Abstract
OBJECTIVE: The 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. METHODS: A 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). RESULTS: Seven 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). CONCLUSION: GnRHa, 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 REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42022351423.