Supplementary file 2_Oocyte maturation triggering in high responders in IVF treatment: a systematic review and network meta-analysis.docx

ObjectiveThe aim of this study was to compare and rank the efficacy and safety of four final oocyte maturation trigger strategies—human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonist (GnRHa), dual, and double trigger—in predicted high responders undergoing in vitro fertilization (IVF) with GnRH antagonist protocols, using a network meta-analysis (NMA) approach.
MethodsA systematic search of MEDLINE, EMBASE, CENTRAL, clinical trial registries, and the Cochrane Database of Systematic Reviews was conducted through December 2024. Eligible studies were randomized controlled trials (RCTs) including high responders, defined by elevated antral follicle count, anti-Müllerian hormone, or estradiol levels. Studies using GnRHa triggers followed by fresh embryo transfer were included only if intensive luteal phase support was provided. Oocyte donation cycles, quasi-randomized designs, and trials lacking outcome data were excluded. Data extraction and risk of bias assessment were independently conducted by two reviewers. Study integrity was evaluated using the TRACT checklist. NMA was performed in STATA (v16), and treatment ranking was based on Surface Under the Cumulative Ranking curve (SUCRA).
ResultsSeven high-quality RCTs comprising 632 women were included. There were no significant differences in the number of oocytes retrieved between GnRHa and hCG triggers (mean difference [MD] 1.08, 95% CI –1.06 to 3.22), dual and hCG (MD 0.61, 95% CI –1.53 to 2.74), or GnRHa and dual (MD 1.08, 95% CI –1.06 to 3.22). Similarly, there were no significant differences in mature oocyte yield, clinical pregnancy rate (CPR), or miscarriage rate across comparisons. However, GnRHa trigger significantly reduced the risk of moderate to severe ovarian hyperstimulation syndrome (OHSS) compared with hCG (RR 0.23, 95% CI 0.07–0.82). There were no significant differences in OHSS risk between dual and hCG (RR 0.28, 95% CI 0.05–1.64) or between GnRHa and dual (RR 0.28, 95% CI 0.05–1.64).
ConclusionGnRHa, hCG, and dual triggers demonstrate similar efficacy in terms of oocyte yield, maturity, and clinical pregnancy rates in predicted high responders. The GnRHa trigger, however, offers a superior safety profile by significantly lowering the risk of OHSS. Larger multicenter RCTs are required to evaluate live birth outcomes and the potential role of the double trigger in this population.
Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022351423.

研究目的 本研究旨在采用网络荟萃分析（network meta-analysis, NMA）方法，对比并排序四种最终卵母细胞成熟触发策略——人绒毛膜促性腺激素（human chorionic gonadotropin, hCG）、促性腺激素释放激素激动剂（gonadotropin-releasing hormone agonist, GnRHa）、双触发及双重触发——在采用GnRH拮抗剂方案进行体外受精（in vitro fertilization, IVF）的预估卵巢高反应人群中的有效性与安全性。

研究方法 本研究系统检索了MEDLINE、EMBASE、CENTRAL、临床试验注册平台及Cochrane系统评价数据库，检索时限截至2024年12月。纳入的合格研究为针对卵巢高反应人群的随机对照试验（randomized controlled trials, RCTs），卵巢高反应的定义为窦卵泡计数增多、抗米勒管激素或雌二醇水平升高。仅当研究采用GnRHa触发后行新鲜胚胎移植且辅以强化黄体支持时，方可纳入。排除卵母细胞捐赠周期、半随机设计研究及缺乏结局数据的试验。由两名评价员独立完成数据提取及偏倚风险评估，采用TRACT检查表评价研究完整性。采用STATA软件（版本16）进行网络荟萃分析，基于累积排序曲线下面积（Surface Under the Cumulative Ranking curve, SUCRA）对干预措施进行排序。

研究结果 最终纳入7项高质量随机对照试验，共涉及632名受试者。GnRHa与hCG触发组间获卵数差异无统计学意义（均数差[mean difference, MD]=1.08，95%置信区间[95% CI]=–1.06至3.22），双触发与hCG组间差异亦无统计学意义（MD=0.61，95% CI=–1.53至2.74），GnRHa与双触发组间差异同样无统计学意义（MD=1.08，95% CI=–1.06至3.22）。类似地，各组间成熟卵母细胞获取数、临床妊娠率（clinical pregnancy rate, CPR）及流产率均无显著差异。但与hCG组相比，GnRHa触发可显著降低中重度卵巢过度刺激综合征（ovarian hyperstimulation syndrome, OHSS）的发生风险（相对危险度[relative risk, RR]=0.23，95% CI=0.07至0.82）。双触发与hCG组间OHSS风险差异无统计学意义（RR=0.28，95% CI=0.05至1.64），GnRHa与双触发组间OHSS风险亦无显著差异（RR=0.28，95% CI=0.05至1.64）。

研究结论 在预估卵巢高反应人群中，GnRHa、hCG及双触发策略在卵母细胞获取数、成熟率及临床妊娠率方面的有效性相当；但GnRHa触发可显著降低OHSS风险，安全性更优。未来需开展更大样本的多中心随机对照试验，以评估活产结局及双重触发在该人群中的潜在应用价值。

系统评价注册信息 https://www.crd.york.ac.uk/prospero/，标识符为CRD42022351423。