indicated that this conclusion was not modified by whether the women abstained from further acts of intercourse or not (P = 0.18 for the interaction test), or by the time elapsed (within or after 72 h) from intercourse to treatment administration (P = 0.90 for the interaction test). There were no statistically significant differences in most types of the side effects between the two regimens except that the frequencies of headache (RR 1.14; 95% CI 1.01 to 1.30) and heavy menses (RR 1.48; 95% CI 1.08 to 2.04) of the single-dose regimen were significantly higher than those of the two-dose regimen (Analysis 4.6).

Figure 4. Forest plot of comparison: 4 Levonorgestrel single versus split-dose, outcome: 4.1 Observed number of pregnancy (all women).


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5. Mid-dose mifepristone (25-50 mg) versus LNG Twenty trials (Chen 2008; Cheng 2009; Gan XH 2007; Han 1999a; Hu X 2003; Li A 2000; Li J 2005; Liang 2001; Liao 2003; Liu RQ 2009; Qi M 2003; Shao XY 2010; Su 2001; Sun 2000; Sun P 2003; Wang Q 2000; Wang Y 2003; Xu 2000; Xu Z 2000; Zhang JQ 2000 ), all conducted in China, compared LNG (2422 women, all used split-dose) with mid-dose mifepristone (2595 women). Overall, effectiveness of mid-dose mifepristone was better than that of LNG (RR 0.64; 95% CI 0.45 to 0.92) (Figure 5; Analysis 5.1). This result was confirmed with simulated ITT analyses; when

it was supposed that all missing had the event in the LNG group, but none in the mifepristone group, the estimated RR was 0.50 (95% CI 0.32 to 0.77) and when it was supposed that all missing did not have event in LNG group, but did in the mifepristone group, the estimated RR was 0.57 (95% CI 0.37 to 0.88). The overall side effect rate was reported in 13 trials and mifepristone was more tolerable than LNG (RR 0.58; 95% CI 0.41 to 0.82; Analysis 5.5). More women who took mifepristone had a delay in menses than those who took LNG (12 trials; RR 1.26; 95% CI 1.03 to 1.54; Analysis 5.7).

Figure 5. Forest plot of comparison: 5 Levonorgestrel 1.5 mg versus mifepristone mid-dose (25-50 mg), outcome: 5.1 Observed number of pregnancies (all women).

6. Low-dose mifepristone (< 25 mg) versus LNG Nine Chinese (Bu 2006; Dong 2009; Li W 2002; Lin 2000; Liu 2000; Pei 2001; Sheng A 2002; Wang C 2000; Wu 1999a), one UK (Hamoda 2004) and one multinational WHO trial (Von Hertzen 2002) compared LNG (4856 women) with low-dose mifepristone

(3480 women). There was a statistically significant difference in effectiveness between LNG and low-dose mifepristone regimens when all studies were included (RR 0.70; 95% CI 0.50 to 0.97) (Figure 6; Analysis 6.1). When only high-quality studies (Hamoda 2004; Liu 2000; Von Hertzen 2002; Wu 1999a) were included in the meta-analysis, the difference was not significant at the 0.05


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level (RR 0.70; 95% CI 0.49 to 1.01) but it was significant at the 0.10 level (RR 0.70; 95% CI 0.52 to 0.95). Additional analysis of data from one trial (Von Hertzen 2002) indicated that the above conclusions were not modified by whether women abstained from further acts of intercourse or not (P = 0.14 for the interaction test) or (Hamoda 2004; Von Hertzen 2002) by the time elapsed (within or after 72 h) from intercourse to treatment administration (P = 0.99 for the interaction test). When assuming that all the loss of follow-up being pregnant in LNG group but none of the loss being pregnant in mifepristone group, results indicated that mifepristone was associated with significantly lower risk of pregnancy than LNG (RR 0.70; 95% CI 0.50 to 0.98) (Figure 7; Analysis 6.8). This

association was not evident when it was supposed that there was no loss in LNG but all loss in mifepristone with pregnancy (RR 0.90; 95% CI 0.76 to 0.1.05) (Figure 8; Analysis 6.9). Three trials reported most types of side effects (Hamoda 2004; Von Hertzen 2002; Wu 1999a). Only a few significant differences were identified between the two regimens in these trials. Menstrual delay was less frequent (RR 1.75; 95% CI 1.51 to 2.03) and early return of menstruation was more frequent (RR 0.44; 95% CI 0.33 to 0.58) in the LNG group than in the mifepristone group (Analysis 6.7). Low-dose mifepristone was associated with lower risk of bleeding in the first days than LNG (RR 0.62; 95% CI 0.55 to 0.70; Analysis 6.6).

Figure 6. Forest plot of comparison: 6 Levonorgestrel 1.5 mg versus mifepristone low dose (< 25 mg), outcome: 6.1 Observed number of pregnancies (all women).


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Figure 7. Forest plot of comparison: 6 Levonorgestrel 1.5 mg versus mifepristone low dose (< 25 mg), outcome: 6.8 ITT (all loss follow-up as pregnancy in LNG, and no preg in mifepristone).

Figure 8. Forest plot of comparison: 6 Levonorgestrel 1.5 mg versus mifepristone low dose (< 25 mg), outcome: 6.9 ITT (all loss follow-up as no pregnancy in LNG, and preg in mifepristone).

There were no trials that compared LNG with high-dose (> 50 mg) mifepristone. 7. UPA (all doses) versus LNG UPA is a second-generation progesterone receptor modulator. Creinin 2006 compared LNG split-dose regimen with UPA unmicronised 50 mg single-dose orally within 72 hours. Glasier 2010 compared LNG single-dose regimen with UPA micronised 30 mg single-dose orally within 120 hours of unprotected intercourse. Since both the European Medicines Agency (EMA) and the Food

and Drug Administration (FDA, US) accepted the bioequivalence of the two regimens, data from the two trials were combined for meta-analysis in this review. UPA appeared to have prevented more pregnancies (RR 0.63) than LNG within 72 hours after unprotected intercourse. However, the difference was not statistically significant at the 0.05 level (95% CI 0.37 to 1.07) but was significant at the 0.10 level (95% CI 0.40 to 0.98). When all the five-day data from the Glasier 2010 trial were combined with the three-day data from Creinin 2006 trial, the pregnancy rate was sta-


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tistically significantly lower among women using UPA (RR 0.59; 95% CI 0.35 to 0.99) (Figure 9; Analysis 7.1) than among LNG users. When the data were stratified by time of treatment, no significant difference in pregnancy between LNG and UPA regimens was identified during any segment of time. It was noted that the sample size of any subgroup of data was relatively small. Somewhat unexpectedly, further analysis showed that UPA prevented more pregnancies in the low-risk population (RR 0.54; 95% CI 0.30 to 0.97). Women who took UPA were less likely to have earlier return of menses (return before the expected date), compared with those who received LNG (RR 0.43; 95% CI 0.37 to 0.50) and UPA users were more likely to have later return of next menses (return after the expected date) than those who received LNG (RR 1.65; 95% CI 1.42 to 1.92) (Analysis 7.8). Figure 9. Forest plot of comparison: 7 Levonorgestrel 1.5 mg versus UPA (all doses), outcome: 7.1 Observed number of pregnancy (all women).

8. LNG versus anordrin One trial from China (Xu Z 2000) compared LNG split-dose regimen with anordrin (7.5 mg two dose 12 h apart, then 7.5 mg/day for eight days) in 172 women. No difference in the risk of pregnancy between the two regimens was identified (RR 0.67; 95% CI 0.11 to 3.89) (Analysis 8.2). However, the sample size of this trail may be too small to identify a subtle difference between the two regimens.

9. Mifepristone low dose (10 mg) versus mifepristone low dose (5 mg) Two trials (Lan XL 2006; Zhang Y 1998) compared the effectiveness of mifepristone 10 mg to that of mifepristone 5 mg among 392 women in China. The effectiveness was similar between the two regimens (RR 0.70; 95% CI 0.12 to 4.17) (Analysis 9.1).

10. Mifepristone mid-dose (25-50 mg) versus mifepristone low dose (< 25 mg) Twenty-five trials were included in this comparison. Seventeen trials were two-arm comparisons of mifepristone 25 mg versus mifepristone 10 mg (Chen 2009; Du 2002; Fan 2001; Han L 2001; Lai Z 2004; Qi 2000b; Sang 1999; Wang SZ 2001; Wang L 2004; Wang J 2006; Wang ZW 2008; Wei RH 2002; Wei H 2011; Xiao 2002; Xie HH 2010; Zeng MY 2008; Zuo 1999 ). Seven trials had three arms (Cheng 1999a; Ding 2005; Tan L 2003; WHO 1999; Zhang Y 1998; Zhang Y 2002; Zhao J 2003) and one trial had four comparisons (Cao 1999). Except for the WHO trial (WHO 1999), all other trials were conducted in China. Although the pooled data showed that the mid-dose regimen was more effective than the low-dose regimen (RR 0.73; 95% CI 0.55 to 0.97; Analysis 10.1), this finding was not evident when the analysis was limited to the six trials with adequate allocation concealment (RR 0.75; 95% CI 0.50 to 1.10) (Qi 2000b; Sang 1999; Wang SZ 2001; WHO 1999; Xiao 2002; Zuo 1999). Additional analysis of the trials Cheng 1999a, WHO 1999 and Xiao 2002 indicated that the results were not modified when women who abstained


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from further acts of intercourse were not included (P = 0.77 for the interaction test). Mid-dose mifepristone was associated with higher risks of bleeding (11 trials; RR 1.85; 95% CI 1.55 to 2.20) and menstrual delay (22 trials; RR 1.28; 95% CI 1.11 to 1.47) than low-dose mifepristone (Analysis 10.4).

overall side effects (RR 2.64; 95% CI 1.57 to 4.43) and delays in subsequent menses (8 trials; RR 1.56; 95% CI 1.37 to 1.78) were significantly more frequent in the high-dose regimen group (Analysis 13.3; Analysis 13.4; Analysis 13.5). 14. Mifepristone versus Yuzpe regimen

11. Mifepristone mid dose (50 mg) versus mifepristone mid dose (25 mg) Thirteen Chinese trials (Cao 1999; Chen 2002 Cheng 1999a; Fang 2000; Han 1996; Li 2000; Li H 2000; Lou C 2002; Tan 1999; Xie 1998; Yang F 2003; Zhang JQ 2000; Zhao J 2003) compared mifepristone 50 mg with mifepristone 25 mg. The metaanalysis indicated that the two regimens had similar effectiveness (RR 0.72; 95% CI 0.41 to 1.27; Analysis 11.1), but the 50 mg regimen was associated with a significantly higher probability of menstrual delay (RR 1.32; 95% CI 1.12 to 1.56; Analysis 11.5) than the 25 mg regimen. One trial (Zhang X 1999a) compared three different regimens of mifepristone (1) mifepristone 25 mg orally two doses 12 hours apart; (2) mifepristone 10 mg/day for five days and (3) mifepristone 10 mg/day for three days. It is worth noting that the sample size of this trial was too small to make a firm conclusion. 12. Mifepristone high dose (> 50 mg) versus mifepristone low dose (< 25 mg) Six trials, one with two (Zheng A 2005; 600 mg vs 25 mg), one with four (Cao 1999; 100 mg vs 50 mg vs 25 mg vs 10 mg) and four with three (WHO 1999; 600 mg vs 50 mg vs 10 mg; Ding 2005; 75 mg vs 50 mg vs 10 mg; Tan L 2003; 150 mg vs 50 mg vs 12.5 mg; Zhang Y 2002; 100 mg vs 50 mg vs 10 mg) treatment arms were included in the analysis comparing a high-dose mifepristone regimen with a low-dose regimen. In the Cao 1999 and Tan L 2003 trials, the high-dose mifepristone regimen showed lower risk of pregnancy than the low-dose regimen, whereas in the WHO 1999 and Ding 2005 trials, the risk of pregnancy was similar between the two regimens. The overall side effects (RR 13.04; 95% CI 5.13 to 33.15), spotting/bleeding (RR 2.36; 95% CI 1.89 to 2.95) and delays of subsequent menses (4 trials; RR 1.98; 95% CI 1.66 to 2.37) were significantly more frequent in the high-dose mifepristone group than in the low-dose one (Analysis 12.4). 13. Mifepristone high dose (> 50 mg) versus mifepristone mid dose (25-50 mg) Eight Chinese trials (Cao 1999; Ding 2005; Li H 2000; Qian 1999; Tan L 2003; Xie 1998; Zhang Y 1998; Zheng A 2005) and one WHO trial (WHO 1999) were included in this comparison. The WHO trial had three study arms (600 mg, 50 mg and 10 mg). The frequency of pregnancy was similar between high- and mid-dose groups (RR 0.93; 95% CI 0.50 to 1.72; Analysis 13.1). However, bleeding episodes (RR 1.32; 95% CI 1.12 to 1.56),

Three trials conducted in the UK compared high-dose mifepristone (100 mg and 600 mg) with the Yuzpe regimen (Webb 1992 (600 mg), Glasier 1992 (600 mg) and Ashok 2002 (100 mg)). The Webb 1992 trial included danazol as a third arm. This trial was stopped early because mifepristone showed higher effectiveness than the Yuzpe and danazol (number of pregnancies: 0/195 with mifepristone vs 9/193 with danazol vs 5/191 with Yuzpe). The risk of pregnancy among mifepristone users was only 14% of that among the Yuzpe users (RR 0.14; 95% CI 0.05 to 0.41; Analysis 14.1). One trial investigated whether the effectiveness was influenced by high- or low-risk behaviour (Glasier 1992). No pregnancy was observed among women who abstained from further intercourse, but the sample size of this study was relatively small. There were significantly fewer complaints of nausea (RR 0.63; 95% CI 0.53 to 0.76), vomiting (RR 0.12; 95% CI 0.07 to 0.20), headache (RR 0.75; 95% CI 0.61 to 0.91), dizziness (Ashok 2002; RR 0.58; 95% CI 0.42 to 0.80), fatigue (Ashok 2002; RR 0.81; 95% CI 0.68 to 0.95), low abdominal pain (Ashok 2002; RR 0.76; 95% CI 0.61 to 0.95), hot flushes (Ashok 2002; RR 0.58; 95% CI 0.40 to 0.83) and tiredness (Ashok 2002; RR 0.75; 95% CI 0.59 to 0.95) observed in women receiving mifepristone (Analysis 14.6). The delay in menses was significantly more frequently reported by women receiving mifepristone compared to those who used the Yuzpe regimen (RR 2.83; 95% CI 2.30 to 3.47; Analysis 14.7). 15. Mifepristone versus danazol Two trials (Webb 1992; Yang 2001) compared mifepristone (50 mg or 600 mg) with danazol (400 mg or 600 mg repeated after 12 h). Mifepristone showed significantly lower risk of pregnancy (RR 0.10; 95% CI 0.02 to 0.55; Analysis 15.1) and lower risk of any side effect (RR 0.35; 95% CI 0.13 to 0.95; Analysis 15.2) than danazol. Meta-analysis indicated that delay of menses was similar between women using mifepristone and users of danazol ( RR 2.39; 0.56 to 10.27; Analysis 15.4), although the former showed a significantly higher risk of menstrual delay than the latter in one trial (Webb 1992). 16. Mifepristone versus anordrin Seven trials (Chen 2001; Fu X 2000; Han 1995; Liu L 2001; Wang 1999; Xu Z 2000; Yang 2001) compared mid-dose mifepristone with anordrin in different regimens (the total dosage ranging from 15 mg to 90 mg). Mifepristone was more effective in preventing pregnancy than anordrin (RR 0.26; 95% CI 0.11 to 0.63; Analysis


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16.1). Mifepristone had fewer overall side effects than anordrin (4 trials; RR 0.62; 95% CI 0.43 to 0.91), but no significant differences were evident in spotting/bleeding (Analysis 16.4) and delay in the onset of next menses (Analysis 16.5).

17. Mifepristone low- or mid-dose versus mifepristone plus anordrin Five trials (Han 1995; Han 1996; Lou X 2005; Sang 1999; Zhang YM 2002) compared low- or mid-doses of mifepristone with mifepristone combined with anordrin. The risks of pregnancies in the two comparison groups were similar (RR 1.32; 95% CI 0.73 to 2.41). However, the combination regimen showed significantly higher risks of nausea (RR 0.53; 95% CI 0.44 to 0.65), vomiting (RR 0.26: 95% CI 0.14 to 0.50), fatigue (RR 0.66: 95% CI 0.49 to 0.89) and menstrual delay (RR 0.79; 95% CI 0.65 to 0.97), but a significantly lower risk of spotting/bleeding (RR 1.80; 95% CI 1.33 to 2.43) than the mifepristone-only regimen (Analysis 17.4).

18. Mifepristone (25 mg) versus mifepristone with methotrexate (5 mg) Two trials (Chen 2002a and Zeng XY 2007) compared mid-dose mifepristone (25 mg) regimen with regimen of mifepristone combined with methotrexate (5 mg). Two women were pregnant in the mifepristone alone group, and none in the combination group. The difference was not statistically significant (RR 3.00; 95% CI 0.32 to 28.36), Since only 100 women were recruited in each arm, the non-significant result may be due partly to small sample sizes of these two trials (Analysis 18.1).

19. Mifepristone low dose versus mifepristone with tamoxifen (20 mg) One double-blind trial (He CH 2002) compared low-dose mifepristone with mifepristone combined with tamoxifen (20 mg). There were no statistically significant differences in preventing pregnancy (RR 3.00; 95% CI 0.31 to 28.60) and delay of next menses (RR 1.79; 95% CI 0.93 to 3.43) between the two regimens (Analysis 19.1).

20. Mifepristone low dose versus mifepristone with misoprostol (200 µg) Wu 2002 compared low-dose mifepristone with mifepristone combined with misoprostol (200 µg). There were more pregnancies with the mifepristone alone regimen but the difference was not statistically significant (7/300 with mifepristone vs 2/299 with misoprostol; RR 3.49; 95% CI 0.73 to 16.65; Analysis 20.1). The combination regimen showed significantly higher risks of abdominal pain than the mifepristone alone regimen (RR 0.31; 95% CI 0.10 to 0.93; Analysis 20.6).

21. Mifepristone versus Cu-IUD Liu L 2002 compared mifepristone 50 mg with Cu-IUD. One pregnancy occurred in the mifepristone group and none in the Cu-IUD group (RR 1.51; 95% CI 0.06 to 36.67; Analysis 21.1). However, the sample size of this study was relatively small (195 women with mifepristone vs 95 women with Cu-IUD). Cu-IUD users showed significantly higher risks of abdominal pain than mifepristone users (RR 0.01; 95% CI 0.00 to 0.22; Analysis 21.6)

22. Mifepristone versus gestrinone Wu 2010 conducted a randomised double-blind multicentre clinical trial (996 women) comparing mifepristone 10 mg with gestrinone 10 mg (a 19-nortestosterone derivative with anti-progestagenic, anti-oestrogenic and anti-gonadotropic properties). There were no statistically significant differences in preventing pregnancy (RR 0.75; 95% CI 0.32 to 1.76; Analysis 22.1) and in the overall side effects (RR 1.08; 95% CI 0.88 to 1.33; Analysis 22.2) between the two medications. Mifepristone was associated with higher risk of menstrual delay than gestrinone (RR 1.37; 95% CI 1.03 to 1.82; Analysis 22.3). Gestrinone showed significantly higher risk of early return to next menses than mifepristone (RR 0.37; 95% CI 0.20 to 0.69; Analysis 22.3)

23. Danazol versus Yuzpe regimen Danazol was compared to the Yuzpe regimen in one trial (Rowlands 1983) and to the Yuzpe regimen and mifepristone (600 mg) in a three-arm trial (Webb 1992). The sample sizes of both trials were not enough to make a firm conclusion on whether danazol and the Yuzpe regimen differed in efficacy (RR 1.78; 95% CI 0.61 to 5.22). Nausea (RR 0.38; 95% CI 0.30 to 0.47) and vomiting (RR 0.13; 95% CI 0.06 to 0.27) were statistically significantly less common in danazol group (Analysis 23.4). No significant differences of complaints of breast tenderness (RR 1.14; 95% CI 0.75 to 1.72; Analysis 23.4) and delay of menses (RR 1.53; 95% CI 0.74 to 3.18; Analysis 23.5) were identified between the two regimens. Other side effects were not reported in this trial.

24. High-dose oestrogen versus Yuzpe regimen One trial conducted in the early 1980s compared the Yuzpe regimen with a five-day ethinyl oestradiol 5 mg regimen (standard treatment at that time) in a double-blind trial (Van Santen 1985a). One pregnancy in the Yuzpe group (200 women) and two in the ethinyl oestradiol group (184 women) were reported. The difference of risks of pregnancy was not statistically significant (RR 2.17; 95% CI 0.20 to 23.77; Analysis 24.1).

25. Half-dose Yuzpe regimen versus standard Yuzpe regimen


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Ellertson et al. (Ellertson 2003) compared the standard Yuzpe regimen (of two doses 12 h apart) to a half dose given only once, and to a standard regimen replacing norgestrel with norethindrone in a three-arm trial. There was no statistically significant difference in effectiveness (23/648 with half-dose vs 17/675 with standard dose; RR 1.41; 95% CI 0.76 to 2.61; Analysis 25.1) between the half dose and the standard regimen. The side-effect profile was significantly improved with the half dose (any side effect: RR 0.85; 95% CI 0.77 to 0.93; Analysis 25.2; nausea: RR 0.86; 95% CI 0.77 to 0.97; vomiting: RR 0.50; 0.36 to 0.69; Analysis 25.3).

26. Risk status Eleven trials (Cheng 1999a; Dada 2010; Glasier 1992; Glasier 2010; Ho 1993; Ngai 2005; Von Hertzen 2002; WHO 1998; WHO 1999; Xiao 2002; Zhang JQ 2000) reported the numbers of women of high-risk status (4852 women had further acts of intercourse during the same cycle in which EC was used) and of low-risk status (14,848 women without further acts of coitus during that cycle). We pooled the pregnancy numbers of each of the two groups of women regardless the regimens they used. Result of meta-analysis indicates that the risk of pregnancy was statistically significantly higher in the high-risk group of women (RR 2.67; 95% CI 2.11 to 3.39; Analysis 26.1) than in the lowrisk group.

27. Time elapsed since intercourse (coitus-treatment interval) Seven trials reported the time of coitus-treatment interval. Ashok 2002, Creinin 2006, Ho 1993 and WHO 1998, compared three different time intervals elapsed since intercourse (≤ 24 h vs > 24-48 h vs > 48-72 h) ; Hamoda 2004 and Von Hertzen 2002 compared two different time intervals (within 72 h vs > 72 h); Glasier 2010 compared five different time intervals (≤ 24 h vs 25-48 h vs 49-72 h vs 73-96 h vs 97-120 h). Additional analysis was done by pooling all the data by time intervals and types of medications: progesterone-only ECP (LNG), anti-progestin ECPs (mifepristone and UPA ) and Yuzpe . Comparing the risk of pregnancy of women taking LNG on the first day with those taking it on the second or the third day, the difference was not significant at the 0.05 level. This risk was also similar between the second and the third day. We performed further Chi2 test for linear trend on the risk of pregnancy during the few days after unprotected intercourse. The linear trend was not significant at the 0.05 level (P = 0.106). However, compared with women taking LNG after 48 hours, those taking it within 48 hours appeared less likely to be pregnant (RR 0.54; 95% CI 0.27 to 1.11;Analysis 28.3). Moreover, comparing women taking LNG within 72 hours of intercourse with those taking it after 72 hours, the former had a significantly lower risk of pregnancy than the latter (RR 0.51; 95% CI 0.31 to 0.84; Analysis 28.4). These

results indicate that the effectiveness of LNG is increased by taking it earlier. The non-significant linear trend is perhaps due to small sample size of available data. Women taking Yuzpe within 24 hours after unprotected intercourse had significantly lower risk of pregnancy than women taking it between 24-48 hours (RR 0.47; 95% CI 0.26 to 0.88; Analysis 30.1). Moreover, the latter group of women had significantly lower risk of pregnancy than women taking it between 48-72 hours (RR 0.41; 95% CI 0.18 to 0.89; Analysis 30.2). It was not evident that the coitus-treatment time interval affects the effectiveness of anti-progestin ECPs (including mifepristone Analysis 27.1, Analysis 27.2, Analysis 27.3, Analysis 27.4 and UPA, Analysis 29.1; Analysis 29.2; Analysis 29.3; Analysis 29.4). Ectopic pregnancies Five cases of ectopic pregnancy were identified among the included 100 trials. Of them, WHO 1999 reported two cases after 50 mg mifepristone, Sang 1999 reported one case after 10 mg mifepristone, and Su 2001 and Von Hertzen 2002 reported one case each after split-dose of LNG. Pregnancy outcome after ECP failure Eleven healthy infants were reported to be delivered following the use of ECPs (Arowojolu 2002; Glasier 2010; Webb 1992) in this review. Seven mothers used LNG, two used the Yuzpe regimen, one used danazol and one used mifepristone.

DISCUSSION Nineteen new trials have been added to this review since its last publication in 2008. Although, as before, most trials were conducted in China, the availability of several large multicentre trials was helpful in increasing the power and generalisation of study findings of this review. The available evidence indicated that EC is a safe and effective contraceptive method. Although the risk of pregnancy following unprotected intercourse had been overestimated in previous trials (e.g. Ellertson 2003), a substantial percentage of expected pregnancies can be prevented with the use of this method. Since it was evident that emergency contraceptives were effective, most recent studies on EC were aimed to reduce the dosage or the times of medication administration so that client’s compliance or cost of treatment, or both, could be improved. Because of this reason, many EC trials were designed as equivalence trials rather than superiority trials (trying to show that two treatments are as good as each other rather than one is more effective than the other). It is common to claim an equivalent effectiveness when the difference between two treatment groups is not statistically significant. Nevertheless, only a few trials in this review calculated their sample sizes on the basis of an equivalence approach


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that usually requires a large study sample. Thus conclusion may not be reliable when the study sample size is not enough. Another concern of this review is that blindness of treatments was uncommon in most trials. However, since pregnancy was an objective outcome, the lack of blindness probably had little influence on results. Among ECPs, the focus was on mifepristone and LNG. Both of the methods appeared to be more effective and better tolerated than the classical Yuzpe regimen. However, the Yuzpe regimen may still be the only available regimen in some places. The results of the Ellertson trial suggested that the half dose Yuzpe regimen had a more favourable side-effect profile. It was difficult to make any conclusion regarding the relative effectiveness. Further research is needed to narrow the CIs, in other words, to increase the precision of the estimate. It is probably safe to continue the standard Yuzpe regimen where mifepristone or LNG is not available. Three trials investigated the efficacies of LNG 1.5 mg single-dose and 0.75 mg two-dose regimens. These three trials were all of good quality and a heterogeneity test indicated that the variation in study outcomes between trials was not statistically significant. The result of the meta-analysis (RR 0.84; 95% CI 0.53 to 1.33) suggested that the effect of the single-dose regimen was similar to that of two-dose regimen. Hence we can safely conclude that the single-dose is clinically equivalent to the split-dose regimen. One double-blind randomised multicentre trial conducted in China (Ngai 2005) that compared two regimens of LNG split-dose administrated at 24 hours or 12 hours apart showed that the two regimens had similar overall effectiveness (RR 0.98; 95% CI 0.53 to 1.82). However, among high-risk women, the 24-hour splitdose regimen appeared more effective than the 12-hour split-dose regimen, although this association was not statistically significant. These findings are of important clinical implication because a client’s compliance to the timing of the second dose is a crucial issue. This is the case for both LNG and Yuzpe regimens. LNG versus mid-dose mifepristone trials were not methodologically sound in terms of allocation concealment. It is therefore not clear how robust the meta-analysis results are. This updated review indicates that the anti-progestin mifepristone is the most effective hormonal emergency contraceptive. For example, the mid-dose of mifepristone (25-50 mg) proved significantly more effective than the standard LNG regimen. This finding was evident in the 2004 version of this review; with addition of new reports, the difference of effectiveness between mifepristone and LNG regimens became larger and the estimated CIs were narrowed. More women who took mid-dose mifepristone had a delay in menses than LNG users, although other types of side effects were less common among mifepristone users. Low-dose mifepristone was less effective than mid-dose mifepristone in preventing pregnancy in the meta-analysis of 25 trials (RR 0.73; 95% CI 0.55 to 0.97). However, limiting the data to the six

trials with good study quality led to a RR of 0.75 with a 95% CI ranging from 0.50 to 1.10, indicating that effectiveness difference between low- and mid-dose mifepristone regimens is not very affirmative. As expected, menstrual delay was more common with the mid-dose regimen. UPA is a second-generation progesterone receptor modulator, which has been marked in Europe since 2009 and was approved by FDA in 2010. It inhibits or significantly delays follicular rupture for over five days if given immediately before ovulation by postponing the luteinising hormone (LH) peak concentration (Brache 2010). As a new drug entity, UPA is only available on prescription in Europe and US. Two trials compared UPA (Creinin 2006: unmicronised 50 mg single-dose; Glasier 2010: micronised 30 mg) with LNG 1.5 mg single dose. The bioequivalence of the two regimens was accepted by the EMA and FDA. Data from these trials were thus combined in a meta-analysis. UPA appeared more effective (RR 0.63) than LNG within 72 hours after unprotected intercourse, which was significant at a marginal level (P = 0.08). When the 72- to 120-hour data from the Glasier 2010 trial were included in meta-analysis, UPA was associated with lower risk of pregnancy than LNG and the difference was significant at the 0.05 level. Since the Creinin 2006 trial did not recruit participants who had unprotected intercourse after 72 hours, the rationale of combining all five-day data from the Glasier 2010 trial in the analysis is debatable. It is noted that the Glasier 2010 trial was single blind (participants blinded, investigator not blinded), slightly more participants were excluded in the UPA group than in the control group in the analysis and the manufacturer was involved in trial. We may need more trials conducted by independent investigators to make a firm conclusion. Gestrinone is a 19-nortestosterone derivative with anti-progestagenic, anti-oestrogenic and anti-gonadotropic properties. Only one trial compared gestrinone with mifepristone (10 mg), and no significant difference of effectiveness between the two medications was identified. We also compared the efficacies of mifepristone 50 mg with 25 mg, and mifepristone 10 mg with 5 mg. This update review included 14 trials for the two comparisons. Results showed that either paired regimens had similar effectiveness of pregnancy prevention and similar probability of delayed menses. Hence, we conclude that there are no important differences between the paired regimens. We assessed the effects of a woman’s risk status and time elapsed after intercourse on the success of treatments. Participants and pregnancy outcomes were stratified by the two factors. Results showed that neither woman’s risk status nor the time elapsed after intercourse impacted the comparative effectiveness between LNG single dose and split-dose and between LNG and the Yuzpe regimen. We also conducted ITT simulation analyses (for main comparisons) with extreme scenarios to see if post-randomisation exclusions and losses to follow-up could affect the results, but did


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not find any substantive threat to the validity of the results. In this version of the review, we did additional analyses comparing pregnancy risk in high-risk women with that in low-risk women, and comparing the risk between time intervals elapsed after intercourse among women using each of three different types of emergency contraceptives. Results indicated that the high-risk women were significantly more likely to be pregnant than their low-risk counterparts (RR 2.67; 95% CI 2.11 to 3.39); women taking LNG within 72 hours after unprotected intercourse had a significantly lower risk of pregnancy than those taking the pills after 72 hours (RR 0.51; 95% CI 0.31 to 0.84); women taking the Yuzpe regimen within 24 hours were significantly less likely to be pregnant than those taking the pills between 24 and 48 hours after unprotected intercourse (RR 0.47; 95% CI 0.26 to 0.88); the latter group of women had a significantly lower risk of pregnancy than those who adopted the method between 48 and 72 hours of intercourse (RR 0.41; 95% CI 0.18 to 0.89). It is not evident that the coitus-treatment interval affected the effectiveness of antiprogestin ECPs (mifepristone and UPA). Nevertheless, these results should be used with caution because they are not primary comparison analyses. Several studies compared regimens that combined anordrin, tamoxifen, danazol or misoprostol with mifepristone with regimens containing mifepristone alone. The combination regimens did not show any major advantage over the single regimens and thus merit no further research.

Ectopic pregnancy Van Look 1993 reported that ectopic pregnancies accounted for about 10% of the pregnancies among EC users with oestrogen (such as Yuzpe). One explanation might be that post-coital administration of oestrogen usually prevents uterine pregnancy but not ectopic implantation. For this reason, a history of ectopic pregnancy was generally considered as a contraindication for postcoital oestrogen therapy (Van Look 1993). However, only five cases were identified among 55,666 EC users in this review, indicating that ectopic pregnancy was a rare event among women using any particular EC regimen. This result is in agreement with the findings of Cleland 2010 (a systematic review), which included 136 studies that investigated the effects of LNG and mifepristone as EC. They also found that the ECPs appeared to be effective in lowering the probability of ectopic pregnancy.

Pregnancy outcome after the emergency contraceptive failure LNG ECPs would not harm the development of a foetus if women take it by mistake early in pregnancy. Zhang and colleagues reported in a cohort study (Zhang L 2009) that the rates of miscarriage and malformations and sex ratio at birth were not statistically significantly different between women who used LNG for

EC during their conception cycle and those who did not use any hormonal medications. A total of 11 infants were born following the use of ECPs (LNG, Yuzpe regimen, danazol and mifepristone) were identified in this review and all the infants are healthy.

IUD The effectiveness of inserting an intrauterine device as an emergency contraceptive method has not been adequately investigated. This review only includes one small trial (Liu L 2002) that compared mifepristone with a Cu-IUD (Analysis 21.1). Only one pregnancy occurred in the mifepristone group in this trial. Although there were some barriers to using intrauterine devices as EC (Reuter 1999), data from non-randomised studies (Ban 2001; Fan H 2001; Han Y 2001; Wang C 2000; Wu S 2010; Zhang J 1999), which were all conducted in China, suggested that inserting Cu-IUDs for EC could be effective in preventing unintended pregnancy (3 pregnancies/3470 women, failure rate: 0.09%), and more than 80% women kept the Cu-IUD in place after EC as a long-term contraceptive method.

Counselling Counselling and good service can reduce the risk of ’user failure’ (Cheng 1999b). Other aspects of EC intervention, such as raising awareness among the general public and healthcare delivery systems, are helpful to maximise the utilisation and increase the effectiveness of the interventions and should deserve more attention.

AUTHORS’ CONCLUSIONS Implications for practice EC should be offered to all women requesting this service. Where readily available, mifepristone should be the first choice for hormonal EC. UPA seemed slightly more effective than LNG and can be an alternative where this medicine is accessible and affordable. Where UPA or mifepristone is not available, single-dose LNG 1.5 mg can be a choice. In places where UPA or mifepristone or LNG are not available, the Yuzpe regimen should be offered. Women receiving mifepristone should be informed that there may be a few days of delay in onset of menses. If using LNG or the Yuzpe regimen for EC, women should start the method as soon as possible to obtain the highest effectiveness (Piaggio 1999). CuIUD insertion can be offered to women presenting too late for ECPs, with no risk of sexually transmitted diseases and preferring long-term contraception.


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Implications for research In order to demonstrate the relative effectiveness of UPA against LNG more data are needed. The effectiveness of LNG, UPA and mifepristone in relation to time since unprotected intercourse is not confirmed and more studies are needed. Moreover, effectiveness of intrauterine devices should be further evaluated. There is also a need to compare the effectiveness and safety of UPA with those of mifepristone in countries where it is applicable so as to inform clients and service providers. The trial protocols should clearly state when equivalence is sought and powered accordingly. Most of the trials included in this review did not have sufficiently detailed reporting to enable satisfactory methodological quality assessment. Future trials should report the methods in sufficient detail to allow this assessment.

We are grateful to Drs A. Glasier, J. Guillebaud, P.C. Ho, S. Rowlands, A. Webb, Xiao Bilian, A. Templeton and H. von Hertzen who responded to our requests for information about their (ongoing) trials. We are particularly indebted to Mr. A. Peregoudov for providing additional data from the WHO 1998 trial. We thank Dr. R. Guidotti for his assistance with translation, Dr. C. van Oel for her work on the initial review and Dr. H. von Hertzen for her comments on earlier drafts. In the 2007 update of the review David Grimes, Laureen Lopez and Carol Manion made substantive contributions to the review by updating the literature searches, extraction of duplicates and re-appraisal of allocation concealment scores for all trials. We own great gratitude to Drs Gilda G.P. Piaggio, Enrique E. Ezcurra and Paul P.F.A. Van Look, who were coauthors of previous versions of this review and made a valuable contribution to the success of this review. In this updated review Ms. Carol Manion and Mr. Dongbing Chen did the literature searches, and Dr. Qiuju Chen duplicated the data extraction.

ACKNOWLEDGEMENTS

REFERENCES

References to studies included in this review Arowojolu 2002 {published data only} Arowojolu AO, Okewole LA, Adekunle AO. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception 2002;66:269–73. Ashok 2002 {published data only} Ashok PW, Stalder C, Wagaarachchi PT, Flett GM, Melvin L, Templeton A. A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for emergency contraception. BJOG 2002;109:553–60. Askalani 1987 {published data only} Askalani AH, Al-Senity AM, Al-Agizy HM, Salam HI, AlMasry GI, El-Sadek SM. Evaluation of copper T-200 as a post-coital contraceptive. Egyptian Journal of Obstetrics and Gynaecology 1987;13:63–6. Bu 2006 {published data only (unpublished sought but not used)} Bu GY, Yang MY, Cao XL. Clinical study on administration of low dose of mifepristone and levonorgestrel in urgent postcoital contraception. Progress in Modern Biomedicine 2006;6(2):53–4. Cao 1999 {published data only} Cao P, Li M, Xu J, Li Q. Different doses of mifepristone for emergency contraception. Chinese Journal of Practical Gynaecology and Obstetrics 1999;15:295–6. Chen 2001 {published data only} Chen G. Mifepristone for emergency contraception. Journal of Guangxi Traditional Chinese Medical University 2001;4: 22–4.

Chen 2002 {published data only} Chen R, Li Q, Zhang Y, Huang M, Chen Y, Zhong X, et al.A comparative study of low-dose mifepristone for emergency contraception. Shi Yong Yi Xue Zha zi 2002;18: 1028–9. Chen 2002a {published data only} Chen H, Min X. Mifepristone in combination with MTX for emergency contraception. Strait Pharmaceutical Journal 2002;14:51–2. Chen 2008 {published data only} Chen Y. A comparative study of mifepristone and LNG for emergency contraception. China Foreign Medical Treatment 2008;34(34):60. Chen 2009 {published data only} Chen S, An HB, Wang D, Jin FB. Different dose of mifepristone for emergency contraception. China Health Care Nutrition - Clinical Medicine Journal 2009;(2):28–9. Cheng 1999a {published data only} Cheng L, Tong CH, Xiao ZH. Low doses of mifepristone for emergency postcoital contraception. Chinese Journal of Obstetrics and Gynaecology 1999;34:335–8. Cheng 2009 {published data only} Cheng S. Clinical observation on YUTING for emergency contraception. Chinese Journal of Modern Drug Application 2009;3(8):147–8. Creinin 2006 {published data only} Creinin MD, Schlaff W, Archer DF, Wan L, Frezieres R, Tomas M, et al.Progesterone receptor modulator for emergency contraception. A randomized controlled trial. Obstetrics & Gynecology 2006;108:1089–97.


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Dada 2010 {published data only} Dada OA, Godfrey EM, Piaggio G, von Hertzen H, Nigerian Network for Reproductive Health Research and Training. A randomized, double-blind, noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria. Contraception 2010;82(4):373–8. Ding 2005 {published data only} Ding G. Different doses of mifepristone for emergency contraception. Journal of Practice Diagnosis and Treatment 2005;19:226–7. Dong 2009 {published data only} Dong JF. Two different methods for emergency contraception. Practical Clinical Journal of Integrated Traditional Chinese and Western Medicine 2009;9(1):58–9. Du 2002 {published data only} Du J. Low dose of mifepristone for emergency contraception. Henan Yi Yao Xin Xi 2002;10:14–5. Ellertson 2003 {published data only} Ellertson C, Webb A, Blanchard K, Bigrigg A, Haskell S, Shochet T, et al.Modifying the Yuzpe regimen of emergency contraception: a multicenter randomized controlled trial. Obstetrics and Gynecology 2003;101:1160–7. Fan 2001 {published data only} Fan H, Cheng Y, Guo F, Wu S, Tan Y, Chen X, Wu X. Low dose of mifepristone for emergency contraception. Hubei Yu Fang Yi Xue Zha Zi 2001;23:52. Fang 2000 {published data only} Fang Q, Guo X, Pan J, Xiao J, Li Y. A comparative study on different doses of mifepristone for emergency contraception. Maternal and Child Health Care of China 2000;15:48–9. Farajkhoda 2009 {published data only} Farajkhoda T, Khoshbin A, Enjezab B, Bokaei M, Karimi Zarchi M. Assessment of two emergency contraceptive regimens in Iran: levonorgestrel versus the Yuzpe. Niger Journal of Clinical Practice 2009;12(4):450–2. Fu X 2000 {published data only} Fu X, Wang L, Jiang Q, Yang X. Anordrin and mifepristone for emergency contraception. Journal of Qinghai Medical College 2000;21:43–4. Gan XH 2007 {published data only} Gan XH, Jiang H, Li LP. A clinical study of lowdose mifepristone for emergency contraception. Modern Medicine Health 2007;23(11):1634–5. Glasier 1992 {published and unpublished data} Glasier A, Thong KJ, Dewar M, Mackie M, Baird D. Postcoital contraception with mifepristone (letter). Lancet 1991;337:1414–5. ∗ Glasier A, Thong KJ, Dewar M, Mackie M, Baird DT. Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception. New England Journal of Medicine 1992;327:1041–4. Glasier 2010 {published data only} Glasier AF, Cameron ST, Fine PM, Logan SJ, Casale W, Van Horn J, et al.Ulipristal acetate versus levonorgestrel for

emergency contraception: a randomised non-inferiority trial and meta-analysis. Lancet 2010;375(9714):555–62. Hamoda 2004 {published data only} Hamoda H, Ashok PW, Stalder C, Flett GMM, Kennedy E, Templeton A. A randomized trial of mifepristone (10 mg) and levonorgestrel for emergency contraception. Obstetrics & Gynecology 2004;104:1307–13. Han 1995 {published data only} Han X, Weng L, Zhang L, Zeng T, Xiao B. Clinical trial of mifepristone and anordrin for emergency contraception. Journal of Reproductive Medicine (China) 1995;4:206–11. Han 1996 {published data only} ∗ Han X, Weng L, Xiao B. Emergency contraception with mifepristone and anordrin. Chinese Journal of Obstetrics and Gynecology 1996;31:526–9. Han 1999a {published data only} Han X, Jin X, Weng L. A comparative study of mifepristone with levonorgestrel for emergency contraception. Chinese Journal of Practical Gynaecology and Obstetrics 1999;15: 294–6. Han L 2001 {published data only} Han L, Ma Y, Li H. Low doses of mifepristone for emergency contraception. Fudan University Journal of Medical Sciences 2001;28:176–7. He CH 2002 {published data only} He CH, Gui YL, Yang J, Wang BS, Zheng E, Gao ES, et al.A randomized comparative study on mifepristone alone and in combination with tamoxifen for emergency contraception. Contraception 2002;66:221–4. Ho 1993 {published and unpublished data} ∗ Ho PC, Kwan MSW. A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception. Human Reproduction 1993;8: 389–92. Hu X 2003 {published data only} Hu X, Lu C. A comparative study of mifepristone with levonorgestrel for emergency contraception. Sichuan Medical Journal 2003;24:F004. Lai Z 2004 {published data only} Lai Z, Wang J, Zhou Z, Lu H, Song X, Sun J. A comparative study of low-dose Mifepristone for emergency contraception. Maternal and Child Health Care of China 2004;19:36–8. Lan XL 2006 {published data only} Lan XL, Chen LP, Ye QH. Clinical study of low-dose mifepristone for emergency contraception. Clinical Medicine 2006;26(11):68–9. Li 2000 {published data only} Li Q, Chen R, Zhang Y, Huang M, Chen RX, Zhong X. A comparative study of mifepristone 50 mg and 25 mg for emergency contraception. Guangdon Medical Journal 2000; 22:884–5.


