Reproductive Medicine Unit, University College London Hospital, London, United Kingdom; Institute for Women's Health, University College London, London, United Kingdom.
Reproductive Medicine Unit, University College London Hospital, London, United Kingdom; Institute for Women's Health, University College London, London, United Kingdom.
Eur J Obstet Gynecol Reprod Biol. 2024 Oct;301:87-94. doi: 10.1016/j.ejogrb.2024.07.063. Epub 2024 Aug 2.
Adenomyosis can reduce the chance of clinical pregnancy in women undergoing assisted conception. Treatment with prolonged gonadotrophin-releasing hormone analogue (GnRHa) downregulation prior to IVF/ICSI has been postulated to improve pregnancy outcomes.
We aimed to evaluate the effectiveness and safety of prolonged GnRHa treatment (minimum one month) versus no pre-treatment in women with adenomyosis undergoing IVF/ICSI using a systematic review and meta-analysis.
We searched electronic databases: Embase (OVID), MEDLINE® (OVID), APA PsycInfo (OVID), Maternity & Infant Care Database (MIDIRS (OVID), HMIC Health Management Information Consortium (OVID) and ClinicalTrials.gov from inception until 27th of March 2023.
We included studies that reported on women with adenomyosis receiving GnRHa to down-regulate the hypothalamic-pituitary-ovarian axis for one to six months before IVF/ICSI. We pooled data using the Haensel-Mantel method and reported using Odds Ratio (OR) with 95 % confidence intervals (CI). We assessed the quality of included studies using the Newcastle-Ottowa Scale and confidence in evidence using the GRADE criteria. Bias analysis was conducted via the Cochrane recommended tool (RevMan Web, Academic License).
We screened 365 citations and eight retrospective studies were included in the meta-analysis (n = 2422 women). The median age was 34 years [IQR 31.95-35.05], median BMI 21.30 kg/m [IQR 21.05-23.55] and median duration of GnRHa downregulation was 2.5 months [Range 1-4; IQR 1.37-3]. Women with adenomyosis receiving prolonged GnRHa treatment had a higher implantation rate 1/OR 1.69 [95 % CI 1.09, 2.56], I = 81 %, (P = 0.02) and clinical pregnancy rate 1/OR 1.42 [95 % CI 1.03, 2.0], I 70 %, P = 0.03. There was no overall difference in live birth rate 1/OR 1.12 [95 % CI 0.70, 1.79], I = 78 %, p = 0.63), miscarriage rate 1/OR 0.92 [95 % CI 0.63, 1.28, P = 0.61, I 0 % or mean number of oocytes retrieved (10 oocytes [IQR 8.95; 11.15] vs. 9.28 [IQR 8; 10.20], p = 0.22) between groups.
The benefit of prolonged GnRHa treatment in women with adenomyosis undergoing assisted conception treatment is uncertain based on existing retrospective studies. Implantation and clinical pregnancy rates were higher following prolonged downregulation in this population, though there was no statistically significant difference in live birth and miscarriage rates. Given the limited, low-quality existing data, there is a need for a well-designed, prospective randomised controlled trial to precisely evaluate the effectiveness of prolonged GnRHa treatment in this population.
重要性：子宫腺肌病会降低接受辅助受孕的女性临床妊娠的机会。在 IVF/ICSI 前使用长效促性腺激素释放激素类似物（GnRHa）下调治疗已被提出可以改善妊娠结局。
目的：我们旨在使用系统评价和荟萃分析评估在接受 IVF/ICSI 的子宫腺肌病患者中使用长效 GnRHa 治疗（至少一个月）与无预处理相比的有效性和安全性。
数据来源：我们搜索了电子数据库：Embase（OVID）、MEDLINE®（OVID）、APA PsycInfo（OVID）、Maternity & Infant Care Database（MIDIRS（OVID）、HMIC Health Management Information Consortium（OVID）和 ClinicalTrials.gov 从成立到 2023 年 3 月 27 日。
研究选择和综合：我们纳入了报告接受 GnRHa 下调下丘脑-垂体-卵巢轴一个月至六个月以进行 IVF/ICSI 的子宫腺肌病妇女的研究。我们使用 Haensel-Mantel 方法汇总数据，并使用比值比（OR）和 95%置信区间（CI）报告。我们使用纽卡斯尔-渥太华量表评估纳入研究的质量，并使用 GRADE 标准评估证据的可信度。偏倚分析通过 Cochrane 推荐的工具（RevMan Web，学术许可证）进行。
主要结果和结论：我们筛选了 365 条引文，其中 8 项回顾性研究被纳入荟萃分析（n=2422 名女性）。中位年龄为 34 岁[IQR 31.95-35.05]，中位 BMI 为 21.30kg/m[IQR 21.05-23.55]，中位 GnRHa 下调时间为 2.5 个月[范围 1-4；IQR 1.37-3]。接受长效 GnRHa 治疗的子宫腺肌病患者的着床率更高（1/OR 1.69 [95%CI 1.09, 2.56]，I=81%，P=0.02）和临床妊娠率（1/OR 1.42 [95%CI 1.03, 2.0]，I=70%，P=0.03）。两组间活产率（1/OR 1.12 [95%CI 0.70, 1.79]，I=78%，p=0.63）、流产率（1/OR 0.92 [95%CI 0.63, 1.28，P=0.61，I=0%）或平均取卵数（10 个卵母细胞[IQR 8.95；11.15] vs. 9.28 [IQR 8；10.20]，p=0.22）无总体差异。
结论和相关性：根据现有的回顾性研究，在接受辅助受孕治疗的子宫腺肌病患者中，长效 GnRHa 治疗的益处尚不确定。在该人群中，延长下调后着床率和临床妊娠率更高，但活产率和流产率无统计学显著差异。鉴于现有数据有限且质量较低，需要进行精心设计的前瞻性随机对照试验，以准确评估延长 GnRHa 治疗在该人群中的有效性。
