Medical methods for first trimester abortion

 

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.

 

Plain language summary

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.

 

摘要

背景

第一孕期流產的藥物方法

自1960年代起，以抽吸術或擴括術進行手術流產，就是懷孕63天前的首選流產方式。隨著1970年代prostaglandin以及1980年代antiprogesterones的出現，藥物流產成為第一孕期終止妊娠的替代方案。最廣泛被研究的藥物包括單用prostaglandins (PGs)、單用mifepristone、單用methotrexate, 併用mifepristone與prostaglandins 以及併用methotrexate與prostaglandins.

目標

比較不同藥物作為第一孕期人工流產的方法

搜尋策略

Cochrane Controlled Trials Register, MEDLINE 和 Popline皆有系統性地搜尋。取得的論文的參考文獻清單也被搜尋了。WHO/HRP的專家也有取得聯繫。

選擇標準

研究類型:行醫療性流產時，使用不同之藥物方法(如單一藥物、複合藥物)、不同投藥方式、或不同劑量、單一或複合藥物的比較之隨機對照研究。有適當的隱匿分組、適當採隨機步驟並適當追蹤的研究會被評估且選入本回顧。 參加者為使用藥物方法行中止妊娠的第一孕期女性。 用於第一孕期中止妊娠的不同藥物，其彼此之間的比較或與安慰劑的比較，會被選入本回顧。 評估結果包括死亡、未達成完全性流產、手術抽吸術(緊急手術、非緊急手術、或未定義)、追蹤時仍持續懷孕、排出懷孕組織的時間(>3−6小時)、輸血、失血(計量或者臨床上相關的血紅素低落)、出血的天數、採行步驟導致疼痛(由受試女性報告主觀感覺或由止痛藥使用的評估)、使用額外的宮縮劑、受試女性對於採行步驟不滿意、噁心嘔吐、腹瀉。

資料收集與分析

兩名回顧者各自由上述搜尋策略所得的結果中選擇要選入的研究。要選入本篇回顧的研究，會由兩名回顧者以前述的搜尋策略各自選擇。有被列入考慮的研究，會被評估選入的適合性以及實驗方法的品質，而不考慮其研究結果。資料的選取會以設計的表格進行協助。資料的處理是以Revman軟體進行。

主要結論

共有39篇研究收入本回顧。 除非另行說明，以下的效用成果(Effectiveness outcomes)均指打算使用的方法“未達成完全性流產”。 1)複合處方mifepristone/prostaglandin: Mifepristone 600mg與200mg比較，其達到完全性流產的有效性是相似的 (共4項研究, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol以口服比起經陰道給予，效用較差(較多失敗) (RR 3.00, 95% CI 1.44 to 6.24)。這可能與較多副作用如噁心、腹瀉有關。 2) 單用Mifepristone 比起複合處方mifepristone/prostaglandin效用較差(RR 3.76 95% CI 2.30 to 6.15)。3) 相似地，五個有包含prosaglandin 與複合處方的比較，其中四個皆顯示複合處方比起prostaglandin，其效用較好。 這些研究結果並未整合，但單用prostaglandin 的RR在1.4到3.75之間，且其95%信賴區間具有統計意義。 4) 一項研究比較gemeprost 0.5 mg 和misoprostol 800 mcg。Misoprostol 比較有效(gemeprost的失敗: RR 2.86, 95% CI 1.14 – 7.18)。 5) 分割劑量與單一劑量給予prostaglandin並無差異。 6) 複合處方methotrexate/prostaglandin: methotrexate以肌肉注射給予或口服給予，在未達成完全性流產方面，沒有統計上的顯著差異(RR 2.04, 95% CI 0.51 to 8.07). 相似地，prostaglandin的早期給予(第3天)比起晚期給予(第5天)，沒有顯著差異(RR 0.72, 95% CI 0.36 to 1.43)。一項研究比較tamoxifen與methotrexate的效用。這兩組也沒有統計上的顯著差異.

作者結論

安全且有效的藥物流產方法是可用的。複合處方比起單一用藥較為有效。以複合處方使用時，mifeprisone的劑量可以低於200mg，而不會顯著降低此法的有效性。陰道給予Misoprostol比口服有效。有些結論僅由小規模研究得來，因此還有些不確定性。幾乎所有研究皆在醫院環境模式下進行，並能獲得良好的支援及緊急醫療處理。因此，這些結果是否能直接應用於資源缺乏的環境尚不清楚，這些地方即使藥物可取得，但支援醫療欠缺。

翻譯人

本摘要由臺灣大學附設醫院楊育絜翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

以藥物行早期中止妊娠可以是安全且有效的。也有一些不同的手術技術可用於早期中止妊娠(於懷孕最初三個月行流產術)。許多藥物可以單用或合併使用，以早期中止妊娠。此即藥物流產，可用prodtaglandins和/或methotrexate。文獻回顧發現，以藥物行早期中止妊娠可以是安全且有效的。最多證據支持合併使用mifepristone及misoprostol(一種prostaglandin)的有效性。幾乎所有研究皆在資源充足的醫院環境模式下進行，受試女性即在該處回診檢查。