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Li A 2000 {published data only} Li A, Zhang Y. Low dose of mifepristone for emergency contraception. Journal of Guangxi Medical University 2000; 17:857. Liang 2001 {published data only} Liang JZ, Zhou MR. A randomised comparative study on mifepristone and levonorgestrel for emergency contraception. Heilongjiang Medical Journal 2001;25:594. Liao 2003 {published data only} Liao AH, Chang CF, Zhu JW. Randomised controlled prospective studies of mifepristone in small doses and levonorgestrel for emergency contraception. Chinese Journal of Practical Gynaecology and Obstetrics 2003;19:25–7. Li H 2000 {published data only} Li H, Chang JP, Li J. A study of low-dose mifepristone for emergency contraception. Heilongjiang Medical Journal 2000;23:90. Li J 2005 {published data only} Li J. A comparative study of mifepristone with levonorgestrel for emergency contraception. Anthology of Medicine 2005; 24:754. Lin 2000 {published data only} Lin N, Cheng W, Yang Y, Shao L. A comparative study of mifepristone and LNG for emergency contraception. Tianjing Medical Journal 2000;28:601–3. Liu 2000 {published data only} Liu JL, Liu LH, Li KZ, Liu HL. Comparative study of the efficacy of low-dose mifepristone and levonorgestrel on the emergency contraception. Practical Preventive Medicine 2000;7:126–7. Liu L 2001 {published data only} Liu L, Wang Z, Li L. Mifepristone and anordrin for emergency contraception. Zhong Guo Yiu Sheng Yu Yi Chuan Zha Zi 2001;9:108–11. Liu L 2002 {published data only} Liu L, Chen A. A comparative study of mifepristone with Cu-IUD for emergency contraception. Journal of Changzhi Medical College 2002;61:198–9. Liu RQ 2009 {published data only} Liu RQ. A comparative study of mifepristone and LNG for emergency contraception. China Pharmaceuticals 2009;18 (19):68–9. Li W 2002 {published data only} Li W. A comparative study of mifepristone with levonorgestrel for emergency contraception. Guizhou Journal of Medicine 2002;26:457.

Ngai 2005 {published data only} Ngai SW, Fan S, Li S, Cheng L, Ding J, Jing X, et al.A randomized trial to compare 24 h versus 12 h double dose regimen of levonorgestrel for emergency contraception. Human Reproduction 2005;20:307–11. Pei 2001 {published data only} Pei JH, Wang ZX. A randomised comparative study of mifepristone in small doses and levonorgestrel for emergency contraception. Haerbin Medicine 2001;21:32–3. Qi 2000b {published data only} Qi Y, Zhang J, Cao Y, Zhang Z. A comparative clinical trial on two low doses of mifepristone for emergency contraception. Maternal and Child Health Care of China 2000;15:701–4. Qian 1999 {published data only} Qian L. Three doses of mifepristone for emergency contraception. Chinese Journal of Family Planning 1999;7: 322–3. Qi M 2003 {published data only} Qi M, Wang Y, Yan L. A comparative study of lowdose mifepristone with levonorgestrel for emergency contraception - 288 cases report. Journal of Qinghai Medical College 2003;24:255–6. Rowlands 1983 {published data only} ∗ Rowlands S, Guillebaud J, Bounds W, Booth M. Side effects of danazol compared with an ethinyloestradiol/ norgestrel combination when used for postcoital contraception. Contraception 1983;27:39–49. Rowlands S, Kubba AA, Guillebaud J, Bounds W. A possible mechanism of action of danazol and an ethinylestradiol/ norgestrel combination used as postcoital contraceptive agents. Contraception 1986;33:539–45. Sang 1999 {published data only} Sang GW, Shao Q, Zhang J, Zhang M, Chen S, Song S, et al.A randomized multicentre clinical trial on different doses of mifepristone alone and in combination with anordrin as emergency contraception [Mifepristone in combination with anordrin for emergency contraception: a randomized multicentre study]. Chinese Journal of Obstetrics and Gynaecology 1999;34:331–4. Shao XY 2010 {published data only} Shao XY. Clinical observation on mifepristone for emergency contraception. Practical Clinical Journal of Integrated Traditional Chinese and Western Medicine 2010; 10(3):55.

Lou C 2002 {published data only} Lou C. Low-dose Mifepristone for emergency contraception. Xian Dai Shi Yong YI Xue 2002;14:485.

Sheng A 2002 {published data only} Sheng A. Clinical observation of the efficacy of mifepristone and levonorgestrel on the emergency contraception. Academic Journal of Jiangsu University (Medicine) 2002;12: 246–9.

Lou X 2005 {published data only} Lou X, Ma L, Yang Y. Mifepristone and C53 contraceptive in postcoital contraception. Journal of Chinese Modern Gynaecology and Obstetrics 2005;2:405–6.

Sheng SY 2008 {published data only} Sheng SY. A clinical study of LNG-COC for emergency contraception. Asia-Pacific Traditional Medicine 2008;4(9): 93–4.


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Su 2001 {published data only} Su W, Chui JY, Liu P. A comparative study of IUCD with mifepristone and with levonorgestrel for emergency contraception. Journal of Baotou Medicine 2001;25:24.

Wang Q 2000 {published data only} Wang Q, Li A. A comparative study of levonorgestrel with low dose mifepristone for emergency contraception. Northwestern Pharmaceutical Journal 2000;15:72.

Sun 2000 {published data only} Sun Y, Wang X. A clinical comparative study of mifepristone with levonorgestrel for emergency contraception. Chinese Journal of Family Planning 2000;8:172–3.

Wang SZ 2001 {published data only} Wang SZ, Huang ZK, Li S. Clinical trial of mifepristone in different dose for emergency contraception. Chinese Journal of Practical Gynaecology and Obstetrics 2001;17:534–6.

Sun MX 2007 {published data only} Sun MX. A clinical comparative study of LNG vs. LNGCOC for emergency contraception. Chinese Journal of Family Planning 2007;6:366–7.

Wang Y 2003 {published data only} Wang Y, Liu H. A comparative study on low doses of mifepristone with levonorgestrel for emergency contraception. Chinese Journal of Family Planning 2003;8: 505–6.

Sun P 2003 {published data only} Sun P. Mifepristone for emergency contraception. Journal of Chinese Practice Medicine 2003;5:92. Tan 1999 {published data only} Tan K, Mai T, He P, Lin H, Li S. Low doses of mifepristone for emergency contraception. Chinese Journal of Family Planning 1999;7:470–1. Tan L 2003 {published data only} Tan L, Zheng G, Li J. Mifepristone for emergency contraception - 150 cases report. Wei Sheng Zhi Yie Jiao Yu 2003;21:138–9. Van Santen 1985a {published data only} ∗ Van Santen MR, Haspels AA. A comparison of high-dose estrogens versus low-dose ethinylestradiol and norgestrel combination in postcoital interception: a study in 493 women. Fertility and Sterility 1985;43:206–13. Van Santen MR, Haspels AA. Comparative randomized double-blind study of high dosage ethinylestradiol versus ethinylestradiol and norgestrel combination in postcoital contraception. Acta Endocrinologica 1982;99(suppl 246):2.

Wang ZW 2008 {published data only} Wang ZW, Qu HW. Two different doses of mifepristone for emergency contraception. Chinese Journal of Misdiagnosis 2008;8(20):4819–20. Webb 1992 {published data only} Webb AM. Alternative treatments in oral postcoital contraception: interim results. Advances in Contraception 1991;7:271–9. ∗ Webb AMC, Russell J, Elstein M. Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception. BMJ 1992;305:927–31. Wei H 2011 {published data only} Wei H, He CB, Liu J. Low dose mifepristone for emergency contraception. Chinese and Foreign Women Health 2011;19 (3):70. Wei RH 2002 {published data only} Wei RH. Low dose of mifepristone for emergency contraception - 200 cases report. Shanghai Sheng Wu Yi Xue Gong Cheng Zha Zi 2002;23:39–42.

Von Hertzen 2002 {published data only} von Hertzen H, Piaggio G, Ding J, Chen J, Song S, Bartfai G, et al.Low dose mifepristone and two regimens of levonorgestrel for emergency contraception. Lancet 2002; 360:1803–10.

WHO 1998 {published data only} WHO Task Force on Postovulatory Methods of Fertility Regulation. Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Lancet 1998;352:428–33.

Wang 1999 {published data only} Wang Z, Liu L, Liu Q, Zhang H. A clinical comparative study of mifepristone with anordrin for emergency contraception. Chinese Journal of Family Planning 1999;7: 320–1.

WHO 1999 {published data only} WHO Task Force on Postovulatory Methods of Fertility Regulation. Comparison of three single doses of mifepristone as emergency contraception: a randomised trial. Lancet 1999;353:697–702.

Wang C 2000 {published data only} Wang C, Tian M, Chang Y, Shao M. A clinical comparative observation among copper IUD, lower dose mifepristone and levonorgestrel for emergency contraception. Journal of Chinese Physician 2000;2:271–3.

Wu 1999a {published data only} Wu S, Wang C, Wang Y, Cheng W, Zuo S, Li H, et al.A randomized, double-blind, multicentre study on comparing levonorgestrel and mifepristone for emergency contraception. Chinese Journal of Obstetrics and Gynaecology 1999;34:327–30.

Wang J 2006 {published data only} Wang J. A comparative study on different doses of mifepristone for emergency contraception. Journal Huaihai Medicine 2006;24:19–20. Wang L 2004 {published data only} Wang L, Lv Y, Guan D, Zhang H, Yao L. 12.5mg Mifepristone for emergency contraception. Chinese General Practice 2004;7:1477–8.

Wu 2002 {published data only} Wu XZ, Sao JY, Chen CQ, Yan Y, Fa YY, Liu JH, et al.A comparative study on methods for emergency contraception. Reproduction & Contraception (China) 2002;22:152–5. Wu 2010 {published data only} Wu S, Dong J, Cong J, Wang CP, Von Hertzen H, Godfrey EM. Gestrinone compared with mifepristone for emergency


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contraception: a randomized controlled trial. Obstetrics and Gynecology 2010;115(4):740–4. Xiao 2002 {published data only} Xiao BL, von Hertzen H, Piaggio G. A randomized doubleblind comparison of two single doses of mifepristone for emergency contraception. Human Reproduction 2002;17: 3084–9. Xie 1998 {published data only} Xie X, Liu Y, Lin X. A clinical study on 600 cases of mifepristone for emergency contraception. Reproduction & Contraception (China) 1998;18:224–6. Xie HH 2010 {published data only} Xie HH, Shang XM, Dai WY. Analysis of emergency contraception use mifepristone by different doses. Guide of China Medicine 2010;8(14):34–5. Xu 2000 {published data only} Xu L, Wang Z. A comparative study on low dose mifepristone with levonorgestrel for emergency contraception. Chinese Journal of Family Planning 2000;8: 419–20. Xu Z 2000 {published data only} Xu Z. A comparative study of Mifepristone, anordrin and levonorgestrel for emergency contraception. Journal of Yichun Medical College 2000;12:248–9. Yang 2001 {published data only} Yang LJ. A comparative study on mifepristone, anordrin and danazol for emergency contraception. Guangzhou Medical Journal 2001;32:12–3. Yang F 2003 {published data only} Yang F. A comparative study on two low doses of mifepristone for emergency contraception. Journal of Clinical Research 2003;20:630–1. Zeng MY 2008 {published data only} Zeng MY, Zhu LF, Huang Y. A comparative study of low-dose mifepristone for emergency contraception. International Medicine Health Guidance News 2008;14(14): 68–70. Zeng XY 2007 {published data only} Zeng XY. A clinical study of Mifepristone in combination with MTX for emergency contraception. Practical Clinical Journal of Integrated Chinese and Western Medicine 2007;7 (3):62–3. Zhang JQ 2000 {published data only} Zhang JQ. Emergency contraception in high-land. Chinese Journal of Family Planning 2000;8:552–4. Zhang L 2005 {published data only} Zhang L, Lai L, Deng X. Single and small dose of Mifepristone for emergency contraception of curative effect observe. Journal of Gannan Medical College 2005;25: 328–30. Zhang X 1999a {published data only} Zhang X, Gao G, Shi J, Qu C, Leng Y. A clinical study on low doses of mifepristone for emergency contraception. Chinese Journal of Family Planning 1999;7:175–6.

Zhang Y 1998 {published data only} Zhang Y, Qiao G, Zhu P, Zhang S, Zhang J, Zhu N. Clinical observation of three lower doses of mifepristone for emergency contraception. Chinese Journal of Family Planning 1998;6:343–5. Zhang Y 2002 {published data only} Zhang Y, Wen L, Li S, Wang Y. Mifepristone for emergency contraception. Henan YI Yao Xin XI 2002;10:20–1. Zhang YM 2002 {published data only} Zhang Y, Zhang W, Wang L. Low- dose of Mifepristone and anordrin for emergency contraception: observation of 116 cases. Journal of Qiqihar Medical College 2002;23:415. Zhao J 2003 {published data only} Zhao J, Liu R, Li H, Zhang Y. Different doses of Mifepristone for emergency contraception. Journal of Shandong University (Health Sciences) 2003;41:468. Zheng A 2005 {published data only} Zheng A. Low-dose of mifepristone for emergency contraception. Youjiang Medical Journal 2005;33:375–6. Zuo 1999 {published data only} Zuo SH, Wu J, Liu L, Liu J, Gao Y. A clinical trial on two low doses of mifepristone for emergency contraception. Reproduction & Contraception (China) 1999;19:352–6.

References to studies excluded from this review Ashok 2001 {published data only} Ashok PW, Wagaarachchi PT, Flett GM, Templeton A. Mifepristone as a late post-coital contraceptive. Human Reproduction 2001;16:72–5. Ashok 2004 {published data only} Ashok PW, Hamoda H, Flett GMM, Templeton A. Mifepristone versus the Yuzpe regimen (PC4) for emergency contraception. International Journal of Gynecology and Obstetrics 2004;87:188–93. Ban 2001 {published data only} Ban X, Xiao Y, Fan H, Liu G, Liu Q, Yu L. A comparative clinical study on Tcu380A and Cu-IUD for emergency contraception. Maternal & Child Health Care of China 2001;16:498–501. Benagiano G 2010 {published data only} Benagiano G, von Hertzen H. Towards more effective emergency contraception?. Lancet 2010;375(9714): 527–28. Byamugisha 2010 {published data only} Byamugisha JK, Mirembe FM, Faxelid E, Tumwesigye NM, Gemzell-Danielsson K. A randomized clinical trial of two emergency contraceptive pill regimens in a Ugandan population. Acta Obstetricia et Gynecologica 2010;89:670–6. Creinin 1997 {published data only} Creinin MD. A reassessment of efficacy of the Yuzpe regimen of emergency contraception. Human Reproduction 1997;12:496–8. D’Souza 2003 {published data only} D’Souza RE, Masters T, Bounds W, Guillebaud J. Randomised controlled trial assessing the acceptability of


25

GyneFix versus Gyne-T389S for emergency contraception. Journal of Family Planning and Reproductive Health Care 2003;29:23–9. Dixon 1980 {published data only} Dixon GW. Ethinylestradiol and conjugated estrogens as postcoital contraceptives. JAMA 1980;244:1336–9. Dong 2007 {published data only} Dong SZ, Wu SH. comparing mifepristone, levonorgestrel and the copper IUD for emergency contraception: a report of 268 cases. Journal of Chinese Modern Gynecology and Obstetrics 4;2:127–9. Ellertson 2003a {published data only} Ellertson C, Evans M, Ferden S, Leadbetter C, Spears A, Johnestone K, et al.Extending the time limit for starting the Yuzpe regimen of emergency contraception to 120 hours. Obstetrics & Gynecology 2003;101:1168–71. Espinos 1999 {published data only} Espinos JJ, Senosiain R, Vanrell C, Armengol J, Cuberas N, Calaf J. Safety and effectiveness of hormonal postcoital contraception: a prospective study. European Journal of Contraception and Reproductive Health Care 1999;4:27–33. Fan 1998 {published data only} Fan Ai, Wang Y, Wang Z. Clinical study on 518 cases of emergency contraception. Chinese Journal of Family Planning 1998;6:408–9. Fan H 2001 {published data only} Fan H, Zhou L. Emergency contraception with Multiload Cu 375 SL IUD: a multicentre clinical trial. Journal of Reproductive Medicine (China) 2001;10:70–7. Fasoli 1989 {published data only} Fasoli M, Parazzini F, Cecchetti G, Vecchia CL. Postcoital contraception: an overview of published studies. Contraception 1989;39:459–69. Fine 2010 {published data only} Fine P, Mathe H, Ginde S, Cullins V, Morfesis J, Gainer E. Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception. Obstetrics and Gynecology 2010; 115(2):247–63.

Gottardi 1979 {published data only} Gottardi G, Marzi MM, Pozzi S. Postcoital estrogen or IUD? [Oestrogène postcoital ou DIU?]. IPPF Europe Bulletin d’Information Régional 1979;8:7–8. Gottardi 1986 {published data only} Gottardi G, Spreafico A, de Orchi L. The postcoital IUD as an effective continuing contraceptive method. Contraception 1986;34:549–58. Guillebaud 1983 {published data only} Guillebaud J, Kubba A, Rowlands S, White J, Elder EG. Postcoital contraception with danazol, compared with an ethinyloestradiol-norgestrel combination or insertion of a intrauterine device. Journal of Obstetrics and Gynaecology 1983;suppl 1:s64–8. Gu XY 2002 {published data only} Gu XY, Yie TF. Clinical study of the effect of Multiload 375 SL and levo-norgestrel on emergency contraception. Chinese Journal of Family Planning 2002;10:740–2. Halpern V 2010 {published data only} Halpern V, Raymond EG, Lopez LM. Repeated use of pre- and postcoital hormonal contraception for prevention of pregnancy. Cochrane Database of Systematic Reviews. http://apps.who.int/rhl/fertility/contraception/cd007595/en/ index.html 2010, Issue 1. No.: CD007595. DOI: 10.1002/ 14651858.CD007595.pub2. Han 1999b {published data only} Han X, Wong L, Sun J. A clinical study on mifepristone alone and in combination with anodrin for emergency contraception. Chinese Journal of Family Planning 1999;7: 411–4. Han Y 2001 {published data only} Han Y. The clinical observation of GyneFix IUD for emergency contraception. Journal of Practical Obstetrics and Gynecology 2001;17:171–2. Haspels 1976 {published data only} Haspels AA. Interception: post-coital estrogens in 3016 women. Contraception 1976;14:375–81.

Gan 1999 {published data only} Gan SH, Chang M, Hu S, Zhang P, Chang M, Xu X. A clinical study on mifepristone 10mg for emergency contraception. Reproduction and Contraception (China) 1999;19:311–3.

He 1991 {published data only} He C, Shi Y, Xu J, Van Look PFA. A multicenter clinical study on two types of levonorgestrel tablets administered for postcoital contraception. International Journal of Gynecology and Obstetrics 1991;36:43–8.

Gan SX 2001 {published data only} Gan SX, Li SS, Lu Y. Comparative study of the efficacy of mifepristone and levonorgestrel on the emergency contraception. Chinese Journal of Family Planning 2001;9: 178–81.

Hoffman 1983 {published data only} Hoffman KOK. Postcoital contraception: experiences with ethinyl oestradiol/norgestrel and levonorgestrel only. In: Harrison RF, Bonnar J, Thompson W editor(s). Fertility and Sterility. Dublin: IFFS Fertility and Sterility, 1983: 311–6.

Gao ER 2001 {published data only} Gao ER, Zhao Sh, Lou CH. Study on the acceptability of emergency contraception among those who underwent induced abortion. Reproduction & Contraception (China) 2001;21:104–9.

Jiang 2000 {published data only} Jiang L, Duan Y, Sun Y. A comparative study of mifepristone with levonorgestrel for emergency contraception. Chinese Journal of Family Planning 2000;8:463–4.


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Jiang 2002 {published data only} Jiang DX, Wu ER. Effects of gestrinone (R2323) on emergency contraception: a clinical observation of 120 cases. Journal of Reproductive Medicine 2002;11:326–30. Jin 2005 {published data only} Jin J, Weisberg E, Fraser IS. Comparison of three single doses of mifepristone as mifepristone as emergency contraception: a randomised controlled trial. Australian and New Zealand Journal of Obstetrics and Gynaecology 2005;45: 489–94. Kesserü 1973 {published data only} Kesserü E, Larranaga A, Parada J. Postcoital contraception with d-norgestrel. Contraception 1973;7:367–79. Li F 2002 {published data only} Li F, Chen YX, Tang JH. Emergency contraception by lowdose mifepristone: observation of 150 cases. Journal of First Military Medical University 2002;22:466. Li F 2005 {published data only} ∗ Li F, Qian X, Wu W. A comparative study of mifepristone with Cu-IUD for emergency contraception. Journal of Practice Medicine 2005;21:2313–4. Lippes 1976 {published data only} Lippes J, Malik T, Tatum HJ. The postcoital copper-T. Advances in Planned Parenthood 1976;11:24–9. Lippes 1979 {published data only} Lippes J, Tatum HJ, Maulid D, et al.A continuation of the study of post-coital IUDs. Family Planning Perspectives 1979;11:195–8. Liu Y 2002 {published data only} Liu Y, Chen X. A comparative study of mifepristone with Cu-IUD for emergency contraception. Journal of Qiqihar Medical College 2002;23:890–1. Li XY 2001 {published data only} Li XY, Hu LY. A study of low-dose mifepristone for emergency contraception. Chinese Journal of Practical Gynaecology and Obstetrics 2001;17:619–20.

Piaggio 2003 {published data only} Piaggio G, Heng Z, von Hertzen H, Bilian X, Linan C. Combined estimates of effectiveness of mifepristone 10mg in emergency contraception. Contraception 2003;68: 439–46. Piaggio 2003a {published data only} Piaggio G, von Hertzen H, Zhao H, Xiao BL, Cheng L. Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Contraception 2003;68:447–52. Qi 2000 {published data only} Qi Y, Zhang J, Cao Y, Yan W, Zhang Z. A clinical study on mifepristone at low dose for emergency contraception. Chinese Journal of Family Planning 2000;8:305–7. Qiao 2002 {published data only} Qiao Y. A clinical trial of mifepristone in combination with MTX for emergency contraception. Journal of Jining Medical College 2002;25:44. Qin 2000 {published data only} Qin C. A clinical study on 137 cases of emergency contraception with mifepristone. Zhejiang Journal of Clinical Medicine 2000;2:302–3. Raymond 2000 {published data only} Raymond EG, Creinin MD, Barnhart KT, Lovvorn AE, Rountree RE, Trussell J. Meclizine for prevention of nausea associated with use of emergency contraceptive pills: a randomized trial. Obstetrics and Gynecology 2000;95:271–7. Raymond 2006 {published data only} Raymond EG, Stewart F, Weaver M, Monteith C, Van Der Pol B. Impact of increased access to emergency contraceptive pills. Obstetrics and Gynecology 2006;108(5):1098–106. Roye 2001 {published data only} Roye CF. Routine provision of emergency contraception to teens and subsequent condom use: a preliminary study. Journal of Adolescent Health 2001;28:165–6.

Luerti 1986 {published data only} Luerti M, Tonta A, Feria P, Molla R, Santini F. Post-coital contraception by estrogen-progestagen combination or IUD insertion. Contraception 1986;33:61–8.

Scarduelli 1998 {published data only} Scarduelli C, Anselmino M, Caccamo A, Sezzi E, Lombroso Finzi GC. Emergency contraception: a new evaluation of effectiveness. P-159. Abstracts of the 14th Annual Meeting of the ESHRF, Göteborg. 1998:208–9.

Ma 2001 {published data only} Ma J. A study on 110 cases of emergency contraception. Chinese Journal of Practical Gynaecology and Obstetrics 2001; 17:189.

Schilling 1979 {published data only} Schilling LH. An alternative to the use of high dose estrogen for postcoital contraception. Journal of American College of Health Association 1979;27:247–9.

Mo 2004 {published data only} Mo Y. A clinical observation on different dose of mifepristone for emergency contraception. Hainan Yi Xue 2004;15:42–3.

Schreiber 2010 {published data only} Schreiber CA, Ratcliffe SJ, Barnhart KT. A randomized controlled trial of the effect of advanced supply of emergency contraception in postpartum teens: a feasibility study. Contraception 2010;81:435–40.

Mor 2005 {published data only} Mor E, Saadat P, Kives S, White E, Reid RL, Paulson RJ, et al.Comparison of vaginal and oral administration of emergency contraception. Fertility and Sterility 2005;84: 40–5.

Shen HX 2010 {published data only} Shen HX. A observational study of mifepristone for emergency contraception. Journal of China Traditional Chinese Medicine Information 2010;2(28):163.


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Shochet 2004 {published data only} Shochet T, Blanchard K, King H, Henchcliffe B, Hunt J. Side effects of the Yuzpe regimen of emergency contraception and modifications. Contraception 2004;69: 301–7. Song ZH 2007 {published data only} Song ZH, Wang Y, Chen P, Wang D, Lu WH. A clinical study of mifepristone and the copper IUD for emergency contraception. Chinese Medicine of Factory and Mine 2007; 20(6):630–1. Sun 2005 {published data only} Sun Y, Che Y, Ding Y, Zhou W, Han Y, Fang K, et al.Systematic review of emergency contraception. Chinese Journal of Family Planning 2005;4:217–22. Tian Q 2000 {published data only} Tian Q. A comparative study of mifepristone with Cu-IUD for emergency contraception. Journal of Henan Medical College for Staff and Workers 2000;12:51. Turok 2010 {published data only} Turok DK, Gurtcheff SE, Handley E, Simonsen SE, Sok C, Murphy P. A pilot study of the copper T380A IUD and oral levonorgestrel for emergency contraception. Contraception 2010;82:520–5. Van Santen 1983 {published data only} Van Santen MR, Haspels AA. Postcoital contraception with an IUD [Contraccezione con D.I.U. post–coitale]. Contraccezione, Fertilita, Sessualita 1983;10:549–57. Van Santen 1985b {published data only} Van Santen MR, Haspels AA. Interception II: postcoital low-dose estrogens and norgestrel combination in 633 women. Contraception 1985;31:275–93. Virjo 1999 {published data only} Virjo I, Kirkkola AL, Isokoski M, Mattila K. Use and knowledge of hormonal emergency contraception. Advances in Contraception 1999;15:85–94. Wang CP 2006 {published data only} Wang CP, Liu Y, Chang YF, Shao WQ. A comparing study of the copper intrauterine device and low dose of mifepristone for emergency contraception. Journal of Reproductive Medicine 2006;15(4):271–3. Wei R 2002 {published data only} Wei R. Low-dose of mifepristone for emergency contraception: observation of 309 cases. Jiangxi Medical Journal 2002;37:102–4. Wu 1999b {published data only} Wu C, Zhang Y. An extend study on using single dose of mifepriston 25mg for emergency contraception. Chinese Journal of Family Planning 1999;7:358–60. Wu 2005 {published data only} Wu S, Zhou Y. Clinical use of emergency contraception pill. Chinese Journal of Practical Gynaecology and Obstetrics 2005; 21:15–7.

Xiao 2004 {published data only} Xiao BL. Clinical study of emergency contraception with low-dose mifepristone. Chinese Journal of Obstetrics and Gynecology 2004;39:35–8. Yang 2002 {published data only} Yang Y, Liang X, Liu X. Low-dose of mifepristone for emergency contraception: observation of 106 cases. Heilongjiang Medical Journal 2002;26:283. Yu 2001 {published data only} Yu MD. A primary discussion of the drugs for emergency contraception. Anhui Medical and Pharmaceutical Journal 2001;5:95–6. Yuzpe 1974 {published data only} Yuzpe AA, Thurlow HJ, Ramzy I, Leushon JL. Postcoital contraception - a pilot study. Journal of Reproductive Medicine 1974;1:53–8. Yuzpe 1977 {published data only} Yuzpe AA, Lancee WJ. Ethinylestradiol and dl-norgestrel as a postcoital contraceptive. Fertility and Sterility 1977;28: 932–6. Yuzpe 1982 {published data only} Yuzpe AA, Percival Smith R, Rademaker AW. A multicentre clinical investigation employing ethinylestradiol combined with dl-norgestrel as a postcoital contraceptive agent. Fertility and Sterility 1982;37:508–13. Zhang J 1999 {published data only} Zhang J, Jing X, Wong L. Cu-IUD versus mifepristone for emergency contraception. Chinese Journal of Obstetrics and Gynecology 1999;34:569–70. Zhang M 1999 {published data only} Zhang M, Yang H, Wang Z, Liang X, Wang Y. A study on mifepristone alone and in combination with anordrin for emergency contraception. Zhejiang Journal of Practical Medicine 1999;4:1–2. Zhang X 1999 {published data only} Zhang X, Du M, Ying Y. A study on mifepristone alone and in combination with anordrin for emergency contraception. Reproduction and Contraception (China) 1999;19:163–8. Zhang X 1999b {published data only} Zhang X, Leng Y, Shi J, Gao G, Xu Y, Sun H. A study on LNG for emergency contraception. Chinese Journal of Family Planning 1999;7:375–6. Zhao 2006 {published data only} Zho H, Han L. Analysis of the reason for failure of emergency contraception. Journal of China-Japan Friendship Hospital 2006;20:207–10. Zhao H 2001 {published data only} Zhao H, Tang JR, Wu MH, Cheng H. A comparative study of mifepristone with IUCD for emergency contraception. Journal of Capital University of Medical Sciences 2001;22: 273–4. Zhu 1999 {published data only} Zhu P, Chai J, Wang N, Li G. An initial observation of mifepristone combined with MTX for the use of emergency


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contraception. Guangdong Journal of Medicine 1999;20: 11–2. Zhu YH 2007 {published data only} Zhu YH, Ou YL. Clinical observational study of three methods for emergency contraception. Journal of Medical Theory and Practice 2007;20(2):200–2. Zuliani 1990 {published data only} Colombo UF, Zuliani G, Benzi G, Bregozzo T, Viezzoli T. [Contraccezione post coitale ormonale con danazolo: ristati di due differenti schemi posologici]. Pediatric and Adolescent Gynaecology. Paper presented at the III European Symposium on Pediatric and Adolescent Gynaecology; 1987 Oct 7-10; Florence. Florence, Italy: CIC Edizioni Internazionali, 1987:206–11. Zuliani G, Colombo UF, Luerti M, Casolati E, Viezzoli T. Postcoital contraception with an ethinylestradiol-norgestrel combination and two different danazol regimens. In: Genazzani AR, Petraglia F, Volpe A, Facchinetti F editor(s). Recent Research on Gynecological Endocrinology. New Jersey: Parthenon Publishing, 1988. Zuliani G, Colombo UF, Molla R. Hormonal postcoital contraception with an ethinylestradiol-norgestrel combination and two danazol regimens. European Journal of Obstetrics Gynecology and Reproductive Biology 1990;37: 253–60. Zuliani G, Colombo UF, Molla R, Bregozzo T, Mojana G. [Confronto tra danazolo e etinilestradiolo–norgestrel utilzzati come intercettori post–coitali ormonali: studio clinico randomizzato]. Congresso Internazionale di Endocrinologia Ginecologica. Madonna di Campiglio, 1986 16-22 Mar, Bologna. 1986:341–4.

Higgins 2011 Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org. ICEC 2012a International Consortium for Emergency Contraception (ICEC). Knowledge and ever used of emergency contraception in Latin America. http://www.cecinfo.org/UserFiles/File/DHS/Emergency%20Contraception%20in%20Latin%20America.pdf (accessed 30 April 2012). ICEC 2012b ICEC. Knowledge and ever used of emergency contraception in Africa. http://www.cecinfo.org/UserFiles/File/DHS/ Emergency%20Contraception%20in%20Africa.pdf (accessed 30 April 2012). ICEC 2012c ICEC. Knowledge and ever used of emergency contraception in Europe and West Asia.. http: //www.cecinfo.org/UserFiles/File/DHS/Emergency%20Contraception%20in%20Europe%20and%20West%20Asia.pdf (accessed 30 April 2012). INEI 2011 Instituto Nacional De Estadística E Informática (INEI) and ICF Macro. Peru: DHS, 2010 - Final report continuous (2010). ORC Macro / Measure DHS+, May 2011. Piaggio 1999 Piaggo P, Von Hertzen H, Grimes DA, Van Look PFA. Timing of emergency contraception with levonorgestrel or the Yuzpe regimen. Lancet 1999;353:721.

Cheng 1999b Cheng L. Current situation and development of emergency contraception. Chinese Journal of Obstetrics and Gynaecology 1999;34:325–6.

Reuter 1999 Reuter S. Barriers to the use of IUDs as emergency contraception. British Journal of Family Planning 1999;25: 63–8. Sedgh 2012 Sedgh G, Singh S, Shah IH, Ahman E, Henshaw SK, Bankole A. Induced abortion: incidence and trends worldwide from 1995 to 2008. Lancet 2012;379(9816): 625–32. STATA 2001 StataCorp. Stata Statistical Software: Release 7.0. College Station, TX: Stata Corporation, 2001.

Cleland 2010 Cleland K, Raymond E, Trussell J, Cheng L, Zhu H. Ectopic pregnancy and emergency contraceptive pills. Obstetrics and Gynecology 2010;115:1263–6.

Thompson 2002 Thompson SG, Higgins JPT. How should meta-regression analyses be undertaken and interpreted?. Statistics in Medicine 2002;21:1559–73.

Glasier 1997 Glasier A. Emergency postcoital contraception. New England Journal of Medicine 1997;337:1058–64.

Trussell 2012 Trussell J, Raymond EG. Emergency contraception: a last chance to prevent unwanted pregnancy. April 2012. http:// ec.princeton.edu/questions/ec-review.pdf (accessed 3 June 2012).

Additional references Brache 2010 Brache V, Cochon L, Jesam C, Maldonado R, Salvatierra AM, Levy DP, et al.Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture. Human Reproduction 2010;25(9):2256–63.

Grimes 1997 Grimes DA. Emergency contraception: expanding opportunities for primary prevention. New England Journal of Medicine 1997;337:1078–9.

Van Look 1993 Van Look PFA, von Hertzen H. Emergency contraception. British Medical Bulletin 1993;49:158–70.


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Webb 1995 Webb A. Emergency contraception. Fertility Control Reviews 1995;4:3–7.

et al.Copper T380A intrauterine device for emergency contraception: a prospective, multicentre, cohort clinical trial. BJOG 2010;117(10):1205–10.

WHO 1990 World Health Organization. The TCu380A, TCu220C, Multiload 250 and Nova T IUDs at 3, 5 and 7 years of use. Contraception 1990;42:141–58.

Zhang L 2009 Zhang L, Chen J, Wang Y, Ren F, Yu W, Cheng L. Pregnancy outcome after levonorgestrel-only emergency contraception failure: a prospective cohort study. Human Reproduction 2009;1:1–7. ∗ Indicates the major publication for the study

Wu S 2010 Wu S, Godfrey E, Wojdyla D, Dong J, Cong J, Wang C,


30

CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID] Arowojolu 2002 Methods

Randomised double-blind, multicentre trial. Random number generation done centrally Similar looking placebos were used

Participants

1160 healthy women recruited into the study from family planning clinics, University College Hospital, Ibadan, and Planned Parenthood Federation of Nigeria, Ikolaba, Ibadan Included women with regular menstrual periods (21-35 days), who had a single act of unprotected intercourse within 72 h of attending the clinic Excluded women who were not available for follow-up, were pregnant, on hormonal contraception in the current cycle and those had contraindications to the use of hormonal contraceptive pills. 1118 into efficacy analysis, 1062 into safety analysis

Interventions

LNG 0.75 mg 2 doses 12 h apart orally (split dose) vs LNG 1.5 mg (single dose)

Outcomes

Observed number of pregnancies, side effects and changes in menstrual pattern

Notes

• Loss to follow-up: split-dose 15/560 and single dose 27/600 • Observed pregnancy/total number of women: split-dose LNG 7/545, single-dose LNG 4/573 • Of the failed cases 3 women in split-dose group and 1 in single-dose group continued with their pregnancies and delivered live health babies, while the others were lost to follow-up

Risk of bias Bias

Authors’ judgement

Support for judgement

Allocation concealment (selection bias)

Low risk

A - Adequate

Ashok 2002 Methods

Women randomised into 2 groups by opening sequentially numbered, sealed opaque envelopes that were prepared using random number tables The study was not blinded and the clinician and patient were both aware of the treatment allocat ion

Participants

1000 women attending a hospital in Aberdeen, UK. Women had regular menstrual periods a nd a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 100 mg orally vs Yuzpe regimen ( 2 tablets each with ethinyl oestradiol 50 µ g and LNG 0.25 mg) orally 2 doses 12 h apart

Outcomes

Observed number of pregnancies, side effects, change in menstrual pattern and patient acceptability


31

Ashok 2002

(Continued)

Notes

• Lost to follow-up: Mife 13/500; Yuzpe 29/500 • Observed pregnancy/expected pregnancy/total number of women: Mife 3/39/487; Yuzpe 17/39/471

Risk of bias Bias




Low risk

A - Adequate

Askalani 1987 Methods

’Randomly allocated’ women to 2 groups. The numbers enrolled in 2 groups we re 2:1 between treatment and control. Although 2:1 randomisation wa s not specifically mentioned, the trial w as included because it is explicitly stated that the allocation was random No details of allocation concealment or other methodological aspects are mentioned

Participants

300 women attending the family planning clinic of the Al-Azhar University, Cairo, Egypt Included women who had unprotected intercourse around the time of ovulation and attended the clinic within 4 days of unprotected intercourse

Interventions

Cu-T 200 vs control (no treatment)

Outcomes

Pregnancy rates

Notes

• No loss to follow-up or exclusions were reported

Risk of bias Bias




High risk

C - Inadequate

Bu 2006 Methods

Women were randomly allocated to 2 groups. The method of randomi sation not reported

Participants

100 women attending Fulaerji District Hospital, Qiqihaer, Helongjiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 10 mg single- dose orally vs LNG 0.75 mg 2-dose 12 h apart orally

Outcomes



32

Bu 2006

(Continued)

Notes

• Observed pregnancy/total number of women: Mife 10 mg: 1/50; LNG: 1/50 • Side effects: ◦ Mife: nausea 2/50; dizziness 1/50; low abdominal pain 3/50; diarrhoea 2/50 ◦ LNG: nausea 3/50; dizziness 1/50; low abdominal pain 4/50; diarrhoea 1/50 • Changes in menstrual pattern: ◦ Early: Mife 4/49; LNG 9/49 ◦ Delay: Mife 9/49; LNG 5/49 ◦ Spotting: Mife 1/49; LNG 2/49

Risk of bias Bias




High risk

C - Inadequate

Cao 1999 Methods

Women ’randomly allocated’ to 4 groups. Me thod of randomisation not reported

Participants

543 women (aged 18-47 years old) attending the outpatient clinic of the No. 477 Military Hospital, China. Women had regular menstrual periods a nd unprotected intercourse within 72 h of attending the clinic

Interventions

Mife (single dose) 100 mg vs Mife 50 mg vs Mife 25 mg vs Mife 10 mg orally

Outcomes


Notes

• No mention of post-randomisation exclusion and loss to follow-up • Observed pregnancy/expected pregnancy/total number of women: Mife 100 mg 0/ 13/120; Mife 50 mg 0/16/147; Mife 25 mg 2/14/136; Mife 10 mg 8/14/140

Risk of bias Bias




High risk

C - Inadequate

Chen 2001 Methods


Participants

88 women attending the gyn clinic in a general hospital, Guangxi, China. Women had regular menstrual periods a nd a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg vs a nordrin 7.5 mg 2-dose 12 h apart orally


33

Chen 2001

(Continued)

Outcomes

Observed number of pregnancies

Notes

• Observed pregnancy/expected pregnancy/total number of women: Mife 0/4/47; anordrin 2/4/41

Risk of bias Bias




High risk

C - Inadequate

Chen 2002 Methods

Women ’randomly allocated’ to 2 groups. Me thod of randomi sation not reported

Participants

312 women attending the clinic in 4 family planning centres, Guangdong, China Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic

Interventions

Mife 50 mg vs Mife 25 mg single dose orally

Outcomes

Observed number of pregnancies and changes in menstrual pattern

Notes

• 10 women excluded after recruitment, 2 loss to follow-up • Observed pregnancy/total number of women: Mife 50 mg 2/154; Mife 25 mg 4/148

Risk of bias Bias




High risk

C - Inadequate

Chen 2002a Methods


Participants

100 women attending the gyn clinic in a general hospital, Fujian, China. Women had regular menstrual periods a nd a single act of unprotected intercourse within 120 h of attending the clinic

Interventions

Mife 25 mg+ MTX 5 mg vs Mife 25 mg single dose orally

Outcomes

Observed number of pregnancies, side eff ects and changes in menstrual pattern


34

Chen 2002a

(Continued)

Notes

• No mention of post-randomisation exclusion and loss to follow-up • -Observed pregnancy/expected pregnancy/total number of women: Mife + MTX 0/ 5/50; Mife 1/5/50

Risk of bias Bias




High risk

C - Inadequate

Chen 2008 Methods

Women were randomly allocated to 2 groups. Method of randomis ation not reported

Participants

273 women attending in a family planning clinic, Tongxiang, Zhejiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg single dose vs LNG 0.75 mg 2 doses

Outcomes


Notes

• Observed pregnancy/total number of women: Mife: 2/129; LNG: 3/136 • Side effects: ◦ Mife: total side effect 14/129; ◦ LNG: total side effect 53/136 • Changes in menstrual pattern: ◦ Early: Mife 8/118; LNG 7/125 ◦ Delay: Mife 13/118; LNG 1/125

Risk of bias Bias




High risk

C - Inadequate

Chen 2009 Methods

Women were randomly allocated to 2 groups. The method of randomisation not reported

Participants

62 women attending in a family planning clinic, Liaoning province. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

M ife 25 mg vs Mife 10 mg single dose


35

Chen 2009

(Continued)

Outcomes


Notes

• Observed pregnancy/total number of women: Mife 25 mg: 1/30; Mife 10 mg: 1/32 • Side effects: ◦ Mife 25 mg: nausea and vomiting 4/30; diarrhoea 4/30; dizziness 2/30; headache 4/30; fatigue 5/30 ◦ Mife 10 mg: nausea and vomiting 2/32; diarrhoea 2/32; dizziness 1/32; headache 3/32; fatigue 4/32 • Changes in menstrual pattern: ◦ Mife 25 mg: delay: 29/29; spotting: 1/29 ◦ Mife 10 mg: delay: 30/31; spotting: 1/31

Risk of bias Bias




Unclear risk

C - Inadequate

Cheng 1999a Methods

Women ’randomly allocated’ to 3 groups. Random number table used to generate the allocation sequence There were no concealment of allocation and no blinding Side eff ects were assessed by women on a chart

Participants

639 women in Shanghai, China, attending 17 district MCH hospitals Included if they had regular menstrual periods (21-35 days), aged 18-45 years, with a single act of unprotected intercourse within 120 h of attending the clinic Excluded women on oral contraceptives, with contraindications to Mife and those that were considered difficult to follow- up

Interventions

Mife single dose (Chinese domestic product): 50 mg vs Mife 25 mg vs Mife 10 mg

Outcomes

Observed number of pregnancies, side eff ects, changes in menstrual pattern

Notes

• Randomised 639 of the 657 screened cases • No mention of post-randomisation exclusion • Loss to follow-up: 4.38%; Mife 50 mg 9/214; Mife 25 mg 9/214; Mife 10 mg 10/ 211 • -Observed pregnancy/expected pregnancy/total number of women: Mife 50 mg: 2/ 15/205; Mife 25 mg: 1/15/205; Mife 10 mg: 5/16/201

