Table Of ContentWeb annexes: Medical management of abortion: evidence summary*
3b. Medical management of induced abortion at ≥ 12 weeks of
gestation
* This publication forms part of the WHO guideline entitled Medical management of abortion. The full guideline and other web annexes are available at:
https://www.who.int/reproductivehealth/publications/medical-management-abortion/en/
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WHO/RHR/18.36
© World Health Organization 2018
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Suggested citation. Medical management of abortion: evidence base for medical management of induced abortion at ≥ 12 weeks of gestation. Geneva: World Health
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Contents
Recommendation 3b: Medical management of induced abortion at ≥ 12 weeks of gestation....................................................................................................................................1
Comparison 1: Mifepristone and misoprostol in combination compared with misoprostol alone..............................................................................................................................1
Summary of Findings table for Comparison 1 ............................................................................................................................................................................................................1
Forest plots for Comparison 1 .....................................................................................................................................................................................................................................4
Comparison 2: Simultaneous mifepristone and misoprostol compared with mifepristone given 24–38 hours before misoprostol...................................................................... 14
Summary of Findings table for Comparison 2 ......................................................................................................................................................................................................... 14
Forest plots for Comparison 2 .................................................................................................................................................................................................................................. 17
Comparison 3: Mifepristone 24 hours before compared with 48 hours before misoprostol .................................................................................................................................... 26
Summary of Findings table for Comparison 3 ......................................................................................................................................................................................................... 26
Forest plots for Comparison 3 .................................................................................................................................................................................................................................. 29
Comparison 4: 200 mg compared with 600 mg mifepristone before misoprostol for medical abortion at ≥ 12 weeks ......................................................................................... 38
Summary of Findings table for Comparison 4 ......................................................................................................................................................................................................... 38
Forest plots for Comparison 4 .................................................................................................................................................................................................................................. 40
Comparison 5: Mifepristone plus vaginal loading dose compared with no loading dose before oral misoprostol................................................................................................. 44
Summary of Findings table for Comparison 5 ......................................................................................................................................................................................................... 44
Forest plots for Comparison 5 .................................................................................................................................................................................................................................. 46
Comparison 6: 200 mg mifepristone 24 hours before vaginal misoprostol every 3 hours compared with 100 mg mifepristone 24 hours and 48 hours before vaginal
misoprostol every 12 hours ............................................................................................................................................................................................................................................ 50
Summary of Findings table for Comparison 6 ......................................................................................................................................................................................................... 50
Forest plots for Comparison 6 .................................................................................................................................................................................................................................. 53
Comparison 7: ................................................................................................................................................................................................................................................................. 57
200 mg mifepristone plus 400 µg oral misoprostol every 3 hours compared with 200 mg mifepristone plus 600 µg vaginal misoprostol loading dose then 400 µg vaginal
misoprostol every 6 hours .............................................................................................................................................................................................................................................. 57
Summary of Findings table for Comparison 7 ......................................................................................................................................................................................................... 57
Forest plots for Comparison 7 .................................................................................................................................................................................................................................. 59
Comparison 8: ................................................................................................................................................................................................................................................................. 61
Mifepristone plus oral misoprostol compared with plus vaginal misoprostol ........................................................................................................................................................... 61
Summary of Findings table for Comparison 8 ......................................................................................................................................................................................................... 61
Forest plots for Comparison 8 .................................................................................................................................................................................................................................. 64
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Comparison 9: ................................................................................................................................................................................................................................................................. 73
Mifepristone plus oral misoprostol compared with mifepristone plus sublingual misoprostol ................................................................................................................................ 73
Summary of Findings table for Comparison 9 ......................................................................................................................................................................................................... 73
Forest plots for Comparison 9 .................................................................................................................................................................................................................................. 75
