In vitro fertilisation for unexplained subfertility

 

Abstract

Background

In vitro fertilisation (IVF) is now a widely accepted treatment for unexplained infertility (RCOG 1998). However, with estimated live-birth rates per cycle varying between 13% and 28%, its effectiveness has not been rigorously evaluated in comparison with other treatments. With increasing awareness of the role of expectant management and less invasive procedures such as intrauterine insemination, concerns about multiple complications and costs associated with IVF, it is extremely important to evaluate the effectiveness of IVF against other treatment options in couples with unexplained infertility.

Objectives

The aim of this review is to determine, in the context of unexplained infertility, whether IVF improves the probability of live-birth compared with (1) expectant management, (2) clomiphene citrate (CC), (3) intrauterine insemination (IUI) alone, (4) IUI with controlled ovarian stimulation, and (5) gamete intrafallopian transfer (GIFT).

Search methods

We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched 23 March 2004), the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 3, 2004), MEDLINE (1970 to August 2004), EMBASE (1985 to August 2004) and reference lists of articles. We also handsearched relevant conference proceedings and contacted researchers in the field.

Selection criteria

Only randomised controlled trials were included. Live-birth rate per woman was the primary outcome of interest.

Data collection and analysis

Two reviewers independently assessed eligibility and quality of trials.

Main results

Ten randomised controlled trials were identified. In two we could not extract data separately for unexplained infertility cases, two were non-randomised, one did not report valid rates (included in the review but not in the meta-analysis); leaving four trials for analysis. One trial compared two different interventions (IVF versus IUI with or without ovarian stimulation) and one study compared three interventions (IVF versus IUI with ovarian stimulation and GIFT). The numbers of trials assessing the effectiveness of IVF with the other treatments were as follows: IVF versus expectant management (two), IVF versus IUI (one), IVF versus IUI with ovarian stimulation (two) and IVF versus GIFT (three). Live-birth rate per woman was reported in three studies and three studies determined clinical pregnancy rate per woman. Multiple pregnancy rate was reported in three trials. Two studies reported ovarian hyperstimulation syndrome (OHSS) as an outcome measure. There were no comparative data for clomiphene citrate and no comparative data on live-birth rates for GIFT. There was no evidence of a difference in live-birth rates between IVF and IUI either without (OR 1.96; 95% CI 0.88 to 4.4) or with (OR 1.15; 95% CI 0.55 to 2.4) ovarian stimulation. There were significantly higher clinical pregnancy rates with IVF in comparison to expectant management (OR 3.24; 95% CI 1.07 to 9.80). There was no significant difference between IVF and GIFT for the one RCT that reported live-birth rates (OR 2.57; 95% CI 0.93 to 7.08). However, there was a significant difference in the clinical pregnancy rates between IVF and GIFT, with pregnancy rates greater for IVF (OR 2.14; 95% CI 1.08 to 4.2). There was no evidence of a difference in the multiple pregnancy rates between IVF and IUI with ovarian stimulation (OR 0.63; 95% CI 0.27 to 1.5), however, IVF had a higher rate than GIFT (OR 6.3; 95% CI 1.7 to 23). Clinical heterogeneity was present among the studies included. However, there was no evidence of statistical heterogeneity, which allowed the studies to be combined for statistical analysis.

Authors' conclusions

Any effect of IVF relative to expectant management, clomiphene citrate, IUI with or without ovarian stimulation and GIFT in terms of live-birth rates for couples with unexplained subfertility remains unknown. The studies included are limited by their small sample size so that even large differences might be hidden. Live-birth rates are seldom reported. Periods of follow up are inadequate and unequal. Adverse effects such as multiple pregnancies and ovarian hyperstimulation syndrome have also not been reported in most studies. Larger trials with adequate power are warranted to establish the effectiveness of IVF in these women. Future trials should not only report rates per woman/couple but also include adverse effects and costs of the treatments as outcomes. Factors that have a major effect on these outcomes such as fertility treatment, female partner's age, duration of infertility and previous pregnancy history should also be considered.

 

Plain language summary

In vitro fertilisation (IVF) might result in more pregnancies than other options for unexplained infertility, but this is still uncertain and more research is needed on birth rates, adverse outcomes and costs

IVF is becoming popular when there is no specific explanation for infertility as it may be able to overcome a variety of problems. However, it is expensive, complicated and can have many adverse effects (including multiple births). Other options for unexplained infertility include drugs to stimulate the ovaries ('fertility drugs'), insemination and GIFT (gamete intrafallopian transfer, a more invasive method than IVF). The review of trials found that IVF may result in more pregnancies than other techniques for couples with unexplained infertility, but the research is not conclusive. Adverse outcomes and costs have not been adequately addressed in the trials.

 

摘要

背景

針對不明原因之次不孕症所用的體外受精

針對不明原因的不孕症而言，體外受精已經成為普遍接受的治療方法(RCOG 1998)。然而，因為在每個週期中，預估能夠產下活胎的比率會在13% 到28% 之間不等，所以人們也就沒有將它與其他的治療方法進行比較，然後針對它的功效來進行嚴格的評估。隨著人們對於期待治療及較少侵入性處置 (如人工授精) 的認知提高，加上考量到體外授精伴隨而來的諸多併發症如多胞妊娠及花費，使得針對患有不明原因之不孕症夫婦而言，比較體外授精及其他治療這件事顯得格外重要。

目標

本篇回顧的目的是要在不明原因之不孕症的背景之下，確認體外受精是否可以提升產下活胎的可能性，至於比較的對象則包括了(1)期待治療，(2)clomiphene的citrate (CC) ，(3)單獨使用子宮內的人工授精(IUI)，(4)子宮內的人工授精加上受到管控的卵巢刺激，以及(5)配子輸卵管內植入術(GIFT)。

