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辅助生殖技术周期中植入前糖皮质激素的应用

Peri-implantation glucocorticoid administration for assisted reproductive technology cycles.

作者信息

Boomsma Carolien M, Keay Stephen D, Macklon Nick S

机构信息

Obstetrics and Gynaecology, University Medical Center Utrecht, Utrecht, Netherlands. 2Centre for Reproductive Medicine, UHCWNHS Trust, Coventry, UK.

出版信息

Cochrane Database Syst Rev. 2012 Jun 13(6):CD005996. doi: 10.1002/14651858.CD005996.pub3.

Abstract

BACKGROUND

In order to improve embryo implantation for in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles the use of glucocorticoids has been advocated. It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and normalise the cytokine expression profile in the endometrium and by suppression of endometrial inflammation.

OBJECTIVES

To investigate whether the administration of glucocorticoids around the time of implantation improved clinical outcomes in subfertile women undergoing IVF or ICSI when compared to no glucocorticoid administration.

SEARCH METHODS

The Cochrane Menstrual Disorders and Subfertility Group Trials Register (September 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2011), MEDLINE (1966 to September 2011), EMBASE (1976 to September 2011), CINAHL (1982 to September 2011) and Science Direct (1966 to September 2011) were searched. Reference lists of relevant articles and relevant conference proceedings were handsearched.

SELECTION CRITERIA

All randomised controlled trials (RCTs) addressing the research question were included.

DATA COLLECTION AND ANALYSIS

Two review authors independently assessed eligibility and quality of trials and extracted relevant data.

MAIN RESULTS

Fourteen studies (involving 1879 couples) were included. Three studies reported live birth rate and these did not identify a significant difference after pooling the (preliminary) results (OR 1.21, 95% CI 0.67 to 2.19). With regard to pregnancy rates, there was also no evidence that glucocorticoids improved clinical outcome (13 RCTs; OR 1.16, 95% CI 0.94 to 1.44). However, a subgroup analysis of 650 women undergoing IVF (6 RCTs) revealed a significantly higher pregnancy rate for women using glucocorticoids (OR 1.50, 95% CI 1.05 to 2.13). There were no significant differences in adverse events, but these were poorly and inconsistently reported.

AUTHORS' CONCLUSIONS: Overall, there was no clear evidence that administration of peri-implantation glucocorticoids in ART cycles significantly improved the clinical outcome. The use of glucocorticoids in a subgroup of women undergoing IVF (rather than ICSI) was associated with an improvement in pregnancy rates of borderline statistical significance and should be interpreted with care. These findings were limited to the routine use of glucocorticoids and cannot be extrapolated to women with autoantibodies, unexplained infertility or recurrent implantation failure. Further well designed randomised studies are required to elucidate the possible role of this therapy in well defined patient groups.

摘要

背景

为提高体外受精(IVF)或卵胞浆内单精子注射(ICSI)周期的胚胎着床率,有人主张使用糖皮质激素。有人提出,糖皮质激素可通过作为免疫调节剂来减少子宫自然杀伤(NK)细胞数量并使子宫内膜中的细胞因子表达谱正常化,以及通过抑制子宫内膜炎症来改善子宫内环境。

目的

探讨与不使用糖皮质激素相比,在着床期前后给予糖皮质激素是否能改善接受IVF或ICSI的不育妇女的临床结局。

检索方法

检索了Cochrane月经失调与不育症小组试验注册库(2011年9月)、Cochrane对照试验中央注册库(CENTRAL)(2011年9月)、医学期刊数据库(MEDLINE,1966年至2011年9月)、荷兰医学文摘数据库(EMBASE,1976年至2011年9月)、护理学与健康照护数据库(CINAHL,1982年至2011年9月)以及科学Direct数据库(1966年至2011年9月)。对相关文章的参考文献列表和相关会议论文集进行了手工检索。

选择标准

纳入所有针对该研究问题的随机对照试验(RCT)。

数据收集与分析

两位综述作者独立评估试验的纳入资格和质量,并提取相关数据。

主要结果

纳入了14项研究(涉及1879对夫妇)。三项研究报告了活产率,汇总(初步)结果后未发现显著差异(比值比1.21,95%置信区间0.67至2.19)。关于妊娠率,也没有证据表明糖皮质激素能改善临床结局(13项RCT;比值比1.16,95%置信区间0.94至1.44)。然而,对650名接受IVF的妇女进行的亚组分析(6项RCT)显示,使用糖皮质激素的妇女妊娠率显著更高(比值比1.50,95%置信区间1.05至2.13)。不良事件方面没有显著差异,但报告质量差且不一致。

作者结论

总体而言,没有明确证据表明在辅助生殖技术周期中植入期前后给予糖皮质激素能显著改善临床结局。在接受IVF(而非ICSI)的一部分妇女中使用糖皮质激素与妊娠率有边缘统计学意义的改善相关,对此应谨慎解读。这些发现仅限于糖皮质激素的常规使用,不能外推至有自身抗体、不明原因不育或反复植入失败的妇女。需要进一步设计良好的随机研究来阐明这种治疗方法在明确界定的患者群体中的可能作用。

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