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Intervention Review

Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles

  1. Luiz Eduardo Trevisan Albuquerque1,*,
  2. Humberto Saconato2,
  3. Maria Cecília Romano Maciel3,
  4. L O Tso4

Editorial Group: Cochrane Menstrual Disorders and Subfertility Group

Published Online: 24 JAN 2005

Assessed as up-to-date: 16 NOV 2004

DOI: 10.1002/14651858.CD002808.pub2


How to Cite

Trevisan Albuquerque LE, Saconato H, Maciel MCR, Tso LO. Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD002808. DOI: 10.1002/14651858.CD002808.pub2.

Author Information

  1. 1

    Fertivitro Centro de Reprodução Humana, Human Reproduction Center, São Paulo, Brazil

  2. 2

    Federal University of Rio Grande do Norte, Department of Medicine, São Paulo, Vila Clementino, Brazil

  3. 3

    Sao Paulo, Brazil

  4. 4

    Federal University of São Paulo (UNIFESP), Gynecology, São Paulo, Vila Clementino, Brazil

*Luiz Eduardo Trevisan Albuquerque, Human Reproduction Center, Fertivitro Centro de Reprodução Humana, Av. Indianopolis 843, B. Moema, São Paulo, Brazil. leta@osite.com.br.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 24 JAN 2005

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Gonadotrophin-releasing hormone agonist (GnRHa) has been widely used in cycles of in vitro fertilization (IVF). Among the various types of GnRHa ovarian stimulation protocols, the long protocol presents the best clinical pregnancy rates per cycle initiated (GnRHa administration until the suppression of ovarian activity is evident, within approximately 14 days). There are two types of GnRHa administration that can be used to lead to hypophysis desensitization in the IVF cycle in the long protocol: one consisting of daily GnRHa low doses, and another with the administration of analogues in higher long-acting doses (depot). There are controversies in the data as far as the number of ampoules to be used in the cycles with the depot GnRHa treatment, as well as regarding the number of follicles made available, the number of oocytes, fertilization, implantation and pregnancy rates.

Objectives

The objective of this study is to compare the use of a single long-acting depot dose to that of daily GnRHa doses in in vitro fertilization cycles.

Search methods

We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched 15 April 2004), Cochrane Central Register of Controlled Trials (Issue 2, 2004), MEDLINE (1984 to April 2004), EMBASE (1984 to June 2003), LILACS (1984 to April 2004) and reference lists of articles.

Selection criteria

Types of studies: RCTs comparing depot and daily administration of GnRHa for long protocols in IVF treatment cycles.
Types of participants: Couples with any cause of infertility.
Types of interventions: Ovarian stimulation with human follicle stimulating hormone (hFSH) and/or human menopausal gonadotropin (hMG) and/or recombinant follicle stimulating hormone (rFSH) in IVF treatment cycles.
Types of outcome measures: Clinical pregnancy rates per woman, per oocyte retrieval procedure, per embryo transfer, number of oocytes retrieved, oocyte fertilization rates, ongoing/delivered pregnancy rates per cycle started, abortion rates, multiple pregnancy rates, number of ampoules of gonadotropin employed, ovarian hyperstimulation syndrome (OHSS) incidence rates, cost analysis and patient convenience.

Data collection and analysis

The reviewers evaluated allocation concealment, classified as adequate, uncertain or inadequate. Two reviewers extracted the data independently. All analyses were performed according to the intention-to-treat method.

Main results

Six studies, with a total of 552 women, were included and analysed. The studies do not indicate that there is statistically significant difference between the use of depot GnRHa or daily GnRHa in the primary outcome, clinical pregnancy rates per woman (OR 0.94, 95% CI 0.65 to 1.37). However, there was sufficient evidence that the use of depot GnRHa for pituitary desensitization in IVF cycles increased the number of gonadotrophins ampoules (WMD 3.30, 95% CI 1.27 to 5.34) and the duration of the ovarian stimulation (WMD 0.56, 95% CI 0.31 to 0.81), as compared with daily GnRHa.

Authors' conclusions

Although we recognise that the clinical pregnancy rates per woman are not the ideal primary outcome, we found no evidence of differences between the long protocol using depot or daily GnRHa for IVF cycles. However, the use of depot GnRHa is associated with increased requirements for gonadotrophins and a longer time required for ovarian stimulation. If these differences could be shown to translate into economic benefit, depot GnRHa should increase the overall costs of IVF treatment.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Long-acting GnRHa instead of a daily dose in IVF cycles increases costs, without improving pregnancy rates or other outcomes

In vitro fertilisation (IVF) cycles involve women taking a series of hormones. Using the hormone drug GnRHa (gonadotrophin-releasing hormone analogues) during one stage of this process increases the chance of pregnancy. There are several options for GnRHa use. Long courses can be either daily low doses, or a higher longer acting dose (depot version). The review found that depot and daily GnRHa have similar rates of pregnancy and adverse effects. However, depot GnRHa increases the cost of an IVF cycle, because it lengthens the period to ovulation and women need to use more of other hormone drugs in the cycle.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