Risk of bias Bias




36

Cheng 1999a

(Continued)


High risk

C - Inadequate

Cheng 2009 Methods

Women were randomly allocated to 2 groups. Method of randomisation not reported

Participants

166 women attending in an o bs/ gyn clinic, Huadu D istrict H ospital, Guangzhou, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

LNG 0.75 mg in 2 doses vs Mife 25 mg single dose

Outcomes


Notes

• Observed pregnancy/total number of women: LNG 9/83; Mife 12/83 • Side effects: no data • Changes in menstrual pattern: ◦ Delay: LNG 6/74; Mife 12/71

Risk of bias Bias




High risk

C - Inadequate

Creinin 2006 Methods

Randomised, double-blinded non-inferiority trial S tudy drug was supplied in sequentially numbered sealed packages containing 2 opaque capsules. The packages either contained a single opaque capsule with UPA (CDB-2914) 50 mg plus an identical placebo capsule or 2 opaque capsules, each with a tablet of LNG 0.75 mg The identification of the contents of the capsules was unknown to the investigators and the subjects

Participants

1672 healthy women aged at least 18 years of age not using any hormonal contraception who requested EC within 72 h after unprotected intercourse as a result of using no contraception, condom breakage or slippage, or failure of another barrier method To be eligible for enrolment, they were required to have had a recent history of regular menstrual cycles (24-42 days). At least 1 normal menstrual cycle ( 2 menses) was required after delivery, abortion or discontinuation of hormonal contraceptive

Interventions

Women randomly assigned to receive a single dose of UPA (CDB-2914) 50 mg plus a placebo 12 h later or 2 doses of LNG 0.75 mg taken 12 h apart

Outcomes



37

Creinin 2006

(Continued)

Notes

• Loss of follow-up: UPA 40/832; LNG 54/840 • Post-randomisation exclusions: UPA 17/832; LNG 12/840 • Observed pregnancy/expected pregnancy/total number of women: UPA 7/47/775; LNG 13/42/774

Risk of bias Bias




Low risk

A - Adequate

Dada 2010 Methods

Women were randomly allocated to 2 groups. M ethod of randomi s ation of double-blind trial was mentioned in the paper

Participants

3022 Nigeria women with regular menstrual cycles (24-42 days’ duration with variation of no more than 5 days), Desired EC within 120 h after a single act of unprotected coitus during the present menstrual cycle, agreed to abstain from further acts of intercourse during that cycle or to use a condom or diaphragm if this was not possible Available for follow-up over the next 6 weeks

Interventions

2 -dose LNG: participants received 2 doses of LNG 0.75 mg administrated 12 h apart Single-dose LNG: p articipants received 1 dose of LNG 1.5 mg and 1 LNG placebo 12 h apart

Outcomes


Notes

• Randomisation sequence computer-generated by WHO in fixed blocks of 8 • Loss follow-up: 2-dose LNG 103/1512; single-dose LNG: 96/1510 • Observed pregnancy/expected pregnancy/total number of women: 2-dose LNG: 8/ 165.8/1409; single-dose LNG: 9/169.1/1414 • Side effects: ◦ Nausea: -2-dose LNG: 332/1512; single-dose LNG: 328/1510 ◦ Vomiting: 2-dose LNG: 132/1512; single-dose LNG: 137/1510 ◦ Fatigue: 2-dose LNG: 188/1512; single-dose LNG: 189/1510 ◦ Headache: 2-dose LNG: 175/1512; single-dose LNG: 181/1510 ◦ Dizziness: 2-dose LNG: 153/1512; single-dose LNG: 130/1510

Risk of bias Bias




Low risk

A - Adequate


38

Ding 2005 Methods


Participants

240 women attending the clinic in an MCH hospital, Henan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic

Interventions

Mife 75 mg vs Mife 50 mg vs Mife 10 mg orally

Outcomes


Notes

• Loss to follow-up: Mife 75 mg: 2; Mife 50 mg: 3; Mife 10 mg: 6 • Observed pregnancy/total number of women: Mife 75 mg: 1/78; Mife 50 mg: 1/77; Mife 10 mg: 1/74

Risk of bias Bias




High risk

C - Inadequate

Dong 2009 Methods

Women allocated to 2 groups. M ethod of randomisation not reported

Participants

200 women attending in a family planning clinic, Yuhuan, Zhejiang, China. Women had regular menstrual periods, and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 10 mg 2 doses 12 h apart orally vs LNG 0.75 mg 2 doses 12 h apart orally

Outcomes


Notes

• Observed pregnancy/total number of women: Mife: 0/100; LNG: 1/100 • Side effects: no detailed data • Changes in menstrual pattern: no detailed data

Risk of bias Bias




High risk

C - Inadequate


39

Du 2002 Methods


Participants

180 women attending a general hospital, Henan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• No mention of post-randomisation exclusion and loss to follow-up • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg: 1/8/ 90; Mife 10 mg: 1/7/90

Risk of bias Bias




High risk

C - Inadequate

Ellertson 2003 Methods

Randomised, double-blind controlled trial Each dose of therapy was inserted in opaque gelatin capsules and then packaged in opaque envelopes labelled either ’first dose’ or ’second dose’ Following computer generated randomisation the pairs were inserted into sequentially numbered opaque envelopes and sealed

Participants

2041 women at 5 centres in the US and UK within 72 h of a single, unprotected intercourse that occurred between 10 days before and 6 days after the estimated day of ovulation Included w omen aged 16-45 years, willing to abstain further in the current cycle, could attend follow-ups, keep a diary of side effects and refused the insertion of Cu-IUDs Excluded w omen who had used hormonal contraception during the past 2 months, had not had 2 normal periods in the previous 2 cycles, breastfeeding and those who had a positive pregnancy test

Interventions

Standard 2-dose Yuzpe regimen vs modified Yuzpe using norethindrone 2.0 mg instead of norgestrel 1.0 mg vs single dose of the standard Yuzpe regimen (followed 12 h later by a placebo)

Outcomes


Notes

• ITT analysis reported • Overall 3.3% lost to follow-up; standard Yuzpe 21/696; modified Yuzpe 26/676; single-dose Yuzpe 21/669

Risk of bias Bias



Support for judgement 40

Ellertson 2003

(Continued)


Low risk

A - Adequate

Fan 2001 Methods


Participants

103 women attending an MCH hospital, Hubei, China. Women had regular menstrual periods a nd a single act of unprotected intercourse within 96 h of attending the clinic

Interventions


Outcomes


Notes

• Loss to follow-up total 5 women, 6 women excluded after randomisation • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg 0/3/ 53; Mife 10 mg 1/2/39

Risk of bias Bias




High risk

C - Inadequate

Fang 2000 Methods


Participants

200 women attending an MCH clinic in Guangzhou, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 50 mg vs Mife 25 mg orally single dose

Outcomes


Notes

• No mention of post-randomisation exclusion and loss to follow-up • Observed pregnancy/expected pregnancy/total number of women: Mife 50 mg 0/ 12/100, Mife 25 mg 1/13/100 • No loss to follow-up

Risk of bias Bias




High risk

C - Inadequate


41

Farajkhoda 2009 Methods

Women randomly allocated to 2 groups. M ethod of randomi sation not reported

Participants

P rospective, randomis ed, comparative study, includ ing 124 healthy volunteers who, in the observed cycle, had had only 1 act of unprotected intercourse within 72 h of treatment R andomly allocated to LNG (n = 62) and Yuzpe (n = 62)

Interventions

Yuzpe: involved 2 doses of combined oestrogen/progestin pills, with each dose containing 100 µg of ethinyl oestradiol and 500 µ g of LNG LNG: LNG 0.75 mg taken within 72 h of unprotected coitus and LNG 0.75 mg taken 12 h later

Outcomes


Notes

• Observed pregnancy/total number of women: Yuzpe: 5/60 (2 lost to follow-up); LNG: 0/62 • Side effects: ◦ Nausea: Yuzpe 41/60; LNG 4/62 ◦ Vomiting: Yuzpe 15/60; LNG 0/62 ◦ Headache: Yuzpe 13/60; LNG 0/62 ◦ Weakness: Yuzpe 10/60; LNG 1/62 ◦ Hot flushes: Yuzpe 4/60; LNG 2/62

Risk of bias Bias




High risk

C - Inadequate

Fu X 2000 Methods


Participants

186 women attending an MCH hospital, Qinghai, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Anordrin 7.5 mg twice daily 12 h apart for 2 days vs Mife 50 mg

Outcomes


Notes

• No mention of post-randomisation exclusion and loss to follow-up • Observed pregnancy/expected pregnancy/total number of women: anordrin 3/8/90; Mife 1/5/96

Risk of bias Bias




42

Fu X 2000

(Continued)


High risk

C - Inadequate

Gan XH 2007 Methods

Women randomly allocated to 2 groups. The method of randomis ation not reported

Participants

456 women attending in an o bs/ gyn clinic, Boluo county hospital, Guangdong, China. Women had regular menstrual periods, and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg single dose orally vs LNG 0.75 mg 2 doses 12 h apart orally

Outcomes


Notes

• Observed pregnancy/total number of women: Mife 2/250; LNG 2/206 • Side effects: ◦ Total side effects: Mife 32/250; LNG 30/206 • Changes in menstrual pattern: ◦ Early: Mife 14/248; LNG 20/204 ◦ Delay: Mife 40/248; LNG 22/204 ◦ Spotting: Mife 4/248; LNG 3/204

Risk of bias Bias




High risk

C - Inadequate

Glasier 1992 Methods

Randomly allocated women to 2 treatment groups within pre-defined age groups (16-25 years, 26-34 years, 35-45 years). Cards with the treatment names on were put in sealed envelopes and allocation was made by shuffling the cards There was no blinding, placebos were not used. Side eff ects were assessed by women

Participants

800 women attending a family planning clinic and an accident and emergency department in Edinburgh, UK Included women with regular menstrual periods, aged 16-45 years who had had a single act of unprotected intercourse within 72 h of coming to the clinic Excluded women on oral contraceptives, regular prescription drugs, with medical contraindications, who were difficult to follow up and who would continue with the pregnancy in case of a failure

Interventions

Yuzpe (ethinyl oestradiol 100 µ g + norgestrel 1 mg, repeated after 12 h) vs Mife 600 mg single dose


43

Glasier 1992

(Continued)

Outcomes Notes

Observed number of pregnancies, side eff ects and changes in menstrual pattern • Loss to follow-up: 26/800 (3.3%), 3 with Mife; 23 with Yuzpe • Observed pregnancy/expected pregnancy rates not reported

Risk of bias Bias




Low risk

A - Adequate

Glasier 2010 Methods

Enrolled women randomly assigned to receive UPA 30 mg or LNG 1·5 mg orally. Randomisation schedule stratified by site and time from unprotected sexual intercourse to treatment (within 72 h and 72-120 h) with a block size of 4 Single blind (women masked to treatment assignment, whereas those giving the interventions and study investigators were not, since the study drugs differed in appearance (different tablet size and blister pack))

Participants

Women with regular menstrual cycles who presented to a participating family planning clinic requesting emergency contraception within 5 days of unprotected sexual intercourse were eligible for enrolment Randomised, multicentre, non-inferiority trial 2221 women randomly assigned to UPA (CDB-2914) (n = 1104) or LNG (n = 1117)

Interventions

UPA 30 mg vs LNG 1.5 mg single dose orally

Outcomes


Notes

• • • • •

Loss to follow-up: UPA 48/1104 women; LNG 40/1117(total 4%) Observed pregnancy/total number of women: UPA 15/941; LNG 25/958 Pregnancy in high-risk cases: UPA 4/53; LNG 5/51 Pregnancy in low-risk cases: UPA 11/888; LNG 20/907 Changes in menses: ◦ Early: UPA 67/1013; LNG 191/1031 ◦ Delay: UPA 177/1013; LNG 103/1031

Risk of bias Bias




Low risk

A - Adequate


44

Hamoda 2004 Methods

Women presenting within 72 h of unprotected intercourse enroll ed . Women presenting beyond 72 h and up to 120 h were offered a Cu-IUD insertion as the first treatment choice. Those declining IUD insertion were randomis ed to receive Mife 10 mg single tablet or 2 LNG 750 µ g tablets 12 h apart by opening sequentially numbered opaque sealed envelopes prepared using random number tables. The randomi sation envelopes were prepared in the Family Planning Clinic in Aberdeen, UK by a healthcare assistant not involved in the recruitment or data collection The study was not blinded, and both medical staff and patients were aware of the treatment assigned

Participants

Eligible participants were women > 16 years of age with regular menstrual cycles (2135 days), who requested EC within 120 h of unprotected sexual intercourse. Advice was given to women to avoid further episodes of unprotected sexual intercourse within that cycle. Women with more than 1 episode of unprotected sexual intercourse within 120 h of presentation were also included in the study 2065 women recruited; 2043 women included in the data analysis. Mife 1022 women; LNG 1021 women Treatment outcome for women was known for 860 women (84.2%) in the Mife group and 858 (84.1%) in the LNG group

Interventions

Mife 10 mg single dose orally vs LNG 0.75 mg 2 doses 12 h apart

Outcomes


Notes

• Loss to follow-up: Mife 162/1022; LNG 163/1021 • Post-randomisation exclusion: Mife 8/1030; LNG 12/1035 • Observed pregnancy/total number of women: Mife 13/860; LNG 20/858

Risk of bias Bias




Low risk

A - Adequate

Han 1995 Methods


Participants

139 women attending the outpatient clinic of a hospital in Beijing, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg orally 2 doses 12 h apart vs anordrin 7.5 mg orally 2 doses 12 h apart vs Mife 25 mg + anordrin 7.5 mg orally single dose

Outcomes



45

Han 1995

(Continued)

Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg twice: 0/4/46; anordrin 7.5 mg twice: 2/3/46; Mife + anordrin: 0/3/47 • The pregnancy rates in relation to risk factors were not reported

Risk of bias Bias




High risk

C - Inadequate

Han 1996 Methods


Participants

300 healthy women in Beijing, China, with regular menstrual periods, aged 18-48 years, with a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg orally 2 doses 12 h apart vs Mife 25 mg orally single dose, vs Mife 25 mg + anordrin 7.5 mg single dose

Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg twice 0/7/100; Mife 25 mg single dose 1/6/99; Mife + anordrin 1/7/101

Risk of bias Bias




High risk

C - Inadequate

Han 1999a Methods

Women ’randomly allocated’ into 2 groups in a 2:1 ratio. Me thod of randomisation not reported

Participants

214 women aged 21-45 years attending the o bs/ gyn clinic Chao Yang Hospital, Beijing, China. Women had regular menstrual periods a nd unprotected intercourse within 72 h of attending the clinic

Interventions

LNG 0.75 mg 2 doses 12 h apart vs Mife 25 mg single dose orally

Outcomes



46

Han 1999a

(Continued)

Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: LNG 5/13/144; Mife 1/5/70

Risk of bias Bias




High risk

C - Inadequate

Han L 2001 Methods


Participants

100 women attending a hospital clinic in Shanghai, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic

Interventions

Mife single dose 25 mg vs Mife 10 mg

Outcomes


Notes

• No loss to follow-up and exclusions reported • No pregnancies in either group

Risk of bias Bias




High risk

C - Inadequate

He CH 2002 Methods

Randomised double-blind multicentre trial. Random number generation done centrally, double-blinded by use of identical placebos

Participants

400 healthy women recruited into study from family planning clinics in Shanghai, China Included women with regular menstrual periods (24-42 days), who had a single act of unprotected intercourse within 120 h of attending the clinic, and they were willing to avoid further acts of unprotected coitus during that cycle and willing to have an induced abortion if pregnancy was diagnosed following intake of the study drug during the study period Excluded women: current pregnancy or breastfeeding, on hormonal contraception in the current cycle and those with uncertain dates of last menstrual period and no contraindication to use of Mife or tamoxifen

Interventions

Mife (single dose) 10 mg + placebo vs Mife 10 mg + tamoxifen 20 mg


47

He CH 2002

(Continued)

Outcomes


Notes

• Loss to follow-up: Mife + placebo 2/200; Mife + tamoxifen 3/200 • Observed pregnancy/total number of women: Mife + placebo 3/200; Mife + tamoxifen 1/200

Risk of bias Bias




Low risk

A - Adequate

Ho 1993 Methods

Women ’randomly allocated’ to 2 groups. A random number table used to generate the allocation sequence and allocation was done by sealed envelopes. Placebos were not used. Side eff ects were recorded by women

Participants

880 healthy women attending Family Planning Association clinics in Hong Kong Included women with regular menstrual periods (21-35 days), aged 18-45 years, with a single act of unprotected intercourse within 48 h of attending the clinic

Interventions

Yuzpe (ethinyl oestradiol 100 µ g + norgestrel 1 mg, repeated after 12 h) vs LNG 0.75 mg, orally, 2 doses 12 h apart

Outcomes


Notes

• Observed pregnancy/expected pregnancy/total number of women: Yuzpe 15/22/ 424; LNG 12/20/410 • Loss to follow-up: Yuzpe 16/440 (3.6%); LNG 30/440 (6.8%)

Risk of bias Bias




Low risk

A - Adequate

Hu X 2003 Methods

Women ’randomly allocated’ to 2 groups. Me thod of randomisation not recorded

Participants

240 women attending the clinic in a general hospital, Zhejiang, China. Women had regular menstrual periods a nd a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

LNG 0.75 mg 2-dose regimen vs Mife 25 mg single- dose orally


48

Hu X 2003

(Continued)

Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: LNG 4/13/120; Mife 2/13/120

Risk of bias Bias




High risk

C - Inadequate

Lai Z 2004 Methods


Participants

300 women attending the gyn clinic in a general hospital, Qinghai, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic

Interventions


Outcomes


Notes

• 20 women excluded after recruitment, 1 loss to follow-up • Observed pregnancy/expected pregnancy/total number of women: Mife 10 mg 2/ 13/149; Mife 25 mg 2/11/130

Risk of bias Bias




High risk

C - Inadequate

Lan XL 2006 Methods

Women randomly allocated to 2 groups. Method of randomis ation not reported

Participants

200 women attending in o bs/ gyn clinic, No. 8 people’ s hospital, Wenzhou, Zhejiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending clinic

Interventions


Outcomes



49

Lan XL 2006

(Continued)

Notes

• Observed pregnancy/total number of women: Mife 5 mg 1/100; Mife 10 mg 1/100 • Side effects: ◦ Mife 5 mg: no side effects recorded ◦ Mife 10 mg: nausea 3/100; breast tenderness 1/100

Risk of bias Bias




High risk

C - Inadequate

Li 2000 Methods


Participants

160 women attending a family planning clinic in Tianjing, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 50 mg vs Mife 25 mg single dose

Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/total number women: Mife 50 mg 0/79; Mife 25 mg 2/78 • Change in menstrual pattern: not reported

Risk of bias Bias




High risk

C - Inadequate

Li A 2000 Methods


Participants

234 women attending the clinic in an MCH hospital, Hainan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg single dose vs LNG 0.75 mg 2-dose regimen orally

Outcomes



50

Li A 2000

(Continued)

Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 3/13/119; LNG 4/11/115

Risk of bias Bias




High risk

C - Inadequate

Li H 2000 Methods

Women ’randomly allocated’ to 2 groups

Participants

90 women attending a clinic in Heilongjiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 150 mg vs Mife 50 mg vs Mife 25 mg single dose

Outcomes

Observed number of pregnancies, side eff ects and change in menstrual pattern

Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/total number of women: Mife 150 mg 0/30; Mife 50 mg 0/30; Mife 25 mg 1/30

Risk of bias Bias




High risk

C - Inadequate

Li J 2005 Methods


Participants

202 women attending the gyn clinic in a general hospital, Guangxi, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg vs LNG 0.75 mg 2-dose regimen orally

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/total number of women: Mife 1/100; LNG 2/102


51

Li J 2005

(Continued)

Risk of bias Bias




High risk

C - Inadequate

Li W 2002 Methods


Participants

255 women attending the family planning clinics in Guizhou, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic

Interventions

Mife 10 mg orally single dose vs LNG 0.75 mg orally 2 doses 12 h apart

Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/total number of women: Mife 2/120; LNG 3/135

Risk of bias Bias




High risk

C - Inadequate

Liang 2001 Methods


Participants

400 women attending an MCH hospital c linic in Heilongjiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg orally vs LNG 0.75 mg orally 2 doses 12 h apart

Outcomes

Observed number of pregnancies and side eff ects

Notes

• Post-randomisation exclusions not reported, loss of follow: Mife 2 women; LNG 3 women • Observed pregnancy/expected pregnancy/total number of women: Mife 2/15/198; LNG 4/17/197

Risk of bias


52

Liang 2001

(Continued)

Bias




High risk

C - Inadequate

Liao 2003 Methods


Participants

200 women attending a Reproductive Medical Clinic in Wuhan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• Post-randomisation exclusion or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 1/9/100; LNG 1/9/100

Risk of bias Bias




High risk

C - Inadequate

Lin 2000 Methods

Double-blind randomised trial. Me thod of randomisation not reported

Participants

120 women attending a family planning clinic in Tianjing, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 10 mg + placebo 12 h apart vs LNG 0.75 mg 2 doses 12 h apart

Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number women: Mife + placebo 0/5/ 60; LNG 0/5/60

Risk of bias Bias




53

Lin 2000

(Continued)


Unclear risk

B - Unclear

Liu 2000 Methods


Participants

100 healthy women recruited in the study from Henan Research Institute for family planning Included women with regular menstrual periods, who had a single act of unprotected intercourse or had multi-intercourse but the first one within 72 h of attending the clinic Excluded women who were breastfeeding, on hormonal contraception in the current cycle and those with uncertain dates of last menstrual period

Interventions

Mife (single dose) 10 mg vs LNG 0.75 mg 2 doses 12 h apart orally

Outcomes


Notes

• Loss to follow-up: Mife 2 women; LNG 2 women • -Observed pregnancy/expected pregnancy/total number of women: Mife 0/4/48; LNG 2/4/48

Risk of bias Bias




Low risk

A - Adequate

Liu L 2001 Methods


Participants

142 women attending the gyn clinic in a general hospital, Sichuan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg 2-doses 12 h apart vs a nordrin 7.5 mg 12 h later repeat 1 dose, then 7.5 mg per night for 10 days

Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 0/10/76; anordrin 3/8/66

Risk of bias


54

Liu L 2001

(Continued)

Bias




High risk

C - Inadequate

Liu L 2002 Methods

Women ’randomly allocated ’ into 2 groups in a 2:1 ratio. Me thod of randomisation not reported

Participants

285 women attending the g yn clinic in a general hospital, Hubei, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 50 mg orally vs Cu-IUD

Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 1/20/190; Cu-IUD 0/11/95

Risk of bias Bias




High risk

C - Inadequate

Liu RQ 2009 Methods

Women randomly allocated to 2 groups. The method of randomi sation was not described

Participants

280 women attending in a family planning clinic, Wangdu, Hebei, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg single dose vs LNG 0.75 mg 2 doses 12 h apart orally

Outcomes


Notes

• Observed pregnancy/total number of women: Mife 3/140; LNG 2/140 • Side effects: ◦ Mife: nausea and dizziness 6/140; breast tenderness 10/140 ◦ LNG: nausea and dizziness 8/140; breast tenderness 14/140 • Changes in menstrual pattern: Mife 11/140; LNG 2/140

Risk of bias Interventions for emergency contraception (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

55

Liu RQ 2009

(Continued)

Bias




High risk

C - Inadequate

Lou C 2002 Methods


Participants

283 women attending the g yn clinic in a general hospital, Zhejiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic

Interventions


Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 50 mg 1/ 14/147; Mife 25 mg 2/14/136

Risk of bias Bias




High risk

C - Inadequate

Lou X 2005 Methods


Participants


Interventions

Mife 10 mg + a nordrin 5 mg vs Mife 10 mg single dose orally

Outcomes


Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/total number of women: Mife + anordrin 1/66; Mife 3/76

Risk of bias Bias




56

Lou X 2005

(Continued)


High risk

C - Inadequate

Ngai 2005 Methods

The pharmacy department in Queen Mary Hospital generated the randomis ation sequence by computer program. D rug package was prepared by the pharmacy department according to the randomis ation list. Clinicians and participants were unaware of the drug assignment. The pharmacy kept the randomis ation list and it was revealed only at the final analysis. LNG and placebo w er e supplied by the WHO. P lacebo was identical in colour, shape and size to LNG

Participants

2071 healthy women aged > 16 years were recruited from 5 sites in China (Beijing, Hong Kong, Nanjing, Shanghai and Shenzhen). All w o men had regular menstrual cycles (every 24-42 days) and requested EC within 120 h of a single act of unprotected intercourse; they were willing to abstain from further acts of unprotected intercourse and were available for follow-up over the next 6 weeks Exclusion criteria: post-abortion or post-partum patients whose period had not yet returned, regular use of prescription drugs before admission to the study and intercourse during the treatment cycle > 120 h before admission into the study. Women satisfying these criteria were admitted into the study after they had given written informed consent. 2060 women into efficacy analysis, 2071 women into safety analysis

Interventions

LNG 0.75 mg 2 doses 24 h apart orally vs LNG 0.75 mg 2 doses 12 h apart

Outcomes


Notes

• Loss to follow-up: 24 h apart LNG 24/1044; 12 h apart LNG 29/1027 • Protocol violations: 24 h apart 6/1020; 12 h apart 5/998 • Observed pregnancy/expected pregnancy/total number of women: 24 h apart LNG 20/71/1038; 12 h apart LNG 20/74/1022

Risk of bias Bias




Low risk

A - Adequate

Pei 2001 Methods


Participants

200 women attending a hospital clinic in Shanxi, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions



57

Pei 2001

(Continued)

Outcomes Notes

Observed number of pregnancies, side eff ects and change in menstrual pattern • Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/total number of women: Mife 1/100; LNG 2/100

Risk of bias Bias




High risk

C - Inadequate

Qi 2000b Methods

Double-blind randomised multicentre trial Random number generation done centrally. Double-blinded by use of identical placebos

Participants

1209 women attending the family planning clinics in 11 provinces of China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg vs Mife 10 mg single dose

Outcomes


Notes

• Total of 85 cases lost to follow-up or missed data (7.03%) • Observed pregnancy/expected pregnancy/total number women: Mife 25 mg 5/91/ 579; Mife 10 mg 12/78/545

Risk of bias Bias




Low risk

A - Adequate

Qi M 2003 Methods


Participants

288 women attending the gyn clinic in a general hospital, Qinghai, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes



58

Qi M 2003

(Continued)

Notes

• Post-randomisation exclusions or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 2/17/150; LNG 9/15/138

Risk of bias Bias




High risk

C - Inadequate

Qian 1999 Methods


Participants

252 women attending a family planning clinic in Shenzhen, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife (single dose) orally 150 mg vs Mife 50 mg vs Mife 25 mg

Outcomes


Notes

• Post-randomisation exclusion or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 150 mg 1/ 7/86; Mife 50 mg 0/8/82; Mife 25 mg 1/8/84

Risk of bias Bias




High risk

C - Inadequate

Rowlands 1983 Methods

Women r andomly allocated to 2 treatments. Side eff ects assessed through interviews with the women

Participants

101 healthy women attending a family planning clinic (Margaret Pyke Centre) in London, UK Included women who had unprotected intercourse within 120 h (included some women who had multiple acts of unprotected intercourse)

Interventions

Yuzpe (ethinyl oestradiol 100 µ g + norgestrel 1 mg, repeated after 12 h) vs danazol 400 mg repeated after 12 h

Outcomes



59

Rowlands 1983

(Continued)

Notes

• Additional data provided by the authors. 6 women in the danazol group and 12 in the Yuzpe group were excluded after randomisation

Risk of bias Bias




High risk

C - Inadequate

Sang 1999 Methods

Single-blind randomised trial. Power calculation reported

Participants

2400 women attending urban hospital and family planning clinics in 5 cities in China Included only women who came after 24 h to 96 h of unprotected intercourse Excluded women who had irregular menstrual periods, multiple acts of intercourse, who had been using other oral contraceptives and whose normal menses had not resumed after an abortion or delivery

Interventions

Mife 25 mg vs Mife 25 mg + anordrin 7.5 mg vs Mife 10 mg + anordrin 5 mg vs M ife 10 mg

Outcomes


Notes

• Post-randomisation exclusions: 2 women • Loss to follow-up: total of 11 cases (0.5%): Mife 25 mg 1; Mife 25 mg + anordrin 7. 5 mg 5; Mife 10 mg + anordrin 5 mg 6; Mife 10 mg 1 • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg 10/ 42/599; Mife 25 mg + anordrin 7.5 mg 9/47.5/595; Mife 10 mg + anordrin 5 mg 7/42.6/ 594; Mife 10 mg 17/39.7/599 • 1 ectopic pregnancy in Mife 10 mg group

Risk of bias Bias




Low risk

A - Adequate

Shao XY 2010 Methods

Women randomly allocated to 2 groups. M ethod of randomis ation not reported

Participants

102 women attending in a Chinese traditional medicine hospital, Tonglu, Zhejiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic


60

Shao XY 2010

(Continued)

Interventions

M ife 25 mg single dose vs LNG 0.75 mg 2-dose regimen

Outcomes


Notes

• Observed pregnancy/total number of women: Mife 1/57; LNG 2/45 • Side effects: ◦ Mife: nausea 4/57; dizziness and headache 3/57; breast tenderness 4/57 ◦ LNG: nausea 4/45; dizziness and headache 4/45; breast tenderness 5/45 • Changes in menstrual pattern: ◦ Early: Mife 6/56; LNG 5/43 ◦ Delay: Mife 15/56; LNG 10/43 ◦ Spotting: Mife 3/56; LNG 11/43

Risk of bias Bias




High risk

C - Inadequate

Sheng A 2002 Methods


Participants

200 women attending a family planning centre, Jiangsu, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• Post-randomisation exclusion or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 1/10/100; LNG 2/11/100

Risk of bias Bias




High risk

C - Inadequate


61

Sheng SY 2008 Methods


Participants

200 women attending in a family planning clinic, Tongxiang, Zhejiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

LNG-COC 4 tablets (total ethinyl oestradiol 0.12 mg and LNG 0.6 mg) 2-dose 12 h apart orally vs LNG 0.75 mg 2-dose 12 h apart orally

Outcomes


Notes

• Observed pregnancy/total number of women: LNG-COC: 1/100; LNG: 1/100 • Side effects: ◦ LNG-COC: nausea 33/100; vomiting 5/100; dizziness and fatigue 12/100 ◦ LNG: nausea 15/100; vomiting 3/100; dizziness and fatigue 9/100 • Changes in menstrual pattern: ◦ Early: LNG-COC 10/100; LNG 14/100 ◦ Delay: LNG-COC 8/100; LNG 10/100

Risk of bias Bias




High risk

C - Inadequate

Su 2001 Methods

Women who had had unprotected intercourse within 72 h were ’ randomly allocated ’ to Mife or LNG groups, and women had unprotected intercourse 72-120 h were assigned to an IUD group. Random isation took place between 2 types of pills

Participants

315 women attending a hospital clinic, Baotou, China. Women had regular menstrual periods and a single unprotected intercourse within 72 to 120 h (in the case of IUDs)

Interventions

Mife 25 mg single dose vs LNG 0.75 mg twice orally vs Cu-IUD

Outcomes

Observed number of pregnancies

Notes

• Post-randomisation exclusion or loss to follow-up not reported • Observed pregnancy/total number of women: IUD 1/162; Mife 2/64; LNG 5/89 (1 ectopic pregnancy)

Risk of bias Bias




High risk

C - Inadequate


62

Sun 2000 Methods


Participants

200 women attending a family planning clinic in Haerbing, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg (single dose) orally vs LNG 0.75 mg orally 2 doses 12 h apart

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/total number of women: Mife 1/100, LNG 2/100

Risk of bias Bias




High risk

C - Inadequate

Sun MX 2007 Methods


Participants

1100 women attending in a village clinic, Miyun county, Beijing, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

LNG 0.75 mg 2-dose 12 h apart orally vs LNG-COC 4 tablets (total ethinyloestradiol 0. 12 mg and LNG 0.6 mg) 2-dose 12 h apart orally

Outcomes


Notes

• Observed pregnancy/total number of women: LNG 11/557 (user’s failure 4); LNGCOC: 14/553 (user’s failure 6) • Side effects: ◦ LNG: nausea and vomiting 100/557; dizziness and fatigue 39/557 ◦ LNG-COC: nausea and vomiting 227/553; dizziness and fatigue 45/553 • Changes in menstrual pattern: ◦ Early: LNG 76/557; LNG-COC 68/553 ◦ Delay: LNG 66/557; LNG-COC 55/553 ◦ Spotting: LNG 61/557; LNG-COC 73/553

Risk of bias Bias




High risk

C - Inadequate


63

Sun P 2003 Methods


Participants

60 women attending the clinic in a general hospital, Hubei, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg vs LNG 0.75 2-dose 12 h apart orally

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/total number of women: Mife 2/30; LNG 8/30

Risk of bias Bias




High risk

C - Inadequate

Tan 1999 Methods


Participants

145 women (aged 18-47 years) attending the family planning clinics in Guangzhou, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 12.5 mg orally 2 doses 12 h apart vs Mife 25 mg orally 2 doses 12 h apart

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 12.5 mg twice 0/6/62; Mife 25 mg twice 2/5/83

Risk of bias Bias




High risk

C - Inadequate


64

Tan L 2003 Methods


Participants

150 women attending the clinic in a general hospital, Hubei, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 12.5 mg vs Mife 25 mg 2-dose 12 h apart vs Mife 150 mg orally

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 12.5 mg 1/ 4/50; Mife 25 mg 0/3/50; Mife 150 mg 0/3/50

Risk of bias Bias




High risk

C - Inadequate

Van Santen 1985a Methods

Randomised, double-blind trial. Random number sequence generated from a random number table. A numbered strip containing the capsules given to participating women. Masking achieved by giving each woman the active and corresponding placebo treatments. Side eff ects were assessed by women

Participants

465 healthy women attending Utrecht State University Hospital, the Netherlands Included women with regular menstrual periods, who had a single act of unprotected intercourse Excluded women who were breastfeeding, on medications and difficult to follow up

Interventions

Yuzpe (ethinyl oestradiol 100 µ g + norgestrel 1 mg, repeated after 12 h) on day 1 + placebo capsules for 4 days vs ethinyl oestradiol 5 mg dose followed by a placebo capsule 12 h later followed by ethinyl oestradiol 5 mg single daily dose for 4 days

Outcomes


Notes

• Observed pregnancy/expected pregnancy/total number of women: Yuzpe 1/11/200; ethinyl oestradiol 5 mg 2/12/184 • Loss to follow-up 5.7% altogether

Risk of bias Bias




Low risk

A - Adequate


65

Von Hertzen 2002 Methods

Randomised double-blind multicentre trial. Random number generation done centrally, double-blinded by use of identical placebos. Allocation concealment achieved by sealed, sequentially numbered, treatment packs

Participants

4136 healthy women recruited in the study from 15 family planning clinics in 10 countries Included women with regular menstrual periods, aged 14-52 years, who had a single act of unprotected intercourse within 120 h of attending the clinic Excluded women who were breastfeeding, on hormonal contraception in the current cycle and those with uncertain dates of last menstrual period

Interventions

Mife (single dose) 10 mg vs LNG 1.5 mg (single dose) vs LNG 0.75 mg 2 doses 12 h apart orally

Outcomes


Notes

• Observed pregnancy/expected pregnancy/total number of women: Mife 10 mg 21/ 108/1359; single-dose LNG 20/111/1356; split-dose LNG 24/106/1356 (1 ectopic pregnancy) • Lost to follow-up: Mife 10 mg 20/1380; single-dose LNG 22/1379; split-dose LNG 19/1377 • ITT: 4071 into efficacy analysis, 4084 into safety analysis

Risk of bias Bias




Low risk

A - Adequate

Wang 1999 Methods


Participants

108 women attending the o bs/ gyn clinic in Tianjing No. 1 People’s Hospital, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg orally 2 doses 12 h apart vs anordrin 7.5 mg on the first day 2 doses 12 h apart, then 7.5 mg /day for 10 days, total dosage of a nordrin 90 mg

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 0/6/52; anordrin 3/7/56

Risk of bias Bias



Support for judgement 66

Wang 1999

(Continued)


High risk

C - Inadequate

Wang C 2000 Methods

Women were given choice for Cu-IUD or ECPs and those choosing ECPs were randomly allocated to 2 ECP groups. Me thod of randomisation not reported

Participants

150 women attending the family planning clinics in Shandong, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic

Interventions

Mife 10 mg single dose vs LNG 0.75 mg 2 doses 12 h apart

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnant/total number women: Mife 1/3/50; LNG 1/4/50

Risk of bias Bias




High risk

C - Inadequate

Wang J 2006 Methods


Participants

198 women attending the g yn clinic in a general hospital, Anhui, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 10 mg 1/9/ 98; Mife 25 mg 1/9/100

Risk of bias Bias




High risk

C - Inadequate


67

Wang L 2004 Methods


Participants

1200 women attending the gyn clinic in a general hospital, Shandong, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 12.5 mg vs Mife 25 mg single dose orally

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 12.5 mg 6/ 55/600; Mife 25 mg 6/53/600

Risk of bias Bias




High risk

C - Inadequate

Wang Q 2000 Methods

W omen ’r andomly allocated’ to 2 groups. Me thod of randomisation not reported

Participants

131 women attending an MCH hospital in Guangdong, China Included women who had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

LNG 0.75 mg 2 doses 12 h apart vs Mife 25 mg single dose

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number women: LNG 2/5/63; Mife 1/4/68

Risk of bias Bias




High risk

C - Inadequate


68

Wang SZ 2001 Methods


Participants

200 healthy women recruited in the study from an o bs/g yn clinic in Wuhan, China Included women with regular menstrual periods, aged 22-42 years, who had a single act of unprotected intercourse within 72 h of attending the clinic Excluded women who were on hormonal contraception in the current cycle and those with uncertain dates of last menstrual period

Interventions

Mife (single dose) 10 mg vs Mife 25 mg orally

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 10 mg 1/ 10/100; Mife 25 mg 1/10/100

Risk of bias Bias




Low risk

A - Adequate

Wang Y 2003 Methods


Participants

262 women attending the clinic in an MCH hospital, Shanxi, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg vs LNG 0.75 mg 2-dose regimen orally

Outcomes


Notes

• Loss to follow: Mife 2; LNG 1 • Observed pregnancy/expected pregnancy/total number of women: Mife 2/17/132; LNG 3/13/127

Risk of bias Bias




High risk

C - Inadequate


69

Wang ZW 2008 Methods


Participants

100 women attending in an obs/ gyn clinic, No. 5 hospital, Haerbin Medical University, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• Observed pregnancy/total number of women: Mife 25 mg 1/50; Mife 10 mg 1/50 • Side effects: ◦ Mife 25 mg: nausea and vomiting 3/50; dizziness 2/50; breast tenderness 1/50; fatigue 2/50; diarrhoea 3/50 ◦ Mife 10 mg: nausea and vomiting 2/50; dizziness 1/50; breast tenderness 1/50; fatigue 2/50; diarrhoea 2/50 • Changes in menstrual pattern: ◦ Early: Mife 25 mg 1/49; Mife 10 mg 1/49 ◦ Delay: Mife 25 mg 6/49; Mife 10 mg 5/49 ◦ Spotting: Mife 25 mg 1/49; Mife 10 mg 1/49

Risk of bias Bias




High risk

C - Inadequate

Webb 1992 Methods

Women ’r andomly allocated’ to 3 groups. Random number generation by computer. Schedule prepared by someone not involved in recruitment and outcome assessment. No blinding or use of placebos reported. Side eff ects were recorded by women

Participants

616 healthy women attending a community family planning clinic in Liverpool, UK Included women with regular menstrual periods (21-35 days), aged 16-45 years, with a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Yuzpe (ethinyl oestradiol 100 µ g + norgestrel 1 mg, repeated after 12 h ) vs danazol 600 mg twice 12 h apart vs Mife 600 mg single dose

Outcomes


Notes

• Loss to follow-up: 27/616 (4.4%). Pregnancy outcome assessed in 94%, side effects in 94%, menstrual changes in 92% of women • Trial stopped after recruitment of 616 of the 1200 initially targeted because of differences in efficacy in an interim analysis • Observed pregnancy/expected pregnancy/total number of women: Yuzpe: 5/11/191; danazol: 9/12/193; Mife 0/12/195


70

Webb 1992

(Continued)

Risk of bias Bias




Low risk

A - Adequate

Wei H 2011 Methods

Women randomly allocated to 2 groups. Me thod of randomisation not reported

Participants

100 women attending in a clinic, Anhui, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• Observed pregnancy/total number of women: Mife 25 mg 1/50; Mife 10 mg 0/50 • Side effects: ◦ Any side effect: Mife 25 mg 4/50; Mife 10 mg 3/50 • Changes in menstrual pattern: ◦ Spotting: Mife 25 mg 7/49; Mife 10 mg 3/50

Wei RH 2002 Methods

Randomis ed double-blind trial by use of identical placebos

Participants

200 women attending the g yn clinic in a general hospital, Hainan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes


Risk of bias Bias




Unclear risk

B - Unclear


71

WHO 1998 Methods

Randomised double-blind multinational trial. Random number generation done centrally. Double-blinded by use of identical placebos. Allocation concealment achieved by sealed, sequentially numbered, tinted bottles filled and labelled by the manufacturer

Participants

1998 healthy women at 21 centres worldwide Included women with regular menstrual periods, aged 18-45 years, who had a single act of unprotected intercourse within 72 h of attending the clinic Excluded women who were breastfeeding, on hormonal contraception in the current cycle and those with uncertain dates of last menstrual period 1955 women into the final analysis

Interventions

Yuzpe (ethinyl oestradiol 100 µ g + LNG 0.50 mg , repeated after 12 h ) vs LNG 0.75 mg twice 12 h apart

Outcomes


Notes

• Loss to follow-up: Yuzpe 18/997 (1.8%); LNG 25/1001 (2.5%) • Post-randomisation exclusion (ITT analysis) not reported • Observed pregnancy/expected pregnancy/total number of women: Yuzpe 31/72/ 979; LNG 11/75.3/976

Risk of bias Bias




Low risk

A - Adequate

WHO 1999 Methods

Randomised controlled multinational trial. Randomisation sequence was generated centrally at the WHO and women randomised to 3 groups within centres. Sequentially numbered bottles, each containing 3 pills were given to women at the centre. Each bottle contained the active and placebo pills accordingly. However, 200 mg pills were slightly larger and, therefore, not all pills were identical. Power calculation was made

Participants

1717 women attending family planning clinics in 11 centres in 6 countries Included women with regular menstrual cycles, within 120 h of a single act of unprotected intercourse and who were willing to avoid intercourse for the rest of the current cycle Excluded women who were breastfeeding, with uncertain date of last menstrual period, use of hormonal contraception in the current cycle and those with a contraindication to M ife use 1684 women included in the final analysis

Interventions

Mife 600 mg vs Mife 50 mg vs Mife 10 mg. All taken orally as a single dose at the time of enrolment

Outcomes



72

WHO 1999

(Continued)

Notes

• Loss to follow-up: 32/1717 (1.9%) • Exclusion: 1 woman was excluded because she was pregnant at the time of enrolment. There were 15 protocol violations (cycle length outside admissible range, treatment after 120 h, further use of EC in the same cycle) but these were included in the analysis • Observed pregnancy/expected pregnancy/total number of women: Mife 600 mg 7/ 45/559; Mife 50 mg 6/43/560; Mife 10 mg 7/48/565 • 2 ectopic pregnancies in Mife 50 mg group

