Medical methods for first trimester abortion: Cochrane systematic review
Assessed as up to date: 2010/02/27
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.
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.
Kulier Regina, Kapp Nathalie, Gülmezoglu A Metin, Hofmeyr G Justus, Cheng Linan, Campana Aldo
Medical methods for early termination of pregnancy can be safe and effective
There are several different surgical techniques for abortion during the first three months. Several drugs can also be prescribed alone or in combination to terminate early pregnancy. This is called medical abortion, and uses the hormones prostaglandins and/or mifepristone (an antiprogesterone often called RU486), and/or methotrexate. This review of trials found that medical methods for abortion in early pregnancy can be safe and effective, with the most evidence of effectiveness for a combination of mifepristone and misoprostol (a prostaglandin). Almost all of the trials were done in well-resourced settings where women returned for a check-up.
Implications for practice
The available data from this review demonstrates that the combination mifepristone/misoprostol is a safe and effective abortion method in the first trimester up to 63 days. The effectiveness is not reduced by lowering the currently licensed dose of 600 mg of mifepristone to 200mg. Data on methotrexate/prostaglandin regimen is scarce.
This review does not address introducing medical abortion where back-up facilities are not available and women are less likely to attend for the follow up.
Implications for research
Methotrexate in combination with a prostaglandin may be an alternative to the mifepristone/prostaglandin regimen in places where mifepristone is either unaffordable or unavailable. However, further research should be conducted to compare the methotrexate/prostaglandin combination regimen with the standard mifepristone/prostaglandin regimen.
There is scarce data on issues such as which method is preferable when in addressing specific side-effects, bleeding patterns, acceptability or financial impact of the different methods.
Good quality acceptability studies are important to investigate the components of medical abortion regimens that affect acceptability in different settings.
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