Medical methods for first trimester abortion

Regina Kulier, Nathalie Kapp, A Metin Gülmezoglu, G Justus Hofmeyr, Linan Cheng, Aldo Campana, Regina Kulier, Nathalie Kapp, A Metin Gülmezoglu, G Justus Hofmeyr, Linan Cheng, Aldo Campana

Abstract

Background: Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s and anti-progesterones in the 1980s. The most widely researched drugs are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins.

Objectives: To compare different medical methods for first trimester abortion.

Search methods: The Cochrane Controlled Trials Register, MEDLINE and Popline were systematically searched. Reference lists of retrieved papers were also searched. Experts in WHO/HRP were contacted.

Selection criteria: Types of studies Randomised controlled trials comparing different medical methods for abortion during first trimester (e.g. single drug, combination) were considered. Trials were assessed and included if they had adequate concealment of allocation, randomisation procedure and follow-up. Women, pregnant during the first trimester, undergoing medical abortion were the participants. The outcomes were mortality, failure to achieve complete abortion, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the procedure.

Data collection and analysis: Two reviewers independently selected trials for inclusion from the results of the search strategy described previously.The selection of trials for inclusion in the review was performed independently by two reviewers after employing the search strategy described previously. Trials under consideration were evaluated for appropriateness for inclusion and methodological quality without consideration of their results. Data were processed using Revman software.

Main results: Fifty-eight trials were included in the review. The effectiveness outcomes below refer to 'failure to achieve complete abortion' with the intended method unless otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone 600 mg compared to 200 mg shows similar effectiveness in achieving complete abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI 1.44 to 6.24) and may be associated with more frequent side effects such as nausea and diarrhoea. Sublingual and buccal routes were similarly effective compared to the vaginal route, but had higher rates of side effects. 2) Mifepristone alone is less effective when compared to the combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3) Five trials compared prostaglandin alone to the combined regimen (mifepristone/prostaglandin). All but one reported higher effectiveness with the combined regimen. The results of these studies could not be combined but the RR of failure with prostaglandin alone is reportedly between 1.4 to 3.75 with the 95% confidence intervals indicating statistical significance. 4) In one trial comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no difference in effectiveness with use of a divided dose compared to a single dose of prostaglandin. 6) Combined regimen methotrexate/prostaglandin demonstrates similar rates of failure to complete abortion when comparing intramuscular to oral methotrexate administration (RR 2.04, 95% CI 0.51 to 8.07). Similarly, day 3 vs. day 5 administration of prostaglandin following methotrexate administration showed no significant differences (RR 0.72, 95% CI 0.36 to 1.43). One trial compared the effect of tamoxifen vs. methotrexate and no statistically significant differences were observed in effectiveness between the groups.

Authors' conclusions: Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all trials were conducted in settings with good access to emergency services, which may limit the generalizability of these results.