Risk of bias Bias




Low risk

A - Adequate

Wu 1999a Methods

Double-blind randomised trial. Random number generation done centrally. Doubleblinded by use of identical placebos. Allocation concealment achieved by sealed, sequentially numbered, tinted bottles filled and labelled by the manufacturer

Participants

1324 women in 16 urban family planning clinics in China Included only women who came within 72 h of unprotected intercourse Excluded women with irregular menstrual periods, with multiple acts of intercourse, on oral contraceptives and post-abortal women whose menstrual periods had not returned to normal

Interventions

LNG 0.75 mg 2 doses 12 h apart vs Mife 10 mg single dose

Outcomes


Notes

• 20 women excluded altogether (reasons not stated) • Loss to follow-up 28 (2.1%) in the 2 groups • Observed pregnancy/expected pregnancy/total number of women: LNG 20/49/643; Mife 9/44/633

Risk of bias Bias




Low risk

A - Adequate


73

Wu 2002 Methods

Randomised double-blind multicentre trial. Random number generation done centrally, double-blinded by use of identical placebos. Allocation concealment achieved by sealed, sequentially numbered, tinted bottles filled and labelled by manufacturer

Participants

903 healthy women recruited in the study from 10 clinics in Shanghai, China Included women with regular menstrual periods (22-42 days), who had a single act of unprotected intercourse within 120 h of attending the clinic and they were willing to avoid further acts of unprotected coitus during that cycle and willing to have an induced abortion if pregnancy was diagnosed following intake of the study drug during the study period Excluded women with current pregnancy or breastfeeding, on hormonal contraception in the current cycle and those with uncertain dates of last menstrual period

Interventions

Mife 25 mg, 24 h later misoprostol 0.2 mg vs Mife 10 mg, 24 h later misoprostol 0.2 mg vs M ife (single dose) 10 mg + placebo

Outcomes


Notes

• Loss to follow-up: total 3 cases, 1 case protocol violation • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg + misoprostol 2/22/300; Mife 10 mg + misoprostol 2/21/299; Mife 10 mg + placebo 7/22/ 300

Risk of bias Bias




Low risk

A - Adequate

Wu 2010 Methods

Women randomly allocated to 2 groups. M ethod of randomis ation double-blind trial was reported

Participants

998 healthy women with regular menstrual cycles and negative urine pregnancy tests who were requesting emergency contraception up to 72 h after unprotected coitus to receive single-dose gestrinone 10 mg or M ife 10 mg

Interventions

Gestrinone: 4 gestrinone 2.5 mg capsules, and 1 placebo tablet identical in appearance to M ife Mife : 1 Mife 10 mg tablet and 4 placebo capsules identical in appearance to gestrinone

Outcomes


Notes

• Observed pregnancy/expected pregnancy/total number of women: gestrinone 12/ 37/498; Mife 9/38/498 • Lost to follow-up: 2/998 • Side effects: ◦ Nausea: gestrinone 38/498; Mife 51/498


74

Wu 2010

(Continued)

◦ ◦ ◦ ◦

Vomiting: gestrinone 1/498; Mife 1/498 Diarrhoea: gestrinone 4/498; Mife 1/498 Fatigue: gestrinone 9/498; Mife 18/498 Dizziness: gestrinone 8/498; Mife 13/498

Risk of bias Bias




Low risk

A - Adequate

Xiao 2002 Methods

Randomised double-blind multicentre trial. Random number generation done centrally Double-blinded by use of identical placebos

Participants

3052 healthy women recruited in the study from the 10 centres in China Included women with regular menstrual periods, aged 19-49 years, who had a single act of unprotected intercourse within 120 h of attending the clinic Excluded women who were breastfeeding, on hormonal contraception in the current cycle and those with uncertain dates of last menstrual period 3030 into efficacy analysis, 3033 into safety analysis

Interventions


Outcomes


Notes

• Loss to follow-up: Mife 10 mg 11/1527; Mife 25 mg 11/1525 • Observed pregnancy/expected pregnancy/total number of women: Mife 10 mg 17/ 115/1516; Mife 25 mg 17/126/1514

Risk of bias Bias




Low risk

A - Adequate

Xie 1998 Methods

Women r andomly allocat ed to 2 groups. Me thod of randomisation not reported

Participants

600 women attending an urban MCH Hospital in Fuzhou, China Excluded women attending after 72 h , irregular menstrual periods and who had multiple acts of intercourse

Interventions

Mife 150 mg vs M ife 50 mg vs Mife 25 mg, all single dose


75

Xie 1998

(Continued)

Outcomes


Notes

• Post-randomisation exclusion or loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 150 mg 5/ 17/200; Mife 50 mg 8/15/200; Mife 25 mg 5/15/200

Risk of bias Bias




High risk

C - Inadequate

Xie HH 2010 Methods

Women allocated to 3 groups. The method was not reported

Participants

120 women attending in a family planning clinic, Shenzhen, China

Interventions

Mife 25 mg single dose vs Mife 10 mg single dose

Outcomes


Notes

• Observed pregnancy/total number of women: Mife 25 mg 8/60; Mife 10 mg 7/60 • Side effects: ◦ Total side effects: Mife 25 mg 11/60; Mife 10 mg 9/60 • Changes in menstrual pattern: ◦ Early: Mife 25 mg 15/52; Mife 10 mg 15/53 ◦ Delay: Mife 25 mg 7/52; Mife 10 mg 8/53

Risk of bias Bias




High risk

C - Inadequate

Xu 2000 Methods

Women r andomly allocat ed to 2 groups. Me thod of randomisation not reported

Participants

400 women attending the family planning clinic in Zhejiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg single dose vs LNG 0.75 mg 2 doses 12 h apart


76

Xu 2000

(Continued)

Outcomes


Notes

• • 197 • •

Post-randomisation exclusion and loss of follow-up not reported Observed pregnancy/expected/total number women: Mife 2/15/198; LNG 4/17/ Side effects: Mife 16/198; LNG 21/197 Lost to follow-up: Mife 2/200; LNG 3/200

Risk of bias Bias




High risk

C - Inadequate

Xu Z 2000 Methods


Participants

266 women attending a family planning centre, Jianfsu, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg vs anordrin 7.5 mg 12 h late repeat 1 dose, then 7.5 mg per night for 8 days vs LNG 0.75 mg 2-dose regimen

Outcomes


Notes

• Post-randomisation exclusion and loss of follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 2/9/94; anordrin 3/8/86; LNG 2/8/86

Risk of bias Bias




High risk

C - Inadequate

Yang 2001 Methods


Participants

358 healthy women recruited into the study from clinics of MCH hospital in Guangzhou, China Included women with regular menstrual periods, aged 17-46 years, who had a single act of unprotected intercourse within 72 h of attending the clinic and they were willing to use condom for further acts of unprotected coitus during that cycle Excluded women on hormonal contraception in the current cycle and those with uncertain


77

Yang 2001

(Continued)

dates of last menstrual period Interventions

Mife 25 mg twice , 12 h apart vs anordrin 7.5 mg ,twice 12 h apart vs danazol 400 mg , twice 12 h apart

Outcomes


Notes

• Loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 1/14/121; anordrin 4/13/117; danazol 5/14/120

Risk of bias Bias




High risk

C - Inadequate

Yang F 2003 Methods


Participants

92 women attending the clinic in a general hospital, Hunan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• Post-randomisation exclusion and loss of follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg 1/5/ 52; Mife 50 mg 0/4/40

Risk of bias Bias




High risk

C - Inadequate

Zeng MY 2008 Methods


Participants

100 women attending in an MCH hospital, Wuhua county, Guangzhou, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic


78

Zeng MY 2008

(Continued)

Interventions


Outcomes


Notes

• Observed pregnancy/total number of women: Mife 10 mg 1/60; Mife 25 mg 1/40 • Side effects: ◦ Total side effects: Mife 10 mg 3/60; Mife 25 mg 4/40 • Changes in menstrual pattern: ◦ Delay: Mife 10 mg 8/60; Mife 25 mg 4/40 ◦ Spotting: Mife 10 mg 9/59; Mife 25 mg 2/39

Risk of bias Bias




High risk

C - Inadequate

Zeng XY 2007 Methods

Women allocated to 2 groups. The method of allocation was not reported

Participants

100 women attending in a county hospital, Zhejiang, China. Women had regular menstrual periods and a single act of unprotected intercourse within 120 h of attending the clinic

Interventions

Mife 25 mg + MTX 5 mg vs Mife 25 mg single dose orally

Outcomes


Notes

• Observed pregnancy/total number of women: Mife + MTX: 0/50; Mife: 1/50 • Side effects: ◦ Nausea and vomiting: Mife + MTX 6/50; Mife 5/50 • Changes in menstrual pattern: ◦ Delay: Mife + MTX 22/50; Mife 20/49

Zhang JQ 2000 Methods

Women ’randomly allocated’ into 4 groups

Participants

782 women attending a hospital clinic in Qinhai, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg 2 doses 12 h apart vs LNG 0.75 mg 2 doses 12 h apart vs M ife 25 mg single dose vs Mife 25 mg + LNG 0.75 mg

Outcomes



79

Zhang JQ 2000

(Continued)

Notes

• -Post-randomisation exclusion and loss to follow-up not reported • -Observed pregnancy/expected pregnancy/total number women: Mife 25 mg twice 1/15/212; LNG 1/16/205; Mife 25 mg 3/13/182; Mife 25 + LNG 4/13/183

Risk of bias Bias




High risk

C - Inadequate

Zhang L 2005 Methods

Double-blind randomis ed single centre trial

Participants

220 women attending the gyn clinic in a general hospital, Guangdong, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 10 mg single dose vs Mife 10 mg 2-dose 12 h apart orally

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: single-dose Mife 1/11/112; 2-dose Mife 1/11/108

Risk of bias Bias




Unclear risk

B - Unclear

Zhang X 1999a Methods

Women ’randomly allocated’ into 3 groups. Me thod of randomisation not reported

Participants

360 women attending the family planning clinics in Chengwu (a county in Shandong), China. W omen had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions

Mife 25 mg orally 2 doses 12 h apart vs Mife 10 mg qd for 5 days vs Mife 10 mg qd for 3 days

Outcomes



80

Zhang X 1999a

(Continued)

Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg twice 2/13/120; Mife 10 mg qd/5 days 0/12/118; Mife 10 mg qd/3 days 1/11/116

Risk of bias Bias




High risk

C - Inadequate

Zhang Y 1998 Methods

Randomis ed trial. Me thod of randomisation not reported

Participants

309 women attending family planning clinics in Beijing, China Included only women attending within 72 h of an unprotected intercourse Excluded women with irregular menstrual periods, who used oral contraceptives and those who had not resumed normal menses after an abortion or delivery

Interventions

Mife 25 mg vs Mife 10 mg vs Mife 5 mg

Outcomes


Notes

• Post-randomisation exclusions not reported • Loss to follow-up 5.8% (18/309) altogether • Observed pregnancy/expected pregnancy/total number of women: Mife 25 mg 1/6/ 99; Mife 10 mg 1/7/92; Mife 5 mg 2/7/100

Risk of bias Bias




High risk

C - Inadequate

Zhang Y 2002 Methods


Participants

135 women attending the clinic in a general hospital, Henan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes



81

Zhang Y 2002

(Continued)

Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/total number of women: Mife 100 mg 0/45; Mife 50 mg 0/45; Mife 10 mg 0/45

Risk of bias Bias




High risk

C - Inadequate

Zhang YM 2002 Methods


Participants


Interventions

Mife 10 mg + a nordrin 5 mg vs Mife 25 mg

Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/total number of women: Mife + anordrin 0/58; Mife 0/58

Risk of bias Bias




High risk

C - Inadequate

Zhao J 2003 Methods


Participants

270 women attending the gyn clinic in a general hospital, Shandong, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• Post-randomisation exclusion and loss to follow-up not reported • Observed pregnancy/expected pregnancy/total number of women: Mife 50 mg 1/8/ 90; Mife 25 mg 1/9/90; Mife 10 mg 1/9/90


82

Zhao J 2003

(Continued)

Risk of bias Bias




High risk

C - Inadequate

Zheng A 2005 Methods


Participants

200 women attending the gyn clinic in a general hospital, Hunan, China. Women had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes


Risk of bias Bias




High risk

C - Inadequate

Zuo 1999 Methods

Double-blind randomised trial Random number generation done centrally. Double-blinded by use of identical placebos

Participants

668 women recruited from 14 family planning clinics in Changsha, China. Women aged < 40 years had regular menstrual periods and a single act of unprotected intercourse within 72 h of attending the clinic

Interventions


Outcomes


Notes

• Loss to follow-up 8/668 • Observed pregnancy/expected pregnancy/total number of women: Mife 10 mg 3/ 26/321; Mife 25 mg 2/24/339


83

Zuo 1999

(Continued)

Risk of bias Bias




Low risk

A - Adequate

COC: combined oral contraceptive; Cu-IUD: copper intrauterine device; EC: emergency contraception; h: hour; ITT: intention to treat; IUD: intrauterine device; LNG: levonorgestrel; MCH: maternal and child health; Mife: mifepristone; MTX: methotrexate; qd: four times daily; UPA: ulipristal acetate; WHO: World Health Organization 21

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Ashok 2001

Not an RCT or quasi-RCT

Ashok 2004

It is the same clinical trial as Ashok 2002. The objective of this paper was to compare side effects, women’s acceptance and satisfaction with Mife 100 mg vs the Yuzpe regimen for EC

Ban 2001

Not an RCT

Benagiano G 2010

Not an RCT

Byamugisha 2010

RCT to compare LNG vs Yuzpe in 4 clinics. The primary objective of this study was to determine side effects and acceptability of 2 ECP regimens among users in Kampala, Uganda. There was no effectiveness result in the data and the side effects were assessed on a semi-quantitative scale

Creinin 1997

Meta-analysis, not a clinical trial

D’Souza 2003

An RCT in an outpatient clinic setting. Objective was to assess insertion-linked pain and the short-term useracceptability and safety of the GyneFix as compared with T-framed IUDs. No effectiveness result mentioned in this paper

Dixon 1980

Comparative study of ethinyl oestradiol 5 mg/day and conjugated oestrogens at 30 mg/day for 5 days. The study was conducted in 5 centres, 2 of which prescribed the drugs alternately. In these 2 centres, none of the 137 women who received ethinyl oestradiol became pregnant while 6 out of 132 women receiving conjugated oestrogens became pregnant. No other details were available for these centres

Dong 2007

An observational study on Mife vs LNG vs Cu-IUD for EC, not an RCT

Ellertson 2003a

An observational study, not an RCT


84

(Continued)

Espinos 1999

Not an RCT

Fan 1998

Not an RCT 518 women used Mife 25 mg + anordrin 7.5 mg for EC, 1 observed pregnancy/40 expected pregnancies

Fan H 2001

Not an RCT 1013 women used Cu-IUD for EC, 2 women got pregnant

Fasoli 1989

Review paper

Fine 2010

A prospective, multicentre, open-label study to evaluate the effectiveness and safety of UPA as EC in women presenting 48-120 h after unprotected intercourse. 1241 women from 45 planned parenthood clinics were treated with a single dose of UPA 30 mg

Gan 1999

Not an RCT 200 women used Mife 10 mg for EC, 2 observed pregnancies/15 expected pregnancies

Gan SX 2001

No mention of random allocation

Gao ER 2001

Not an RCT

Gottardi 1979

Not an RCT

Gottardi 1986

Not an EC study

Gu XY 2002

Not an RCT

Guillebaud 1983

Randomised and non-randomised groups of women analysed together. Randomised groups were published separately and included in this review (Rowlands 1983)

Halpern V 2010

A systematic review, not an RCT

Han 1999b

Part of Sang 1999 study

Han Y 2001

Not an RCT 126 women used GyneFix IUD for EC, no one got pregnant/12 expected pregnancies

Haspels 1976

Not an RCT

He 1991

Not an EC study; it is a study on regular postcoital use of LNG

Hoffman 1983

Not an RCT or quasi-RCT

Jiang 2000

No mention of random allocation

Jiang 2002

Not an RCTor quasi-RCT 120 women used R2323 (gestrinone) 5 mg as ECPwithin 120 h of intercourse


85

(Continued)

Jin 2005

Part of a large WHO multicentre dose-finding study of Mife (see WHO 1999)

Kesserü 1973

Not an RCT; also it is a study on regular postcoital contraception

Li XY 2001

Not an RCT or quasi-RCT 100 women used Mife 25 mg as ECPs within 72 h of intercourse. 2 women got pregnant

Li F 2002

Not an RCT 150 women used Mife 25 mg as ECPs within 72 h of intercourse. 3 women got pregnant

Li F 2005

Not an RCT After introduction of IUD and ECPs, women chose one of the EC methods that they wanted 2 groups (Cu375-IUD vs Mife 25 mg single dose orally). Observed/expected pregnancy/total number of women: IUD 0/12/150; Mife 4/13/150

Lippes 1976

Not an RCT

Lippes 1979

Not an RCT

Liu Y 2002

Not an RCT After introduction of IUD and ECPs, women chose the method that wanted to use 2 groups (Cu375-IUD vs Mife 25 mg single dose orally). Observed/expected pregnancy/total number of women: IUD 1/8/80; Mife 1/9/80

Luerti 1986

Not an RCT

Ma 2001

Not an RCT 110 women used Mife 25 mg single dose for EC, 1 got pregnant

Mo 2004

An RCT, but the loss of follow was 20%

Mor 2005

A prospective, open-label, cross-over study comparing the physiological effects of vaginally and orally administered EC. They concluded the vaginal route of administration of EC regimens may be as efficacious as the oral route

Piaggio 2003

A meta-analyses of Mife 10 mg for EC

Piaggio 2003a

A meta-analyses of effectiveness of different dosages of Mife for EC

Qi 2000

Not an RCT 622 women used Mife 25 mg for EC. 5 got pregnant, the effective rate was 91.25%

Qiao 2002

Not an RCT 140 women used Mife 25 mg in combination with MTX 5 mg for EC. No one got pregnant

Qin 2000

Not an RCT

Raymond 2000

An RCT of meclizine to prevent nausea associated with Yuzpe regimen


86

(Continued)

Raymond 2006

A study to assess how a strategy to maximise access to ECP would affect rates of pregnancy and sexually transmitted infections

Roye 2001

Not an RCT. It is a letter to the editor

Scarduelli 1998

Not an RCT

Schilling 1979

Not an RCT

Schreiber 2010

Conducted to assess the role of advanced supply of EC to teenage mothers

Shen HX 2010

Not an RCT

Shochet 2004

Not an RCT. Investigated side effects after the standard Yuzpe regimen or 2 modifications

Song ZH 2007

Not an RCT

Sun 2005

Review

Tian Q 2000

Not an RCT After introduction of IUD and ECPs, women chose one of the two methods that they wanted 2 groups (Cu375-IUD vs Mife 25 mg single dose orally). Observed/expected pregnancy/total number of women: IUD 0/8/80; Mife 2/7/80

Turok 2010

A prospective observational study, not an RCT

Van Santen 1983

Not an RCT

Van Santen 1985b

This study has been excluded because the report includes 1 group of a randomised comparison study published elsewhere and another cohort of women receiving the same treatment (Yuzpe regimen)

Virjo 1999

Not an RCT

Wang CP 2006

Not an RCT

Wei R 2002

Not an RCT 309 women used Mife 25 mg for EC. 209 women taken the pill within 72 h, and 3 of them got pregnant; 100 women took the pill 72-120 h and 2 of them got pregnant

Wu 1999b

Not an RCT 793 women used Mife 25 mg single dose, 6 observed pregnancies/58 expected pregnancies

Wu 2005

Review

Xiao 2004

Not an RCT A total of 4945 women were recruited in 31 clinical centres in 18 provinces and municipalities in China in a descriptive clinical trial with 1 dose (Mife 10 mg) treatment. 28 cases lost to follow-up. An analysis of 4917 cases showed a pregnancy rate of 1.4% (95% CI 1.1% to 1.8%) and an effectiveness of prevention of pregnancy


87

(Continued)

of 82.2% (95% CI 77.5% to 86.2%). No trend of increase of pregnancies with delay of treatment was found. Increase of risk of pregnancy in women who had unprotected intercourse after treatment is about 11.1 times higher. Side effects were mild and in small proportion of women, such as nausea and vomiting in 9.2% and other side effects in 0.7% to 3.7% of women. Delay of menstruation over 7 days occurred in 6.5% of women Yang 2002

Not an RCT 106 women used Mife 10 mg for EC within 72 h of intercourse. Among them, 1 case pregnancy and 1 loss to follow-up

Yu 2001

Review

Yuzpe 1974

No randomised comparison

Yuzpe 1977


Yuzpe 1982


Zhang J 1999

Not an RCT 200 women were divided into 2 groups (Mife 25 mg or IUD). Women who had unprotected intercourse within 72 h were given Mife and within 72-120 h given IUD. 0 pregnancy/10 expected pregnancies in IUD group, 2 observed pregnancies/8 expected pregnancies in Mife group

Zhang M 1999

Part of Sang 1999 study

Zhang X 1999

Results have been included in Sang 1999

Zhang X 1999b

Not an RCT 123 women used LNG 0.75 mg orally 2 doses 12 h apart, 1 observed pregnancy/13 expected pregnancies

Zhao 2006

Not an RCT A questionnaire survey among 301 women who had LNG EC failure and had abortion

Zhao H 2001

Not an RCT

Zhu 1999

Not an RCT. 17 women used Mife 25 mg + MTX 5 mg for EC, no one got pregnant

Zhu YH 2007

Not an RCT

Zuliani 1990

Study conducted in Milan, Italy, which started reporting in 1986. The first report refers to an ongoing randomised trial comparing ethinyl oestradiol-norgestrel combination (Yuzpe regimen) to danazol 800 mg in 835 women. Subsequently, it is reported that 1000 women were randomised trial and, afterwards, a third group (danazol 1200 mg) comparison was added. There was no report from which the results for the 1000 women randomised to Yuzpe and danazol 800 mg can be extracted. In subsequent reports in 1988 and 1990, the results are reported with randomised and non-randomised groups together and, therefore, this study has been excluded from analysis


88

CI: confidence interval; Cu-IUD: copper-intrauterine device; EC: emergency contraception; ECP: emergency contraceptive pill; IUD: intrauterine device; LNG: levonorgestrel; Mife: mifepristone; MTX: methotrexate; RCT: randomised controlled trial; UPA: ulipristal acetate


89

DATA AND ANALYSES

Comparison 1. Intrauterine contraceptive device versus control

Outcome or subgroup title 1 Observed number of pregnancies

No. of studies

No. of participants

1

300

Statistical method Risk Ratio (M-H, Fixed, 95% CI)

Effect size 0.09 [0.03, 0.26]

Comparison 2. Levonorgestrel versus Yuzpe

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancies (time from intercourse) 3.1 Within 24 h 3.2 25-48 h 3.3 49-72 h 3.4 Later than 72 h 4 Need for extra dose 5 Any side effect 6 Specific side effects 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Abdominal pain 6.8 Hot flushes 6.9 Spotting/bleeding after treatment 7 Menses 7.1 Early 7.2 Delay

No. of studies

No. of participants

5

4221

Risk Ratio (M-H, Fixed, 95% CI)

0.54 [0.36, 0.80]

2

2781


0.50 [0.31, 0.82]

2 2 2

888 1893 2632

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.39 [0.19, 0.80] 0.64 [0.32, 1.26] 0.48 [0.28, 0.82]

2 2 1 0 1 1 5 5 4 2 2 2 5 1 1 2

1343 952 337 0 1955 1955 4221 3111 2789 2077 2789 4221 1955 122 1944

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.51 [0.19, 1.34] 0.42 [0.19, 0.94] 0.57 [0.19, 1.77] 0.0 [0.0, 0.0] 0.53 [0.38, 0.75] 0.80 [0.75, 0.86] Subtotals only 0.42 [0.38, 0.46] 0.23 [0.18, 0.30] 0.84 [0.69, 1.01] 0.78 [0.65, 0.94] 0.72 [0.61, 0.85] 0.63 [0.55, 0.71] 0.84 [0.70, 1.01] 0.48 [0.09, 2.54] 0.86 [0.64, 1.15]

3 2 3

3298 1310 1988


1.19 [0.99, 1.44] 1.15 [0.86, 1.52] 1.23 [0.96, 1.57]

Statistical method


Effect size

90

Comparison 3. Levonorgestrel split-dose 24 hours versus 12 hours

Outcome or subgroup title 1 Observed number of pregnancy (all women) 2 Observed number of pregnancy (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancy (time from intercourse) 3.1 Within 72 h 3.2 Later than 72 4 Need for extra dose 5 Any side effect 6 Specific side effects 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Lower abdominal pain 6.8 Diarrhoea 6.9 Spotting/bleeding after treatment 6.10 Heavy menses 7 Menses 7.1 Early 7.2 Delay

No. of studies

No. of participants

1

2060


0.98 [0.53, 1.82]

1

2012


0.98 [0.53, 1.81]

1 1 0

446 1566 0


0.39 [0.13, 1.23] 1.56 [0.71, 3.42] 0.0 [0.0, 0.0]

0 0 0 0 1 1 1 1 1 1 0 1 0 0

0 0 0 0 2071 2071 2071 2071 2071 0 2071 0 0

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] Subtotals only 0.96 [0.72, 1.29] 0.83 [0.37, 1.85] 0.60 [0.40, 0.91] 0.89 [0.58, 1.36] 1.23 [0.86, 1.74] 0.0 [0.0, 0.0] 0.76 [0.53, 1.08] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 1 0 1

0 1978 0 1978

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.79 [0.53, 1.17] 0.0 [0.0, 0.0] 0.79 [0.53, 1.17]

Statistical method

Effect size

Comparison 4. Levonorgestrel single dose versus split-dose

Outcome or subgroup title 1 Observed number of pregnancy (all women) 2 Observed number of pregnancy (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancy (time from intercourse) 3.1 Within 72 h 3.2 Later than 72 h 4 Need for extra dose

No. of studies

No. of participants

3

6653


0.84 [0.53, 1.33]

1

2712


0.83 [0.46, 1.49]

1 1 2

792 1920 5489


0.56 [0.22, 1.41] 1.10 [0.51, 2.40] 0.95 [0.57, 1.57]

2 2 0

4873 616 0


0.86 [0.48, 1.54] 1.26 [0.46, 3.43] 0.0 [0.0, 0.0]

Statistical method


Effect size

91

5 Any side effect 6 Specific side effects 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Lower abdominal pain 6.8 Diarrhoea 6.9 Spotting/bleeding after treatment 6.10 Heavy menses 7 Menses 7.1 Early 7.2 Delay

0 3 3 3 2 3 3 2 2 1 1 1 2 1 2

0 6804 6804 3782 6804 6804 5742 3782 2720 2720

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] Subtotals only 0.97 [0.88, 1.07] 1.01 [0.83, 1.22] 1.12 [0.91, 1.37] 1.14 [1.01, 1.30] 0.91 [0.79, 1.05] 1.01 [0.88, 1.15] 0.90 [0.77, 1.05] 1.21 [0.81, 1.79] 1.00 [0.90, 1.12]

1062 4902 1118 3784


1.48 [1.08, 2.04] 0.91 [0.78, 1.05] 0.67 [0.54, 0.82] 1.18 [0.96, 1.46]

Comparison 5. Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancies (time from intercourse) 4 Need for extra dose 5 Any side effect 6 Specific side effect 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Abdominal pain 6.8 Spotting/bleeding after treatment 7 Menses 7.1 Early 7.2 Delay 8 ITT (all loss follow-up as pregnancy in LNG, and no preg in Mife)

No. of studies

No. of participants

20

5012


0.64 [0.45, 0.92]

1

599


1.63 [0.26, 10.24]

1 1 0

77 522 0


1.14 [0.11, 12.05] 2.57 [0.12, 53.29] 0.0 [0.0, 0.0]

0 13 7 4 0 4 1 2 0 1 5

0 3532 713 0 713 131 302 0 200 1266

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.58 [0.41, 0.82] Subtotals only 0.81 [0.48, 1.36] 0.0 [0.0, 0.0] 0.88 [0.52, 1.49] 0.66 [0.22, 1.98] 0.85 [0.26, 2.80] 0.0 [0.0, 0.0] 0.43 [0.11, 1.61] 0.63 [0.39, 1.02]

12 3 12 15

3593 794 2799 3758


1.17 [0.97, 1.40] 0.76 [0.47, 1.23] 1.26 [1.03, 1.54] 0.50 [0.32, 0.77]

Statistical method


Effect size

92

9 ITT (all loss follow-up as no pregnancy in LNG, and preg in Mife)

15

3758


0.57 [0.37, 0.88]

Comparison 6. Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancies (time from intercourse) 3.1 Within 72 h 3.2 Later than 72 h 4 Need for extra dose 5 Any side effect 6 Specific side effect 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Low abdominal pain 6.8 Diarrhoea 6.9 Spotting/bleeding after treatment 6.10 Heavy menses 6.11 Hot flushes 7 Menses 7.1 Early 7.2 Delay 8 ITT (all loss follow-up as pregnancy in LNG, and no preg in Mife) 9 ITT (all loss follow-up as no pregnancy in LNG, and preg in Mife)

No. of studies

No. of participants

11

8336


0.70 [0.50, 0.97]

1

4071


0.92 [0.55, 1.55]

1 1 2

1235 2836 6074


1.32 [0.67, 2.60] 0.59 [0.25, 1.35] 0.85 [0.56, 1.28]

2 2 0 2 5 5 3 3 3 4 3 4 2 2

5553 521 0 455 6384 6085 6084 6082 6181 6077 5105 4184 4182

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI)

0.82 [0.53, 1.27] 1.11 [0.35, 3.57] 0.0 [0.0, 0.0] 0.24 [0.15, 0.37] Subtotals only 0.95 [0.84, 1.09] 1.22 [0.55, 2.68] 1.03 [0.88, 1.21] 1.06 [0.83, 1.37] 0.92 [0.79, 1.08] 1.06 [0.94, 1.21] 0.94 [0.83, 1.06] 1.26 [0.93, 1.73] 0.62 [0.55, 0.70]

0 1 6 2 6 9

0 723 8488 1384 7104 8429

Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.93 [0.65, 1.33] 1.24 [1.09, 1.40] 0.44 [0.33, 0.58] 1.75 [1.51, 2.03] 0.70 [0.50, 0.98]

9

8429


0.90 [0.76, 1.05]

Statistical method


Effect size

93

Comparison 7. Ulipristal acetate (all doses) versus Levonorgestrel

Outcome or subgroup title 1 Observed number of pregnancy (all women) 2 Observed number of pregnancy (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancy (time from intercourse) 3.1 Within 24 h 3.2 24-48 h 3.3 > 48-72 h 3.4 > 72-96 h 3.5 > 96-120 h 4 Observed number of pregnancy within 0-72 h 5 Need for extra dose 6 Any side effect 7 Specific side effects 7.1 Nausea 7.2 Vomiting 7.3 Breast tenderness 7.4 Headache 7.5 Dizziness 7.6 Fatigue 7.7 Lower abdominal pain 7.8 Diarrhoea 7.9 Spotting/bleeding after treatment 7.10 Dysmenorrhoea 7.11 Abdominal pain 7.12 Upper abdominal pain 7.13 Back pain 8 Menses 8.1 Early 8.2 Delay

No. of studies

No. of participants

2

3448


0.59 [0.35, 0.99]

2

3445


0.58 [0.35, 0.97]

2 2 2

171 3274 3447


0.79 [0.25, 2.46] 0.54 [0.30, 0.97] 0.61 [0.37, 1.00]

2 2 2 1 1 2

1185 1213 846 136 67 3245

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.40 [0.15, 1.05] 1.33 [0.59, 3.00] 0.34 [0.11, 1.06] 0.23 [0.01, 4.73] 0.32 [0.01, 7.68] 0.63 [0.37, 1.07]

0 0 2 2 1 1 2 2 2 1 1 1

0 0 3770 1549 1549 3770 3770 3770 1549 1549 1549

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0] Subtotals only 1.14 [0.93, 1.41] 1.00 [0.14, 7.07] 1.07 [0.53, 2.14] 1.02 [0.87, 1.20] 1.06 [0.78, 1.45] 1.22 [0.91, 1.62] 1.15 [0.69, 1.90] 1.09 [0.48, 2.45] 0.71 [0.23, 2.24]

1 1 1 1 2 2 2

2221 2221 2221 2221 7186 3593 3593

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.90 [0.73, 1.11] 0.76 [0.54, 1.06] 0.81 [0.53, 1.24] 1.31 [0.80, 2.15] 0.83 [0.75, 0.92] 0.43 [0.37, 0.50] 1.65 [1.42, 1.92]

Statistical method


Effect size

94

Comparison 8. Levonorgestrel (all doses) versus anordrin (all doses)

Outcome or subgroup title 1 Observed number of pregnancy (all women) 2 Observed number of pregnancy (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancy (time from intercourse) 3.1 Within 72 h 3.2 Later than 72 h 4 Need for extra dose 5 Any side effect 6 Specific side effects 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Lower abdominal pain 6.8 Diarrhoea 6.9 Spotting/bleeding after treatment 6.10 Heavy menses 7 Menses 7.1 Early 7.2 Delay

No. of studies

No. of participants

1

172


0.67 [0.11, 3.89]

0

0


0.0 [0.0, 0.0]

0 0 0

0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 0 0 1 0 0 0 0 0 0 0 0 0 0

0 0 0 172 0 0 0 0 0 0 0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.75 [0.27, 2.07] Subtotals only 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 0 0 0

0 0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

Statistical method

Effect size

Comparison 9. mifepristone low dose (10 mg) versus low dose (5 mg)

Outcome or subgroup title 1 Observed number of pregnancy (all women) 2 Observed number of pregnancy (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancy (time from intercourse) 3.1 Within 24 h 3.2 24-48 h 3.3 > 48-72 h

No. of studies

No. of participants

2

392


0.70 [0.12, 4.17]

0

0


0.0 [0.0, 0.0]

0 0 0

0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 0 0

0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

Statistical method


Effect size

95

4 Need for extra dose 5 Any side effect 6 Specific side effects 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Lower abdominal pain 6.8 Diarrhoea 6.9 Spotting/bleeding after treatment 7 Delay of menses 7.1 Early 7.2 Delay

0 0 1 1 0 1 0 0 0 0 0 0 0 0 0

0 0 200 0 200 0 0 0 0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] Subtotals only 7.0 [0.37, 133.78] 0.0 [0.0, 0.0] 3.0 [0.12, 72.77] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

Comparison 10. Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Any side effect 4 Specific side effects 4.1 Nausea 4.2 Vomiting 4.3 Breast tenderness 4.4 Headache 4.5 Dizziness 4.6 Fatigue 4.7 Abdominal pain 4.8 Diarrhoea 4.9 Spotting/bleeding after treatment 5 Menses 5.1 Early 5.2 Delay

No. of studies

No. of participants

25

11914


0.73 [0.55, 0.97]

3

4715


0.83 [0.50, 1.38]

3 3 11 18 13 6 9 6 10 12 4 9 11

1544 3171 2464 7948 6082 6010 6329 3512 8209 4870 5746 5078

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.72 [0.36, 1.42] 0.99 [0.45, 2.17] 1.31 [1.01, 1.70] Subtotals only 1.10 [0.97, 1.24] 1.22 [0.68, 2.17] 0.91 [0.64, 1.29] 0.96 [0.76, 1.22] 1.14 [0.79, 1.63] 0.99 [0.86, 1.15] 1.02 [0.78, 1.32] 1.03 [0.68, 1.55] 1.85 [1.55, 2.20]

2136 11282

Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI)

Subtotals only 1.09 [0.87, 1.36] 1.28 [1.11, 1.47]

21 7 21

Statistical method


Effect size

96

Comparison 11. Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Any side effect 4 Specific side effects 4.1 Nausea 4.2 Vomiting 4.3 Breast tenderness 4.4 Headache 4.5 Dizziness 4.6 Fatigue 4.7 Abdominal pain 4.8 Early menses 4.9 Spotting/bleeding after treatment 5 Delay in menses 5.1 > 3 days 5.2 > 5 days 5.3 > 7 days

No. of studies

No. of participants

13

3123


0.72 [0.41, 1.27]

0

0


0.0 [0.0, 0.0]

0 0 6 3 1 1 1 1 1 1 1 1 2

0 0 1465 418 418 418 418 418 418 418 178 617

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 1.79 [1.39, 2.31] Subtotals only 0.92 [0.44, 1.91] 0.20 [0.01, 4.10] 0.40 [0.08, 2.02] 0.74 [0.17, 3.28] 1.49 [0.54, 4.10] 2.97 [0.12, 72.53] 2.10 [0.93, 4.77] 1.8 [0.63, 5.16] 1.35 [0.82, 2.20]

8 3 1 4

1945 816 92 1037


1.32 [1.12, 1.56] 1.00 [0.75, 1.34] 1.04 [0.45, 2.39] 1.57 [1.26, 1.94]

Statistical method

Effect size

Comparison 12. Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Any side effect 4 Specific side effects 4.1 Nausea 4.2 Vomiting 4.3 Breast tenderness 4.4 Headache 4.5 Dizziness 4.6 Fatigue 4.7 Abdominal pain 4.8 Diarrhoea

No. of studies

No. of participants

5

1726


0.52 [0.23, 1.17]

1

1102


0.99 [0.29, 3.41]

0 1 3 3 1 0 1 0 1 2 0 1

0 1102 512


0.0 [0.0, 0.0] 0.99 [0.29, 3.41] 13.04 [5.13, 33.15] Subtotals only 1.67 [0.42, 6.56] 0.0 [0.0, 0.0] 5.0 [0.25, 101.31] 0.0 [0.0, 0.0] 1.5 [0.26, 8.55] 1.25 [1.00, 1.56] 0.0 [0.0, 0.0] 1.5 [0.26, 8.55]

90 0 90 0 90 1210 0 90

Statistical method


Effect size

97

4.9 Spotting/bleeding after treatment 5 Menses 5.1 Early 5.2 Delay

2

1224


2.36 [1.89, 2.95]

4 0 4

1574 0 1574


1.98 [1.66, 2.37] 0.0 [0.0, 0.0] 1.98 [1.66, 2.37]

Comparison 13. Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Any side effect 4 Specific side effects 4.1 Nausea 4.2 Vomiting 4.3 Breast tenderness 4.4 Headache 4.5 Dizziness 4.6 Fatigue 4.7 Abdominal pain 4.8 Diarrhoea 4.9 Spotting/bleeding after treatment 5 Menses 5.1 Early 5.2 Delay

No. of studies

No. of participants

9

3009


0.93 [0.50, 1.72]

0

0


0.0 [0.0, 0.0]

0 0 5 5 1 0 1 0 1 1 0 1 4

0 0 1310 90 0 90 0 90 90 0 90 1509

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 2.64 [1.57, 4.43] Subtotals only 1.25 [0.36, 4.35] 0.0 [0.0, 0.0] 2.0 [0.19, 21.28] 0.0 [0.0, 0.0] 1.0 [0.21, 4.69] 2.0 [0.19, 21.28] 0.0 [0.0, 0.0] 1.0 [0.21, 4.69] 1.32 [1.12, 1.56]

8 2 8

3144 290 2854


1.56 [1.37, 1.78] 10.0 [1.30, 76.66] 1.53 [1.34, 1.75]

Statistical method

Effect size

Comparison 14. Mifepristone (all doses) versus Yuzpe

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancies (time from intercourse) 3.1 within 24 h

No. of studies

No. of participants

3

2144


0.14 [0.05, 0.41]

1

800


0.10 [0.01, 1.90]

1 1 1

322 478 958


0.10 [0.01, 1.90] 0.0 [0.0, 0.0] 0.19 [0.06, 0.59]

1

269


0.14 [0.01, 2.72]

Statistical method


Effect size

98

3.2 25-48 h 3.3 49-72 h 4 Need for extra dose 5 Any side effect 6 Specific side effects 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Abdominal pain 6.8 Spotting/bleeding after treatment 6.9 Hot flushes 6.10 Lethargy 7 Menses 7.1 Early 7.2 Delay

1 1 1 2 3 3 3 3 2 1 1 1 0

429 260 958 1693

1 1 3 0 3

1000 1000

2186 2186 2186 1800 1000 1000 1000 0

0 1924

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI)

0.15 [0.02, 1.18] 0.24 [0.05, 1.16] 0.11 [0.03, 0.49] 0.83 [0.77, 0.88] Subtotals only 0.63 [0.53, 0.76] 0.12 [0.07, 0.20] 0.86 [0.54, 1.39] 0.75 [0.61, 0.91] 0.58 [0.42, 0.80] 0.81 [0.68, 0.95] 0.76 [0.61, 0.95] 0.0 [0.0, 0.0]

Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.58 [0.40, 0.83] 0.75 [0.59, 0.95] Subtotals only 0.0 [0.0, 0.0] 2.83 [2.30, 3.47]

Comparison 15. Mifepristone (all doses) versus danazol (all doses)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Any side effect 3 Specific side effect 3.1 Nausea 3.2 Vomiting 3.3 Breast tenderness 3.4 Others 4 Menses 4.1 Delay

No. of studies

No. of participants

2

629


0.10 [0.02, 0.55]

1 1 1 1 1 1 2 2

241

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Random, 95% CI) Risk Ratio (M-H, Random, 95% CI)

0.35 [0.13, 0.95] Subtotals only 1.22 [0.92, 1.61] 0.82 [0.25, 2.63] 0.85 [0.56, 1.29] 2.94 [0.31, 28.01] 2.39 [0.56, 10.27] 2.39 [0.56, 10.27]

390 390 390 390 621 621

Statistical method

Effect size

Comparison 16. Mifepristone (all doses) versus anordrin (all doses)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk-status) 2.1 High-risk women 2.2 Low-risk women

No. of studies

No. of participants

7

1035


0.26 [0.11, 0.63]

0

0


0.0 [0.0, 0.0]

0 0

0 0

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

Statistical method


Effect size

99

3 Any side effect 4 Specific side effects 4.1 Nausea 4.2 Vomiting 4.3 Breast tenderness 4.4 Headache 4.5 Dizziness 4.6 Fatigue 4.7 Abdominal pain 4.8 Spotting/bleeding after treatment 5 Menses 5.1 Delay

4 2 0 0 0 0 0 0 0 2

746 0 0 0 0 0 0 0 331

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.62 [0.43, 0.91] Subtotals only 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 1.82 [0.69, 4.77]

4 4

667 667


1.14 [0.78, 1.68] 1.14 [0.78, 1.68]

Comparison 17. Mifepristone alone (all doses) versus mifepristone + anordrin (all doses)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Any side effect 4 Specific side effects 4.1 Nausea 4.2 Vomiting 4.3 Breast tenderness 4.4 Headache 4.5 Dizziness 4.6 Fatigue 4.7 Abdominal pain 4.8 Diarrhoea 4.9 Spotting/bleeding after treatment 5 Delay in menses 5.1 Early 5.2 Delay

No. of studies

No. of participants

5

3038


1.32 [0.73, 2.41]

0

0


0.0 [0.0, 0.0]

0 0 2 5 1 1 1 1 1 1 1 0 5

0 0 442 2387 2387 2387 2387 2387 2387 2387 0 3038


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.83 [0.49, 1.41] Subtotals only 0.53 [0.44, 0.65] 0.26 [0.14, 0.50] 0.93 [0.65, 1.32] 0.81 [0.53, 1.25] 0.77 [0.54, 1.10] 0.66 [0.49, 0.89] 1.18 [0.83, 1.67] 0.0 [0.0, 0.0] 1.80 [1.33, 2.43]

3 0 3

2781 0 2781


0.79 [0.65, 0.97] 0.0 [0.0, 0.0] 0.79 [0.65, 0.97]

Statistical method


Effect size

100

Comparison 18. Mifepristone alone (all doses) versus mifepristone + MTX (all doses)