搜尋策略

我們搜尋 Cochrane Menstrual Disorders以及Subfertility Group Trials Register (2004年3月23日搜尋) 、Cochrane Central Register of Controlled Trials (Cochrane Library Issue 3, 2004) 、MEDLINE (1970年2004年8月) 、EMBASE (1985年2004年8月) 以及文章的參考資料清單。我們也人工搜尋本領域相關的研討會的手冊，並與相關研究人員聯繫。

選擇標準

當中只收集了隨機對照試驗。關於每1名婦女產下活胎的比率，是我們關心的主要結果。

資料收集與分析

有2位審稿者獨立地評估了試驗的合格程度與品質。

主要結論

當中共確認了10份隨機對照試驗。在其中的2份試驗當中，我們沒有辦法針對不明原因的不孕症例子而分開擷取出資料，有2份則是沒有經過隨機化，有1份則是沒有針對有效的比率而加以報告(涵蓋在本篇回顧當中，但是並沒有出現在統合分析當中)；共留下了4份試驗可以用於分析。有1份試驗曾經比較了2種不同的介入行為(體外受精相較於子宮內的人工授精，並且搭配或不搭配卵巢刺激)，同時有1份研究曾經比較了3種介入行為(體外受精相較於子宮內的人工授精搭配卵巢刺激，以及配子輸卵管內植入術)。在體外受精與其他的治療方法之間，有關於曾經評估過其功效的試驗數目則如下所列：體外受精相較於期待治療(2份)、體外受精相較於子宮內的人工授精(1份)、體外受精相較於子宮內的人工授精搭配卵巢刺激(2份)，以及體外受精相較於配子輸卵管內植入術(3份)。在3份研究當中，曾經報告過每名婦女產下活胎的比率，也有3份研究曾經確認過每名婦女的臨床懷孕比率。在3份試驗當中，曾經報告過懷上多胞胎的比率。有2份研究曾經將卵巢過度刺激症候群(OHSS)當作某種結果方面的測量方法來進行報告。對於clomiphene citrate而言，並沒有可以相提並論的資料，而對於配子輸卵管內植入術而言，在產下活胎的比率方面也沒有可以相提並論的資料。不論是未搭配(OR 1.96；95% CI 0.88到4.4)或是有搭配(OR 1.15；95% CI 0.55到2.4)卵巢刺激，在體外受精與子宮內的人工授精之間，就產下活胎的比率來看，並沒有證據顯示出任何差異存在。期待治療比較起來，使用體外受精的時候，很明顯地可以得到比較高的臨床懷孕比率(OR 3.24；95% CI 1.07到9.80)。有一份報告顯示產下活胎的比率在體外授精及配子輸卵管植入術兩組之間並無差異(OR 2.57；95% CI 0.93到7.08)。然而，在體外受精與配子輸卵管內植入術之間，就臨床的懷孕比率來看，卻有著很明顯的差異存在，其中以體外受精會得到較高的懷孕比率(OR 2.14；95% CI 1.08到4.2)。在體外受精與子宮內的人工授精搭配上卵巢刺激之間，就懷上多胞胎的比率來看，並沒有證據可以顯示出任何的差異(OR 0.63；95% CI 0.27到1.5)，然而，跟配子輸卵管內植入術比較起來，體外受精卻有著某種更高的比率(OR 6.3；95% CI 1.7到23)。在這些被收集在內的研究之間，呈現了臨床方面的質異性。然而，對於統計學方面的質異性而言，並沒有任何的證據，因此也就使得這些研究能夠合併起來進行統計學分析。

作者結論

對於患有不明原因的次不孕症婦女而言，接受體外授精相對於期待治療使用clomiphene citrate 。人工授精搭配或不搭配卵巢刺激及配子輸卵管內植入術，在活產率方面的影響仍不清楚。這些被收集在內的研究都因為它們過小的樣本規模而受到限制，以致於即便有大型的差異存在，卻有可能被隱藏起來了。很少有對於產下活胎之比率方面的報告提出。這些追蹤的時間都不合適而且不平等。在大多數的研究之中，像是多胞胎妊娠，以及卵巢過度刺激症候群，也都沒有被報告出來。對於這些婦女們而言，有必要進行大型的、具有適當份量的試驗，以確立出體外受精的功效。將來的試驗就不應該只是針對對每名婦女/每對夫妻的比率來進行報告，還應該要包含不良影響與這些治療所需的花費來作為結果。這些結果共包含了受孕的治療、女性伴侶的年齡、不孕的時間長度，以及過去懷孕的經歷，而對於這些結果造成某種重大影響的各種因素，也都應該要被列入考量。

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

對於不明原因的不孕症而言，跟其他的選擇比較起來，體外受精(IVF)可能會帶來更多懷孕的例子，但是這個部分仍然是不明確的，而且針對出生的比率、不良的結果，以及費用等方面，還需要有更多的研究。對於無法解釋的不孕症，體外受精便被普遍施行，因為它或許能夠克服很多不同的問題。然而，它卻很昂貴、複雜，而且還有可能造成許多不良的影響(包括了產下多胞胎)。對於不明原因的不孕症而言，其他的選擇還包括了用來刺激卵巢的藥物(「受孕藥物」)、人工授精，以及GIFT(配子輸卵管內植入術，跟體外受精比較起來，是1種侵入性比較低的方法)。本篇試驗的回顧發現，對於患有不明原因之不孕症的夫妻們而言，跟其他的各項技術比較起來，體外受精可能會帶來更多懷孕的例子，但是這樣的研究還不是確定的。在這些試驗當中，都還沒有針對不良的結果與花費而進行適當的說明。