Progestogen for preventing miscarriage

 

Abstract

Background

Progesterone, a female sex hormone, is known to induce secretory changes in the lining of the uterus essential for successful implantation of a fertilised egg. It has been suggested that a causative factor in many cases of miscarriage may be inadequate secretion of progesterone. Therefore, progestogens have been used, beginning in the first trimester of pregnancy, in an attempt to prevent spontaneous miscarriage.

Objectives

To determine the efficacy and safety of progestogens as a preventative therapy against miscarriage.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (January 2008), CENTRAL (The Cochrane Library 2006, Issue 4), MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), CINAHL (1982 to June 2006), NHMRC Clinical Trials Register (June 2006) and Meta-Register (June 2006). We searched references from relevant articles, attempting to contact authors where necessary, and contacted experts in the field for unpublished works.

Selection criteria

Randomised or quasi-randomized controlled trials comparing progestogens with placebo or no treatment given in an effort to prevent miscarriage.

Data collection and analysis

Two review authors assessed trial quality and extracted data.

Main results

Fifteen trials (2118 women) are included. The meta-analysis of all women, regardless of gravidity and number of previous miscarriages, showed no statistically significant difference in the risk of miscarriage between progestogen and placebo or no treatment groups (Peto odds ratio (Peto OR) 0.98; 95% confidence interval (CI) 0.78 to 1.24) and no statistically significant difference in the incidence of adverse effect in either mother or baby.

In a subgroup analysis of three trials involving women who had recurrent miscarriages (three or more consecutive miscarriages), progestogen treatment showed a statistically significant decrease in miscarriage rate compared to placebo or no treatment (Peto OR 0.38; 95% CI 0.20 to 0.70). No statistically significant differences were found between the route of administration of progestogen (oral, intramuscular, vaginal) versus placebo or no treatment.

Authors' conclusions

There is no evidence to support the routine use of progestogen to prevent miscarriage in early to mid-pregnancy. However, there seems to be evidence of benefit in women with a history of recurrent miscarriage. Treatment for these women may be warranted given the reduced rates of miscarriage in the treatment group and the finding of no statistically significant difference between treatment and control groups in rates of adverse effects suffered by either mother or baby in the available evidence. Larger trials are currently underway to inform treatment for this group of women.

 

Plain language summary

Progestogen for preventing miscarriage

No evidence that progestogen can prevent miscarriage.

Hormones called progestogens prepare the womb (uterus) to receive and support the newly fertilised egg. It has been suggested that some women who miscarry may not make enough progesterone, so supplementing with progesterone has been suggested as a possible way to prevent miscarriage. This review of fifteen trials (2118 women) found no evidence that progestogens can prevent miscarriage in general. There was evidence, however, that women who have suffered three or more miscarriages may benefit from progestogen during pregnancy but more trials are needed and are under way, particularly where potential adverse effects on the baby are measured.

 

摘要

背景

用於預防流產的黃體素(progestogen)

黃體酮(progesterone)是一種女性荷爾蒙，我們知道它可以在子宮內層引發內分泌的變化，而這樣的過程對於受精卵的成功著床而言是必要。在許多流產的例子中，人們認為有一種誘發的因素或許就是黃體素的分泌不正常。因此，醫護人員已經開始在懷孕的妊娠第1期使用黃體激素類藥物(progestational agents)，以用來避免自發性的流產

目標

關於使用黃體素類藥物來當作一種對抗流產的預防性療法，要確認它們的效力與安全性

搜尋策略

我們搜尋了the Cochrane Pregnancy and Childbirth Group trials register(2003年四月)、CENTRAL、MEDLINE(1966年到2003年四月)、EMBASE(1980年到2003年四月)、CINAHL(1982年到2003年四月)、NHMRC Clinical Trials Register(2003年四月)，以及MetaRegister(2003年四月)。我們從相關文章中搜尋了參考文獻，並且在必要的時候嘗試要與作者聯繫，還針對未發表的研究與該領域的專家進行諮詢

選擇標準

在嘗試著要預防流產的工作中，這些隨機與半隨機的對照試驗，將黃體素類藥物與安慰劑或是不採取任何治療進行了比較

資料收集與分析

在起初的研究之中，共確認了30組研究。至少有2位審稿者評估了試驗的品質並擷取出資料。針對所有預後而言，資料都歸類成二分法，使用Peto法勝算比(Peto odds ratio)來進行統合分析

主要結論

共有14組試驗(1988名婦女)符合結論的標準。經由統合分析後顯示，不論之前是否有懷孕及流產的所有婦女，在黃體素與安慰劑或是不採取治療的組別之間的流產風險，在統計學上並沒有明顯的差異(勝算比(OR) .05, 95% 信賴區間(CI) 0.83 to 1.34)，而且不論就母親或嬰兒之副作用的發生率而言，在統計學上也沒有明顯的差異。在包含有3組試驗之次群組分析顯示，把曾發生過復發性流產的婦女(三次或更多次的流產)跟安慰劑或是不採取任何治療比較起來，用黃體素治療後，在統計學上可以很明顯地降低流產的比例(O .39, 95% CI 0.17 to 0.91)。在黃體素的給藥途徑(口服、肌肉注射、置入陰道)相對於安慰劑或是不採取治療之間，統計學上並沒有顯著的差異

作者結論

在早期到中期的妊娠之中，對於例行性地使用黃體素來預防流產，並沒有證據可以支持。然而，或許值得在帶有復發性流產病史的婦女身上作更深入的試驗，但前提是，在可取得的證據中來看，在這些婦女之中，要有趨勢顯示胎兒存活的比例較高，而且對於母親或嬰兒來說，針對任何一方發生副作用的比例，不能在治療與對照組之間歸納出具有統計學上的明顯差異

翻譯人

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

總結

沒有關於黃體素可以預防流產的證據。被稱作黃體素類的荷爾蒙，會讓孕育處(子宮)準備要接收並支援新產生的受精卵。一般都認為有些流產的婦女可能沒有製造出足夠的黃體酮，所以黃體酮的補充被認為是一種預防流產的可行方法。本篇試驗的回顧發現，並沒有任何關於黃體素類可以預防流產的證據。然而，卻有一些證據顯示，已經發生過3次或更多次流產的婦女，或許會在懷孕期間因為黃體素而得到助益，但是還需要有更多的試驗，尤其是要測量在嬰兒身上的潛在副作用