Outcome or subgroup title 1 Observed number of pregnancy (all women) 2 Observed number of pregnancy (time from intercourse) 2.1 Within 72 h 2.2 Later than 72 h 3 Observed number of pregnancy (by risk status) 3.1 High-risk women 3.2 Low-risk women 4 Need for extra dose 5 Any side effect 6 Menses 6.1 Early 6.2 Delay

No. of studies

No. of participants

2

200


3.0 [0.32, 28.36]

0

0


0.0 [0.0, 0.0]

0 0 0

0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 0 0 2 2 1 2

0 0 0 200 299 100 199

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.75 [0.33, 1.70] 0.95 [0.63, 1.43] 1.5 [0.26, 8.60] 0.91 [0.60, 1.39]

Statistical method

Effect size

Comparison 19. Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 3 Observed number of pregnancies (time from intercourse) 3.1 Within 72 h 3.2 Later than 72 h 4 Need for extra dose 5 Any side effect 6 Specific side effect 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Abdominal pain 6.8 Diarrhoea 6.9 Spotting/bleeding after treatment 6.10 Heavy menses 7 Menses

No. of studies

No. of participants

1

400


3.0 [0.31, 28.60]

0

0


0.0 [0.0, 0.0]

1

400


2.33 [0.35, 15.56]

1 1 0 0 1 1 1 1 1 1 1 1 1 1

198 202 0 0 400 400 400 400 400 400 400 400 400


0.98 [0.06, 15.45] 5.10 [0.25, 104.90] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] Subtotals only 0.74 [0.38, 1.43] 2.0 [0.18, 21.88] 0.5 [0.05, 5.47] 3.0 [0.12, 73.20] 5.0 [0.24, 103.49] 1.17 [0.40, 3.41] 3.0 [0.31, 28.60] 3.0 [0.12, 73.20] 0.71 [0.35, 1.44]

1 1

396 396


5.56 [1.25, 24.74] 1.79 [0.93, 3.43]

Statistical method


Effect size

101

7.1 Delay

1

396


1.79 [0.93, 3.43]

Comparison 20. Mifepristone versus mifepristone + misoprostol (all doses)

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk) 3 Observed number of pregnancies (time from intercourse) 4 Need for extra dose 5 Any side effect 6 Specific side effect 6.1 Nausea 6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Abdominal pain 6.8 Diarrhoea 6.9 Spotting/bleeding after treatment 7 Menses

No. of studies

No. of participants

1

599


3.49 [0.73, 16.65]

0

0


0.0 [0.0, 0.0]

0

0


0.0 [0.0, 0.0]

0 0 1 1 1 1 1 1 1 1 1 1

0 0 599 599 599 599 599 599 599 599 599


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] Subtotals only 0.86 [0.48, 1.56] 0.50 [0.05, 5.47] 0.20 [0.01, 4.13] 0.50 [0.05, 5.47] 0.50 [0.09, 2.70] 1.00 [0.06, 15.86] 0.31 [0.10, 0.93] 0.25 [0.03, 2.22] 0.61 [0.35, 1.06]

0

0


0.0 [0.0, 0.0]

Statistical method

Effect size

Comparison 21. Mifepristone (all doses) versus copper intrauterine device

Outcome or subgroup title 1 Observed number of pregnancy (all women) 2 Observed number of pregnancy (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancy (time from intercourse) 3.1 Within 72 h 3.2 Later than 72 h 4 Need for extra dose 5 Any side effect 6 Specific side effects 6.1 Nausea

No. of studies

No. of participants

1

285


1.51 [0.06, 36.67]

0

0


0.0 [0.0, 0.0]

0 0 0

0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 0 0 1 1 0

0 0 0 285

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 16.59 [1.01, 273.52] Subtotals only 0.0 [0.0, 0.0]

0

Statistical method


Effect size

102

6.2 Vomiting 6.3 Breast tenderness 6.4 Headache 6.5 Dizziness 6.6 Fatigue 6.7 Lower abdominal pain 6.8 Diarrhoea 6.9 Spotting/bleeding after treatment 6.10 Heavy menses 7 Menses 7.1 Early 7.2 Delay

0 0 0 0 0 1 0 0

0 0 0 0 0 285 0 0

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.01 [8.27, 0.22] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 1 0 1

0 284 0 284


0.0 [0.0, 0.0] 4.27 [1.56, 11.69] 0.0 [0.0, 0.0] 4.27 [1.56, 11.69]

Comparison 22. Mifepristone versus gestrinone

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Side effects 2.1 Nausea 2.2 Vomiting 2.3 Diarrhoea 2.4 Fatigue 2.5 Dizziness 2.6 Headache 2.7 Breast tenderness 2.8 Lower abdominal pain 2.9 Bleeding or spotting 3 Menses 3.1 Early 3.2 Delay

No. of studies

No. of participants

1

996


0.75 [0.32, 1.76]

1 1 1 1 1 1 1 1 1 1 1 1 1

8964 996 996 996 996 996 996 996 996 996 1950 975 975


1.08 [0.88, 1.33] 1.34 [0.90, 2.00] 1.0 [0.06, 15.94] 0.25 [0.03, 2.23] 2.0 [0.91, 4.41] 1.63 [0.68, 3.89] 0.67 [0.19, 2.35] 0.57 [0.17, 1.94] 0.89 [0.35, 2.29] 0.94 [0.70, 1.26] 1.03 [0.80, 1.33] 0.37 [0.20, 0.69] 1.37 [1.03, 1.82]

Statistical method

Effect size

Comparison 23. Danazol (all doses) versus Yuzpe

Outcome or subgroup title 1 Any side effect 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Observed number of pregnancies (all women)

No. of studies

No. of participants

0 0

0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 0 2

0 0 485


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 1.78 [0.61, 5.22]

Statistical method


Effect size

103

4 Specific side effects 4.1 Nausea 4.2 Vomiting 4.3 Breast tenderness 4.4 Headache 4.5 Dizziness 4.6 Fatigue 4.7 Abdominal pain 4.8 Spotting/bleeding after treatment 5 Menses 5.1 Early 5.2 Delay

2 2 2 1 0 0 0 0 0

538 538 384 0 0 0 0 0

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

Subtotals only 0.38 [0.30, 0.47] 0.13 [0.06, 0.27] 1.14 [0.75, 1.72] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

1 0 1

384 0 384


1.53 [0.74, 3.18] 0.0 [0.0, 0.0] 1.53 [0.74, 3.18]

Comparison 24. High-dose oestrogens versus Yuzpe

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Observed number of pregnancies (by risk status) 2.1 High-risk women 2.2 Low-risk women 3 Any side effect 4 Specific side effects 4.1 Nausea 4.2 Vomiting 4.3 Breast tenderness 4.4 Headache 4.5 Dizziness 4.6 Fatigue 4.7 Abdominal pain 4.8 Spotting/bleeding after treatment 5 Menses 5.1 Early 5.2 Delay

No. of studies

No. of participants

1

384


2.17 [0.20, 23.77]

0

0


0.0 [0.0, 0.0]

0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0 0 0 0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] Subtotals only 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

0 0 0

0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

Statistical method


Effect size

104

Comparison 25. Half-dose Yuzpe versus standard Yuzpe

Outcome or subgroup title 1 Observed number of pregnancies (all women) 2 Any side effect 3 Specific side effects 3.1 Nausea 3.2 Vomiting 3.3 Breast tenderness 3.4 Headache 3.5 Dizziness 3.6 Fatigue 3.7 Abdominal pain 3.8 Spotting/bleeding after treatment 4 Delay in menses 4.1 Early 4.2 Delay

No. of studies

No. of participants

1

1323


1.41 [0.76, 2.61]

1 1 1 1 0 1 1 0 1 0

1288 1288 1275 0 1288 1288 0 1288 0

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.85 [0.77, 0.93] Subtotals only 0.86 [0.77, 0.97] 0.50 [0.36, 0.69] 0.0 [0.0, 0.0] 0.92 [0.68, 1.24] 0.66 [0.40, 1.07] 0.0 [0.0, 0.0] 0.77 [0.43, 1.37] 0.0 [0.0, 0.0]

0 0 0

0 0 0


0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]

Statistical method

Effect size

Comparison 26. High-risk women versus low-risk women (all hormonal methods)

Outcome or subgroup title 1 Observed number of pregnancies

No. of studies

No. of participants

11

19700

Statistical method Risk Ratio (M-H, Fixed, 95% CI)

Effect size 2.67 [2.11, 3.39]

Comparison 27. Time elapsed since intercourse (coitus-treatment interval) in mifepristone

Outcome or subgroup title 1 ≤ 24 h vs > 24-48 h 2 ≤ 24 h vs > 48-72 h 3 > 24-48 h vs > 48-72 h 4 < 72 h vs > 72 h

No. of studies

No. of participants

2 2 2 2

1136 841 979 2373

Statistical method Risk Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)


Effect size 1.01 [0.29, 3.54] 0.44 [0.13, 1.51] 0.43 [0.13, 1.42] 0.59 [0.20, 1.71]

105

Comparison 28. Time elapsed since intercourse in levonorgestrel


No. of studies

No. of participants

4 3 3 4

2336 1646 1551 7453

Statistical method Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

Effect size 0.93 [0.50, 1.73] 0.60 [0.31, 1.19] 0.54 [0.27, 1.11] 0.51 [0.31, 0.84]

Comparison 29. Time elapsed since intercourse in ulipristal acetate


No. of studies

No. of participants

2 2 2 1

1182 1022 1034 970

Statistical method Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

Effect size 0.42 [0.16, 1.12] 0.84 [0.24, 2.95] 2.29 [0.77, 6.82] 4.66 [0.28, 77.39]

Comparison 30. Time elapsed since intercourse in Yuzpe

Outcome or subgroup title 1 ≤ 24 h vs > 24-48 h 2 ≤ 24 h vs > 48-72 h 3 > 24-48 h vs > 48-72 h

No. of studies

No. of participants

3 2 2

1527 863 857

Statistical method Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Odds Ratio (M-H, Fixed, 95% CI)


Effect size 0.47 [0.26, 0.88] 0.41 [0.18, 0.89] 0.71 [0.35, 1.41]

106

Analysis 1.1. Comparison 1 Intrauterine contraceptive device versus control, Outcome 1 Observed number of pregnancies. Review:

Interventions for emergency contraception

Comparison: 1 Intrauterine contraceptive device versus control Outcome: 1 Observed number of pregnancies

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Askalani 1987

4/200

22/100

100.0 %

0.09 [ 0.03, 0.26 ]

Total (95% CI)

200

100

100.0 %

0.09 [ 0.03, 0.26 ]

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

Total events: 4 (Treatment), 22 (Control) Heterogeneity: not applicable Test for overall effect: Z = 4.53 (P < 0.00001) Test for subgroup differences: Not applicable

0.001 0.01 0.1 Favours treatment

1

10 100 1000 Favours control


107

Analysis 2.1. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 2 Levonorgestrel versus Yuzpe Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

0/62

5/60

8.4 %

0.09 [ 0.00, 1.56 ]

12/410

15/424

22.2 %

0.83 [ 0.39, 1.75 ]

1/100

1/100

1.5 %

1.00 [ 0.06, 15.77 ]

Sun MX 2007 (1)

11/557

14/553

21.2 %

0.78 [ 0.36, 1.70 ]

WHO 1998

11/976

31/979

46.7 %

0.36 [ 0.18, 0.70 ]

2105

2116

100.0 %

0.54 [ 0.36, 0.80 ]

Farajkhoda 2009 Ho 1993 Sheng SY 2008

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI


Total events: 35 (Treatment), 66 (Control) Heterogeneity: Chi2 = 5.27, df = 4 (P = 0.26); I2 =24% Test for overall effect: Z = 3.02 (P = 0.0025) Test for subgroup differences: Not applicable

0.01

0.1

Favours treatment

1

10

100

Favours control

(1) In the paper of Sun MY 2007 and Sheng SY, Yuzpe was replaced by LNG -COC 4 tablets (total EE 0.12mg and LNG 0.6MG) two-dose 12hr apart orally.


108

Analysis 2.2. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 2 Observed number of pregnancies (by risk status). Review:


Comparison: 2 Levonorgestrel versus Yuzpe Outcome: 2 Observed number of pregnancies (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

4/79

6/77

13.2 %

0.65 [ 0.19, 2.21 ]

6/372

19/360

41.9 %

0.31 [ 0.12, 0.76 ]

451

437

55.1 %

0.39 [ 0.19, 0.80 ]

M-H,Fixed,95% CI


1 High-risk women Ho 1993 WHO 1998

Subtotal (95% CI)

Total events: 10 (Treatment), 25 (Control) Heterogeneity: Chi2 = 0.95, df = 1 (P = 0.33); I2 =0.0% Test for overall effect: Z = 2.58 (P = 0.010) 2 Low-risk women Ho 1993

8/331

9/341

19.2 %

0.92 [ 0.36, 2.34 ]

WHO 1998

5/602

12/619

25.7 %

0.43 [ 0.15, 1.21 ]

933

960

44.9 %

0.64 [ 0.32, 1.26 ]

1397

100.0 %

0.50 [ 0.31, 0.82 ]

Subtotal (95% CI)

Total events: 13 (Treatment), 21 (Control) Heterogeneity: Chi2 = 1.13, df = 1 (P = 0.29); I2 =12% Test for overall effect: Z = 1.29 (P = 0.20)

Total (95% CI)

1384

Total events: 23 (Treatment), 46 (Control) Heterogeneity: Chi2 = 2.99, df = 3 (P = 0.39); I2 =0.0% Test for overall effect: Z = 2.76 (P = 0.0058) Test for subgroup differences: Chi2 = 0.96, df = 1 (P = 0.33), I2 =0.0%

0.01

0.1

Favours treatment

1

10

100

Favours control


109

Analysis 2.3. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 3 Observed number of pregnancies (time from intercourse). Review:


Comparison: 2 Levonorgestrel versus Yuzpe Outcome: 3 Observed number of pregnancies (time from intercourse)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Ho 1993

4/217

3/217

7.6 %

1.33 [ 0.30, 5.89 ]

WHO 1998

2/450

9/459

22.5 %

0.23 [ 0.05, 1.04 ]

667

676

30.1 %

0.51 [ 0.19, 1.34 ]

M-H,Fixed,95% CI


1 Within 24 h

Subtotal (95% CI) Total events: 6 (Treatment), 12 (Control)

Heterogeneity: Chi2 = 2.70, df = 1 (P = 0.10); I2 =63% Test for overall effect: Z = 1.37 (P = 0.17) 2 25-48 h Ho 1993

4/114

6/130

14.2 %

0.76 [ 0.22, 2.63 ]

WHO 1998

4/338

15/370

36.2 %

0.29 [ 0.10, 0.87 ]

452

500

50.3 %

0.42 [ 0.19, 0.94 ]

5/187

7/150

19.6 %

0.57 [ 0.19, 1.77 ]

187

150

19.6 %

0.57 [ 0.19, 1.77 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

1306

1326

100.0 %

0.48 [ 0.28, 0.82 ]


Heterogeneity: Chi2 = 1.30, df = 1 (P = 0.25); I2 =23% Test for overall effect: Z = 2.10 (P = 0.036) 3 49-72 h WHO 1998

Subtotal (95% CI) Total events: 5 (Treatment), 7 (Control) Heterogeneity: not applicable

Test for overall effect: Z = 0.97 (P = 0.33) 4 Later than 72 h

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable

Total (95% CI)

Total events: 19 (Treatment), 40 (Control) Heterogeneity: Chi2 = 4.17, df = 4 (P = 0.38); I2 =4% Test for overall effect: Z = 2.67 (P = 0.0076) Test for subgroup differences: Chi2 = 0.20, df = 2 (P = 0.91), I2 =0.0%

0.01

0.1

Favours treatment

1

10

100

Favours control


110

Analysis 2.4. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 4 Need for extra dose. Review:


Comparison: 2 Levonorgestrel versus Yuzpe Outcome: 4 Need for extra dose

Study or subgroup

WHO 1998

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

47/976

89/979

100.0 %

0.53 [ 0.38, 0.75 ]

976

979

100.0 %

0.53 [ 0.38, 0.75 ]

M-H,Fixed,95% CI


Total events: 47 (Treatment), 89 (Control) Heterogeneity: not applicable Test for overall effect: Z = 3.64 (P = 0.00027) Test for subgroup differences: Not applicable

0.01

0.1

1

Favours treatment

10

100

Favours control

Analysis 2.5. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 5 Any side effect. Review:


Comparison: 2 Levonorgestrel versus Yuzpe Outcome: 5 Any side effect

Study or subgroup

WHO 1998

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

534/976

667/979

100.0 %

0.80 [ 0.75, 0.86 ]

976

979

100.0 %

0.80 [ 0.75, 0.86 ]

M-H,Fixed,95% CI


Total events: 534 (Treatment), 667 (Control) Heterogeneity: not applicable Test for overall effect: Z = 6.02 (P < 0.00001) Test for subgroup differences: Not applicable

0.01

0.1

Favours treatment

1

10

100

Favours control


111

Analysis 2.6. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 6 Specific side effects. Review:


Comparison: 2 Levonorgestrel versus Yuzpe Outcome: 6 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

4/62

41/60

4.2 %

0.09 [ 0.04, 0.25 ]

Ho 1993

66/410

197/424

19.6 %

0.35 [ 0.27, 0.44 ]

Sheng SY 2008

15/100

33/100

3.3 %

0.45 [ 0.26, 0.78 ]

Sun MX 2007

100/557

227/553

23.0 %

0.44 [ 0.36, 0.54 ]

WHO 1998

226/976

494/979

49.9 %

0.46 [ 0.40, 0.52 ]

2105

2116

100.0 %

0.42 [ 0.38, 0.46 ]

0/62

15/60

5.3 %

0.03 [ 0.00, 0.51 ]

11/410

95/424

31.4 %

0.12 [ 0.07, 0.22 ]

3/100

5/100

1.7 %

0.60 [ 0.15, 2.44 ]

55/976

184/979

61.7 %

0.30 [ 0.22, 0.40 ]

1548

1563

100.0 %

0.23 [ 0.18, 0.30 ]

65/410

88/424

42.3 %

0.76 [ 0.57, 1.02 ]

105/976

118/979

57.7 %

0.89 [ 0.70, 1.14 ]

1386

1403

100.0 %

0.84 [ 0.69, 1.01 ]

0/62

13/60

6.5 %

0.04 [ 0.00, 0.59 ]

164/976

198/979

93.5 %

0.83 [ 0.69, 1.00 ]

1038

1039

100.0 %

0.78 [ 0.65, 0.94 ]

M-H,Fixed,95% CI


1 Nausea Farajkhoda 2009

Subtotal (95% CI)

Total events: 411 (Treatment), 992 (Control) Heterogeneity: Chi2 = 13.77, df = 4 (P = 0.01); I2 =71% Test for overall effect: Z = 17.56 (P < 0.00001) 2 Vomiting Farajkhoda 2009 Ho 1993 Sheng SY 2008 WHO 1998

Subtotal (95% CI)

Total events: 69 (Treatment), 299 (Control) Heterogeneity: Chi2 = 11.21, df = 3 (P = 0.01); I2 =73% Test for overall effect: Z = 11.30 (P < 0.00001) 3 Breast tenderness Ho 1993 WHO 1998

Subtotal (95% CI)

Total events: 170 (Treatment), 206 (Control) Heterogeneity: Chi2 = 0.64, df = 1 (P = 0.42); I2 =0.0% Test for overall effect: Z = 1.84 (P = 0.066) 4 Headache Farajkhoda 2009 WHO 1998

Subtotal (95% CI)

Total events: 164 (Treatment), 211 (Control)

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


112

(. . .

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI

Continued)


Heterogeneity: Chi2 = 5.09, df = 1 (P = 0.02); I2 =80% Test for overall effect: Z = 2.65 (P = 0.0081) 5 Dizziness 76/410

98/424

37.2 %

0.80 [ 0.61, 1.05 ]

109/976

163/979

62.8 %

0.67 [ 0.54, 0.84 ]

1386

1403

100.0 %

0.72 [ 0.61, 0.85 ]

1/62

10/60

2.0 %

0.10 [ 0.01, 0.73 ]

98/410

156/424

30.7 %

0.65 [ 0.52, 0.80 ]

Sheng SY 2008

9/100

12/100

2.4 %

0.75 [ 0.33, 1.70 ]

Sun MX 2007

39/557

45/553

9.0 %

0.86 [ 0.57, 1.30 ]

165/976

279/979

55.8 %

0.59 [ 0.50, 0.70 ]

2105

2116

100.0 %

0.63 [ 0.55, 0.71 ]

172/976

205/979

100.0 %

0.84 [ 0.70, 1.01 ]

976

979

100.0 %

0.84 [ 0.70, 1.01 ]

2/62

4/60

100.0 %

0.48 [ 0.09, 2.54 ]

62

60

100.0 %

0.48 [ 0.09, 2.54 ]

Ho 1993

12/410

12/424

13.9 %

1.03 [ 0.47, 2.28 ]

Sun MX 2007

61/557

73/553

86.1 %

0.83 [ 0.60, 1.14 ]

967

977

100.0 %

0.86 [ 0.64, 1.15 ]

Ho 1993 WHO 1998

Subtotal (95% CI)

Total events: 185 (Treatment), 261 (Control) Heterogeneity: Chi2 = 1.01, df = 1 (P = 0.32); I2 =1% Test for overall effect: Z = 3.74 (P = 0.00018) 6 Fatigue Farajkhoda 2009 Ho 1993

WHO 1998

Subtotal (95% CI)

Total events: 312 (Treatment), 502 (Control) Heterogeneity: Chi2 = 6.22, df = 4 (P = 0.18); I2 =36% Test for overall effect: Z = 7.28 (P < 0.00001) 7 Abdominal pain WHO 1998

Subtotal (95% CI)

Total events: 172 (Treatment), 205 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.85 (P = 0.064) 8 Hot flushes Farajkhoda 2009

Subtotal (95% CI) Total events: 2 (Treatment), 4 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.86 (P = 0.39) 9 Spotting/bleeding after treatment

Subtotal (95% CI)

Total events: 73 (Treatment), 85 (Control) Heterogeneity: Chi2 = 0.26, df = 1 (P = 0.61); I2 =0.0% Test for overall effect: Z = 1.02 (P = 0.31)

0.01

0.1

Favours treatment

1

10

100

Favours control


113

Analysis 2.7. Comparison 2 Levonorgestrel versus Yuzpe, Outcome 7 Menses. Review:


Comparison: 2 Levonorgestrel versus Yuzpe Outcome: 7 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Sheng SY 2008

14/100

10/100

5.5 %

1.40 [ 0.65, 3.00 ]

Sun MX 2007

76/557

68/553

37.8 %

1.11 [ 0.82, 1.51 ]

657

653

43.3 %

1.15 [ 0.86, 1.52 ]

M-H,Fixed,95% CI


1 Early

Subtotal (95% CI)

Total events: 90 (Treatment), 78 (Control) Heterogeneity: Chi2 = 0.31, df = 1 (P = 0.58); I2 =0.0% Test for overall effect: Z = 0.95 (P = 0.34) 2 Delay Ho 1993

49/331

40/347

21.6 %

1.28 [ 0.87, 1.90 ]

Sheng SY 2008

10/100

8/100

4.4 %

1.25 [ 0.51, 3.04 ]

Sun MX 2007

66/557

55/553

30.6 %

1.19 [ 0.85, 1.67 ]

988

1000

56.7 %

1.23 [ 0.96, 1.57 ]

1653

100.0 %

1.19 [ 0.99, 1.44 ]

Subtotal (95% CI)


Total (95% CI)

1645


0.01

0.1

Favours treatment

1

10

100

Favours control


114

Analysis 3.1. Comparison 3 Levonorgestrel split-dose 24 hours versus 12 hours, Outcome 1 Observed number of pregnancy (all women). Review:


Comparison: 3 Levonorgestrel split-dose 24 hours versus 12 hours Outcome: 1 Observed number of pregnancy (all women)

Study or subgroup

Ngai 2005

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

20/1038

20/1022

100.0 %

0.98 [ 0.53, 1.82 ]

1038

1022

100.0 %

0.98 [ 0.53, 1.82 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


115

Analysis 3.2. Comparison 3 Levonorgestrel split-dose 24 hours versus 12 hours, Outcome 2 Observed number of pregnancy (by risk status). Review:


Comparison: 3 Levonorgestrel split-dose 24 hours versus 12 hours Outcome: 2 Observed number of pregnancy (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

4/225

10/221

49.9 %

0.39 [ 0.13, 1.23 ]

225

221

49.9 %

0.39 [ 0.13, 1.23 ]

16/792

10/774

50.1 %

1.56 [ 0.71, 3.42 ]

792

774

50.1 %

1.56 [ 0.71, 3.42 ]

995

100.0 %

0.98 [ 0.53, 1.81 ]

M-H,Fixed,95% CI


1 High-risk women Ngai 2005


Test for overall effect: Z = 1.60 (P = 0.11) 2 Low-risk women Ngai 2005

Subtotal (95% CI)

Total events: 16 (Treatment), 10 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.12 (P = 0.26)

Total (95% CI)

1017

Total events: 20 (Treatment), 20 (Control) Heterogeneity: Chi2 = 3.82, df = 1 (P = 0.05); I2 =74% Test for overall effect: Z = 0.07 (P = 0.95) Test for subgroup differences: Chi2 = 3.81, df = 1 (P = 0.05), I2 =74%

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


116

Analysis 3.6. Comparison 3 Levonorgestrel split-dose 24 hours versus 12 hours, Outcome 6 Specific side effects. Review:


Comparison: 3 Levonorgestrel split-dose 24 hours versus 12 hours Outcome: 6 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

82/1044

84/1027

100.0 %

0.96 [ 0.72, 1.29 ]

1044

1027

100.0 %

0.96 [ 0.72, 1.29 ]

11/1044

13/1027

100.0 %

0.83 [ 0.37, 1.85 ]

1044

1027

100.0 %

0.83 [ 0.37, 1.85 ]

35/1044

57/1027

100.0 %

0.60 [ 0.40, 0.91 ]

1044

1027

100.0 %

0.60 [ 0.40, 0.91 ]

39/1044

43/1027

100.0 %

0.89 [ 0.58, 1.36 ]

1044

1027

100.0 %

0.89 [ 0.58, 1.36 ]

66/1044

53/1027

100.0 %

1.23 [ 0.86, 1.74 ]

1044

1027

100.0 %

1.23 [ 0.86, 1.74 ]

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI


1 Nausea Ngai 2005

Subtotal (95% CI)

Total events: 82 (Treatment), 84 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.27 (P = 0.79) 2 Vomiting Ngai 2005

Subtotal (95% CI)

Total events: 11 (Treatment), 13 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.45 (P = 0.65) 3 Breast tenderness Ngai 2005

Subtotal (95% CI)

Total events: 35 (Treatment), 57 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.40 (P = 0.016) 4 Headache Ngai 2005

Subtotal (95% CI)

Total events: 39 (Treatment), 43 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.53 (P = 0.60) 5 Dizziness Ngai 2005

Subtotal (95% CI)

Total events: 66 (Treatment), 53 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.13 (P = 0.26) 6 Fatigue

Subtotal (95% CI)

0


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


117

(. . . Study or subgroup

Risk Ratio

Weight

Continued) Risk Ratio

Treatment

Control

n/N

n/N

50/1044

65/1027

100.0 %

0.76 [ 0.53, 1.08 ]

1044

1027

100.0 %

0.76 [ 0.53, 1.08 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

Heterogeneity: not applicable Test for overall effect: not applicable 7 Lower abdominal pain Ngai 2005

Subtotal (95% CI)

Total events: 50 (Treatment), 65 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.52 (P = 0.13) 8 Diarrhoea

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 9 Spotting/bleeding after treatment

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 10 Heavy menses


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


118

Analysis 3.7. Comparison 3 Levonorgestrel split-dose 24 hours versus 12 hours, Outcome 7 Menses. Review:


Comparison: 3 Levonorgestrel split-dose 24 hours versus 12 hours Outcome: 7 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

41/1000

51/978

100.0 %

0.79 [ 0.53, 1.17 ]

1000

978

100.0 %

0.79 [ 0.53, 1.17 ]

978

100.0 %

0.79 [ 0.53, 1.17 ]

M-H,Fixed,95% CI


1 Early

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Delay Ngai 2005

Subtotal (95% CI)


Total (95% CI)

1000


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


119

Analysis 4.1. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 1 Observed number of pregnancy (all women). Review:


Comparison: 4 Levonorgestrel single dose versus split-dose Outcome: 1 Observed number of pregnancy (all women)

Study or subgroup

Arowojolu 2002 Dada 2010 Von Hertzen 2002

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

4/573

7/545

18.3 %

0.54 [ 0.16, 1.85 ]

9/1414

8/1409

20.4 %

1.12 [ 0.43, 2.90 ]

20/1356

24/1356

61.2 %

0.83 [ 0.46, 1.50 ]

3343

3310

100.0 %

0.84 [ 0.53, 1.33 ]

M-H,Fixed,95% CI


Total events: 33 (Treatment), 39 (Control) Heterogeneity: Chi2 = 0.84, df = 2 (P = 0.66); I2 =0.0% Test for overall effect: Z = 0.75 (P = 0.46) Test for subgroup differences: Not applicable

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


120

Analysis 4.2. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 2 Observed number of pregnancy (by risk status). Review:


Comparison: 4 Levonorgestrel single dose versus split-dose Outcome: 2 Observed number of pregnancy (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Von Hertzen 2002

7/404

12/388

50.7 %

0.56 [ 0.22, 1.41 ]

Subtotal (95% CI)

404

388

50.7 %

0.56 [ 0.22, 1.41 ]

13/952

12/968

49.3 %

1.10 [ 0.51, 2.40 ]

952

968

49.3 %

1.10 [ 0.51, 2.40 ]

1356

100.0 %

0.83 [ 0.46, 1.49 ]

M-H,Fixed,95% CI


1 High-risk women

Total events: 7 (Treatment), 12 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.23 (P = 0.22) 2 Low-risk women Von Hertzen 2002

Subtotal (95% CI)


Total (95% CI)

1356


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


121

Analysis 4.3. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 3 Observed number of pregnancy (time from intercourse). Review:


Comparison: 4 Levonorgestrel single dose versus split-dose Outcome: 3 Observed number of pregnancy (time from intercourse)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

5/1257

4/1235

13.1 %

1.23 [ 0.33, 4.56 ]

16/1198

20/1183

65.3 %

0.79 [ 0.41, 1.52 ]

2455

2418

78.4 %

0.86 [ 0.48, 1.54 ]

M-H,Fixed,95% CI


1 Within 72 h Dada 2010 Von Hertzen 2002

Subtotal (95% CI)

Total events: 21 (Treatment), 24 (Control) Heterogeneity: Chi2 = 0.35, df = 1 (P = 0.56); I2 =0.0% Test for overall effect: Z = 0.50 (P = 0.62) 2 Later than 72 h Dada 2010

4/143

3/159

9.2 %

1.48 [ 0.34, 6.51 ]

Von Hertzen 2002

4/150

4/164

12.4 %

1.09 [ 0.28, 4.29 ]

Subtotal (95% CI)

293

323

21.6 %

1.26 [ 0.46, 3.43 ]

2741

100.0 %

0.95 [ 0.57, 1.57 ]


Total (95% CI)

2748


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


122

Analysis 4.6. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 6 Specific side effects. Review:


Comparison: 4 Levonorgestrel single dose versus split-dose Outcome: 6 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

132/544

129/518

19.9 %

0.97 [ 0.79, 1.20 ]

Dada 2010

328/1510

332/1512

50.1 %

0.99 [ 0.86, 1.13 ]

Von Hertzen 2002

189/1359

199/1361

30.0 %

0.95 [ 0.79, 1.14 ]

3413

3391

100.0 %

0.97 [ 0.88, 1.07 ]

42/544

44/518

23.0 %

0.91 [ 0.61, 1.36 ]

137/1510

132/1512

67.3 %

1.04 [ 0.83, 1.31 ]

19/1359

19/1361

9.7 %

1.00 [ 0.53, 1.88 ]

3413

3391

100.0 %

1.01 [ 0.83, 1.22 ]

70/544

46/518

29.1 %

1.45 [ 1.02, 2.06 ]

113/1359

115/1361

70.9 %

0.98 [ 0.77, 1.26 ]

1903

1879

100.0 %

1.12 [ 0.91, 1.37 ]

116/544

75/518

20.1 %

1.47 [ 1.13, 1.92 ]

Dada 2010

181/1510

175/1512

45.8 %

1.04 [ 0.85, 1.26 ]

Von Hertzen 2002

142/1359

130/1361

34.0 %

1.09 [ 0.87, 1.37 ]

3413

3391

100.0 %

1.14 [ 1.01, 1.30 ]

M-H,Fixed,95% CI


1 Nausea Arowojolu 2002

Subtotal (95% CI)

Total events: 649 (Treatment), 660 (Control) Heterogeneity: Chi2 = 0.11, df = 2 (P = 0.94); I2 =0.0% Test for overall effect: Z = 0.52 (P = 0.61) 2 Vomiting Arowojolu 2002 Dada 2010 Von Hertzen 2002

Subtotal (95% CI)

Total events: 198 (Treatment), 195 (Control) Heterogeneity: Chi2 = 0.32, df = 2 (P = 0.85); I2 =0.0% Test for overall effect: Z = 0.06 (P = 0.95) 3 Breast tenderness Arowojolu 2002 Von Hertzen 2002

Subtotal (95% CI)

Total events: 183 (Treatment), 161 (Control) Heterogeneity: Chi2 = 3.10, df = 1 (P = 0.08); I2 =68% Test for overall effect: Z = 1.09 (P = 0.27) 4 Headache Arowojolu 2002

Subtotal (95% CI)


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


123


Risk Ratio

Weight

Continued)

Treatment

Control

n/N

n/N

69/544

72/518

21.6 %

0.91 [ 0.67, 1.24 ]

Dada 2010

130/1510

153/1512

44.8 %

0.85 [ 0.68, 1.06 ]

Von Hertzen 2002

113/1359

115/1361

33.6 %

0.98 [ 0.77, 1.26 ]

3413

3391

100.0 %

0.91 [ 0.79, 1.05 ]

M-H,Fixed,95% CI


5 Dizziness Arowojolu 2002

Subtotal (95% CI)

Total events: 312 (Treatment), 340 (Control) Heterogeneity: Chi2 = 0.73, df = 2 (P = 0.69); I2 =0.0% Test for overall effect: Z = 1.28 (P = 0.20) 6 Fatigue Dada 2010

189/1510

188/1512

50.8 %

1.01 [ 0.83, 1.22 ]

Von Hertzen 2002

184/1359

182/1361

49.2 %

1.01 [ 0.84, 1.23 ]

2869

2873

100.0 %

1.01 [ 0.88, 1.15 ]

85/544

95/518

33.0 %

0.85 [ 0.65, 1.11 ]

183/1359

198/1361

67.0 %

0.93 [ 0.77, 1.12 ]

1903

1879

100.0 %

0.90 [ 0.77, 1.05 ]

53/1359

44/1361

100.0 %

1.21 [ 0.81, 1.79 ]

1359

1361

100.0 %

1.21 [ 0.81, 1.79 ]

426/1359

426/1361

100.0 %

1.00 [ 0.90, 1.12 ]

1359

1361

100.0 %

1.00 [ 0.90, 1.12 ]

84/544

54/518

100.0 %

1.48 [ 1.08, 2.04 ]

544

518

100.0 %

1.48 [ 1.08, 2.04 ]

Subtotal (95% CI)

Total events: 373 (Treatment), 370 (Control) Heterogeneity: Chi2 = 0.00, df = 1 (P = 0.97); I2 =0.0% Test for overall effect: Z = 0.14 (P = 0.89) 7 Lower abdominal pain Arowojolu 2002 Von Hertzen 2002

Subtotal (95% CI)

Total events: 268 (Treatment), 293 (Control) Heterogeneity: Chi2 = 0.25, df = 1 (P = 0.62); I2 =0.0% Test for overall effect: Z = 1.33 (P = 0.18) 8 Diarrhoea Von Hertzen 2002

Subtotal (95% CI)

Total events: 53 (Treatment), 44 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.94 (P = 0.35) 9 Spotting/bleeding after treatment Von Hertzen 2002

Subtotal (95% CI)

Total events: 426 (Treatment), 426 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.03 (P = 0.98) 10 Heavy menses Arowojolu 2002

Subtotal (95% CI)


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


124

Analysis 4.7. Comparison 4 Levonorgestrel single dose versus split-dose, Outcome 7 Menses. Review:


Comparison: 4 Levonorgestrel single dose versus split-dose Outcome: 7 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

114/573

163/545

53.4 %

0.67 [ 0.54, 0.82 ]

573

545

53.4 %

0.67 [ 0.54, 0.82 ]

M-H,Fixed,95% CI


1 Early Arowojolu 2002

Subtotal (95% CI)

Total events: 114 (Treatment), 163 (Control) Heterogeneity: not applicable Test for overall effect: Z = 3.83 (P = 0.00013) 2 Delay Arowojolu 2002

114/573

81/545

26.5 %

1.34 [ 1.03, 1.74 ]

Von Hertzen 2002

62/1334

63/1332

20.1 %

0.98 [ 0.70, 1.38 ]

1907

1877

46.6 %

1.18 [ 0.96, 1.46 ]

2422

100.0 %

0.91 [ 0.78, 1.05 ]

Subtotal (95% CI)


Total (95% CI)

2480


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


125

Analysis 5.1. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Chen 2008

2/129

3/136

4.0 %

0.70 [ 0.12, 4.14 ]

Cheng 2009

12/83

9/83

12.4 %

1.33 [ 0.59, 2.99 ]

Gan XH 2007

2/250

2/206

3.0 %

0.82 [ 0.12, 5.80 ]

Han 1999a

1/70

5/144

4.5 %

0.41 [ 0.05, 3.46 ]

Hu X 2003

2/120

4/120

5.5 %

0.50 [ 0.09, 2.68 ]

Li A 2000

3/116

4/111

5.6 %

0.72 [ 0.16, 3.13 ]

Li J 2005

1/100

2/102

2.7 %

0.51 [ 0.05, 5.54 ]

Liang 2001

2/198

4/197

5.5 %

0.50 [ 0.09, 2.68 ]

Liao 2003

1/100

1/100

1.4 %

1.00 [ 0.06, 15.77 ]

Liu RQ 2009

3/140

2/140

2.7 %

1.50 [ 0.25, 8.84 ]

Qi M 2003

2/150

9/138

12.9 %

0.20 [ 0.04, 0.93 ]

Shao XY 2010

1/57

2/45

3.1 %

0.39 [ 0.04, 4.22 ]

Su 2001

2/64

5/89

5.7 %

0.56 [ 0.11, 2.78 ]

Sun 2000

1/100

2/100

2.7 %

0.50 [ 0.05, 5.43 ]

Sun P 2003

2/30

8/30

11.0 %

0.25 [ 0.06, 1.08 ]

Wang Q 2000

1/68

2/63

2.9 %

0.46 [ 0.04, 4.98 ]

Wang Y 2003

2/132

3/127

4.2 %

0.64 [ 0.11, 3.78 ]

Xu 2000

2/198

4/197

5.5 %

0.50 [ 0.09, 2.68 ]

2/94

2/86

2.9 %

0.91 [ 0.13, 6.35 ]

Zhang JQ 2000

4/394

1/205

1.8 %

2.08 [ 0.23, 18.50 ]

Total (95% CI)

2593

2419

100.0 %

0.64 [ 0.45, 0.92 ]

Xu Z 2000

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1

Favours treatment

1

10

100

Favours control


126

Analysis 5.2. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 2 Observed number of pregnancies (by risk status). Review:


Comparison: 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg Outcome: 2 Observed number of pregnancies (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

2/49

1/28

65.8 %

1.14 [ 0.11, 12.05 ]

49

28

65.8 %

1.14 [ 0.11, 12.05 ]

2/345

0/177

34.2 %

2.57 [ 0.12, 53.29 ]

345

177

34.2 %

2.57 [ 0.12, 53.29 ]

205

100.0 %

1.63 [ 0.26, 10.24 ]

M-H,Fixed,95% CI


1 High-risk women Zhang JQ 2000

Subtotal (95% CI) Total events: 2 (Treatment), 1 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.11 (P = 0.91) 2 Low-risk women Zhang JQ 2000


Test for overall effect: Z = 0.61 (P = 0.54)

Total (95% CI)

394


0.01

0.1

Favours treatment

1

10

100

Favours control


127

Analysis 5.5. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 5 Any side effect. Review:


Comparison: 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg Outcome: 5 Any side effect

Study or subgroup

Treatment

Control

n/N

n/N

0/1

0/1

0.0 [ 0.0, 0.0 ]

Chen 2008

14/129

53/136

0.28 [ 0.16, 0.48 ]

Gan XH 2007

32/250

30/206

0.88 [ 0.55, 1.40 ]

Han 1999a

17/70

32/144

1.09 [ 0.65, 1.83 ]

Hu X 2003

10/120

13/120

0.77 [ 0.35, 1.69 ]

Li A 2000

40/119

47/115

0.82 [ 0.59, 1.15 ]

Liao 2003

18/100

20/100

0.90 [ 0.51, 1.60 ]

Qi M 2003

8/150

19/138

0.39 [ 0.18, 0.86 ]

Sun 2000

11/100

43/100

0.26 [ 0.14, 0.47 ]

Wang Y 2003

14/132

56/127

0.24 [ 0.14, 0.41 ]

Xu 2000

16/198

21/197

0.76 [ 0.41, 1.41 ]

2/94

6/86

0.30 [ 0.06, 1.47 ]

Zhang JQ 2000

27/394

13/205

1.08 [ 0.57, 2.05 ]

Total (95% CI)

1857

1675

0.58 [ 0.41, 0.82 ]

Arowojolu 2002

Xu Z 2000

Risk Ratio MH,Random,95% CI


Total events: 209 (Treatment), 353 (Control) Heterogeneity: Tau2 = 0.27; Chi2 = 46.73, df = 11 (P<0.00001); I2 =76% Test for overall effect: Z = 3.07 (P = 0.0022) Test for subgroup differences: Not applicable

0.01

0.1

Favours treatment


1

10

100

Favours control

128

Analysis 5.6. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 6 Specific side effect. Review:


Comparison: 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg Outcome: 6 Specific side effect

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Liao 2003

5/100

8/100

27.8 %

0.63 [ 0.21, 1.84 ]

Liu RQ 2009

6/140

8/140

27.8 %

0.75 [ 0.27, 2.11 ]

Shao XY 2010

4/57

4/45

15.5 %

0.79 [ 0.21, 2.98 ]

Wang Q 2000

9/68

8/63

28.9 %

1.04 [ 0.43, 2.53 ]

365

348

100.0 %

0.81 [ 0.48, 1.36 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

8/100

6/100

21.7 %

1.33 [ 0.48, 3.70 ]

10/140

14/140

50.6 %

0.71 [ 0.33, 1.55 ]

Shao XY 2010

4/57

5/45

20.2 %

0.63 [ 0.18, 2.22 ]

Wang Q 2000

3/68

2/63

7.5 %

1.39 [ 0.24, 8.05 ]

365

348

100.0 %

0.88 [ 0.52, 1.49 ]

5/68

7/63

100.0 %

0.66 [ 0.22, 1.98 ]

68

63

100.0 %

0.66 [ 0.22, 1.98 ]

2/100

1/100

18.3 %

2.00 [ 0.18, 21.71 ]

M-H,Fixed,95% CI


1 Nausea

Subtotal (95% CI)

Total events: 24 (Treatment), 28 (Control) Heterogeneity: Chi2 = 0.55, df = 3 (P = 0.91); I2 =0.0% Test for overall effect: Z = 0.81 (P = 0.42) 2 Vomiting

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 3 Breast tenderness Liao 2003 Liu RQ 2009

Subtotal (95% CI)

Total events: 25 (Treatment), 27 (Control) Heterogeneity: Chi2 = 1.44, df = 3 (P = 0.70); I2 =0.0% Test for overall effect: Z = 0.47 (P = 0.64) 4 Headache Wang Q 2000