Comparison 10: ............................................................................................................................................................................................................................................................... 81
Mifepristone plus vaginal misoprostol compared with mifepristone plus sublingual misoprostol ......................................................................................................................... 81
Summary of Findings table for Comparison 10 ....................................................................................................................................................................................................... 81
Forest plots for Comparison 10 ................................................................................................................................................................................................................................ 83
Comparison 11: ............................................................................................................................................................................................................................................................... 90
Mifepristone plus vaginal misoprostol compared with mifepristone plus buccal misoprostol ................................................................................................................................ 90
Summary of Findings table for Comparison 11 ....................................................................................................................................................................................................... 90
Forest plots for Comparison 11 ................................................................................................................................................................................................................................ 92
Comparison 12: Mifepristone plus sublingual misoprostol compared with mifepristone plus buccal misoprostol ................................................................................................ 95
Summary of Findings table for Comparison 12 ....................................................................................................................................................................................................... 95
Forest plots for Comparison 12 ................................................................................................................................................................................................................................ 98
Comparison 13: ............................................................................................................................................................................................................................................................. 104
200 µg vaginal misoprostol compared with 400 µg vaginal misoprostol................................................................................................................................................................. 104
Summary of Findings table for Comparison 13 ..................................................................................................................................................................................................... 104
Forest plots for Comparison 13 .............................................................................................................................................................................................................................. 106
Comparison 14: ............................................................................................................................................................................................................................................................. 110
Misoprostol loading dose compared with no loading dose ....................................................................................................................................................................................... 110
Summary of Findings table for Comparison 14 ..................................................................................................................................................................................................... 110
Forest plots for Comparison 14 .............................................................................................................................................................................................................................. 112
Comparison 15: Misoprostol every 3 hours compared with every 6 hours .............................................................................................................................................................. 115
Summary of Findings table for Comparison 15 ..................................................................................................................................................................................................... 115
Forest plots for Comparison 15 .............................................................................................................................................................................................................................. 117
Comparison 16: Misoprostol every 6 hours compared with every 12 hours ............................................................................................................................................................ 121
Summary of Findings table for Comparison 16 ..................................................................................................................................................................................................... 121
Forest plots for Comparison 16 .............................................................................................................................................................................................................................. 123
Comparison 17: Misoprostol dry or moistened with saline compared with misoprostol moistened with acetic acid .......................................................................................... 131
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Summary of Findings table for Comparison 17 ..................................................................................................................................................................................................... 131
Forest plots for Comparison 17 .............................................................................................................................................................................................................................. 134
Comparison 18: Low dose and high frequency compared with high dose and low frequency of misoprostol ...................................................................................................... 141
Summary of Findings table for Comparison 18 ..................................................................................................................................................................................................... 141
Forest plots for Comparison 18 .............................................................................................................................................................................................................................. 144
Comparison 19: Oral compared with vaginal misoprostol ........................................................................................................................................................................................ 150
Summary of Findings table for Comparison 19 ..................................................................................................................................................................................................... 150
Forest plots for Comparison 19 .............................................................................................................................................................................................................................. 152
Comparison 20: Oral compared with sublingual misoprostol ................................................................................................................................................................................... 160
Summary of Findings table for Comparison 20 ..................................................................................................................................................................................................... 160
