Oral versus injectable ovulation induction agents for unexplained subfertility

  • Review
  • Intervention

Authors


Abstract

Background

Oral (anti-oestrogens) and injectable (gonadotrophins) ovulation induction agents have been used to increase the number of eggs produced by a woman per cycle in treatment for unexplained subfertility. It is unclear whether there are significant advantages of one type of treatment over the other in this context or in terms of fertility.

Objectives

To assess the efficacy of oral versus injectable ovulation induction agents for unexplained subfertility.

Search methods

The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of relevant randomised controlled trials.

Selection criteria

All trials where oral ovulation induction agents were compared with injectable ovulation induction agents in treatment groups generated by randomisation, from couples with unexplained subfertility, were considered for inclusion in the review.

Data collection and analysis

Five randomised controlled trials, including a total of 231 identified couples with unexplained subfertility, were found and included in this review. All trials were assessed for quality criteria. The studied outcomes were pregnancy, live birth, miscarriage, multiple birth, occurrence of ovarian hyperstimulation syndrome and cycle cancellation.

Main results

Where trials with important co-interventions were excluded, there was no significant difference in the odds of beneficial outcomes for oral versus injectable ovulation induction agents - live birth per couple (OR 0.06, 95%CI 0.00 to 1.15), pregnancy per woman (OR 0.33, 95%CI 0.09 to 1.20); nor of detrimental outcomes for injectable versus oral agents - miscarriage (OR 0.11, 95%CI 0.00 to 2.84); there were no reported cases of multiple births, cases of ovarian hyperstimulation or discontinued cycles consequent upon overstimulation.

Where trials with the co-intervention of a human chorionic gonadotrophin trigger injection (given only in the injectable ovulation induction agent treatment arm) were not excluded there was no significant difference in the odds of live birth per couple (OR 0.40, 95%CI 0.15 to1.08). However oral ovulation induction agents had significantly reduced odds of pregnancy per woman compared to injectable ovulation induction agents (OR 0.41, 95%CI 0.17 to 0.80). For detrimental outcomes, there were no significant differences in the odds of miscarriage (OR 0.61, 95%CI 0.09 to 4.01) and multiple birth (OR 1.08, 95%CI 0.16 to 7.03) for injectable versus oral agents. No data were available concerning the occurrence of ovarian hyperstimulation syndrome nor cycle cancellation.

Authors' conclusions

There is insufficient evidence to suggest that oral agents are inferior or superior to injectable agents in the treatment of unexplained subfertility. Information on harms is sketchy, and remains compatible with large differences in either direction. Much larger trials than have previously been undertaken are required to provide information on relative harms as well as benefits.

摘要

背景

對於不明原因的次不孕症所使用之誘導排卵藥物而言,將口服型與注射型進行比較

對於不明原因的次不孕症在進行治療的時候,口服型(抗雌激素類)與注射型(促性腺激素類)的誘導排卵藥物,都已經被用來增加婦女在每1個週期中所製造的卵子數目。在這樣的背景之下,或是就受孕的角度來看,跟其他的治療方法比較起來,這些治療方法當中的某1種類型是否明顯地具有優勢,目前還不清楚。

目標

對於不明原因的次不孕症所使用之誘導排卵藥物而言,要評估口服型與注射型的功效。

搜尋策略

使用Menstrual Disorders以及Subfertility Group搜尋方法以找出相關的隨機對照試驗。

選擇標準

在本篇回顧當中,隨機化的收集了不明原因的次不孕症夫婦,針對注射劑型及口服劑型的排卵藥物進行比較。

資料收集與分析

在本篇回顧當中,共發現了5份隨機對照試驗,並將它們收集在內,當中包含了總數為231對經過確認過且患有不明原因之次不孕症的夫妻們。針對品質方面的標準,所有的試驗都經過了評估。這些經過研究之後的結果為懷孕、產下活胎、流產、多胞胎妊娠、發生卵巢過度刺激症候群的情況,以及取消誘導排卵等方面。

主要結論

當這些試驗當中包含了重要的共同介入行為時,它們就會被排除在外,因此,針對口服型相較與注射型之誘導排卵藥物而言,在有利結果的可能性方面,就沒有明顯的差異  每對夫妻產下活胎(OR 0.06,95% CI 0.00 – 1.15)、每名婦女的懷孕情形(OR 0.33,95% CI 0.09 – 1.20);針對注射型相較與口服型之藥物而言,並不包含任何不利的結果流產(OR 0.11,95% CI 0.00 – 2.84);關於產下多胞胎方面的例子、卵巢過度刺激的例子,或是因為過度刺激而造成週期中斷的結果等方面,並沒有任何的報告。當這些試驗中包含了某種以人類的絨毛膜性腺激素注射劑(前提是只能夠在注射型的排卵誘導藥物之治療方式當中)來作為共同介入行為,而且這些試驗又沒有被排除在外的時候,對於每對夫妻產下活胎的可能性(OR 0.40,95% CI 0.15 – 1.08)而言,就沒有明顯的差異存在。然而,跟注射型的排卵誘導藥物比較起來,口服型的誘導排卵藥物卻會顯著地降低每名婦女懷孕的可能性(OR 0.41, 95% CI 0.17 – 0.80)。針對注射型與口服型藥物的比較而言,就不利的結果來看,在流產(OR 0.61,95% CI 0.09 – 4.01)與產下多胞胎(OR 1.08,95% CI 0.16 – 7.03)的可能性之中,並沒有顯著的差異存在。若是要考慮到發生卵巢過度刺激症候群的情況,或是取消誘導排卵的週期,都沒有辦法取得相關的資料。

作者結論

對於不明原因之次不孕症的治療而言,口服型的藥物會比注射型的藥物還要占有劣勢或優勢,並沒有足夠的證據能夠加以推定。就危害方面來看,資訊都只是概略的,而且在各個方面,都還包含著大型的差異。就相關的危害方面來看,就像是我們看待優點的角度一般,跟之前曾經進行過的試驗比較起來,還需要有更大型的試驗來提供資訊。

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

對於許多不能夠懷上孩子的夫妻們來說,經過了研究之後,並沒有任何原因是顯著的(不明原因的次不孕症)。對於這些夫妻們來說,其中一種治療方式便是,給予該名婦女藥物,以增加她在每1個週期中所製造的卵子數目。有時候,這樣的治療方使也會跟某種用來純化伴侶精子的技術合併使用,並且在她受孕的時間點上,透過該名婦女的子宮頸而將它注射進去。本篇試驗的回顧關注的是,對於得到最成功的結果而言,在這些口服型式或是注射型式的藥物之中,哪種類型會是最佳的選擇。雖然從這些試驗中並沒有足夠的資料證明某一種藥物與另一種藥物比較起來有明顯的益處。仍需要有更多的研究來檢查這個問題。

Plain language summary

Oral versus injectable ovulation induction agents for unexplained subfertility

For many couples who cannot become pregnant, no reason is apparent after investigation (unexplained infertility). One treatment option for these couples is for the woman to be given medications to increase the number of eggs she produces each cycle. This treatment is also sometimes combined with a technique of purifying the partner's sperm and injecting it through the woman's cervix at her fertile time. This review of trials looked at which type of these medications, oral-form or injection-form, were the best in producing the most successful outcome. The review found no significant benefit of using one type of medication (oral or injectable) over the other, although there were insufficient data from trials. More research is needed to examine this question.

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