Subtotal (95% CI) Total events: 5 (Treatment), 7 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.74 (P = 0.46) 5 Dizziness Liao 2003

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


129


Treatment

Control

Risk Ratio

Weight

n/N

n/N

3/57

4/45

81.7 %

0.59 [ 0.14, 2.51 ]

157

145

100.0 %

0.85 [ 0.26, 2.80 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

3/100

7/100

100.0 %

0.43 [ 0.11, 1.61 ]

100

100

100.0 %

0.43 [ 0.11, 1.61 ]

4/248

3/204

8.4 %

1.10 [ 0.25, 4.84 ]

Li A 2000

10/116

15/111

39.1 %

0.64 [ 0.30, 1.36 ]

Liao 2003

2/100

4/100

10.2 %

0.50 [ 0.09, 2.67 ]

Qi M 2003

7/150

4/138

10.6 %

1.61 [ 0.48, 5.38 ]

3/56

11/43

31.7 %

0.21 [ 0.06, 0.70 ]

670

596

100.0 %

0.63 [ 0.39, 1.02 ]

Shao XY 2010

Subtotal (95% CI)

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 5 (Treatment), 5 (Control) Heterogeneity: Chi2 = 0.74, df = 1 (P = 0.39); I2 =0.0% Test for overall effect: Z = 0.27 (P = 0.79) 6 Fatigue

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 7 Abdominal pain Liao 2003


Test for overall effect: Z = 1.25 (P = 0.21) 8 Spotting/bleeding after treatment Gan XH 2007

Shao XY 2010

Subtotal (95% CI)


0.01

0.1

Favours treatment

1

10

100

Favours control


130

Analysis 5.7. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 7 Menses. Review:


Comparison: 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg Outcome: 7 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

8/118

7/125

3.7 %

1.21 [ 0.45, 3.23 ]

Gan XH 2007

14/248

20/204

11.8 %

0.58 [ 0.30, 1.11 ]

Shao XY 2010

6/56

5/43

3.0 %

0.92 [ 0.30, 2.82 ]

422

372

18.5 %

0.76 [ 0.47, 1.23 ]

M-H,Fixed,95% CI


1 Early Chen 2008

Subtotal (95% CI)

Total events: 28 (Treatment), 32 (Control) Heterogeneity: Chi2 = 1.66, df = 2 (P = 0.44); I2 =0.0% Test for overall effect: Z = 1.12 (P = 0.26) 2 Delay Chen 2008

13/118

1/125

0.5 %

13.77 [ 1.83, 103.64 ]

Cheng 2009

12/71

6/74

3.2 %

2.08 [ 0.83, 5.25 ]

40/248

22/204

13.0 %

1.50 [ 0.92, 2.43 ]

Han 1999a

3/70

8/144

2.8 %

0.77 [ 0.21, 2.82 ]

Hu X 2003

8/118

7/116

3.8 %

1.12 [ 0.42, 3.00 ]

Li A 2000

23/116

12/115

6.5 %

1.90 [ 0.99, 3.63 ]

Li J 2005

11/100

20/102

10.7 %

0.56 [ 0.28, 1.11 ]

Liao 2003

17/100

12/100

6.5 %

1.42 [ 0.71, 2.81 ]

15/56

10/43

6.1 %

1.15 [ 0.58, 2.31 ]

6/28

3/22

1.8 %

1.57 [ 0.44, 5.59 ]

Wang Q 2000

13/68

6/63

3.4 %

2.01 [ 0.81, 4.96 ]

Zhang JQ 2000

52/394

33/204

23.4 %

0.82 [ 0.55, 1.22 ]

1487

1312

81.5 %

1.26 [ 1.03, 1.54 ]

1684

100.0 %

1.17 [ 0.97, 1.40 ]

Gan XH 2007

Shao XY 2010 Sun P 2003

Subtotal (95% CI)


Total (95% CI)

1909


0.01

0.1

Favours treatment

1

10

100

Favours control


131

Analysis 5.8. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 8 ITT (all loss follow-up as pregnancy in LNG, and no preg in Mife). Review:


Comparison: 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg Outcome: 8 ITT (all loss follow-up as pregnancy in LNG, and no preg in Mife)

Study or subgroup

Treatment

Control

n/N

n/N

Han 1999a

1/70

5/144

5.6 %

0.41 [ 0.05, 3.46 ]

Hu X 2003

2/120

4/120

6.8 %

0.50 [ 0.09, 2.68 ]

Li A 2000

3/119

4/115

7.0 %

0.72 [ 0.17, 3.17 ]

Li J 2005

1/102

2/100

3.5 %

0.49 [ 0.05, 5.32 ]

Liang 2001

4/200

7/200

12.0 %

0.57 [ 0.17, 1.92 ]

Liao 2003

1/100

1/100

1.7 %

1.00 [ 0.06, 15.77 ]

Qi M 2003

2/150

9/138

16.0 %

0.20 [ 0.04, 0.93 ]

Su 2001

2/64

5/89

7.2 %

0.56 [ 0.11, 2.78 ]

Sun 2000

1/100

2/100

3.4 %

0.50 [ 0.05, 5.43 ]

Sun P 2003

2/30

8/30

13.7 %

0.25 [ 0.06, 1.08 ]

Wang Q 2000

1/68

2/63

3.5 %

0.46 [ 0.04, 4.98 ]

Wang Y 2003

2/134

4/128

7.0 %

0.48 [ 0.09, 2.56 ]

Xu 2000

2/198

4/197

6.9 %

0.50 [ 0.09, 2.68 ]

2/94

2/86

3.6 %

0.91 [ 0.13, 6.35 ]

Zhang JQ 2000

4/394

1/205

2.2 %

2.08 [ 0.23, 18.50 ]

Total (95% CI)

1943

1815

100.0 %

0.50 [ 0.32, 0.77 ]

Xu Z 2000

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


132

Analysis 5.9. Comparison 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg, Outcome 9 ITT (all loss follow-up as no pregnancy in LNG, and preg in Mife). Review:


Comparison: 5 Mifepristone mid-dose (25-50 mg) versus Levonorgestrel 1.5 mg Outcome: 9 ITT (all loss follow-up as no pregnancy in LNG, and preg in Mife)

Study or subgroup

Treatment

Control

n/N

n/N

Han 1999a

1/70

5/144

6.0 %

0.41 [ 0.05, 3.46 ]

Hu X 2003

2/120

4/120

7.3 %

0.50 [ 0.09, 2.68 ]

Li A 2000

3/119

4/115

7.5 %

0.72 [ 0.17, 3.17 ]

Li J 2005

1/102

2/100

3.7 %

0.49 [ 0.05, 5.32 ]

Liang 2001

4/200

4/200

7.3 %

1.00 [ 0.25, 3.94 ]

Liao 2003

1/100

1/100

1.8 %

1.00 [ 0.06, 15.77 ]

Qi M 2003

2/150

9/138

17.2 %

0.20 [ 0.04, 0.93 ]

Su 2001

2/64

5/89

7.7 %

0.56 [ 0.11, 2.78 ]

Sun 2000

1/100

2/100

3.7 %

0.50 [ 0.05, 5.43 ]

Sun P 2003

2/30

8/30

14.7 %

0.25 [ 0.06, 1.08 ]

Wang Q 2000

1/68

2/63

3.8 %

0.46 [ 0.04, 4.98 ]

Wang Y 2003

4/134

3/128

5.6 %

1.27 [ 0.29, 5.58 ]

Xu 2000

2/198

4/197

7.4 %

0.50 [ 0.09, 2.68 ]

2/94

2/86

3.8 %

0.91 [ 0.13, 6.35 ]

Zhang JQ 2000

4/394

1/205

2.4 %

2.08 [ 0.23, 18.50 ]

Total (95% CI)

1943

1815

100.0 %

0.57 [ 0.37, 0.88 ]

Xu Z 2000

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


133

Analysis 6.1. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

1/50

1/50

1.00 [ 0.06, 15.55 ]

0/100

1/100

0.33 [ 0.01, 8.09 ]

13/860

20/858

0.65 [ 0.32, 1.30 ]

2/120

3/135

0.75 [ 0.13, 4.41 ]

Lin 2000

0/60

0/60

0.0 [ 0.0, 0.0 ]

Liu 2000

0/48

2/48

0.20 [ 0.01, 4.06 ]

Pei 2001

1/100

2/100

0.50 [ 0.05, 5.43 ]

Sheng A 2002

1/100

2/100

0.50 [ 0.05, 5.43 ]

21/1359

44/2712

0.95 [ 0.57, 1.60 ]

1/50

1/50

1.00 [ 0.06, 15.55 ]

9/633

20/643

0.46 [ 0.21, 1.00 ]

3480

4856

0.70 [ 0.50, 0.97 ]

Bu 2006 Dong 2009 Hamoda 2004 Li W 2002

Von Hertzen 2002 Wang C 2000 Wu 1999a

Total (95% CI)






1


134

Analysis 6.2. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 2 Observed number of pregnancies (by risk status). Review:


Comparison: 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg Outcome: 2 Observed number of pregnancies (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

14/443

19/792

45.8 %

1.32 [ 0.67, 2.60 ]

443

792

45.8 %

1.32 [ 0.67, 2.60 ]

M-H,Fixed,95% CI


1 High-risk women Von Hertzen 2002

Subtotal (95% CI)

Total events: 14 (Treatment), 19 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.79 (P = 0.43) 2 Low-risk women Von Hertzen 2002

7/916

25/1920

54.2 %

0.59 [ 0.25, 1.35 ]

Subtotal (95% CI)

916

1920

54.2 %

0.59 [ 0.25, 1.35 ]

2712

100.0 %

0.92 [ 0.55, 1.55 ]


Total (95% CI)

1359



1



135

Analysis 6.3. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 3 Observed number of pregnancies (time from intercourse). Review:


Comparison: 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg Outcome: 3 Observed number of pregnancies (time from intercourse)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

12/991

19/966

39.4 %

0.62 [ 0.30, 1.26 ]

18/1215

36/2381

49.8 %

0.98 [ 0.56, 1.72 ]

2206

3347

89.2 %

0.82 [ 0.53, 1.27 ]

1/30

0/40

0.9 %

3.97 [ 0.17, 94.13 ]

Von Hertzen 2002

3/137

8/314

9.9 %

0.86 [ 0.23, 3.19 ]

Subtotal (95% CI)

167

354

10.8 %

1.11 [ 0.35, 3.57 ]

3701

100.0 %

0.85 [ 0.56, 1.28 ]

M-H,Fixed,95% CI


1 Within 72 h Hamoda 2004 Von Hertzen 2002

Subtotal (95% CI)

Total events: 30 (Treatment), 55 (Control) Heterogeneity: Chi2 = 1.00, df = 1 (P = 0.32); I2 =0.0% Test for overall effect: Z = 0.89 (P = 0.37) 2 Later than 72 h Hamoda 2004


Total (95% CI)

2373


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


136

Analysis 6.5. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 5 Any side effect. Review:


Comparison: 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg Outcome: 5 Any side effect

Study or subgroup

Li W 2002 Pei 2001

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

13/120

52/135

53.8 %

0.28 [ 0.16, 0.49 ]

8/100

42/100

46.2 %

0.19 [ 0.09, 0.38 ]

220

235

100.0 %

0.24 [ 0.15, 0.37 ]

M-H,Fixed,95% CI


Total events: 21 (Treatment), 94 (Control) Heterogeneity: Chi2 = 0.73, df = 1 (P = 0.39); I2 =0.0% Test for overall effect: Z = 6.44 (P < 0.00001) Test for subgroup differences: Not applicable

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


137

Analysis 6.6. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 6 Specific side effect. Review:


Comparison: 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg Outcome: 6 Specific side effect

Study or subgroup

Treatment

Control


Weight


n/N

n/N

2/50

3/50

0.5 %

0.67 [ 0.12, 3.82 ]

Hamoda 2004

93/364

107/360

29.8 %

0.86 [ 0.68, 1.09 ]

Sheng A 2002

8/100

10/100

2.1 %

0.80 [ 0.33, 1.94 ]

196/1364

388/2720

66.0 %

1.01 [ 0.86, 1.18 ]

7/633

7/643

1.5 %

1.02 [ 0.36, 2.88 ]

2511

3873

100.0 %

0.95 [ 0.84, 1.09 ]

1 Nausea Bu 2006

Von Hertzen 2002 Wu 1999a

Subtotal (95% CI)

Total events: 306 (Treatment), 515 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 1.53, df = 4 (P = 0.82); I2 =0.0% Test for overall effect: Z = 0.71 (P = 0.48) 2 Vomiting Hamoda 2004 Von Hertzen 2002 Wu 1999a

Subtotal (95% CI)

8/364

5/361

25.1 %

1.59 [ 0.52, 4.80 ]

12/1364

38/2720

37.3 %

0.63 [ 0.33, 1.20 ]

27/633

14/643

37.6 %

1.96 [ 1.04, 3.70 ]

2361

3724

100.0 %

1.22 [ 0.55, 2.68 ]

Total events: 47 (Treatment), 57 (Control) Heterogeneity: Tau2 = 0.33; Chi2 = 6.36, df = 2 (P = 0.04); I2 =69% Test for overall effect: Z = 0.49 (P = 0.63) 3 Breast tenderness Hamoda 2004 Von Hertzen 2002 Wu 1999a

Subtotal (95% CI)

88/364

76/360

34.3 %

1.15 [ 0.87, 1.50 ]

114/1364

228/2720

54.0 %

1.00 [ 0.80, 1.24 ]

32/633

36/643

11.7 %

0.90 [ 0.57, 1.44 ]

2361

3723

100.0 %

1.03 [ 0.88, 1.21 ]

Total events: 234 (Treatment), 340 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 0.99, df = 2 (P = 0.61); I2 =0.0% Test for overall effect: Z = 0.41 (P = 0.68) 4 Headache Hamoda 2004 Von Hertzen 2002

85/364

94/358

36.8 %

0.89 [ 0.69, 1.15 ]

140/1364

272/2720

43.6 %

1.03 [ 0.85, 1.25 ]

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


138


Wu 1999a

Subtotal (95% CI)

Treatment

Control


Weight

Continued) Risk Ratio MH,Random,95% CI

n/N

n/N

43/633

27/643

19.6 %

1.62 [ 1.01, 2.58 ]

2361

3721

100.0 %

1.06 [ 0.83, 1.37 ]

Total events: 268 (Treatment), 393 (Control) Heterogeneity: Tau2 = 0.03; Chi2 = 4.86, df = 2 (P = 0.09); I2 =59% Test for overall effect: Z = 0.48 (P = 0.63) 5 Dizziness Bu 2006 Hamoda 2004 Von Hertzen 2002 Wu 1999a

Subtotal (95% CI)

1/50

1/50

0.3 %

1.00 [ 0.06, 15.55 ]

52/363

64/358

21.5 %

0.80 [ 0.57, 1.12 ]

123/1364

258/2720

57.7 %

0.95 [ 0.77, 1.17 ]

58/633

60/643

20.5 %

0.98 [ 0.70, 1.38 ]

2410

3771

100.0 %

0.92 [ 0.79, 1.08 ]

Total events: 234 (Treatment), 383 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 0.89, df = 3 (P = 0.83); I2 =0.0% Test for overall effect: Z = 1.01 (P = 0.31) 6 Fatigue Hamoda 2004 Von Hertzen 2002 Wu 1999a

Subtotal (95% CI)

90/360

97/357

27.4 %

0.92 [ 0.72, 1.18 ]

208/1364

366/2720

67.4 %

1.13 [ 0.97, 1.33 ]

23/633

23/643

5.2 %

1.02 [ 0.58, 1.79 ]

2357

3720

100.0 %

1.06 [ 0.94, 1.21 ]

Total events: 321 (Treatment), 486 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 1.98, df = 2 (P = 0.37); I2 =0.0% Test for overall effect: Z = 0.95 (P = 0.34) 7 Low abdominal pain Bu 2006

3/50

4/50

0.7 %

0.75 [ 0.18, 3.18 ]

Hamoda 2004

119/363

139/358

39.4 %

0.84 [ 0.69, 1.03 ]

Sheng A 2002

7/100

6/100

1.4 %

1.17 [ 0.41, 3.35 ]

191/1364

381/2720

58.5 %

1.00 [ 0.85, 1.17 ]

1877

3228

100.0 %

0.94 [ 0.83, 1.06 ]

Von Hertzen 2002

Subtotal (95% CI)

Total events: 320 (Treatment), 530 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 1.99, df = 3 (P = 0.57); I2 =0.0% Test for overall effect: Z = 1.06 (P = 0.29) 8 Diarrhoea Bu 2006 Von Hertzen 2002

Subtotal (95% CI)

2/50

1/50

1.7 %

2.00 [ 0.19, 21.36 ]

61/1364

97/2720

98.3 %

1.25 [ 0.92, 1.72 ]

1414

2770

100.0 %

1.26 [ 0.93, 1.73 ]

Total events: 63 (Treatment), 98 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 0.15, df = 1 (P = 0.70); I2 =0.0% Test for overall effect: Z = 1.48 (P = 0.14)

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . ) Interventions for emergency contraception (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

139



Weight


Treatment

Control

n/N

n/N

1/49

2/49

0.3 %

0.50 [ 0.05, 5.34 ]

258/1364

832/2720

99.7 %

0.62 [ 0.55, 0.70 ]

1413

2769

100.0 %

0.62 [ 0.55, 0.70 ]

9 Spotting/bleeding after treatment Bu 2006 Von Hertzen 2002

Subtotal (95% CI)

Total events: 259 (Treatment), 834 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 0.03, df = 1 (P = 0.86); I2 =0.0% Test for overall effect: Z = 7.64 (P < 0.00001) 10 Heavy menses

Subtotal (95% CI)

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

49/364

52/359

100.0 %

0.93 [ 0.65, 1.33 ]

364

359

100.0 %

0.93 [ 0.65, 1.33 ]

Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 11 Hot flushes Hamoda 2004

Subtotal (95% CI)


0.01

0.1

Favours treatment

1

10

100

Favours control


140

Analysis 6.7. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 7 Menses. Review:


Comparison: 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg Outcome: 7 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

4/49

9/49

2.4 %

0.44 [ 0.15, 1.35 ]

59/622

144/664

36.5 %

0.44 [ 0.33, 0.58 ]

671

713

38.8 %

0.44 [ 0.33, 0.58 ]

9/49

5/49

1.3 %

1.80 [ 0.65, 4.99 ]

97/622

54/664

13.7 %

1.92 [ 1.40, 2.63 ]

Pei 2001

3/100

7/100

1.8 %

0.43 [ 0.11, 1.61 ]

Sheng A 2002

20/99

22/98

5.8 %

0.90 [ 0.53, 1.54 ]

118/1327

125/2720

21.5 %

1.93 [ 1.52, 2.47 ]

117/633

66/643

17.1 %

1.80 [ 1.36, 2.39 ]

2830

4274

61.2 %

1.75 [ 1.51, 2.03 ]

4987

100.0 %

1.24 [ 1.09, 1.40 ]

M-H,Fixed,95% CI


1 Early Bu 2006 Hamoda 2004

Subtotal (95% CI)

Total events: 63 (Treatment), 153 (Control) Heterogeneity: Chi2 = 0.00, df = 1 (P = 0.98); I2 =0.0% Test for overall effect: Z = 5.91 (P < 0.00001) 2 Delay Bu 2006 Hamoda 2004

Von Hertzen 2002 Wu 1999a

Subtotal (95% CI)

Total events: 364 (Treatment), 279 (Control) Heterogeneity: Chi2 = 11.25, df = 5 (P = 0.05); I2 =56% Test for overall effect: Z = 7.37 (P < 0.00001)

Total (95% CI)

3501

Total events: 427 (Treatment), 432 (Control) Heterogeneity: Chi2 = 86.96, df = 7 (P<0.00001); I2 =92% Test for overall effect: Z = 3.36 (P = 0.00077) Test for subgroup differences: Chi2 = 75.89, df = 1 (P = 0.00), I2 =99%

0.01

0.1

Favours treatment

1

10

100

Favours control


141

Analysis 6.8. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 8 ITT (all loss follow-up as pregnancy in LNG, and no preg in Mife). Review:


Comparison: 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg Outcome: 8 ITT (all loss follow-up as pregnancy in LNG, and no preg in Mife)

Study or subgroup

Treatment

Control

n/N

n/N

13/1022

20/1021

0.65 [ 0.32, 1.30 ]

2/120

3/135

0.75 [ 0.13, 4.41 ]

Lin 2000

0/60

0/60

0.0 [ 0.0, 0.0 ]

Liu 2000

2/50

2/50

1.00 [ 0.15, 6.82 ]

Pei 2001

1/100

2/100

0.50 [ 0.05, 5.43 ]

Sheng A 2002

1/100

2/100

0.50 [ 0.05, 5.43 ]

21/1379

48/2756

0.87 [ 0.53, 1.45 ]

1/50

1/50

1.00 [ 0.06, 15.55 ]

9/633

20/643

0.46 [ 0.21, 1.00 ]

3514

4915

0.70 [ 0.50, 0.98 ]

Hamoda 2004 Li W 2002


Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.1 0.2

0.5

Favours treatment


1

2

5

10

Favours control

142

Analysis 6.9. Comparison 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg, Outcome 9 ITT (all loss follow-up as no pregnancy in LNG, and preg in Mife). Review:


Comparison: 6 Mifepristone low dose (< 25 mg) versus Levonorgestrel 1.5 mg Outcome: 9 ITT (all loss follow-up as no pregnancy in LNG, and preg in Mife)

Study or subgroup

Treatment

Control

n/N

n/N

175/1022

183/1021

0.96 [ 0.79, 1.15 ]

2/120

3/135

0.75 [ 0.13, 4.41 ]

Lin 2000

0/60

0/60

0.0 [ 0.0, 0.0 ]

Liu 2000

2/50

4/50

0.50 [ 0.10, 2.61 ]

Pei 2001

1/100

2/100

0.50 [ 0.05, 5.43 ]

Sheng A 2002

1/100

2/100

0.50 [ 0.05, 5.43 ]

41/1379

89/2756

0.92 [ 0.64, 1.33 ]

1/50

1/50

1.00 [ 0.06, 15.55 ]

9/633

20/643

0.46 [ 0.21, 1.00 ]

3514

4915

0.90 [ 0.76, 1.05 ]

Hamoda 2004 Li W 2002


Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.1 0.2

0.5

Favours treatment


1

2

5

10

Favours control

143

Analysis 7.1. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 1 Observed number of pregnancy (all women). Review:


Comparison: 7 Ulipristal acetate (all doses) versus Levonorgestrel Outcome: 1 Observed number of pregnancy (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Creinin 2006

7/775

13/774

34.4 %

0.54 [ 0.22, 1.34 ]

Glasier 2010

15/941

25/958

65.6 %

0.61 [ 0.32, 1.15 ]

1716

1732

100.0 %

0.59 [ 0.35, 0.99 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


144

Analysis 7.2. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 2 Observed number of pregnancy (by risk status). Review:


Comparison: 7 Ulipristal acetate (all doses) versus Levonorgestrel Outcome: 2 Observed number of pregnancy (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Creinin 2006

1/36

1/31

2.8 %

0.86 [ 0.06, 13.20 ]

Glasier 2010

4/53

5/51

13.4 %

0.77 [ 0.22, 2.71 ]

89

82

16.3 %

0.79 [ 0.25, 2.46 ]

M-H,Fixed,95% CI


1 High-risk women


Heterogeneity: Chi2 = 0.01, df = 1 (P = 0.94); I2 =0.0% Test for overall effect: Z = 0.41 (P = 0.68) 2 Low-risk women Creinin 2006

6/737

12/742

31.5 %

0.50 [ 0.19, 1.33 ]

Glasier 2010

11/888

20/907

52.2 %

0.56 [ 0.27, 1.17 ]

1625

1649

83.7 %

0.54 [ 0.30, 0.97 ]

1731

100.0 %

0.58 [ 0.35, 0.97 ]

Subtotal (95% CI)


Total (95% CI)

1714


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


145

Analysis 7.3. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 3 Observed number of pregnancy (time from intercourse). Review:


Comparison: 7 Ulipristal acetate (all doses) versus Levonorgestrel Outcome: 3 Observed number of pregnancy (time from intercourse)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Creinin 2006

0/273

4/263

11.6 %

0.11 [ 0.01, 1.98 ]

Glasier 2010

5/312

10/337

24.4 %

0.54 [ 0.19, 1.56 ]

585

600

36.1 %

0.40 [ 0.15, 1.05 ]

M-H,Fixed,95% CI


1 Within 24 h


Heterogeneity: Chi2 = 1.09, df = 1 (P = 0.30); I2 =8% Test for overall effect: Z = 1.86 (P = 0.064) 2 24-48 h Creinin 2006

6/268

3/298

7.2 %

2.22 [ 0.56, 8.80 ]

Glasier 2010

7/328

7/319

18.0 %

0.97 [ 0.35, 2.74 ]

596

617

25.3 %

1.33 [ 0.59, 3.00 ]

Subtotal (95% CI)

Total events: 13 (Treatment), 10 (Control) Heterogeneity: Chi2 = 0.89, df = 1 (P = 0.35); I2 =0.0% Test for overall effect: Z = 0.69 (P = 0.49) 3 > 48-72 h Creinin 2006

1/234

6/213

16.0 %

0.15 [ 0.02, 1.25 ]

Glasier 2010

3/203

5/196

12.9 %

0.58 [ 0.14, 2.39 ]

437

409

28.9 %

0.34 [ 0.11, 1.06 ]

0/63

2/73

5.9 %

0.23 [ 0.01, 4.73 ]

63

73

5.9 %

0.23 [ 0.01, 4.73 ]

0/34

1/33

3.9 %

0.32 [ 0.01, 7.68 ]

34

33

3.9 %

0.32 [ 0.01, 7.68 ]


Heterogeneity: Chi2 = 1.10, df = 1 (P = 0.29); I2 =9% Test for overall effect: Z = 1.85 (P = 0.064) 4 > 72-96 h Glasier 2010

Subtotal (95% CI) Total events: 0 (Treatment), 2 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.95 (P = 0.34) 5 > 96-120 h Glasier 2010


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


146


Treatment

Control

n/N

n/N

1715

1732

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI


Total (95% CI)

100.0 %

0.61 [ 0.37, 1.00 ]


0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 7.4. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 4 Observed number of pregnancy within 0-72 h. Review:


Comparison: 7 Ulipristal acetate (all doses) versus Levonorgestrel Outcome: 4 Observed number of pregnancy within 0-72 h

Study or subgroup

Treatment

Control

n/N

n/N

Creinin 2006

7/775

13/774

37.3 %

0.54 [ 0.22, 1.34 ]

Glasier 2010

15/844

22/852

62.7 %

0.69 [ 0.36, 1.32 ]

1619

1626

100.0 %

0.63 [ 0.37, 1.07 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1

Favours experimental

1

10

100

Favours control


147

Analysis 7.7. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 7 Specific side effects. Review:


Comparison: 7 Ulipristal acetate (all doses) versus Levonorgestrel Outcome: 7 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Creinin 2006

29/775

24/774

16.1 %

1.21 [ 0.71, 2.05 ]

Glasier 2010

141/1104

126/1117

83.9 %

1.13 [ 0.90, 1.42 ]

1879

1891

100.0 %

1.14 [ 0.93, 1.41 ]

2/775

2/774

100.0 %

1.00 [ 0.14, 7.07 ]

775

774

100.0 %

1.00 [ 0.14, 7.07 ]

16/775

15/774

100.0 %

1.07 [ 0.53, 2.14 ]

775

774

100.0 %

1.07 [ 0.53, 2.14 ]

M-H,Fixed,95% CI


1 Nausea

Subtotal (95% CI)

Total events: 170 (Treatment), 150 (Control) Heterogeneity: Chi2 = 0.05, df = 1 (P = 0.83); I2 =0.0% Test for overall effect: Z = 1.27 (P = 0.20) 2 Vomiting Creinin 2006

Subtotal (95% CI) Total events: 2 (Treatment), 2 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.00 (P = 1.0) 3 Breast tenderness Creinin 2006

Subtotal (95% CI)

Total events: 16 (Treatment), 15 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.18 (P = 0.86) 4 Headache Creinin 2006

29/775

29/774

12.2 %

1.00 [ 0.60, 1.65 ]

Glasier 2010

213/1104

211/1117

87.8 %

1.02 [ 0.86, 1.21 ]

1879

1891

100.0 %

1.02 [ 0.87, 1.20 ]

Subtotal (95% CI)

Total events: 242 (Treatment), 240 (Control) Heterogeneity: Chi2 = 0.01, df = 1 (P = 0.93); I2 =0.0% Test for overall effect: Z = 0.22 (P = 0.82) 5 Dizziness Creinin 2006

20/775

18/774

24.8 %

1.11 [ 0.59, 2.08 ]

Glasier 2010

57/1104

55/1117

75.2 %

1.05 [ 0.73, 1.50 ]

1879

1891

100.0 %

1.06 [ 0.78, 1.45 ]

Subtotal (95% CI)

Total events: 77 (Treatment), 73 (Control) Heterogeneity: Chi2 = 0.02, df = 1 (P = 0.88); I2 =0.0%

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


148


Risk Ratio

Weight


Treatment

Control

n/N

n/N

Creinin 2006

37/775

37/774

45.8 %

1.00 [ 0.64, 1.56 ]

Glasier 2010

61/1104

44/1117

54.2 %

1.40 [ 0.96, 2.05 ]

1879

1891

100.0 %

1.22 [ 0.91, 1.62 ]

31/775

27/774

100.0 %

1.15 [ 0.69, 1.90 ]

775

774

100.0 %

1.15 [ 0.69, 1.90 ]

12/775

11/774

100.0 %

1.09 [ 0.48, 2.45 ]

775

774

100.0 %

1.09 [ 0.48, 2.45 ]

5/775

7/774

100.0 %

0.71 [ 0.23, 2.24 ]

775

774

100.0 %

0.71 [ 0.23, 2.24 ]

142/1104

160/1117

100.0 %

0.90 [ 0.73, 1.11 ]

1104

1117

100.0 %

0.90 [ 0.73, 1.11 ]

56/1104

75/1117

100.0 %

0.76 [ 0.54, 1.06 ]

1104

1117

100.0 %

0.76 [ 0.54, 1.06 ]

46/1117

100.0 %

0.81 [ 0.53, 1.24 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

Test for overall effect: Z = 0.39 (P = 0.70) 6 Fatigue

Subtotal (95% CI)

Total events: 98 (Treatment), 81 (Control) Heterogeneity: Chi2 = 1.30, df = 1 (P = 0.25); I2 =23% Test for overall effect: Z = 1.34 (P = 0.18) 7 Lower abdominal pain Creinin 2006

Subtotal (95% CI)

Total events: 31 (Treatment), 27 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.53 (P = 0.60) 8 Diarrhoea Creinin 2006

Subtotal (95% CI)

Total events: 12 (Treatment), 11 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.21 (P = 0.84) 9 Spotting/bleeding after treatment Creinin 2006


Test for overall effect: Z = 0.58 (P = 0.56) 10 Dysmenorrhoea Glasier 2010

Subtotal (95% CI)

Total events: 142 (Treatment), 160 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.00 (P = 0.32) 11 Abdominal pain Glasier 2010

Subtotal (95% CI)

Total events: 56 (Treatment), 75 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.64 (P = 0.10) 12 Upper abdominal pain Glasier 2010

37/1104

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


149


Subtotal (95% CI)

Treatment

Control

Risk Ratio

Weight

M-H,Fixed,95% CI


n/N

n/N

1104

1117

100.0 %

0.81 [ 0.53, 1.24 ]

M-H,Fixed,95% CI

35/1104

27/1117

100.0 %

1.31 [ 0.80, 2.15 ]

1104

1117

100.0 %

1.31 [ 0.80, 2.15 ]

Total events: 37 (Treatment), 46 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.95 (P = 0.34) 13 Back pain Glasier 2010

Subtotal (95% CI)


0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 7.8. Comparison 7 Ulipristal acetate (all doses) versus Levonorgestrel, Outcome 8 Menses. Review:


Comparison: 7 Ulipristal acetate (all doses) versus Levonorgestrel Outcome: 8 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Creinin 2006

132/775

271/774

39.5 %

0.49 [ 0.41, 0.58 ]

Glasier 2010

67/1013

191/1031

27.6 %

0.36 [ 0.27, 0.47 ]

1788

1805

67.1 %

0.43 [ 0.37, 0.50 ]

M-H,Fixed,95% CI


1 Early

Subtotal (95% CI)

Total events: 199 (Treatment), 462 (Control) Heterogeneity: Chi2 = 3.60, df = 1 (P = 0.06); I2 =72% Test for overall effect: Z = 10.87 (P < 0.00001) 2 Delay Creinin 2006

194/775

124/774

18.1 %

1.56 [ 1.28, 1.91 ]

Glasier 2010

177/1013

103/1031

14.9 %

1.75 [ 1.39, 2.19 ]

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


150


Subtotal (95% CI)

Treatment

Control

Risk Ratio

Weight

M-H,Fixed,95% CI


n/N

n/N

1788

1805

32.9 %

1.65 [ 1.42, 1.92 ]

M-H,Fixed,95% CI

3610

100.0 %

0.83 [ 0.75, 0.92 ]

Total events: 371 (Treatment), 227 (Control) Heterogeneity: Chi2 = 0.53, df = 1 (P = 0.47); I2 =0.0% Test for overall effect: Z = 6.47 (P < 0.00001)

Total (95% CI)

3576

Total events: 570 (Treatment), 689 (Control) Heterogeneity: Chi2 = 151.00, df = 3 (P<0.00001); I2 =98% Test for overall effect: Z = 3.55 (P = 0.00039) Test for subgroup differences: Chi2 = 150.39, df = 1 (P = 0.00), I2 =99%

0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 8.1. Comparison 8 Levonorgestrel (all doses) versus anordrin (all doses), Outcome 1 Observed number of pregnancy (all women). Review:


Comparison: 8 Levonorgestrel (all doses) versus anordrin (all doses) Outcome: 1 Observed number of pregnancy (all women)

Study or subgroup

Xu Z 2000

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

2/86

3/86

100.0 %

0.67 [ 0.11, 3.89 ]

86

86

100.0 %

0.67 [ 0.11, 3.89 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


151

Analysis 8.5. Comparison 8 Levonorgestrel (all doses) versus anordrin (all doses), Outcome 5 Any side effect. Review:


Comparison: 8 Levonorgestrel (all doses) versus anordrin (all doses) Outcome: 5 Any side effect

Study or subgroup

Xu Z 2000

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

6/86

8/86

100.0 %

0.75 [ 0.27, 2.07 ]

86

86

100.0 %

0.75 [ 0.27, 2.07 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 9.1. Comparison 9 mifepristone low dose (10 mg) versus low dose (5 mg), Outcome 1 Observed number of pregnancy (all women). Review:


Comparison: 9 mifepristone low dose (10 mg) versus low dose (5 mg) Outcome: 1 Observed number of pregnancy (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Lan XL 2006

1/100

1/100

34.3 %

1.00 [ 0.06, 15.77 ]

Zhang Y 1998

1/92

2/100

65.7 %

0.54 [ 0.05, 5.89 ]

Total (95% CI)

192

200

100.0 %

0.70 [ 0.12, 4.17 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


152

Analysis 9.6. Comparison 9 mifepristone low dose (10 mg) versus low dose (5 mg), Outcome 6 Specific side effects. Review:


Comparison: 9 mifepristone low dose (10 mg) versus low dose (5 mg) Outcome: 6 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

3/100

0/100

100.0 %

7.00 [ 0.37, 133.78 ]

100

100

100.0 %

7.00 [ 0.37, 133.78 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

1/100

0/100

100.0 %

3.00 [ 0.12, 72.77 ]

100

100

100.0 %

3.00 [ 0.12, 72.77 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI


1 Nausea Lan XL 2006


Test for overall effect: Z = 1.29 (P = 0.20) 2 Vomiting

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 3 Breast tenderness Lan XL 2006


Test for overall effect: Z = 0.68 (P = 0.50) 4 Headache

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 5 Dizziness

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 6 Fatigue


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


153


Risk Ratio

Weight


Treatment

Control

n/N

n/N

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

7 Lower abdominal pain

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 8 Diarrhoea



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


154

Analysis 10.1. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Cao 1999

2/283

8/140

0.12 [ 0.03, 0.57 ]

Chen 2009

1/30

1/32

1.07 [ 0.07, 16.30 ]

3/410

5/201

0.29 [ 0.07, 1.22 ]

Ding 2005

1/77

1/74

0.96 [ 0.06, 15.08 ]

Du 2002

1/90

1/90

1.00 [ 0.06, 15.74 ]

Fan 2001

0/53

1/39

0.25 [ 0.01, 5.90 ]

Han L 2001

0/50

0/50

0.0 [ 0.0, 0.0 ]

Lai Z 2004

2/130

2/149

1.15 [ 0.16, 8.02 ]

Qi 2000b

5/579

12/545

0.39 [ 0.14, 1.11 ]

Sang 1999

10/599

17/599

0.59 [ 0.27, 1.27 ]

Tan L 2003

0/50

1/50

0.33 [ 0.01, 7.99 ]

Wang J 2006

1/100

1/98

0.98 [ 0.06, 15.45 ]

Wang L 2004

6/600

6/600

1.00 [ 0.32, 3.08 ]

Wang SZ 2001

1/100

1/100

1.00 [ 0.06, 15.77 ]

Wang ZW 2008

1/50

1/50

1.00 [ 0.06, 15.55 ]

Wei H 2011

1/50

0/50

3.00 [ 0.13, 71.92 ]

Wei RH 2002

2/100

1/100

2.00 [ 0.18, 21.71 ]

WHO 1999

6/560

7/565

0.86 [ 0.29, 2.56 ]

17/1514

17/1516

1.00 [ 0.51, 1.95 ]

Xie HH 2010

8/60

7/60

1.14 [ 0.44, 2.95 ]

Zeng MY 2008

1/40

1/60

1.50 [ 0.10, 23.30 ]

Zhang Y 1998

1/99

3/192

0.65 [ 0.07, 6.13 ]

Zhang Y 2002

0/45

0/45

0.0 [ 0.0, 0.0 ]

Zhao J 2003

1/90

1/90

1.00 [ 0.06, 15.74 ]

4/339

3/321

1.26 [ 0.28, 5.60 ]

Cheng 1999a

Xiao 2002

Zuo 1999



1


10 100 1000 Favors control

(Continued . . . )


155


Total (95% CI)

Treatment

Control

n/N

n/N

6098

5816



M-H,Fixed,95% CI

0.73 [ 0.55, 0.97 ]


0.001 0.01 0.1

1

Favours treatment

10 100 1000 Favors control

Analysis 10.2. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 2 Observed number of pregnancies (by risk status). Review:


Comparison: 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg) Outcome: 2 Observed number of pregnancies (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Cheng 1999a

1/17

4/8

17.9 %

0.12 [ 0.02, 0.89 ]

WHO 1999

1/11

2/16

5.4 %

0.73 [ 0.07, 7.07 ]

11/740

11/752

35.9 %

1.02 [ 0.44, 2.33 ]

768

776

59.2 %

0.72 [ 0.36, 1.42 ]

M-H,Fixed,95% CI


1 High-risk women

Xiao 2002

Subtotal (95% CI)

Total events: 13 (Treatment), 17 (Control) Heterogeneity: Chi2 = 3.74, df = 2 (P = 0.15); I2 =47% Test for overall effect: Z = 0.95 (P = 0.34) 2 Low-risk women Cheng 1999a

2/391

1/191

4.4 %

0.98 [ 0.09, 10.71 ]

WHO 1999

5/549

5/549

16.5 %

1.00 [ 0.29, 3.43 ]

Xiao 2002

6/752

6/739

19.9 %

0.98 [ 0.32, 3.03 ]

1692

1479

40.8 %

0.99 [ 0.45, 2.17 ]

Subtotal (95% CI)



1


(Continued . . . )


156


Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Heterogeneity: Chi2 = 0.00, df = 2 (P = 1.00); I2 =0.0% Test for overall effect: Z = 0.03 (P = 0.98)

Total (95% CI)

2460

100.0 %

2255

0.83 [ 0.50, 1.38 ]


0.001 0.01 0.1

1

Favours treatment


Analysis 10.3. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 3 Any side effect. Review:


Comparison: 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg) Outcome: 3 Any side effect

Study or subgroup

Treatment

Control


n/N

n/N

Cao 1999

17/283

0/140

0.9 %

17.38 [ 1.05, 286.86 ]

Cheng 1999a

81/418

34/201

33.5 %

1.15 [ 0.80, 1.65 ]

Ding 2005

14/77

12/74

12.1 %

1.12 [ 0.56, 2.26 ]

Du 2002

16/90

12/90

12.5 %

1.33 [ 0.67, 2.66 ]

Tan L 2003

6/50

3/50

3.7 %

2.00 [ 0.53, 7.56 ]

Wei H 2011

4/50

3/50

3.2 %

1.33 [ 0.31, 5.65 ]

Wei RH 2002

10/100

11/100

9.4 %

0.91 [ 0.40, 2.04 ]

Xie HH 2010

11/60

9/60

9.5 %

1.22 [ 0.55, 2.73 ]

Zeng MY 2008

4/40

3/60

3.2 %

2.00 [ 0.47, 8.46 ]

Zhang Y 1998

7/99

0/192

0.8 %

28.95 [ 1.67, 501.74 ]

0.01

0.1

Favours treatment

1

10

Weight


100

Favours control

(Continued . . . )


157


Treatment

Zhao J 2003

Total (95% CI)

Control


Weight


n/N

n/N

16/90

10/90

11.2 %

1.60 [ 0.77, 3.33 ]

1357

1107

100.0 %

1.31 [ 1.01, 1.70 ]

Total events: 186 (Treatment), 97 (Control) Heterogeneity: Tau2 = 0.02; Chi2 = 11.04, df = 10 (P = 0.35); I2 =9% Test for overall effect: Z = 2.01 (P = 0.045) Test for subgroup differences: Not applicable

0.01

0.1

Favours treatment

1

10

100

Favours control

Analysis 10.4. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 4 Specific side effects. Review:


Comparison: 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg) Outcome: 4 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Risk Ratio

4/30

2/32

2.13 [ 0.42, 10.81 ]

27/418

12/203

1.09 [ 0.57, 2.11 ]

2/53

2/39

0.74 [ 0.11, 5.00 ]

Lai Z 2004

13/130

9/149

1.66 [ 0.73, 3.75 ]

Qi 2000b

126/579

106/545

1.12 [ 0.89, 1.41 ]

Sang 1999

72/599

96/599

0.75 [ 0.56, 1.00 ]

Wang J 2006

7/100

6/98

1.14 [ 0.40, 3.28 ]

Wang SZ 2001

7/100

5/100

1.40 [ 0.46, 4.26 ]

Wang ZW 2008

3/50

2/50

1.50 [ 0.26, 8.60 ]

171/1516

149/1517

1.15 [ 0.93, 1.41 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

1 Nausea Chen 2009 Cheng 1999a Fan 2001

Xiao 2002

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


158


Treatment

Control

Risk Ratio

n/N

n/N

Zhang Y 1998

7/99

0/192

28.95 [ 1.67, 501.74 ]

Zhang Y 2002

4/45

3/45

1.33 [ 0.32, 5.62 ]

17/339

11/321

1.46 [ 0.70, 3.08 ]

4058

3890

1.10 [ 0.97, 1.24 ]

Zuo 1999

Subtotal (95% CI)

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 460 (Treatment), 403 (Control) Heterogeneity: Chi2 = 14.91, df = 12 (P = 0.25); I2 =20% Test for overall effect: Z = 1.44 (P = 0.15) 2 Vomiting Cheng 1999a

2/418

3/203

0.32 [ 0.05, 1.92 ]