在輔助性生殖週期中,針對腦下垂體去敏化所使用的釋放促性腺激素荷爾蒙促進劑計畫而言,長效型給藥與每日給藥的比較

釋放促性腺激素荷爾蒙促進劑(GnRHa)已經被廣泛地使用在體外受精(IVF)的各個週期之中。對於釋放促性腺激素荷爾蒙促進劑的卵巢刺激計畫而言,在各個不同的類型當中,長療程的治療可以為每個起始的週期帶來最佳的臨床懷孕比率(在大約14天的時間內,給予釋放促性腺激素荷爾蒙促進劑,直到卵巢的活性已經明顯地受到抑制)。釋放促性腺激素荷爾蒙促進劑的給藥方式共有2種類型,而在長療程當中,對於體外受精的週期而言,這些給藥方式可以用來促進腦下垂體的去敏化:其中1種類型包含了每天給予低劑量的釋放促性腺激素荷爾蒙促進劑,而另外1種類型則是要配合給予它的類似物,並且以作用時間較長的劑量來給藥(長效型)。當考量到可以取得的卵泡數目、卵母細胞的數目、受精的情況、移植與懷孕的比率等時要用多少劑量的長效型釋放促性腺激素仍有爭議,在這些資料中都出現了許多的爭議。

目標

這份研究的目標,就是要在體外受精的週期之中,針對某種單1型長期作用的長效型劑量,以及每日型的釋放促性腺激素荷爾蒙促進劑劑量,比較它們的使用狀況。

搜尋策略

我們搜尋 Cochrane Menstrual Disorders以及Subfertility Group's specialised register of trials (searched 15 April 2004) 、 Cochrane Central Register of Controlled Trials (Issue 2, 2004) 、 MEDLINE (1984年2004年4月) 、 EMBASE (1984年2003年6月) 、LILACS (1984年2004年4月) 及文章的參考資料清單。

選擇標準

研究的類型:針對長療程的體外受精週期而言,這些隨機對照試驗比較了釋放促性腺激素荷爾蒙促進劑採取長效型與每日型的給藥方式。參與者的類型:患有不孕症之任何1種成因的夫妻們。介入行為的類型:在體外受精治療各個週期之中,以人類卵泡刺激性荷爾蒙(hFSH)以及/或是人類停經期之促性腺激素(hMG)以及/或是重組型之卵泡刺激性荷爾蒙(rFSH)所造成的卵巢刺激。結果之測量方法的類型:每1名婦女、每1個取卵過程、每1次胚胎植入所得到的臨床懷孕比率、取得的卵子數目、卵母細胞受精的比率、每1個已經開始之週期中所得到的正在進行中/已經分娩過的懷孕比率、人工流產的比率、多胞胎妊娠的比率、使用過的促性腺激素之劑量、發生卵巢過度刺激症候群(OHSS)的比率、費用分析,以及病患的方便程度。

資料收集與分析

這些審稿者評估了分配方式的隱藏狀況,並將它們分類為合適、不明確,或是不恰當。有2位審稿者獨立的擷取出了資料。所有的分析都是採取意圖性治療的方法來進行分析的。

主要結論

共有包含了總數為552名婦女的6份研究被收集在內,並經過分析。若是拿每名婦女的臨床懷孕比率當作主要的結果來看,對於長效型的釋放促性腺激素荷爾蒙促進劑或是每日型的釋放促性腺激素荷爾蒙促進劑而言,並沒有顯示出任何統計學上的顯著差異(OR 0.94,95% CI 0.65到1.37)。然而,卻有充分的證據顯示,若是在體外受精的各個週期之中,針對腦下垂體的去敏化而言,跟每日型的釋放促性腺激素荷爾蒙促進劑比較起來,使用長效型的釋放促性腺激素荷爾蒙促進劑的時候,會增加使用促性腺激素的劑量(WMD 3.30,95% CI 1.27到5.34),並且延長卵巢刺激的時間長度(WMD 0.56,95% CI 0.31到0.81)。

作者結論

雖然我們認為以每1名婦女的臨床懷孕比率當成主要預後並不理想,但是我們卻發現,對於體外受精的各個週期而言,在使用長效型或是每日型之釋放促性腺激素荷爾蒙促進劑的長療程之間,並沒有任何證據能夠說明其中的差異。然而,使用長效型的釋放促性腺激素荷爾蒙促進劑之後,會使得婦女對於促性腺激素的需求提高,並且會需要更長的時間來進行卵巢刺激。假使這些差異都能夠被顯示出來,以轉換成經濟方面的利益來看,那麼長效型的釋放促性腺激素荷爾蒙促進劑應該會增加體外受精治療的整體費用。

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

對於體外受精的各個週期而言,若不是採取某種每日型的劑量,而是使用長期作用的釋放促性腺激素荷爾蒙促進劑,就會提高花費,但是卻沒有提升懷孕的比率或是改善其他的結果。體外受精(IVF)的各個週期,包括了婦女們要接受一系列的荷爾蒙。在這個過程當中的某個階段之期間內,使用 GnRHa(釋放促性腺激素荷爾蒙的類似物)這樣的荷爾蒙藥物,可以增加懷孕的機會。若是要使用釋放促性腺激素荷爾蒙促進劑的話,共有好幾個選擇。長期的使用方式可以採取每日型的低劑量,或是某種較長期作用型的較高劑量(長效型版本)。本篇回顧發現,長效型與每日型的釋放促性腺激素荷爾蒙促進劑,都具有類似的懷孕比率以及副作用。然而,長效型的釋放促性腺激素荷爾蒙促進劑會增加每個體外受精之週期的花費,因為它延長了排卵的時間,而且在這個週期之中,婦女們就需要使用更多其他種荷爾蒙類的藥物。