Kulier Regina, Kapp Nathalie, Gülmezoglu A Metin, Hofmeyr G Justus, Cheng Linan, Campana Aldo
World Health Organization, , Geneva, Switzerland.
Cochrane Database Syst Rev. 2011 Nov 9;2011(11):CD002855. doi: 10.1002/14651858.CD002855.pub4.
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.
To compare different medical methods for first trimester abortion.
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.
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.
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.
自20世纪60年代以来，真空吸引术或刮宫术一直是早期妊娠终止的首选方法。随着20世纪70年代初前列腺素的出现以及80年代抗孕激素的问世，药物流产成为孕早期终止妊娠的另一种方法。研究最为广泛的药物有单独使用的前列腺素（PGs）、单独使用的米非司酮、单独使用的甲氨蝶呤、米非司酮与前列腺素联合使用以及甲氨蝶呤与前列腺素联合使用。
比较孕早期不同药物流产方法。
系统检索了Cochrane对照试验注册库、MEDLINE和Popline。还检索了检索到论文的参考文献列表。联系了世界卫生组织/人类生殖研究计划的专家。
研究类型 考虑比较孕早期不同药物流产方法（如单一药物、联合用药）的随机对照试验。如果试验在分配隐藏、随机化程序和随访方面充分，则对其进行评估并纳入。参与者为孕早期接受药物流产的妇女。结局指标为死亡率、未能实现完全流产、手术清宫、随访时持续妊娠、直至排出妊娠物的时间、输血、副作用以及妇女对该程序的不满意程度。
两名综述作者根据上述检索策略的结果独立选择纳入试验。在采用上述检索策略后，由两名综述作者独立进行纳入综述试验的选择。对正在考虑的试验进行纳入适宜性和方法学质量评估，而不考虑其结果。使用Revman软件处理数据。
本综述纳入了58项试验。除非另有说明，以下有效性结果指采用预期方法时“未能实现完全流产”。1）米非司酮/前列腺素联合方案：600 mg米非司酮与200 mg米非司酮相比，在实现完全流产方面效果相似（4项试验，RR 1.07，95%CI 0.87至1.32）。口服米索前列醇的效果不如经阴道途径（更多失败情况，RR 3.00，95%CI 1.44至6.24），且可能与更频繁的副作用如恶心和腹泻有关。与经阴道途径相比，舌下和颊部途径效果相似，但副作用发生率更高。2）与米非司酮/前列腺素联合方案相比，单独使用米非司酮效果较差（RR 3.76，95%CI 2.30至6.15）。3）五项试验将单独使用前列腺素与联合方案（米非司酮/前列腺素）进行了比较。除一项试验外，所有试验均报告联合方案效果更好。这些研究结果无法合并，但据报道单独使用前列腺素的失败RR在1.4至3.75之间，95%置信区间表明具有统计学意义。4）在一项比较0.5 mg吉美前列素与800 mcg米索前列醇的试验中，米索前列醇效果更好（吉美前列素失败：RR 2.86，95%CI 1.14至7.18）。5）与使用单剂量前列腺素相比，分剂量使用在有效性方面无差异。6）在比较甲氨蝶呤肌内注射与口服给药时，甲氨蝶呤/前列腺素联合方案在未能完全流产的发生率方面相似（RR 2.04，95%CI 0.51至8.07）。同样，在甲氨蝶呤给药后第3天与第5天给予前列腺素，差异无统计学意义（RR 0.72，95%CI 0.36至1.43）。一项试验比较了他莫昔芬与甲氨蝶呤的效果，两组在有效性方面未观察到统计学显著差异。
有安全有效的药物流产方法。联合方案比单一药物更有效。在联合方案中，米非司酮剂量可降至200 mg，而不会显著降低方法的有效性。经阴道给予米索前列醇比口服更有效，且副作用比舌下或颊部给药少。一些结果受其所基于的参与者数量较少的限制。几乎所有试验都是在能很好获得急诊服务的环境中进行的，这可能会限制这些结果的普遍性。