Lai Z 2004

2/130

0/149

5.73 [ 0.28, 118.18 ]

Sang 1999

8/599

4/599

2.00 [ 0.61, 6.61 ]

Xiao 2002

12/1516

8/1517

1.50 [ 0.62, 3.66 ]

0/99

0/192

0.0 [ 0.0, 0.0 ]

0/339

3/321

0.14 [ 0.01, 2.61 ]

3101

2981

1.22 [ 0.68, 2.17 ]

Zhang Y 1998 Zuo 1999


Heterogeneity: Chi2 = 6.12, df = 4 (P = 0.19); I2 =35% Test for overall effect: Z = 0.66 (P = 0.51) 3 Breast tenderness Cheng 1999a

7/418

2/203

1.70 [ 0.36, 8.11 ]

Lai Z 2004

1/130

3/149

0.38 [ 0.04, 3.63 ]

Sang 1999

25/599

33/599

0.76 [ 0.46, 1.26 ]

Wang J 2006

2/100

1/98

1.96 [ 0.18, 21.27 ]

Wang SZ 2001

2/100

1/100

2.00 [ 0.18, 21.71 ]

Wang ZW 2008

1/50

1/50

1.00 [ 0.06, 15.55 ]

20/1516

21/1517

0.95 [ 0.52, 1.75 ]

Zhang Y 1998

0/99

0/192

0.0 [ 0.0, 0.0 ]

Zhang Y 2002

1/45

0/45

3.00 [ 0.13, 71.74 ]

3057

2953

0.91 [ 0.64, 1.29 ]

4/30

3/32

1.42 [ 0.35, 5.83 ]

7/418

2/203

1.70 [ 0.36, 8.11 ]

64/579

68/545

0.89 [ 0.64, 1.22 ]

Xiao 2002


Heterogeneity: Chi2 = 3.07, df = 7 (P = 0.88); I2 =0.0% Test for overall effect: Z = 0.54 (P = 0.59) 4 Headache Chen 2009 Cheng 1999a Qi 2000b

0.01

0.1

Favours treatment

1

10

100

Favours control


159


Treatment

Control

Risk Ratio

n/N

n/N

Sang 1999

15/599

21/599

0.71 [ 0.37, 1.37 ]

Xiao 2002

39/1516

33/1517

1.18 [ 0.75, 1.87 ]

0/99

0/192

0.0 [ 0.0, 0.0 ]

3241

3088

0.96 [ 0.76, 1.22 ]

2/30

1/32

2.13 [ 0.20, 22.33 ]

15/418

9/203

0.81 [ 0.36, 1.82 ]

0/53

1/39

0.25 [ 0.01, 5.90 ]

29/599

24/599

1.21 [ 0.71, 2.05 ]

Wang J 2006

5/100

4/98

1.23 [ 0.34, 4.43 ]

Wang SZ 2001

6/100

4/100

1.50 [ 0.44, 5.15 ]

Wang ZW 2008

2/50

1/50

2.00 [ 0.19, 21.36 ]

Zhang Y 1998

0/99

0/192

0.0 [ 0.0, 0.0 ]

Zhang Y 2002

3/45

2/45

1.50 [ 0.26, 8.55 ]

3/339

3/321

0.95 [ 0.19, 4.66 ]

1833

1679

1.14 [ 0.79, 1.63 ]

5/30

4/32

1.33 [ 0.39, 4.50 ]

1/418

7/203

0.07 [ 0.01, 0.56 ]

1/53

0/39

2.22 [ 0.09, 53.14 ]

Lai Z 2004

7/130

5/149

1.60 [ 0.52, 4.93 ]

Qi 2000b

46/579

41/545

1.06 [ 0.70, 1.58 ]

Sang 1999

36/599

32/599

1.13 [ 0.71, 1.79 ]

Wang SZ 2001

2/100

1/100

2.00 [ 0.18, 21.71 ]

Wang ZW 2008

2/50

2/50

1.00 [ 0.15, 6.82 ]

WHO 1999

115/557

110/562

1.05 [ 0.84, 1.33 ]

Xiao 2002

92/1516

105/1517

0.88 [ 0.67, 1.15 ]

0/99

0/192

0.0 [ 0.0, 0.0 ]

Zhang Y 1998

Subtotal (95% CI)

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 129 (Treatment), 127 (Control) Heterogeneity: Chi2 = 2.64, df = 4 (P = 0.62); I2 =0.0% Test for overall effect: Z = 0.32 (P = 0.75) 5 Dizziness Chen 2009 Cheng 1999a Fan 2001 Sang 1999

Zuo 1999


Heterogeneity: Chi2 = 2.47, df = 8 (P = 0.96); I2 =0.0% Test for overall effect: Z = 0.70 (P = 0.49) 6 Fatigue Chen 2009 Cheng 1999a Fan 2001

Zhang Y 1998

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


160


Treatment

Control

Risk Ratio

n/N

n/N

1/45

0/45

3.00 [ 0.13, 71.74 ]

4176

4033

0.99 [ 0.86, 1.15 ]

25/418

9/203

1.35 [ 0.64, 2.84 ]

Fan 2001

3/53

4/39

0.55 [ 0.13, 2.33 ]

Qi 2000b

20/579

24/545

0.78 [ 0.44, 1.40 ]

Xiao 2002

70/1516

65/1517

1.08 [ 0.77, 1.50 ]

2566

2304

1.02 [ 0.78, 1.32 ]

Zhang Y 2002

Subtotal (95% CI)

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 308 (Treatment), 307 (Control) Heterogeneity: Chi2 = 9.65, df = 10 (P = 0.47); I2 =0.0% Test for overall effect: Z = 0.11 (P = 0.91) 7 Abdominal pain Cheng 1999a


Heterogeneity: Chi2 = 2.13, df = 3 (P = 0.55); I2 =0.0% Test for overall effect: Z = 0.13 (P = 0.90) 8 Diarrhoea Chen 2009

4/30

2/32

2.13 [ 0.42, 10.81 ]

Lai Z 2004

1/130

2/149

0.57 [ 0.05, 6.25 ]

Qi 2000b

14/579

17/545

0.78 [ 0.39, 1.56 ]

Wang J 2006

4/100

3/98

1.31 [ 0.30, 5.69 ]

Wang SZ 2001

6/100

4/100

1.50 [ 0.44, 5.15 ]

Wang ZW 2008

3/50

2/50

1.50 [ 0.26, 8.60 ]

9/1516

8/1517

1.13 [ 0.44, 2.91 ]

3/45

2/45

1.50 [ 0.26, 8.55 ]

1/339

3/321

0.32 [ 0.03, 3.02 ]

2889

2857

1.03 [ 0.68, 1.55 ]

1/29

1/31

1.07 [ 0.07, 16.31 ]

Cheng 1999a

38/418

14/203

1.32 [ 0.73, 2.38 ]

Lai Z 2004

24/130

1/149

27.51 [ 3.77, 200.53 ]

Sang 1999

55/599

40/599

1.38 [ 0.93, 2.03 ]

Tan L 2003

2/50

1/50

2.00 [ 0.19, 21.36 ]

24/600

12/600

2.00 [ 1.01, 3.96 ]

1/100

1/100

1.00 [ 0.06, 15.77 ]

Xiao 2002 Zhang Y 2002 Zuo 1999


Heterogeneity: Chi2 = 3.54, df = 8 (P = 0.90); I2 =0.0% Test for overall effect: Z = 0.14 (P = 0.89) 9 Spotting/bleeding after treatment Chen 2009

Wang L 2004 Wang SZ 2001

0.01

0.1

Favours treatment

1

10

100

Favours control


161


Treatment

Control

Risk Ratio

n/N

n/N

Wang ZW 2008

1/49

1/49

1.00 [ 0.06, 15.54 ]

Wei H 2011

7/49

3/50

2.38 [ 0.65, 8.68 ]

WHO 1999

172/560

86/565

2.02 [ 1.60, 2.54 ]

2/39

9/59

0.34 [ 0.08, 1.47 ]

2623

2455

1.85 [ 1.55, 2.20 ]

Zeng MY 2008

Subtotal (95% CI)

M-H,Fixed,95% CI


M-H,Fixed,95% CI


0.01

0.1

1

Favours treatment

10

100

Favours control

Analysis 10.5. Comparison 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg), Outcome 5 Menses. Review:


Comparison: 10 Mifepristone mid-doses (25-50 mg) versus mifepristone low-doses (< 25 mg) Outcome: 5 Menses

Study or subgroup

Treatment

Control


Weight


n/N

n/N

12/130

9/149

7.0 %

1.53 [ 0.67, 3.51 ]

Wang J 2006

2/100

1/98

0.9 %

1.96 [ 0.18, 21.27 ]

Wang L 2004

102/594

96/594

74.8 %

1.06 [ 0.82, 1.37 ]

1/49

1/49

0.6 %

1.00 [ 0.06, 15.54 ]

Xie HH 2010

15/52

15/53

13.2 %

1.02 [ 0.56, 1.87 ]

Zhang Y 2002

0/45

1/45

0.5 %

0.33 [ 0.01, 7.97 ]

Zhao J 2003

5/89

4/89

2.9 %

1.25 [ 0.35, 4.50 ]

1059

1077

100.0 %

1.09 [ 0.87, 1.36 ]

1 Early Lai Z 2004

Wang ZW 2008

Subtotal (95% CI)

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


162


Treatment

Control

n/N

n/N


Weight


Total events: 137 (Treatment), 127 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 1.54, df = 6 (P = 0.96); I2 =0.0% Test for overall effect: Z = 0.75 (P = 0.45) 2 Delay Cao 1999

81/283

34/132

7.1 %

1.11 [ 0.79, 1.57 ]

Chen 2009

29/29

30/31

11.8 %

1.03 [ 0.94, 1.13 ]

111/418

50/203

8.1 %

1.08 [ 0.81, 1.44 ]

Du 2002

22/89

19/89

4.3 %

1.16 [ 0.68, 1.98 ]

Han L 2001

22/50

18/50

5.0 %

1.22 [ 0.75, 1.98 ]

Lai Z 2004

23/130

15/149

3.7 %

1.76 [ 0.96, 3.22 ]

Qi 2000b

34/579

11/545

3.2 %

2.91 [ 1.49, 5.68 ]

Sang 1999

72/599

36/599

6.4 %

2.00 [ 1.36, 2.94 ]

Tan L 2003

8/50

6/50

1.7 %

1.33 [ 0.50, 3.56 ]

Wang J 2006

12/100

8/98

2.2 %

1.47 [ 0.63, 3.44 ]

Wang L 2004

102/594

72/594

8.3 %

1.42 [ 1.07, 1.87 ]

12/100

9/100

2.4 %

1.33 [ 0.59, 3.02 ]

6/49

5/49

1.4 %

1.20 [ 0.39, 3.67 ]

128/550

97/553

9.1 %

1.33 [ 1.05, 1.68 ]

137/1497

149/1499

9.4 %

0.92 [ 0.74, 1.15 ]

Xie HH 2010

7/52

8/53

1.9 %

0.89 [ 0.35, 2.28 ]

Zeng MY 2008

4/40

8/60

1.4 %

0.75 [ 0.24, 2.33 ]

Zhang Y 1998

7/99

11/192

2.0 %

1.23 [ 0.49, 3.08 ]

Zhang Y 2002

10/45

5/45

1.7 %

2.00 [ 0.74, 5.39 ]

9/89

8/89

2.0 %

1.13 [ 0.45, 2.78 ]

71/339

45/321

7.1 %

1.49 [ 1.06, 2.10 ]

5781

5501

100.0 %

1.28 [ 1.11, 1.47 ]

Cheng 1999a

Wang SZ 2001 Wang ZW 2008 WHO 1999 Xiao 2002

Zhao J 2003 Zuo 1999

Subtotal (95% CI)

Total events: 907 (Treatment), 644 (Control) Heterogeneity: Tau2 = 0.04; Chi2 = 45.59, df = 20 (P = 0.00092); I2 =56% Test for overall effect: Z = 3.42 (P = 0.00063)

0.01

0.1

Favours treatment

1

10

100

Favours control


163

Analysis 11.1. Comparison 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Cao 1999

0/147

2/136

9.3 %

0.19 [ 0.01, 3.82 ]

Chen 2002

2/154

4/148

14.6 %

0.48 [ 0.09, 2.58 ]

Cheng 1999a

2/214

1/214

3.6 %

2.00 [ 0.18, 21.89 ]

Fang 2000

0/100

1/100

5.4 %

0.33 [ 0.01, 8.09 ]

Han 1996

0/100

1/99

5.4 %

0.33 [ 0.01, 8.01 ]

Li 2000

0/79

2/78

9.0 %

0.20 [ 0.01, 4.05 ]

Li H 2000

0/30

1/30

5.4 %

0.33 [ 0.01, 7.87 ]

1/147

2/136

7.5 %

0.46 [ 0.04, 5.04 ]

Tan 1999

2/83

0/62

2.0 %

3.75 [ 0.18, 76.75 ]

Xie 1998

8/200

5/200

17.9 %

1.60 [ 0.53, 4.81 ]

0/40

1/52

4.7 %

0.43 [ 0.02, 10.31 ]

1/212

3/182

11.6 %

0.29 [ 0.03, 2.73 ]

1/90

1/90

3.6 %

1.00 [ 0.06, 15.74 ]

1596

1527

100.0 %

0.72 [ 0.41, 1.27 ]

Lou C 2002

Yang F 2003 Zhang JQ 2000 Zhao J 2003

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI




1



164

Analysis 11.3. Comparison 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg), Outcome 3 Any side effect. Review:


Comparison: 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg) Outcome: 3 Any side effect

Study or subgroup

Treatment

Control

n/N

n/N

Cao 1999

10/147

7/136

9.4 %

1.32 [ 0.52, 3.37 ]

Cheng 1999a

55/210

36/208

46.5 %

1.51 [ 1.04, 2.20 ]

7/100

4/99

5.2 %

1.73 [ 0.52, 5.73 ]

Lou C 2002

26/147

9/136

12.0 %

2.67 [ 1.30, 5.50 ]

Yang F 2003

4/50

5/52

6.3 %

0.83 [ 0.24, 2.92 ]

Zhao J 2003

39/90

16/90

20.6 %

2.44 [ 1.47, 4.03 ]

744

721

100.0 %

1.79 [ 1.39, 2.31 ]

Han 1996

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI


Total events: 141 (Treatment), 77 (Control) Heterogeneity: Chi2 = 5.24, df = 5 (P = 0.39); I2 =5% Test for overall effect: Z = 4.54 (P < 0.00001) Test for subgroup differences: Not applicable


1



165

Analysis 11.4. Comparison 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg), Outcome 4 Specific side effects. Review:


Comparison: 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg) Outcome: 4 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

13/210

14/208

100.0 %

0.92 [ 0.44, 1.91 ]

210

208

100.0 %

0.92 [ 0.44, 1.91 ]

0/210

2/208

100.0 %

0.20 [ 0.01, 4.10 ]

210

208

100.0 %

0.20 [ 0.01, 4.10 ]

2/210

5/208

100.0 %

0.40 [ 0.08, 2.02 ]

210

208

100.0 %

0.40 [ 0.08, 2.02 ]

3/210

4/208

100.0 %

0.74 [ 0.17, 3.28 ]

210

208

100.0 %

0.74 [ 0.17, 3.28 ]

9/210

6/208

100.0 %

1.49 [ 0.54, 4.10 ]

210

208

100.0 %

1.49 [ 0.54, 4.10 ]

1/210

0/208

100.0 %

2.97 [ 0.12, 72.53 ]

210

208

100.0 %

2.97 [ 0.12, 72.53 ]

M-H,Fixed,95% CI


1 Nausea Cheng 1999a

Subtotal (95% CI)

Total events: 13 (Treatment), 14 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.22 (P = 0.82) 2 Vomiting Cheng 1999a


Test for overall effect: Z = 1.05 (P = 0.30) 3 Breast tenderness Cheng 1999a


Test for overall effect: Z = 1.11 (P = 0.27) 4 Headache Cheng 1999a


Test for overall effect: Z = 0.39 (P = 0.69) 5 Dizziness Cheng 1999a


Test for overall effect: Z = 0.76 (P = 0.44) 6 Fatigue Cheng 1999a

Subtotal (95% CI)


1


(Continued . . . )


166


Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 1 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.67 (P = 0.50) 7 Abdominal pain Cheng 1999a

17/210

8/208

100.0 %

2.10 [ 0.93, 4.77 ]

210

208

100.0 %

2.10 [ 0.93, 4.77 ]

9/89

5/89

100.0 %

1.80 [ 0.63, 5.16 ]

89

89

100.0 %

1.80 [ 0.63, 5.16 ]

25/210

13/208

52.0 %

1.90 [ 1.00, 3.62 ]

9/100

12/99

48.0 %

0.74 [ 0.33, 1.68 ]

310

307

100.0 %

1.35 [ 0.82, 2.20 ]

Subtotal (95% CI)

Total events: 17 (Treatment), 8 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.78 (P = 0.075) 8 Early menses Zhao J 2003

Subtotal (95% CI) Total events: 9 (Treatment), 5 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.09 (P = 0.27) 9 Spotting/bleeding after treatment Cheng 1999a Han 1996

Subtotal (95% CI)



1



167

Analysis 11.5. Comparison 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg), Outcome 5 Delay in menses. Review:


Comparison: 11 Mifepristone mid-dose (50 mg) versus mifepristone mid-dose (25 mg) Outcome: 5 Delay in menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

54/210

57/208

31.4 %

0.94 [ 0.68, 1.29 ]

Fang 2000

3/100

2/99

1.1 %

1.49 [ 0.25, 8.70 ]

Han 1996

15/100

12/99

6.6 %

1.24 [ 0.61, 2.51 ]

410

406

39.1 %

1.00 [ 0.75, 1.34 ]

8/40

10/52

4.8 %

1.04 [ 0.45, 2.39 ]

40

52

4.8 %

1.04 [ 0.45, 2.39 ]

Cao 1999

43/147

38/136

21.6 %

1.05 [ 0.72, 1.51 ]

Chen 2002

30/152

21/144

11.8 %

1.35 [ 0.81, 2.25 ]

Lou C 2002

53/146

31/134

17.7 %

1.57 [ 1.08, 2.29 ]

Zhao J 2003

39/89

9/89

4.9 %

4.33 [ 2.23, 8.41 ]

534

503

56.1 %

1.57 [ 1.26, 1.94 ]

961

100.0 %

1.32 [ 1.12, 1.56 ]

M-H,Fixed,95% CI


1 > 3 days Cheng 1999a

Subtotal (95% CI)

Total events: 72 (Treatment), 71 (Control) Heterogeneity: Chi2 = 0.70, df = 2 (P = 0.71); I2 =0.0% Test for overall effect: Z = 0.03 (P = 0.98) 2 > 5 days Yang F 2003

Subtotal (95% CI) Total events: 8 (Treatment), 10 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.09 (P = 0.93) 3 > 7 days

Subtotal (95% CI)


Total (95% CI)

984



1



168

Analysis 12.1. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Cao 1999

0/120

8/140

0.07 [ 0.00, 1.18 ]

Ding 2005

1/78

1/74

0.95 [ 0.06, 14.89 ]

Tan L 2003

0/50

1/50

0.33 [ 0.01, 7.99 ]

WHO 1999

7/559

7/565

1.01 [ 0.36, 2.86 ]

Zhang Y 2002

0/45

0/45

0.0 [ 0.0, 0.0 ]

Total (95% CI)

852

874

0.52 [ 0.23, 1.17 ]

M-H,Fixed,95% CI





1


169

Analysis 12.2. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 2 Observed number of pregnancies (by risk status). Review:


Comparison: 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg) Outcome: 2 Observed number of pregnancies (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

5/553

5/549

100.0 %

0.99 [ 0.29, 3.41 ]

553

549

100.0 %

0.99 [ 0.29, 3.41 ]

549

100.0 %

0.99 [ 0.29, 3.41 ]

M-H,Fixed,95% CI


1 High-risk women

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Low-risk women WHO 1999



Total (95% CI)

553



1



170

Analysis 12.3. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 3 Any side effect. Review:


Comparison: 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg) Outcome: 3 Any side effect

Study or subgroup

Treatment

Control

n/N

n/N

Cao 1999

21/120

0/140

10.3 %

50.11 [ 3.07, 818.51 ]

Ding 2005

23/78

1/74

22.9 %

21.82 [ 3.02, 157.52 ]

Tan L 2003

13/50

3/50

66.8 %

4.33 [ 1.31, 14.28 ]

248

264

100.0 %

13.04 [ 5.13, 33.15 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI




1



171

Analysis 12.4. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 4 Specific side effects. Review:


Comparison: 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg) Outcome: 4 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

5/45

3/45

100.0 %

1.67 [ 0.42, 6.56 ]

45

45

100.0 %

1.67 [ 0.42, 6.56 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

2/45

0/45

100.0 %

5.00 [ 0.25, 101.31 ]

45

45

100.0 %

5.00 [ 0.25, 101.31 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

3/45

2/45

100.0 %

1.50 [ 0.26, 8.55 ]

45

45

100.0 %

1.50 [ 0.26, 8.55 ]

135/558

110/562

99.5 %

1.24 [ 0.99, 1.54 ]

2/45

0/45

0.5 %

5.00 [ 0.25, 101.31 ]

603

607

100.0 %

1.25 [ 1.00, 1.56 ]

M-H,Fixed,95% CI


1 Nausea Zhang Y 2002

Subtotal (95% CI) Total events: 5 (Treatment), 3 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.73 (P = 0.47) 2 Vomiting

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 3 Breast tenderness Zhang Y 2002

Subtotal (95% CI) Total events: 2 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.05 (P = 0.29) 4 Headache

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 5 Dizziness Zhang Y 2002

Subtotal (95% CI) Total events: 3 (Treatment), 2 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.46 (P = 0.65) 6 Fatigue WHO 1999 Zhang Y 2002

Subtotal (95% CI)



1


(Continued . . . )


172


Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Heterogeneity: Chi2 = 0.83, df = 1 (P = 0.36); I2 =0.0% Test for overall effect: Z = 1.99 (P = 0.046) 7 Abdominal pain

Subtotal (95% CI)

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

3/45

2/45

100.0 %

1.50 [ 0.26, 8.55 ]

45

45

100.0 %

1.50 [ 0.26, 8.55 ]

5/50

1/50

1.2 %

5.00 [ 0.61, 41.28 ]

198/559

86/565

98.8 %

2.33 [ 1.86, 2.91 ]

609

615

100.0 %

2.36 [ 1.89, 2.95 ]

Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 8 Diarrhoea Zhang Y 2002

Subtotal (95% CI) Total events: 3 (Treatment), 2 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.46 (P = 0.65) 9 Spotting/bleeding after treatment Tan L 2003 WHO 1999

Subtotal (95% CI)



1



173

Analysis 12.5. Comparison 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg), Outcome 5 Menses. Review:


Comparison: 12 Mifepristone high-dose (> 50 mg) versus mifepristone low-dose (< 25 mg) Outcome: 5 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

Cao 1999

41/120

34/140

22.6 %

1.41 [ 0.96, 2.06 ]

Tan L 2003

14/50

6/50

4.3 %

2.33 [ 0.98, 5.58 ]

196/559

97/565

69.5 %

2.04 [ 1.65, 2.53 ]

20/45

5/45

3.6 %

4.00 [ 1.64, 9.73 ]

774

800

100.0 %

1.98 [ 1.66, 2.37 ]

800

100.0 %

1.98 [ 1.66, 2.37 ]

M-H,Fixed,95% CI


1 Early

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Delay

WHO 1999 Zhang Y 2002

Subtotal (95% CI)


Total (95% CI)

774



1



174

Analysis 13.1. Comparison 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Cao 1999

0/120

2/283

0.47 [ 0.02, 9.71 ]

Ding 2005

1/78

1/77

0.99 [ 0.06, 15.50 ]

Li H 2000

0/30

1/60

0.66 [ 0.03, 15.64 ]

Qian 1999

1/86

1/166

1.93 [ 0.12, 30.48 ]

Tan L 2003

0/50

0/50

0.0 [ 0.0, 0.0 ]

WHO 1999

7/559

6/560

1.17 [ 0.40, 3.46 ]

Xie 1998

5/200

13/400

0.77 [ 0.28, 2.13 ]

Zhang Y 2002

0/45

0/45

0.0 [ 0.0, 0.0 ]

Zheng A 2005

2/100

2/100

1.00 [ 0.14, 6.96 ]

Total (95% CI)

1268

1741

0.93 [ 0.50, 1.72 ]

M-H,Fixed,95% CI





1


175

Analysis 13.3. Comparison 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg), Outcome 3 Any side effect. Review:


Comparison: 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg) Outcome: 3 Any side effect

Study or subgroup

Treatment

Control


Weight


n/N

n/N

Cao 1999

21/120

17/283

23.8 %

2.91 [ 1.59, 5.32 ]

Ding 2005

23/78

14/77

24.2 %

1.62 [ 0.90, 2.91 ]

Qian 1999

22/86

5/166

16.3 %

8.49 [ 3.33, 21.64 ]

Tan L 2003

13/50

6/50

17.3 %

2.17 [ 0.89, 5.25 ]

15/200

8/200

18.3 %

1.88 [ 0.81, 4.32 ]

534

776

100.0 %

2.64 [ 1.57, 4.43 ]

Xie 1998

Total (95% CI)


0.01

0.1

Favours treatment

1

10

100

Favours control


176

Analysis 13.4. Comparison 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg), Outcome 4 Specific side effects. Review:


Comparison: 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg) Outcome: 4 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

5/45

4/45

100.0 %

1.25 [ 0.36, 4.35 ]

45

45

100.0 %

1.25 [ 0.36, 4.35 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

2/45

1/45

100.0 %

2.00 [ 0.19, 21.28 ]

45

45

100.0 %

2.00 [ 0.19, 21.28 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

3/45

3/45

100.0 %

1.00 [ 0.21, 4.69 ]

45

45

100.0 %

1.00 [ 0.21, 4.69 ]

2/45

1/45

100.0 %

2.00 [ 0.19, 21.28 ]

45

45

100.0 %

2.00 [ 0.19, 21.28 ]

M-H,Fixed,95% CI


1 Nausea Zhang Y 2002

Subtotal (95% CI) Total events: 5 (Treatment), 4 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.35 (P = 0.73) 2 Vomiting

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 3 Breast tenderness Zhang Y 2002

Subtotal (95% CI) Total events: 2 (Treatment), 1 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.57 (P = 0.57) 4 Headache

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 5 Dizziness Zhang Y 2002

Subtotal (95% CI) Total events: 3 (Treatment), 3 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 6 Fatigue Zhang Y 2002


0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


177


Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Test for overall effect: Z = 0.57 (P = 0.57) 7 Abdominal pain

Subtotal (95% CI)

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

3/45

3/45

100.0 %

1.00 [ 0.21, 4.69 ]

45

45

100.0 %

1.00 [ 0.21, 4.69 ]

Li H 2000

3/30

1/60

0.4 %

6.00 [ 0.65, 55.26 ]

Tan L 2003

5/50

2/50

1.1 %

2.50 [ 0.51, 12.29 ]

198/559

172/560

97.9 %

1.15 [ 0.98, 1.36 ]

25/100

1/100

0.6 %

25.00 [ 3.45, 180.97 ]

739

770

100.0 %

1.32 [ 1.12, 1.56 ]

Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 8 Diarrhoea Zhang Y 2002

Subtotal (95% CI) Total events: 3 (Treatment), 3 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 9 Spotting/bleeding after treatment

WHO 1999 Zheng A 2005

Subtotal (95% CI)


0.01

0.1

Favours treatment

1

10

100

Favours control


178

Analysis 13.5. Comparison 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg), Outcome 5 Menses. Review:


Comparison: 13 Mifepristone high-dose (> 50 mg) versus mifepristone mid-doses (25-50 mg) Outcome: 5 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Risk Ratio

Zhang Y 2002

0/45

0/45

0.0 [ 0.0, 0.0 ]

Zheng A 2005

10/100

1/100

10.00 [ 1.30, 76.66 ]

145

145

10.00 [ 1.30, 76.66 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

1 Early


Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0% Test for overall effect: Z = 2.22 (P = 0.027) 2 Delay Cao 1999

41/120

81/283

1.19 [ 0.88, 1.63 ]

Li H 2000

5/30

4/60

2.50 [ 0.72, 8.64 ]

Qian 1999

18/86

20/166

1.74 [ 0.97, 3.11 ]

Tan L 2003

14/50

8/50

1.75 [ 0.81, 3.80 ]

196/559

128/560

1.53 [ 1.27, 1.85 ]

42/200

53/400

1.58 [ 1.10, 2.29 ]

Zhang Y 2002

20/45

10/45

2.00 [ 1.06, 3.78 ]

Zheng A 2005

20/100

12/100

1.67 [ 0.86, 3.22 ]

1190

1664

1.53 [ 1.34, 1.75 ]

1809

1.56 [ 1.37, 1.78 ]

WHO 1999 Xie 1998

Subtotal (95% CI)


Total (95% CI)

1335

Total events: 366 (Treatment), 317 (Control) Heterogeneity: Chi2 = 7.52, df = 8 (P = 0.48); I2 =0.0% Test for overall effect: Z = 6.54 (P < 0.00001) Test for subgroup differences: Chi2 = 3.25, df = 1 (P = 0.07), I2 =69%

0.1 0.2

0.5

Favours treatment


1

2

5

10

Favours control

179

Analysis 14.1. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 14 Mifepristone (all doses) versus Yuzpe Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Ashok 2002

3/487

17/471

63.2 %

0.17 [ 0.05, 0.58 ]

Glasier 1992

0/402

4/398

16.5 %

0.11 [ 0.01, 2.04 ]

Webb 1992

0/195

5/191

20.3 %

0.09 [ 0.00, 1.60 ]

1084

1060

100.0 %

0.14 [ 0.05, 0.41 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI




1



180

Analysis 14.2. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 2 Observed number of pregnancies (by risk status). Review:


Comparison: 14 Mifepristone (all doses) versus Yuzpe Outcome: 2 Observed number of pregnancies (by risk status)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

0/167

4/155

0.10 [ 0.01, 1.90 ]

167

155

0.10 [ 0.01, 1.90 ]

0/235

0/243

0.0 [ 0.0, 0.0 ]

235

243

0.0 [ 0.0, 0.0 ]

402

398

0.10 [ 0.01, 1.90 ]

M-H,Fixed,95% CI


1 High-risk women Glasier 1992

Subtotal (95% CI) Total events: 0 (Treatment), 4 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.53 (P = 0.13) 2 Low-risk women Glasier 1992

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P < 0.00001)

Total (95% CI) Total events: 0 (Treatment), 4 (Control)

Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0% Test for overall effect: Z = 1.53 (P = 0.13) Test for subgroup differences: Not applicable



1


181

Analysis 14.3. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 3 Observed number of pregnancies (time from intercourse). Review:


Comparison: 14 Mifepristone (all doses) versus Yuzpe Outcome: 3 Observed number of pregnancies (time from intercourse)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0/135

3/134

19.5 %

0.14 [ 0.01, 2.72 ]

135

134

19.5 %

0.14 [ 0.01, 2.72 ]

1/212

7/217

38.5 %

0.15 [ 0.02, 1.18 ]

212

217

38.5 %

0.15 [ 0.02, 1.18 ]

2/140

7/120

42.0 %

0.24 [ 0.05, 1.16 ]

140

120

42.0 %

0.24 [ 0.05, 1.16 ]

471

100.0 %

0.19 [ 0.06, 0.59 ]

M-H,Fixed,95% CI


1 within 24 h Ashok 2002


Test for overall effect: Z = 1.30 (P = 0.19) 2 25-48 h Ashok 2002


Test for overall effect: Z = 1.81 (P = 0.071) 3 49-72 h Ashok 2002



Total (95% CI)

487


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


182

Analysis 14.4. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 4 Need for extra dose. Review:


Comparison: 14 Mifepristone (all doses) versus Yuzpe Outcome: 4 Need for extra dose

Study or subgroup

Ashok 2002

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

2/487

17/471

100.0 %

0.11 [ 0.03, 0.49 ]

487

471

100.0 %

0.11 [ 0.03, 0.49 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 14.5. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 5 Any side effect. Review:


Comparison: 14 Mifepristone (all doses) versus Yuzpe Outcome: 5 Any side effect

Study or subgroup

Treatment

Control

n/N

n/N

Ashok 2002

299/500

321/500

51.6 %

0.93 [ 0.85, 1.03 ]

Glasier 1992

215/347

301/346

48.4 %

0.71 [ 0.65, 0.78 ]

847

846

100.0 %

0.83 [ 0.77, 0.88 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI




1



183

Analysis 14.6. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 6 Specific side effects. Review:


Comparison: 14 Mifepristone (all doses) versus Yuzpe Outcome: 6 Specific side effects

Study or subgroup

Treatment

Control


Weight


n/N

n/N

Ashok 2002

91/500

122/500

28.4 %

0.75 [ 0.59, 0.95 ]

Glasier 1992

137/402

207/398

38.7 %

0.66 [ 0.56, 0.77 ]

Webb 1992

72/195

133/191

32.9 %

0.53 [ 0.43, 0.65 ]

1097

1089

100.0 %

0.63 [ 0.53, 0.76 ]

1 Nausea

Subtotal (95% CI)

Total events: 300 (Treatment), 462 (Control) Heterogeneity: Tau2 = 0.02; Chi2 = 4.87, df = 2 (P = 0.09); I2 =59% Test for overall effect: Z = 4.90 (P < 0.00001) 2 Vomiting Ashok 2002

3/500

46/500

18.2 %

0.07 [ 0.02, 0.21 ]

Glasier 1992

9/402

59/398

51.9 %

0.15 [ 0.08, 0.30 ]

Webb 1992

5/195

42/191

29.9 %

0.12 [ 0.05, 0.29 ]

1097

1089

100.0 %

0.12 [ 0.07, 0.20 ]

Subtotal (95% CI)

Total events: 17 (Treatment), 147 (Control) Heterogeneity: Tau2 = 0.0; Chi2 = 1.53, df = 2 (P = 0.47); I2 =0.0% Test for overall effect: Z = 8.39 (P < 0.00001) 3 Breast tenderness Ashok 2002

79/500

68/500

34.0 %

1.16 [ 0.86, 1.57 ]

Glasier 1992

94/402

158/398

36.4 %

0.59 [ 0.48, 0.73 ]

Webb 1992

34/195

34/191

29.6 %

0.98 [ 0.64, 1.51 ]

1097

1089

100.0 %

0.86 [ 0.54, 1.39 ]

Subtotal (95% CI)

Total events: 207 (Treatment), 260 (Control) Heterogeneity: Tau2 = 0.15; Chi2 = 14.52, df = 2 (P = 0.00070); I2 =86% Test for overall effect: Z = 0.61 (P = 0.54) 4 Headache Ashok 2002

83/500

97/500

35.2 %

0.86 [ 0.66, 1.12 ]

Glasier 1992

170/402

242/398

64.8 %

0.70 [ 0.61, 0.80 ]

902

898

100.0 %

0.75 [ 0.61, 0.91 ]

Subtotal (95% CI)

Total events: 253 (Treatment), 339 (Control) Heterogeneity: Tau2 = 0.01; Chi2 = 1.93, df = 1 (P = 0.16); I2 =48% Test for overall effect: Z = 2.86 (P = 0.0042)

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


184



Weight


Treatment

Control

n/N

n/N

52/500

89/500

100.0 %

0.58 [ 0.42, 0.80 ]

500

500

100.0 %

0.58 [ 0.42, 0.80 ]

157/500

195/500

100.0 %

0.81 [ 0.68, 0.95 ]

500

500

100.0 %

0.81 [ 0.68, 0.95 ]

105/500

138/500

100.0 %

0.76 [ 0.61, 0.95 ]

500

500

100.0 %

0.76 [ 0.61, 0.95 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

41/500

71/500

100.0 %

0.58 [ 0.40, 0.83 ]

500

500

100.0 %

0.58 [ 0.40, 0.83 ]

91/500

122/500

100.0 %

0.75 [ 0.59, 0.95 ]

500

500

100.0 %

0.75 [ 0.59, 0.95 ]

5 Dizziness Ashok 2002

Subtotal (95% CI)

Total events: 52 (Treatment), 89 (Control) Heterogeneity: not applicable Test for overall effect: Z = 3.30 (P = 0.00096) 6 Fatigue Ashok 2002

Subtotal (95% CI)

Total events: 157 (Treatment), 195 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.50 (P = 0.012) 7 Abdominal pain Ashok 2002

Subtotal (95% CI)

Total events: 105 (Treatment), 138 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.42 (P = 0.016) 8 Spotting/bleeding after treatment

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 9 Hot flushes Ashok 2002

Subtotal (95% CI)

Total events: 41 (Treatment), 71 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.96 (P = 0.0031) 10 Lethargy Ashok 2002

Subtotal (95% CI)


0.01

0.1

Favours treatment

1

10

100

Favours control


185

Analysis 14.7. Comparison 14 Mifepristone (all doses) versus Yuzpe, Outcome 7 Menses. Review:


Comparison: 14 Mifepristone (all doses) versus Yuzpe Outcome: 7 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

Ashok 2002

93/380

47/358

45.8 %

1.86 [ 1.35, 2.57 ]

Glasier 1992

137/402

45/398

42.8 %

3.01 [ 2.22, 4.10 ]

Webb 1992

73/195

12/191

11.5 %

5.96 [ 3.35, 10.61 ]

977

947

100.0 %

2.83 [ 2.30, 3.47 ]

M-H,Fixed,95% CI


1 Early

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Delay

Subtotal (95% CI)



1



186

Analysis 15.1. Comparison 15 Mifepristone (all doses) versus danazol (all doses), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 15 Mifepristone (all doses) versus danazol (all doses) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Webb 1992

0/195

9/193

65.5 %

0.05 [ 0.00, 0.89 ]

Yang 2001

1/121

5/120

34.5 %

0.20 [ 0.02, 1.67 ]

316

313

100.0 %

0.10 [ 0.02, 0.55 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 15.2. Comparison 15 Mifepristone (all doses) versus danazol (all doses), Outcome 2 Any side effect. Review:


Comparison: 15 Mifepristone (all doses) versus danazol (all doses) Outcome: 2 Any side effect

Study or subgroup

Yang 2001

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

5/121

14/120

100.0 %

0.35 [ 0.13, 0.95 ]

121

120

100.0 %

0.35 [ 0.13, 0.95 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


187

Analysis 15.3. Comparison 15 Mifepristone (all doses) versus danazol (all doses), Outcome 3 Specific side effect. Review:


Comparison: 15 Mifepristone (all doses) versus danazol (all doses) Outcome: 3 Specific side effect

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

72/197

58/193

100.0 %

1.22 [ 0.92, 1.61 ]

197

193

100.0 %

1.22 [ 0.92, 1.61 ]

5/197

6/193

100.0 %

0.82 [ 0.25, 2.63 ]

197

193

100.0 %

0.82 [ 0.25, 2.63 ]

34/197

39/193

100.0 %

0.85 [ 0.56, 1.29 ]

197

193

100.0 %

0.85 [ 0.56, 1.29 ]

3/197

1/193

100.0 %

2.94 [ 0.31, 28.01 ]

197

193

100.0 %

2.94 [ 0.31, 28.01 ]

M-H,Fixed,95% CI


1 Nausea Webb 1992

Subtotal (95% CI)

Total events: 72 (Treatment), 58 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.35 (P = 0.18) 2 Vomiting Webb 1992


Test for overall effect: Z = 0.34 (P = 0.73) 3 Breast tenderness Webb 1992

Subtotal (95% CI)

Total events: 34 (Treatment), 39 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.75 (P = 0.46) 4 Others Webb 1992



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


188

Analysis 15.4. Comparison 15 Mifepristone (all doses) versus danazol (all doses), Outcome 4 Menses. Review:


Comparison: 15 Mifepristone (all doses) versus danazol (all doses) Outcome: 4 Menses

Study or subgroup

Treatment

Control


Weight


n/N

n/N

Webb 1992

49/188

10/192

49.5 %

5.00 [ 2.61, 9.58 ]

Yang 2001

21/121

18/120

50.5 %

1.16 [ 0.65, 2.06 ]

309

312

100.0 %

2.39 [ 0.56, 10.27 ]

1 Delay

Total (95% CI)


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


189

Analysis 16.1. Comparison 16 Mifepristone (all doses) versus anordrin (all doses), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 16 Mifepristone (all doses) versus anordrin (all doses) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Chen 2001

0/47

2/41

11.8 %

0.18 [ 0.01, 3.54 ]

Fu X 2000

1/96

3/90

13.7 %

0.31 [ 0.03, 2.95 ]

Han 1995

0/46

2/47

11.0 %

0.20 [ 0.01, 4.14 ]

Liu L 2001

0/76

3/66

16.6 %

0.12 [ 0.01, 2.36 ]

Wang 1999

0/52

3/56

15.0 %

0.15 [ 0.01, 2.90 ]

Xu Z 2000

2/94

3/86

13.9 %

0.61 [ 0.10, 3.56 ]

Yang 2001

1/121

4/117

18.0 %

0.24 [ 0.03, 2.13 ]

532

503

100.0 %

0.26 [ 0.11, 0.63 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.001 0.01 0.1 Favours Treatment

1

10 100 1000 Favours Control


190

Analysis 16.3. Comparison 16 Mifepristone (all doses) versus anordrin (all doses), Outcome 3 Any side effect. Review:


Comparison: 16 Mifepristone (all doses) versus anordrin (all doses) Outcome: 3 Any side effect

Study or subgroup

Treatment

Control

n/N

n/N

Fu X 2000

27/96

25/90

46.1 %

1.01 [ 0.64, 1.61 ]

Liu L 2001

2/76

8/66

15.3 %

0.22 [ 0.05, 0.99 ]

Xu Z 2000

2/94

8/86

14.9 %

0.23 [ 0.05, 1.05 ]

Yang 2001

5/121

13/117

23.6 %

0.37 [ 0.14, 1.01 ]

387

359

100.0 %

0.62 [ 0.43, 0.91 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1

Favours Treatment

1

10

100

Favours Control


191

Analysis 16.4. Comparison 16 Mifepristone (all doses) versus anordrin (all doses), Outcome 4 Specific side effects. Review:


Comparison: 16 Mifepristone (all doses) versus anordrin (all doses) Outcome: 4 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI


1 Nausea

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Vomiting

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 3 Breast tenderness

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 4 Headache



Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 7 Abdominal pain


0.01

0.1

Favours Treatment

1

10

100

Favours Control

(Continued . . . )


192


Risk Ratio

Weight


Treatment

Control

n/N

n/N

Han 1995

6/46

2/47

32.7 %

3.07 [ 0.65, 14.41 ]

Yang 2001

5/121

4/117

67.3 %

1.21 [ 0.33, 4.39 ]

167

164

100.0 %

1.82 [ 0.69, 4.77 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

8 Spotting/bleeding after treatment



0.01

0.1

1

Favours Treatment

10

100

Favours Control

Analysis 16.5. Comparison 16 Mifepristone (all doses) versus anordrin (all doses), Outcome 5 Menses. Review:


Comparison: 16 Mifepristone (all doses) versus anordrin (all doses) Outcome: 5 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Fu X 2000

23/95

2/87

4.7 %

10.53 [ 2.56, 43.37 ]

Liu L 2001

4/76

12/63

29.8 %

0.28 [ 0.09, 0.81 ]

Wang 1999

4/52

12/56

26.2 %

0.36 [ 0.12, 1.04 ]

21/121

17/117

39.2 %

1.19 [ 0.66, 2.15 ]

344

323

100.0 %

1.14 [ 0.78, 1.68 ]

M-H,Fixed,95% CI


1 Delay

Yang 2001

Total (95% CI)


0.001 0.01 0.1 Favours Treatment

1

10 100 1000 Favours Control


193

Analysis 17.1. Comparison 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Han 1995

0/46

0/47

0.0 [ 0.0, 0.0 ]