Conflict of interest statement

None

Figures

1
1
Forest plot of comparison: 1 combined regimen mifepristone/prostaglandin: dose of mifepristone, outcome: 1.1 failure to achieve complete abortion.
1.1. Analysis
1.1. Analysis
Comparison 1 combined regimen mifepristone/prostaglandin: dose of mifepristone, Outcome 1 failure to achieve complete abortion.
1.2. Analysis
1.2. Analysis
Comparison 1 combined regimen mifepristone/prostaglandin: dose of mifepristone, Outcome 2 side effects.
1.3. Analysis
1.3. Analysis
Comparison 1 combined regimen mifepristone/prostaglandin: dose of mifepristone, Outcome 3 time until passing of conceptus > 3‐6 hours.
1.4. Analysis
1.4. Analysis
Comparison 1 combined regimen mifepristone/prostaglandin: dose of mifepristone, Outcome 4 ongoing pregnancy.
1.5. Analysis
1.5. Analysis
Comparison 1 combined regimen mifepristone/prostaglandin: dose of mifepristone, Outcome 5 surgical evacuation.
2.1. Analysis
2.1. Analysis
Comparison 2 combined regimen mifepristone/prostaglandin: dose of prostaglandin, Outcome 1 failure to achieve complete abortion.
2.2. Analysis
2.2. Analysis
Comparison 2 combined regimen mifepristone/prostaglandin: dose of prostaglandin, Outcome 2 side effects.
2.3. Analysis
2.3. Analysis
Comparison 2 combined regimen mifepristone/prostaglandin: dose of prostaglandin, Outcome 3 women dissatisfied with the procedure.
2.4. Analysis
2.4. Analysis
Comparison 2 combined regimen mifepristone/prostaglandin: dose of prostaglandin, Outcome 4 ongoing pregnancy.
2.5. Analysis
2.5. Analysis
Comparison 2 combined regimen mifepristone/prostaglandin: dose of prostaglandin, Outcome 5 surgical evacuation.
3.1. Analysis
3.1. Analysis
Comparison 3 combined regimen mifepristone/prostaglandin: type of prostaglandin, Outcome 1 failure to achieve complete abortion.
3.2. Analysis
3.2. Analysis
Comparison 3 combined regimen mifepristone/prostaglandin: type of prostaglandin, Outcome 2 side effects.
3.3. Analysis
3.3. Analysis
Comparison 3 combined regimen mifepristone/prostaglandin: type of prostaglandin, Outcome 3 ongoing pregnancy.
3.4. Analysis
3.4. Analysis
Comparison 3 combined regimen mifepristone/prostaglandin: type of prostaglandin, Outcome 4 time until passing of conceptus > 3‐6 hours.
4.1. Analysis
4.1. Analysis
Comparison 4 combined regimen mifepristone/prostaglandin: time of prostaglandin, Outcome 1 failure to achieve complete abortion.
4.2. Analysis
4.2. Analysis
Comparison 4 combined regimen mifepristone/prostaglandin: time of prostaglandin, Outcome 2 side effects.
4.3. Analysis
4.3. Analysis
Comparison 4 combined regimen mifepristone/prostaglandin: time of prostaglandin, Outcome 3 surgical evacuation.
4.4. Analysis
4.4. Analysis
Comparison 4 combined regimen mifepristone/prostaglandin: time of prostaglandin, Outcome 4 ongoing pregnancy.
4.5. Analysis
4.5. Analysis
Comparison 4 combined regimen mifepristone/prostaglandin: time of prostaglandin, Outcome 5 women dissatisfied with the procedure.
5.1. Analysis
5.1. Analysis
Comparison 5 combined regimen mifepristone/prostaglandin: misoprostol po vs pv, Outcome 1 failure to achieve complete abortion.
5.2. Analysis
5.2. Analysis
Comparison 5 combined regimen mifepristone/prostaglandin: misoprostol po vs pv, Outcome 2 side effects.
6.1. Analysis
6.1. Analysis
Comparison 6 combined regimen mifepristone/prostaglandin: misoprostol buccal vs pv, Outcome 1 failure to achieve complete abortion.
6.2. Analysis
6.2. Analysis
Comparison 6 combined regimen mifepristone/prostaglandin: misoprostol buccal vs pv, Outcome 2 side effects.
7.1. Analysis
7.1. Analysis
Comparison 7 combined regimen mifepristone/prostaglandin: misoprostol buccal vs oral, Outcome 1 failure to achieve complete abortion.
7.2. Analysis
7.2. Analysis
Comparison 7 combined regimen mifepristone/prostaglandin: misoprostol buccal vs oral, Outcome 2 ongoing pregnancy.
7.3. Analysis
7.3. Analysis
Comparison 7 combined regimen mifepristone/prostaglandin: misoprostol buccal vs oral, Outcome 3 side effects.
7.4. Analysis
7.4. Analysis
Comparison 7 combined regimen mifepristone/prostaglandin: misoprostol buccal vs oral, Outcome 4 women dissatisfied with the procedure.
8.1. Analysis
8.1. Analysis
Comparison 8 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs pv, Outcome 1 failure to achieve complete abortion.
8.2. Analysis
8.2. Analysis
Comparison 8 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs pv, Outcome 2 surgical evacuation.
8.3. Analysis
8.3. Analysis
Comparison 8 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs pv, Outcome 3 ongoing pregnancy at follow‐up.
8.4. Analysis
8.4. Analysis