Forest plots for Comparison 20 .............................................................................................................................................................................................................................. 162
Comparison 21: Vaginal compared with sublingual misoprostol.............................................................................................................................................................................. 166
Summary of Findings table for Comparison 21 ..................................................................................................................................................................................................... 166
Forest plots for Comparison 21 .............................................................................................................................................................................................................................. 169
Comparison 22: Vaginal compared with buccal misoprostol .................................................................................................................................................................................... 179
Summary of Findings table for Comparison 22 ..................................................................................................................................................................................................... 179
Forest plots for Comparison 22 .............................................................................................................................................................................................................................. 181
Comparison 23: Vaginal compared with vaginal plus intracervical misoprostol ..................................................................................................................................................... 189
Summary of Findings table for Comparison 23 ..................................................................................................................................................................................................... 189
Forest plots for Comparison 23 .............................................................................................................................................................................................................................. 191
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Recommendation 3b: Medical management of induced abortion at ≥ 12 weeks of gestation
Comparison 1: Mifepristone and misoprostol in combination compared with misoprostol alone
Summary of Findings table for Comparison 1
Outcome Anticipated absolute effect * Relative effect No. of Certainty of the Comment
(95% CI) (95% CI) participants evidence
(studies) (GRADE)1
Risk with Risk with
misoprostol mifepristone plus
alone misoprostol
Efficacy: ongoing pregnancy 32 per 100 4 per 100 RR 0.12 783 ⨁⨁⨁◯ There are probably fewer ongoing pregnancies within 24 h
within 24 h (1–11) (0.04–0.35) (5 RCTs) 1-5 MODERATE a among women given mifepristone plus misoprostol
compared with those given misoprostol alone
Efficacy: ongoing pregnancy 10 per 100 2 per 100 RR 0.22 366 ⨁⨁◯◯ There may be fewer ongoing pregnancies within 48 h
within 48 h (1–6) (0.08–0.60) (4 RCTs) 2,3,6,7 LOW b among women given mifepristone plus misoprostol
compared with those given misoprostol alone
Efficacy: complete abortion 66 per 100 94 per 100 RR 1.42 779 ⨁⨁⨁◯ There are probably more complete expulsions of pregnancy
within 24 h without need for (67–100) (1.01–1.99) (4 RCTs) 1,4–6 MODERATE c within 24 h without the need for surgical intervention among
surgical intervention women given mifepristone plus misoprostol compared with
those given misoprostol alone
Efficacy: complete abortion 81 per 1000 91 per 100 RR 1.13 306 ⨁⨁⨁◯ There are probably more complete expulsions of pregnancy
within 48 h without need for (81–100) (1.01–1.26) (3 RCTs) 2,6,7 MODERATE a within 48 h without the need for surgical intervention among
surgical intervention women given mifepristone plus misoprostol compared with
those given misoprostol alone
Efficacy: induction to — Mean — 868 ⨁⨁⨁◯ There is probably a shorter time to expulsion among
expulsion interval (h) 5.87 h shorter (5 RCTs) 1,4–7 MODERATE c women given mifepristone plus misoprostol compared with
(7.78–3.96 h those given misoprostol alone
shorter)
1 Grading of Recommendations Assessment, Development and Evaluation – more information: http://www.gradeworkinggroup.org
Recommendation 3b: Medical management of induced abortion at ≥ 12 weeks of gestation 1
Outcome Anticipated absolute effect * Relative effect No. of Certainty of the Comment
(95% CI) (95% CI) participants evidence
(studies) (GRADE)1
Risk with Risk with
misoprostol mifepristone plus
alone misoprostol
Safety: serious adverse 0 events 1 event — 246 — We are uncertain of the effect of the intervention on this
events (uterine rupture, (3 RCTs) 2,3,7 outcome as the absolute effect estimate could not be
transfusion) estimated
Side-effects: bleeding — — — — — No direct evidence identified for dichotomous bleeding
outcomes
Side-effects: vomiting 24 per 100 25 per 100 RR 1.03 764 ⨁⨁⨁◯ There is probably little or no difference in the incidence of
(20–31) (0.82–1.30) (5 RCTs) 2,4–7 MODERATE a vomiting among women given mifepristone plus misoprostol
compared with those given misoprostol alone
Side-effects: diarrhoea 28 per 100 23 per 100 RR 0.83 700 ⨁⨁⨁◯ There is probably little or no difference in the incidence of
(19–29) (0.66–1.03) (4 RCTs) 4–7 MODERATE a diarrhoea among women given mifepristone plus
misoprostol compared with those given misoprostol alone
Side-effects: pain 58 per 100 58 per 100 RR 1.01 522 ⨁⨁⨁◯ There is probably little or no difference in the experience of
(57–60) (0.99–1.03) (3 RCTs) 2,4,5 MODERATE a pain among women given mifepristone plus misoprostol
compared with those given misoprostol alone
Satisfaction (“satisfied” or 89 per 100 95 per 100 RR 1.06 378 ⨁⨁⨁⨁ There is little or no difference in satisfaction among women
“very satisfied” overall) (89–99) (1.00–1.11) (2 RCTs) 5,6 HIGH given mifepristone plus misoprostol compared with those
given misoprostol alone
CI: confidence interval; RR: risk ratio
* The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group grades of evidence
High certainty: We are very confident that the true effect is close to the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
Recommendation 3b: Medical management of induced abortion at ≥ 12 weeks of gestation 2
Explanations
a. Downgraded one level in imprecision because of few events.
b. Downgraded two levels in imprecision because of few events.
c. Downgraded one level in inconsistency because of high statistical heterogeneity.
References
1. Akkenapally PL. A Comparative study of misoprostol only and mifepristone plus misoprostol in second trimester termination of pregnancy. J Obstet Gynaecol
India. 2016;66(Suppl 1):251-7.
2. Kapp N, Borgatta L, Stubblefield P, Vragovic O, Moreno N. Mifepristone in second-trimester medical abortion: a randomized controlled trial. Obstet Gynecol.
2007;110(6):1304-10.
3. Kulkarni K. Pre-induction with mifepristone for second trimester termination of pregnancy. J Obstet Gynaecol India. 2014;64(2):102-4.
4. Nagaria TN. Misoprostol vs mifepristone and misoprostol in second trimester termination of pregnancy. J Obstet Gynaecol India. 2011;61(6):659-62.
5. Ngoc Nguyen TN, Shochet T, Raghavan S, Blum J, Nga NT, Minh NT, et al. Mifepristone and misoprostol compared with misoprostol alone for second-
trimester abortion: a randomized controlled trial. Obstet Gynecol. 2011;118(3):601-8.
6. Dabash R, Chelli H, Hajri S, Shochet T, Raghavan S, Winikoff B. A double-blind randomized controlled trial of mifepristone or placebo before buccal
misoprostol for abortion at 14–21 weeks of pregnancy. Int J Gynaecol Obstet. 2015;130(1):40-4.
7. Mukhopadhyay P, Bag T, Kyal A, Bhuniya A, Saha T. Second trimester abortion with vaginal misoprostol: Is there any advantage with prior mifepristone
priming? a comparative study. J SAFOG. 2012;4(1):25-7.
Recommendation 3b: Medical management of induced abortion at ≥ 12 weeks of gestation 3
Forest plots for Comparison 1
Analysis 1. Efficacy: ongoing pregnancy within 24 hours
Recommendation 3b: Medical management of induced abortion at ≥ 12 weeks of gestation 4
Analysis 2. Efficacy: ongoing pregnancy within 48 hours
Recommendation 3b: Medical management of induced abortion at ≥ 12 weeks of gestation 5
Description:This publication forms part of the WHO guideline entitled Medical management of abortion. The full guideline and other web annexes are available at:.