Han 1996

1/199

1/101

0.51 [ 0.03, 8.03 ]

3/76

1/66

2.61 [ 0.28, 24.45 ]

21/1198

16/1189

1.30 [ 0.68, 2.48 ]

0/58

0/58

0.0 [ 0.0, 0.0 ]

1577

1461

1.32 [ 0.73, 2.41 ]

Lou X 2005 Sang 1999 Zhang YM 2002

Total (95% CI)






1


194

Analysis 17.3. Comparison 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses), Outcome 3 Any side effect. Review:


Comparison: 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses) Outcome: 3 Any side effect

Study or subgroup

Han 1996 Lou X 2005

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

11/199

8/101

41.5 %

0.70 [ 0.29, 1.68 ]

15/76

14/66

58.5 %

0.93 [ 0.49, 1.78 ]

275

167

100.0 %

0.83 [ 0.49, 1.41 ]

M-H,Fixed,95% CI



0.01

0.1

Favours treatment

1

10

100

Favours control


195

Analysis 17.4. Comparison 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses), Outcome 4 Specific side effects. Review:


Comparison: 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses) Outcome: 4 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

128/1198

239/1189

100.0 %

0.53 [ 0.44, 0.65 ]

1198

1189

100.0 %

0.53 [ 0.44, 0.65 ]

12/1198

45/1189

100.0 %

0.26 [ 0.14, 0.50 ]

1198

1189

100.0 %

0.26 [ 0.14, 0.50 ]

58/1198

62/1189

100.0 %

0.93 [ 0.65, 1.32 ]

1198

1189

100.0 %

0.93 [ 0.65, 1.32 ]

36/1198

44/1189

100.0 %

0.81 [ 0.53, 1.25 ]

1198

1189

100.0 %

0.81 [ 0.53, 1.25 ]

51/1198

66/1189

100.0 %

0.77 [ 0.54, 1.10 ]

1198

1189

100.0 %

0.77 [ 0.54, 1.10 ]

68/1198

102/1189

100.0 %

0.66 [ 0.49, 0.89 ]

1198

1189

100.0 %

0.66 [ 0.49, 0.89 ]

M-H,Fixed,95% CI


1 Nausea Sang 1999

Subtotal (95% CI)

Total events: 128 (Treatment), 239 (Control) Heterogeneity: not applicable Test for overall effect: Z = 6.22 (P < 0.00001) 2 Vomiting Sang 1999

Subtotal (95% CI)

Total events: 12 (Treatment), 45 (Control) Heterogeneity: not applicable Test for overall effect: Z = 4.12 (P = 0.000037) 3 Breast tenderness Sang 1999

Subtotal (95% CI)

Total events: 58 (Treatment), 62 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.42 (P = 0.68) 4 Headache Sang 1999

Subtotal (95% CI)

Total events: 36 (Treatment), 44 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.94 (P = 0.35) 5 Dizziness Sang 1999

Subtotal (95% CI)

Total events: 51 (Treatment), 66 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.46 (P = 0.14) 6 Fatigue Sang 1999

Subtotal (95% CI)

0.01

0.1

Favours treatment

1

10

100

Favours control

(Continued . . . )


196


Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 68 (Treatment), 102 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.73 (P = 0.0063) 7 Abdominal pain Sang 1999

64/1198

54/1189

100.0 %

1.18 [ 0.83, 1.67 ]

1198

1189

100.0 %

1.18 [ 0.83, 1.67 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

Han 1995

6/46

0/47

0.8 %

13.28 [ 0.77, 229.11 ]

Han 1996

12/199

0/101

1.0 %

12.75 [ 0.76, 213.18 ]

2/66

8/76

11.7 %

0.29 [ 0.06, 1.31 ]

95/1198

49/1189

77.1 %

1.92 [ 1.38, 2.69 ]

3/58

6/58

9.4 %

0.50 [ 0.13, 1.90 ]

1567

1471

100.0 %

1.80 [ 1.33, 2.43 ]

Subtotal (95% CI)

Total events: 64 (Treatment), 54 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.90 (P = 0.37) 8 Diarrhoea


Lou X 2005 Sang 1999 Zhang YM 2002

Subtotal (95% CI)


0.01

0.1

Favours treatment

1

10

100

Favours control


197

Analysis 17.5. Comparison 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses), Outcome 5 Delay in menses. Review:


Comparison: 17 Mifepristone alone (all doses) versus mifepristone + anordrin (all doses) Outcome: 5 Delay in menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

27/199

20/101

13.7 %

0.69 [ 0.40, 1.16 ]

9/73

5/65

2.7 %

1.60 [ 0.57, 4.54 ]

127/1170

162/1173

83.6 %

0.79 [ 0.63, 0.98 ]

1442

1339

100.0 %

0.79 [ 0.65, 0.97 ]

1339

100.0 %

0.79 [ 0.65, 0.97 ]

M-H,Fixed,95% CI


1 Early

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Delay Han 1996 Lou X 2005 Sang 1999

Subtotal (95% CI)


Total (95% CI)

1442


0.01

0.1

Favours treatment

1

10

100

Favours control


198

Analysis 18.1. Comparison 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses), Outcome 1 Observed number of pregnancy (all women). Review:


Comparison: 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses) Outcome: 1 Observed number of pregnancy (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Chen 2002a

1/50

0/50

50.0 %

3.00 [ 0.13, 71.92 ]

Zeng XY 2007

1/50

0/50

50.0 %

3.00 [ 0.13, 71.92 ]

Total (95% CI)

100

100

100.0 %

3.00 [ 0.32, 28.36 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 18.5. Comparison 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses), Outcome 5 Any side effect. Review:


Comparison: 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses) Outcome: 5 Any side effect

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Chen 2002a

4/50

6/50

50.0 %

0.67 [ 0.20, 2.22 ]

Zeng XY 2007

5/50

6/50

50.0 %

0.83 [ 0.27, 2.55 ]

Total (95% CI)

100

100

100.0 %

0.75 [ 0.33, 1.70 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


199

Analysis 18.6. Comparison 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses), Outcome 6 Menses. Review:


Comparison: 18 Mifepristone alone (all doses) versus mifepristone + MTX (all doses) Outcome: 6 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

3/50

2/50

6.3 %

1.50 [ 0.26, 8.60 ]

50

50

6.3 %

1.50 [ 0.26, 8.60 ]

7/50

8/50

25.2 %

0.88 [ 0.34, 2.23 ]

20/49

22/50

68.5 %

0.93 [ 0.59, 1.47 ]

99

100

93.7 %

0.91 [ 0.60, 1.39 ]

150

100.0 %

0.95 [ 0.63, 1.43 ]

M-H,Fixed,95% CI


1 Early Chen 2002a

Subtotal (95% CI) Total events: 3 (Treatment), 2 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.46 (P = 0.65) 2 Delay Chen 2002a Zeng XY 2007



Total (95% CI)

149


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


200

Analysis 19.1. Comparison 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

He CH 2002

3/200

1/200

100.0 %

3.00 [ 0.31, 28.60 ]

Total (95% CI)

200

200

100.0 %

3.00 [ 0.31, 28.60 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


201

Analysis 19.3. Comparison 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses), Outcome 3 Observed number of pregnancies (time from intercourse). Review:


Comparison: 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses) Outcome: 3 Observed number of pregnancies (time from intercourse)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

1/100

1/98

67.1 %

0.98 [ 0.06, 15.45 ]

100

98

67.1 %

0.98 [ 0.06, 15.45 ]

2/100

0/102

32.9 %

5.10 [ 0.25, 104.90 ]

100

102

32.9 %

5.10 [ 0.25, 104.90 ]

200

100.0 %

2.33 [ 0.35, 15.56 ]

M-H,Fixed,95% CI


1 Within 72 h He CH 2002


Test for overall effect: Z = 0.01 (P = 0.99) 2 Later than 72 h He CH 2002



Total (95% CI)

200


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


202

Analysis 19.6. Comparison 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses), Outcome 6 Specific side effect. Review:


Comparison: 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses) Outcome: 6 Specific side effect

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

14/200

19/200

100.0 %

0.74 [ 0.38, 1.43 ]

200

200

100.0 %

0.74 [ 0.38, 1.43 ]

2/200

1/200

100.0 %

2.00 [ 0.18, 21.88 ]

200

200

100.0 %

2.00 [ 0.18, 21.88 ]

1/200

2/200

100.0 %

0.50 [ 0.05, 5.47 ]

200

200

100.0 %

0.50 [ 0.05, 5.47 ]

1/200

0/200

100.0 %

3.00 [ 0.12, 73.20 ]

200

200

100.0 %

3.00 [ 0.12, 73.20 ]

2/200

0/200

100.0 %

5.00 [ 0.24, 103.49 ]

200

200

100.0 %

5.00 [ 0.24, 103.49 ]

7/200

6/200

100.0 %

1.17 [ 0.40, 3.41 ]

200

200

100.0 %

1.17 [ 0.40, 3.41 ]

M-H,Fixed,95% CI


1 Nausea He CH 2002

Subtotal (95% CI)

Total events: 14 (Treatment), 19 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.90 (P = 0.37) 2 Vomiting He CH 2002


Test for overall effect: Z = 0.57 (P = 0.57) 3 Breast tenderness He CH 2002


Test for overall effect: Z = 0.57 (P = 0.57) 4 Headache He CH 2002


Test for overall effect: Z = 0.67 (P = 0.50) 5 Dizziness He CH 2002


Test for overall effect: Z = 1.04 (P = 0.30) 6 Fatigue He CH 2002

Subtotal (95% CI)

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


203


Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 7 (Treatment), 6 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.28 (P = 0.78) 7 Abdominal pain He CH 2002

3/200

1/200

100.0 %

3.00 [ 0.31, 28.60 ]

200

200

100.0 %

3.00 [ 0.31, 28.60 ]

1/200

0/200

100.0 %

3.00 [ 0.12, 73.20 ]

200

200

100.0 %

3.00 [ 0.12, 73.20 ]

12/200

17/200

100.0 %

0.71 [ 0.35, 1.44 ]

200

200

100.0 %

0.71 [ 0.35, 1.44 ]

11/197

2/199

100.0 %

5.56 [ 1.25, 24.74 ]

197

199

100.0 %

5.56 [ 1.25, 24.74 ]


Test for overall effect: Z = 0.96 (P = 0.34) 8 Diarrhoea He CH 2002


Test for overall effect: Z = 0.67 (P = 0.50) 9 Spotting/bleeding after treatment He CH 2002

Subtotal (95% CI)

Total events: 12 (Treatment), 17 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.96 (P = 0.34) 10 Heavy menses He CH 2002

Subtotal (95% CI)


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


204

Analysis 19.7. Comparison 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses), Outcome 7 Menses. Review:


Comparison: 19 Mifepristone alone (all doses) versus mifepristone + tamoxifen (all doses) Outcome: 7 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

23/197

13/199

100.0 %

1.79 [ 0.93, 3.43 ]

197

199

100.0 %

1.79 [ 0.93, 3.43 ]

M-H,Fixed,95% CI


1 Delay He CH 2002

Total (95% CI)


0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 20.1. Comparison 20 Mifepristone versus mifepristone + misoprostol (all doses), Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 20 Mifepristone versus mifepristone + misoprostol (all doses) Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Wu 2002

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

7/300

2/299

100.0 %

3.49 [ 0.73, 16.65 ]

300

299

100.0 %

3.49 [ 0.73, 16.65 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


205

Analysis 20.6. Comparison 20 Mifepristone versus mifepristone + misoprostol (all doses), Outcome 6 Specific side effect. Review:


Comparison: 20 Mifepristone versus mifepristone + misoprostol (all doses) Outcome: 6 Specific side effect

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

19/300

22/299

100.0 %

0.86 [ 0.48, 1.56 ]

300

299

100.0 %

0.86 [ 0.48, 1.56 ]

1/300

2/299

100.0 %

0.50 [ 0.05, 5.47 ]

300

299

100.0 %

0.50 [ 0.05, 5.47 ]

0/300

2/299

100.0 %

0.20 [ 0.01, 4.13 ]

300

299

100.0 %

0.20 [ 0.01, 4.13 ]

1/300

2/299

100.0 %

0.50 [ 0.05, 5.47 ]

300

299

100.0 %

0.50 [ 0.05, 5.47 ]

2/300

4/299

100.0 %

0.50 [ 0.09, 2.70 ]

300

299

100.0 %

0.50 [ 0.09, 2.70 ]

M-H,Fixed,95% CI


1 Nausea Wu 2002

Subtotal (95% CI)

Total events: 19 (Treatment), 22 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.50 (P = 0.62) 2 Vomiting Wu 2002


Test for overall effect: Z = 0.57 (P = 0.57) 3 Breast tenderness Wu 2002


Test for overall effect: Z = 1.04 (P = 0.30) 4 Headache Wu 2002


Test for overall effect: Z = 0.57 (P = 0.57) 5 Dizziness Wu 2002


Test for overall effect: Z = 0.81 (P = 0.42) 6 Fatigue

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


206


Treatment

Control

Risk Ratio

Weight

n/N

n/N

1/300

1/299

100.0 %

1.00 [ 0.06, 15.86 ]

300

299

100.0 %

1.00 [ 0.06, 15.86 ]

4/300

13/299

100.0 %

0.31 [ 0.10, 0.93 ]

300

299

100.0 %

0.31 [ 0.10, 0.93 ]

1/300

4/299

100.0 %

0.25 [ 0.03, 2.22 ]

300

299

100.0 %

0.25 [ 0.03, 2.22 ]

19/300

31/299

100.0 %

0.61 [ 0.35, 1.06 ]

300

299

100.0 %

0.61 [ 0.35, 1.06 ]

Wu 2002

Subtotal (95% CI)

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Total events: 1 (Treatment), 1 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.00 (P = 1.0) 7 Abdominal pain Wu 2002

Subtotal (95% CI)

Total events: 4 (Treatment), 13 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.09 (P = 0.037) 8 Diarrhoea Wu 2002


Test for overall effect: Z = 1.25 (P = 0.21) 9 Spotting/bleeding after treatment Wu 2002

Subtotal (95% CI)


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


207

Analysis 21.1. Comparison 21 Mifepristone (all doses) versus copper intrauterine device, Outcome 1 Observed number of pregnancy (all women). Review:


Comparison: 21 Mifepristone (all doses) versus copper intrauterine device Outcome: 1 Observed number of pregnancy (all women)

Study or subgroup

Liu L 2002

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

1/190

0/95

100.0 %

1.51 [ 0.06, 36.67 ]

190

95

100.0 %

1.51 [ 0.06, 36.67 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 21.5. Comparison 21 Mifepristone (all doses) versus copper intrauterine device, Outcome 5 Any side effect. Review:


Comparison: 21 Mifepristone (all doses) versus copper intrauterine device Outcome: 5 Any side effect

Study or subgroup

Liu L 2002

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

16/190

0/95

100.0 %

16.59 [ 1.01, 273.52 ]

190

95

100.0 %

16.59 [ 1.01, 273.52 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


208

Analysis 21.6. Comparison 21 Mifepristone (all doses) versus copper intrauterine device, Outcome 6 Specific side effects. Review:


Comparison: 21 Mifepristone (all doses) versus copper intrauterine device Outcome: 6 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0/190

18/95

100.0 %

0.01 [ 0.00, 0.22 ]

190

95

100.0 %

0.01 [ 0.00, 0.22 ]

M-H,Fixed,95% CI


1 Nausea

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Vomiting

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 3 Breast tenderness

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 4 Headache



Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 7 Lower abdominal pain Liu L 2002


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


209


Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI

Test for overall effect: Z = 3.01 (P = 0.0026) 8 Diarrhoea

Subtotal (95% CI)

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 9 Spotting/bleeding after treatment

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 10 Heavy menses


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


210

Analysis 21.7. Comparison 21 Mifepristone (all doses) versus copper intrauterine device, Outcome 7 Menses. Review:


Comparison: 21 Mifepristone (all doses) versus copper intrauterine device Outcome: 7 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

34/189

4/95

100.0 %

4.27 [ 1.56, 11.69 ]

189

95

100.0 %

4.27 [ 1.56, 11.69 ]

95

100.0 %

4.27 [ 1.56, 11.69 ]

M-H,Fixed,95% CI


1 Early

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Delay Liu L 2002

Subtotal (95% CI)


Total (95% CI)

189


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


211

Analysis 22.1. Comparison 22 Mifepristone versus gestrinone, Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 22 Mifepristone versus gestrinone Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Wu 2010

Total (95% CI)

Experimental

Control

n/N

n/N

Risk Ratio

Weight

9/498

12/498

100.0 %

0.75 [ 0.32, 1.76 ]

498

498

100.0 %

0.75 [ 0.32, 1.76 ]

M-H,Fixed,95% CI


Total events: 9 (Experimental), 12 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.66 (P = 0.51) Test for subgroup differences: Not applicable

0.01

0.1


1

10

100

Favours control


212

Analysis 22.2. Comparison 22 Mifepristone versus gestrinone, Outcome 2 Side effects. Review:


Comparison: 22 Mifepristone versus gestrinone Outcome: 2 Side effects

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Weight

51/498

38/498

23.9 %

1.34 [ 0.90, 2.00 ]

498

498

23.9 %

1.34 [ 0.90, 2.00 ]

1/498

1/498

0.6 %

1.00 [ 0.06, 15.94 ]

498

498

0.6 %

1.00 [ 0.06, 15.94 ]

1/498

4/498

2.5 %

0.25 [ 0.03, 2.23 ]

498

498

2.5 %

0.25 [ 0.03, 2.23 ]

18/498

9/498

5.7 %

2.00 [ 0.91, 4.41 ]

498

498

5.7 %

2.00 [ 0.91, 4.41 ]

13/498

8/498

5.0 %

1.63 [ 0.68, 3.89 ]

498

498

5.0 %

1.63 [ 0.68, 3.89 ]

4/498

6/498

3.8 %

0.67 [ 0.19, 2.35 ]

498

498

3.8 %

0.67 [ 0.19, 2.35 ]

M-H,Fixed,95% CI


1 Nausea Wu 2010

Subtotal (95% CI)

Total events: 51 (Experimental), 38 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.44 (P = 0.15) 2 Vomiting Wu 2010

Subtotal (95% CI) Total events: 1 (Experimental), 1 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 3 Diarrhoea Wu 2010

Subtotal (95% CI) Total events: 1 (Experimental), 4 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.24 (P = 0.21) 4 Fatigue Wu 2010

Subtotal (95% CI)

Total events: 18 (Experimental), 9 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.72 (P = 0.086) 5 Dizziness Wu 2010

Subtotal (95% CI)

Total events: 13 (Experimental), 8 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.09 (P = 0.28) 6 Headache Wu 2010

Subtotal (95% CI) Total events: 4 (Experimental), 6 (Control)

0.01

0.1


1

10

100

Favours control

(Continued . . . )


213


Risk Ratio

Weight


Experimental

Control

n/N

n/N

4/498

7/498

4.4 %

0.57 [ 0.17, 1.94 ]

498

498

4.4 %

0.57 [ 0.17, 1.94 ]

8/498

9/498

5.7 %

0.89 [ 0.35, 2.29 ]

498

498

5.7 %

0.89 [ 0.35, 2.29 ]

72/498

77/498

48.4 %

0.94 [ 0.70, 1.26 ]

498

498

48.4 %

0.94 [ 0.70, 1.26 ]

4482

100.0 %

1.08 [ 0.88, 1.33 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

Heterogeneity: not applicable Test for overall effect: Z = 0.63 (P = 0.53) 7 Breast tenderness Wu 2010

Subtotal (95% CI) Total events: 4 (Experimental), 7 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.90 (P = 0.37) 8 Lower abdominal pain Wu 2010

Subtotal (95% CI) Total events: 8 (Experimental), 9 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.24 (P = 0.81) 9 Bleeding or spotting Wu 2010

Subtotal (95% CI)

Total events: 72 (Experimental), 77 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.44 (P = 0.66)

Total (95% CI)

4482

Total events: 172 (Experimental), 159 (Control) Heterogeneity: Chi2 = 8.70, df = 8 (P = 0.37); I2 =8% Test for overall effect: Z = 0.75 (P = 0.45) Test for subgroup differences: Chi2 = 8.70, df = 8 (P = 0.37), I2 =8%

0.01

0.1


1

10

100

Favours control


214

Analysis 22.3. Comparison 22 Mifepristone versus gestrinone, Outcome 3 Menses. Review:


Comparison: 22 Mifepristone versus gestrinone Outcome: 3 Menses

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Weight

13/489

35/486

33.7 %

0.37 [ 0.20, 0.69 ]

489

486

33.7 %

0.37 [ 0.20, 0.69 ]

95/489

69/486

66.3 %

1.37 [ 1.03, 1.82 ]

489

486

66.3 %

1.37 [ 1.03, 1.82 ]

972

100.0 %

1.03 [ 0.80, 1.33 ]

M-H,Fixed,95% CI


1 Early Wu 2010

Subtotal (95% CI)

Total events: 13 (Experimental), 35 (Control) Heterogeneity: not applicable Test for overall effect: Z = 3.13 (P = 0.0018) 2 Delay Wu 2010

Subtotal (95% CI)

Total events: 95 (Experimental), 69 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.17 (P = 0.030)

Total (95% CI)

978

Total events: 108 (Experimental), 104 (Control) Heterogeneity: Chi2 = 14.23, df = 1 (P = 0.00016); I2 =93% Test for overall effect: Z = 0.25 (P = 0.80) Test for subgroup differences: Chi2 = 14.03, df = 1 (P = 0.00), I2 =93%

0.01

0.1


1

10

100

Favours control


215

Analysis 23.3. Comparison 23 Danazol (all doses) versus Yuzpe, Outcome 3 Observed number of pregnancies (all women). Review:


Comparison: 23 Danazol (all doses) versus Yuzpe Outcome: 3 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

0/50

0/51

0.0 [ 0.0, 0.0 ]

9/193

5/191

1.78 [ 0.61, 5.22 ]

243

242

1.78 [ 0.61, 5.22 ]

Rowlands 1983 Webb 1992

Total (95% CI)



Total events: 9 (Treatment), 5 (Control) Heterogeneity: Chi2 = 0.00, df = 0 (P<0.00001); I2 =100% Test for overall effect: Z = 1.05 (P = 0.29) Test for subgroup differences: Not applicable



1


216

Analysis 23.4. Comparison 23 Danazol (all doses) versus Yuzpe, Outcome 4 Specific side effects. Review:


Comparison: 23 Danazol (all doses) versus Yuzpe Outcome: 4 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

6/81

33/73

20.6 %

0.16 [ 0.07, 0.37 ]

58/193

133/191

79.4 %

0.43 [ 0.34, 0.55 ]

274

264

100.0 %

0.38 [ 0.30, 0.47 ]

1/81

12/73

23.0 %

0.08 [ 0.01, 0.56 ]

6/193

42/191

77.0 %

0.14 [ 0.06, 0.32 ]

274

264

100.0 %

0.13 [ 0.06, 0.27 ]

39/193

34/191

100.0 %

1.14 [ 0.75, 1.72 ]

193

191

100.0 %

1.14 [ 0.75, 1.72 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI


1 Nausea Rowlands 1983 Webb 1992

Subtotal (95% CI)

Total events: 64 (Treatment), 166 (Control) Heterogeneity: Chi2 = 5.35, df = 1 (P = 0.02); I2 =81% Test for overall effect: Z = 8.40 (P < 0.00001) 2 Vomiting Rowlands 1983 Webb 1992


Heterogeneity: Chi2 = 0.33, df = 1 (P = 0.57); I2 =0.0% Test for overall effect: Z = 5.29 (P < 0.00001) 3 Breast tenderness Webb 1992

Subtotal (95% CI)

Total events: 39 (Treatment), 34 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.60 (P = 0.55) 4 Headache





1


(Continued . . . )


217


Risk Ratio

Weight


Treatment

Control

n/N

n/N

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

Test for overall effect: not applicable 7 Abdominal pain



0.001 0.01 0.1

1

Favours treatment


Analysis 23.5. Comparison 23 Danazol (all doses) versus Yuzpe, Outcome 5 Menses. Review:


Comparison: 23 Danazol (all doses) versus Yuzpe Outcome: 5 Menses

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

17/193

11/191

100.0 %

1.53 [ 0.74, 3.18 ]

193

191

100.0 %

1.53 [ 0.74, 3.18 ]

191

100.0 %

1.53 [ 0.74, 3.18 ]

M-H,Fixed,95% CI


1 Early

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 2 Delay Webb 1992

Subtotal (95% CI)


Total (95% CI)

193


1


(Continued . . . )


218


Treatment

Control

n/N

n/N

Risk Ratio

Weight

M-H,Fixed,95% CI


M-H,Fixed,95% CI


0.001 0.01 0.1

1

Favours treatment


Analysis 24.1. Comparison 24 High-dose oestrogens versus Yuzpe, Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 24 High-dose oestrogens versus Yuzpe Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Van Santen 1985a

2/184

1/200

100.0 %

2.17 [ 0.20, 23.77 ]

Total (95% CI)

184

200

100.0 %

2.17 [ 0.20, 23.77 ]

M-H,Fixed,95% CI




1



219

Analysis 25.1. Comparison 25 Half-dose Yuzpe versus standard Yuzpe, Outcome 1 Observed number of pregnancies (all women). Review:


Comparison: 25 Half-dose Yuzpe versus standard Yuzpe Outcome: 1 Observed number of pregnancies (all women)

Study or subgroup

Ellertson 2003

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

23/648

17/675

100.0 %

1.41 [ 0.76, 2.61 ]

648

675

100.0 %

1.41 [ 0.76, 2.61 ]

M-H,Fixed,95% CI



0.001 0.01 0.1

1

Favours treatment


Analysis 25.2. Comparison 25 Half-dose Yuzpe versus standard Yuzpe, Outcome 2 Any side effect. Review:


Comparison: 25 Half-dose Yuzpe versus standard Yuzpe Outcome: 2 Any side effect

Study or subgroup

Ellertson 2003

Total (95% CI)

Treatment

Control

n/N

n/N

Risk Ratio

Weight

345/628

429/660

100.0 %

0.85 [ 0.77, 0.93 ]

628

660

100.0 %

0.85 [ 0.77, 0.93 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


220

Analysis 25.3. Comparison 25 Half-dose Yuzpe versus standard Yuzpe, Outcome 3 Specific side effects. Review:


Comparison: 25 Half-dose Yuzpe versus standard Yuzpe Outcome: 3 Specific side effects

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

270/628

329/660

100.0 %

0.86 [ 0.77, 0.97 ]

628

660

100.0 %

0.86 [ 0.77, 0.97 ]

50/621

105/654

100.0 %

0.50 [ 0.36, 0.69 ]

621

654

100.0 %

0.50 [ 0.36, 0.69 ]

0

0

0.0 %

0.0 [ 0.0, 0.0 ]

69/628

79/660

100.0 %

0.92 [ 0.68, 1.24 ]

628

660

100.0 %

0.92 [ 0.68, 1.24 ]

25/628

40/660

100.0 %

0.66 [ 0.40, 1.07 ]

628

660

100.0 %

0.66 [ 0.40, 1.07 ]

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI


1 Nausea Ellertson 2003

Subtotal (95% CI)

Total events: 270 (Treatment), 329 (Control) Heterogeneity: not applicable Test for overall effect: Z = 2.45 (P = 0.014) 2 Vomiting Ellertson 2003

Subtotal (95% CI)

Total events: 50 (Treatment), 105 (Control) Heterogeneity: not applicable Test for overall effect: Z = 4.25 (P = 0.000021) 3 Breast tenderness

Subtotal (95% CI) Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable 4 Headache Ellertson 2003

Subtotal (95% CI)

Total events: 69 (Treatment), 79 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.55 (P = 0.58) 5 Dizziness Ellertson 2003

Subtotal (95% CI)

Total events: 25 (Treatment), 40 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.69 (P = 0.091) 6 Fatigue

Subtotal (95% CI)

0

Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

(Continued . . . )


221


Risk Ratio

Weight


Treatment

Control

n/N

n/N

19/628

26/660

100.0 %

0.77 [ 0.43, 1.37 ]

628

660

100.0 %

0.77 [ 0.43, 1.37 ]

0

0.0 %

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

7 Abdominal pain Ellertson 2003

Subtotal (95% CI)

Total events: 19 (Treatment), 26 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.89 (P = 0.37) 8 Spotting/bleeding after treatment

Subtotal (95% CI)

0

Total events: 0 (Treatment), 0 (Control) Heterogeneity: not applicable Test for overall effect: not applicable

0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 26.1. Comparison 26 High-risk women versus low-risk women (all hormonal methods), Outcome 1 Observed number of pregnancies. Review:


Comparison: 26 High-risk women versus low-risk women (all hormonal methods) Outcome: 1 Observed number of pregnancies

Study or subgroup

high risk women

low riske women

n/N

n/N

5/25

3/582

0.4 %

38.80 [ 9.82, 153.34 ]

Dada 2010

3/236

14/2587

3.4 %

2.35 [ 0.68, 8.12 ]

Glasier 1992

4/322

0/478

0.6 %

13.35 [ 0.72, 247.05 ]

Glasier 2010

9/104

31/1795

4.9 %

5.01 [ 2.45, 10.25 ]

Ho 1993

10/156

17/672

9.2 %

2.53 [ 1.18, 5.43 ]

Ngai 2005

14/446

26/1566

16.6 %

1.89 [ 1.00, 3.59 ]

33/1235

32/2836

27.9 %

2.37 [ 1.46, 3.83 ]

25/732

17/1221

18.3 %

2.45 [ 1.33, 4.51 ]

Cheng 1999a

Von Hertzen 2002 WHO 1998

Risk Ratio

Weight

M-H,Fixed,95% CI

0.1 0.2

0.5

1

Favours treatment

2

5


10

Favours control

(Continued . . . )


222


high risk women

Risk Ratio

Weight

n/N

n/N 10/1098

0.7 %

12.20 [ 3.56, 41.84 ]

22/1492

12/1491

17.3 %

1.83 [ 0.91, 3.69 ]

3/77

2/522

0.7 %

10.17 [ 1.73, 59.89 ]

4852

14848

100.0 %

2.67 [ 2.11, 3.39 ]

Zhang JQ 2000

Total (95% CI)

M-H,Fixed,95% CI


3/27

WHO 1999 Xiao 2002

low riske women

M-H,Fixed,95% CI

Total events: 131 (high risk women), 164 (low riske women) Heterogeneity: Chi2 = 29.31, df = 10 (P = 0.001); I2 =66% Test for overall effect: Z = 8.09 (P < 0.00001) Test for subgroup differences: Not applicable

0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 27.1. Comparison 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone, Outcome 1 ≤ 24 h vs > 24-48 h. Review:


Comparison: 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone Outcome: 1 ≤ 24 h vs > 24-48 h

Study or subgroup

Treatment

Control

n/N

n/N

Risk Ratio

Weight

Ashok 2002

0/135

1/212

24.1 %

0.52 [ 0.02, 12.72 ]

Hamoda 2004

4/364

4/425

75.9 %

1.17 [ 0.29, 4.64 ]

Total (95% CI)

499

637

100.0 %

1.01 [ 0.29, 3.54 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


223

Analysis 27.2. Comparison 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone, Outcome 2 ≤ 24 h vs > 48-72 h. Review:


Comparison: 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone Outcome: 2 ≤ 24 h vs > 48-72 h

Study or subgroup

Treatment

Control

Odds Ratio

n/N

n/N

M-H,Fixed,95% CI

Weight

Odds Ratio

Ashok 2002

0/135

2/140

32.5 %

0.20 [ 0.01, 4.30 ]

Hamoda 2004

4/364

4/202

67.5 %

0.55 [ 0.14, 2.22 ]

Total (95% CI)

499

342

100.0 %

0.44 [ 0.13, 1.51 ]

M-H,Fixed,95% CI


0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 27.3. Comparison 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone, Outcome 3 > 24-48 h vs > 48-72 h. Review:


Comparison: 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone Outcome: 3 > 24-48 h vs > 48-72 h

Study or subgroup

Treatment

Control

Odds Ratio

n/N

n/N

M-H,Fixed,95% CI

Weight

Odds Ratio

Ashok 2002

1/212

2/140

30.9 %

0.33 [ 0.03, 3.64 ]

Hamoda 2004

4/425

4/202

69.1 %

0.47 [ 0.12, 1.90 ]

Total (95% CI)

637

342

100.0 %

0.43 [ 0.13, 1.42 ]

M-H,Fixed,95% CI


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


224

Analysis 27.4. Comparison 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone, Outcome 4 < 72 h vs > 72 h. Review:


Comparison: 27 Time elapsed since intercourse (coitus-treatment interval) in mifepristone Outcome: 4 < 72 h vs > 72 h

Study or subgroup

Hamoda 2004 Von Hertzen 2002

Total (95% CI)

Treatment

Control

Odds Ratio

n/N

n/N

M-H,Fixed,95% CI

Weight

Odds Ratio

12/991

1/30

26.5 %

0.36 [ 0.04, 2.83 ]

18/1215

3/137

73.5 %

0.67 [ 0.20, 2.31 ]

2206

167

100.0 %

0.59 [ 0.20, 1.71 ]

M-H,Fixed,95% CI


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


225

Analysis 28.1. Comparison 28 Time elapsed since intercourse in levonorgestrel, Outcome 1 ≤ 24 h vs > 2448 h. Review:


Comparison: 28 Time elapsed since intercourse in levonorgestrel Outcome: 1 ≤ 24 h vs > 24-48 h

Study or subgroup

Experimental

Control

n/N

n/N

Creinin 2006

4/263

3/298

14.2 %

1.51 [ 0.34, 6.69 ]

Glasier 2010

10/337

7/319

36.3 %

1.35 [ 0.52, 3.51 ]

Ho 1993

4/217

4/114

26.5 %

0.53 [ 0.13, 2.06 ]

WHO 1998

2/450

4/338

23.1 %

0.38 [ 0.07, 2.04 ]

1267

1069

100.0 %

0.93 [ 0.50, 1.73 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI


Total events: 20 (Experimental), 18 (Control) Heterogeneity: Chi2 = 2.77, df = 3 (P = 0.43); I2 =0.0% Test for overall effect: Z = 0.23 (P = 0.82) Test for subgroup differences: Not applicable

0.01

0.1


1

10

100

Favours control


226

Analysis 28.2. Comparison 28 Time elapsed since intercourse in levonorgestrel, Outcome 2 ≤ 24 h vs > 4872 h. Review:


Comparison: 28 Time elapsed since intercourse in levonorgestrel Outcome: 2 ≤ 24 h vs > 48-72 h

Study or subgroup

Experimental

Control

n/N

n/N

Creinin 2006

4/263

6/213

33.1 %

0.54 [ 0.15, 1.89 ]

Glasier 2010

10/337

5/196

31.6 %

1.16 [ 0.40, 3.35 ]

WHO 1998

2/450

5/187

35.3 %

0.17 [ 0.03, 0.85 ]

1050

596

100.0 %

0.60 [ 0.31, 1.19 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI


Total events: 16 (Experimental), 16 (Control) Heterogeneity: Chi2 = 3.91, df = 2 (P = 0.14); I2 =49% Test for overall effect: Z = 1.45 (P = 0.15) Test for subgroup differences: Not applicable

0.01

0.1


1

10

100

Favours control


227

Analysis 28.3. Comparison 28 Time elapsed since intercourse in levonorgestrel, Outcome 3 > 24-48 h vs > 48-72 h. Review:


Comparison: 28 Time elapsed since intercourse in levonorgestrel Outcome: 3 > 24-48 h vs > 48-72 h

Study or subgroup

Experimental

Control

n/N

n/N

Creinin 2006

3/298

6/213

35.6 %

0.36 [ 0.09, 1.41 ]

Glasier 2010

7/319

5/196

31.6 %

0.86 [ 0.28, 2.67 ]

WHO 1998

4/338

5/187

32.8 %

0.44 [ 0.12, 1.63 ]

955

596

100.0 %

0.54 [ 0.27, 1.11 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1


1

10

100

Favours control


228

Analysis 28.4. Comparison 28 Time elapsed since intercourse in levonorgestrel, Outcome 4 < 72 h vs > 72 h. Review:


Comparison: 28 Time elapsed since intercourse in levonorgestrel Outcome: 4 < 72 h vs > 72 h

Study or subgroup

Experimental

Control

n/N

n/N

Dada 2010

9/2492

7/302

37.9 %

0.16 [ 0.06, 0.42 ]

Glasier 2010

22/852

3/106

16.2 %

0.91 [ 0.28, 3.00 ]

Hamoda 2004

19/966

0/40

2.9 %

1.65 [ 0.10, 26.91 ]

36/2381

8/314

42.9 %

0.59 [ 0.28, 1.27 ]

6691

762

100.0 %

0.51 [ 0.31, 0.84 ]

Von Hertzen 2002

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1


1

10

100

Favours control


229

Analysis 29.1. Comparison 29 Time elapsed since intercourse in ulipristal acetate, Outcome 1 ≤ 24 h vs > 24-48 h. Review:


Comparison: 29 Time elapsed since intercourse in ulipristal acetate Outcome: 1 ≤ 24 h vs > 24-48 h

Study or subgroup

Experimental

Control

n/N

n/N

Creinin 2006

0/273

6/268

49.0 %

0.08 [ 0.00, 1.33 ]

Glasier 2010

5/312

7/329

51.0 %

0.75 [ 0.24, 2.35 ]

585

597

100.0 %

0.42 [ 0.16, 1.12 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1

1


10

100

Favours control

Analysis 29.2. Comparison 29 Time elapsed since intercourse in ulipristal acetate, Outcome 2 ≤ 24 h vs > 48-72 h. Review:


Comparison: 29 Time elapsed since intercourse in ulipristal acetate Outcome: 2 ≤ 24 h vs > 48-72 h

Study or subgroup

Experimental

Control

n/N

n/N

Creinin 2006

0/273

1/234

30.8 %

0.29 [ 0.01, 6.98 ]

Glasier 2010

5/312

3/203

69.2 %

1.08 [ 0.26, 4.49 ]

585

437

100.0 %

0.84 [ 0.24, 2.95 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1


1

10

100

Favours control


230

Analysis 29.3. Comparison 29 Time elapsed since intercourse in ulipristal acetate, Outcome 3 > 24-48 h vs > 48-72 h. Review:


Comparison: 29 Time elapsed since intercourse in ulipristal acetate Outcome: 3 > 24-48 h vs > 48-72 h

Study or subgroup

Experimental

Control

n/N

n/N

Creinin 2006

6/268

1/234

22.3 %

5.24 [ 0.64, 43.20 ]

Glasier 2010

7/329

3/203

77.7 %

1.44 [ 0.38, 5.50 ]

597

437

100.0 %

2.29 [ 0.77, 6.82 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1


1

10

100

Favours control


231

Analysis 29.4. Comparison 29 Time elapsed since intercourse in ulipristal acetate, Outcome 4 < 72 h vs > 72 h. Review:


Comparison: 29 Time elapsed since intercourse in ulipristal acetate Outcome: 4 < 72 h vs > 72 h

Study or subgroup

Experimental

Control

n/N

n/N

15/844

0/126

100.0 %

4.66 [ 0.28, 77.39 ]

844

126

100.0 %

4.66 [ 0.28, 77.39 ]

Glasier 2010

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI


Total events: 15 (Experimental), 0 (Control) Heterogeneity: not applicable Test for overall effect: Z = 1.07 (P = 0.28) Test for subgroup differences: Not applicable

0.01

0.1

1


10

100

Favours control

Analysis 30.1. Comparison 30 Time elapsed since intercourse in Yuzpe, Outcome 1 ≤ 24 h vs > 24-48 h. Review:


Comparison: 30 Time elapsed since intercourse in Yuzpe Outcome: 1 ≤ 24 h vs > 24-48 h

Study or subgroup

Experimental

Control

n/N

n/N

Ashok 2002

3/134

7/217

18.1 %

0.69 [ 0.18, 2.64 ]

Ho 1993

3/217

6/130

25.5 %

0.30 [ 0.08, 1.18 ]

WHO 1998

9/459

15/370

56.4 %

0.48 [ 0.21, 1.09 ]

810

717

100.0 %

0.47 [ 0.26, 0.88 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1


1

10

100

Favours control


232

Analysis 30.2. Comparison 30 Time elapsed since intercourse in Yuzpe, Outcome 2 ≤ 24 h vs > 48-72 h. Review:


Comparison: 30 Time elapsed since intercourse in Yuzpe Outcome: 2 ≤ 24 h vs > 48-72 h

Study or subgroup

Experimental

Control

n/N

n/N

Ashok 2002

3/134

7/120

41.2 %

0.38 [ 0.10, 1.45 ]

WHO 1998

9/459

7/150

58.8 %

0.42 [ 0.16, 1.11 ]

593

270

100.0 %

0.41 [ 0.18, 0.89 ]

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.01

0.1


1

10

100

Favours control


233

Analysis 30.3. Comparison 30 Time elapsed since intercourse in Yuzpe, Outcome 3 > 24-48 h vs > 48-72 h. Review:


Comparison: 30 Time elapsed since intercourse in Yuzpe Outcome: 3 > 24-48 h vs > 48-72 h

Study or subgroup

Experimental

Control

Odds Ratio

n/N

n/N

M-H,Fixed,95% CI

Ashok 2002

7/217

7/120

47.7 %

0.54 [ 0.18, 1.57 ]

WHO 1998

15/370

7/150

52.3 %

0.86 [ 0.34, 2.16 ]

587

270

100.0 %

0.71 [ 0.35, 1.41 ]

Total (95% CI)

Weight

Odds Ratio M-H,Fixed,95% CI


0.01

0.1

1


10

100

Favours control

WHAT’S NEW Last assessed as up-to-date: 18 July 2011.

Date

Event

Description

15 February 2012

New citation required and conclusions have changed

The number of included studies in this updated review increased from 81 to 100. Compared with levonorgestrel, the risk ratio of pregnancy with mid-dose (25-50 mg) mifepristone was slightly increased from 0. 50 (95% CI 0.32 to 0.79) to 0.64 (95% CI 0.45 to 0.92) in this update. Ulipristal acetate appeared more effective than levonorgestrel, but more data are needed to confirm this association. Ulipristal acetate users were more likely to experience a menstrual return after the expected date than levonorgestrel users did. However, levonorgestrel was associated with higher risk of early menstrual return than ulipristal acetate. Gestrinone was included in this review for the first time. It appeared to have similar effectiveness and overall side effects as mifepristone. The latter was associated with higher risk of menstrual delay than gestrinone


234

HISTORY Protocol first published: Issue 4, 1998 Review first published: Issue 3, 1999

Date

Event

Description

18 February 2008

New citation required and conclusions have changed

Substantive amendment

CONTRIBUTIONS OF AUTHORS AMG had the idea and conducted the initial version of the review with LC. LC contributed to all sections of the review in both the current update and the previous versions. YC checked the statistics and contributed to the text.

DECLARATIONS OF INTEREST LC participated in emergency contraceptive trials included in this review. MG is staff of the WHO, which has a ’Memorandum of understanding’ regarding LNG for EC with Gedeon Richter, one of the companies marketing this preparation. YC declares no conflicts of interest.

SOURCES OF SUPPORT Internal sources • HRP-UNDP/UNFPA/WHO/World Bank Special Programme in Human Reproduction, Geneva, Switzerland. • UK Cochrane Centre, NHS R&D Programme, Oxford, UK. • Shanghai Institute of Planned Parenthood Research, China.

External sources • The David and Lucile Packard Foundation, Los Altos, CA, USA.

INDEX TERMS Medical Subject Headings (MeSH) Contraception, Postcoital [∗ methods]; Contraceptives, Postcoital [∗ administration & dosage]; Drug Administration Schedule; Levonorgestrel [administration & dosage]; Mifepristone [administration & dosage]; Norpregnadienes [administration & dosage]; Randomized Controlled Trials as Topic


235

MeSH check words Female; Humans


236

Cochrane

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