Comparison 8 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs pv, Outcome 4 side effects.
8.5. Analysis
8.5. Analysis
Comparison 8 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs pv, Outcome 5 women dissatisfied with the procedure.
8.6. Analysis
8.6. Analysis
Comparison 8 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs pv, Outcome 6 side effects.
9.1. Analysis
9.1. Analysis
Comparison 9 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs po, Outcome 1 failure to achieve complete abortion.
9.2. Analysis
9.2. Analysis
Comparison 9 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs po, Outcome 2 side effects.
9.3. Analysis
9.3. Analysis
Comparison 9 combined regimen mifepristone/prostaglandin: misoprostol sublingual vs po, Outcome 3 women dissatisfied with the procedure.
10.1. Analysis
10.1. Analysis
Comparison 10 combined regimen mifepristone/prostaglandin: single vs split dose prostaglandin, Outcome 1 failure to achieve complete abortion.
10.2. Analysis
10.2. Analysis
Comparison 10 combined regimen mifepristone/prostaglandin: single vs split dose prostaglandin, Outcome 2 side effects.
11.1. Analysis
11.1. Analysis
Comparison 11 combined regimen mifepristone/prostaglandin:single vs continuous prostaglandin, Outcome 1 failure to achieve complete abortion.
11.2. Analysis
11.2. Analysis
Comparison 11 combined regimen mifepristone/prostaglandin:single vs continuous prostaglandin, Outcome 2 ongoing pregnancy at follow‐up.
11.3. Analysis
11.3. Analysis
Comparison 11 combined regimen mifepristone/prostaglandin:single vs continuous prostaglandin, Outcome 3 nausea.
11.4. Analysis
11.4. Analysis
Comparison 11 combined regimen mifepristone/prostaglandin:single vs continuous prostaglandin, Outcome 4 vomiting.
11.5. Analysis
11.5. Analysis
Comparison 11 combined regimen mifepristone/prostaglandin:single vs continuous prostaglandin, Outcome 5 diarrhoea.
12.1. Analysis
12.1. Analysis
Comparison 12 mifepristone alone vs combined regimen mifepristone/prostaglandin, Outcome 1 failure to achieve complete abortion.
13.1. Analysis
13.1. Analysis
Comparison 13 prostaglandin alone vs combined regimen (all), Outcome 1 failure to achieve complete abortion.
13.2. Analysis
13.2. Analysis
Comparison 13 prostaglandin alone vs combined regimen (all), Outcome 2 side effects.
14.1. Analysis
14.1. Analysis
Comparison 14 prostaglandin alone: route of administration, Outcome 1 failure to achieve complete abortion.
14.2. Analysis
14.2. Analysis
Comparison 14 prostaglandin alone: route of administration, Outcome 2 side effects.
15.1. Analysis
15.1. Analysis
Comparison 15 mifepristone single ‐ high vs low dose, Outcome 1 failure to achieve complete abortion.
15.2. Analysis
15.2. Analysis
Comparison 15 mifepristone single ‐ high vs low dose, Outcome 2 side effects.
16.1. Analysis
16.1. Analysis
Comparison 16 combined regimen methotrexate/prostaglandin: timing of prostaglandin, Outcome 1 failure to achieve complete abortion.
17.1. Analysis
17.1. Analysis
Comparison 17 combined regimen methotrexate/prostaglandin: methotrexate imi vs po, Outcome 1 failure to achieve complete abortion.
17.2. Analysis
17.2. Analysis
Comparison 17 combined regimen methotrexate/prostaglandin: methotrexate imi vs po, Outcome 2 Side effects.
18.1. Analysis
18.1. Analysis
Comparison 18 combined regimen methotrexate/prostaglandin: dose of methotrexate, Outcome 1 failure to achieve complete abortion.
19.1. Analysis
19.1. Analysis
Comparison 19 combined regimen methotrexate/prostaglandin: route of prostaglandin (misoprostol), Outcome 1 failure to achieve complete abortion.
19.2. Analysis
19.2. Analysis
Comparison 19 combined regimen methotrexate/prostaglandin: route of prostaglandin (misoprostol), Outcome 2 side effects.
20.1. Analysis
20.1. Analysis
Comparison 20 tamoxifen vs methotrexate (combined with prostaglandin) : low dose tamoxifen (40), Outcome 1 failure to achieve complete abortion.
20.2. Analysis
20.2. Analysis
Comparison 20 tamoxifen vs methotrexate (combined with prostaglandin) : low dose tamoxifen (40), Outcome 2 side effects.
21.1. Analysis
21.1. Analysis
Comparison 21 tamoxifen vs methotrexate (combined with prostaglandin): high dose tamoxifen (160 mg), Outcome 1 failure to achieve complete abortion.
21.2. Analysis
21.2. Analysis
Comparison 21 tamoxifen vs methotrexate (combined with prostaglandin): high dose tamoxifen (160 mg), Outcome 2 side effects.
22.1. Analysis
22.1. Analysis
Comparison 22 combined regimen mifepristone/prostaglandin vs mifepristone/prostaglandin and tamoxifen, Outcome 1 failure to achieve complete abortion.

Source: PubMed

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