GnRH agonist with low-dose hCG (dual Trigger) versus GnRH agonist only trigger in high responders in GnRH antagonist cycle : a systematic review and meta-analysis.

Introduction Ovarian hyperstimulation syndrome (OHSS) remains a serious complication of assisted reproductive technology, particularly in high ovarian responders. Although a GnRHa-only trigger effectively minimizes the risk of OHSS, it has been associated with reduced oocyte yield and, in some reports, lower oocyte maturity, and may also compromise luteal function. Dual trigger, combining GnRHa with low-dose human chorionic gonadotropin (hCG), was developed to enhance reproductive outcomes, however, concerns persist that even low-dose hCG may reintroduce OHSS risk. This systematic review and meta-analysis aimed to compare the efficacy and safety of dual trigger versus GnRHa-only trigger in high ovarian responders. Methods A systematic search of PubMed, Scopus, and Google Scholar from January 2000 to December 2025 identified studies comparing dual trigger (GnRHa plus low-dose hCG) with GnRHa-only trigger in high responders undergoing IVF/ICSI. Randomized and observational cohort studies reporting reproductive outcomes or moderate-to-severe OHSS were included. Risk ratios (RRs) were calculated for reproductive outcomes, and odds ratios (ORs) were calculated for OHSS using random-effects models. Risk of bias was assessed using ROBINS-I, and the certainty of the evidence was evaluated using the GRADE framework. Results Five retrospective cohort studies were included. Dual trigger did not improve the number of oocytes retrieved, the mature oocyte rate, the fertilization rate, the embryo quality, the clinical pregnancy rate, the live birth rate, the cumulative live birth rate, or the miscarriage rate compared with the GnRHa-only trigger. In contrast, dual trigger was associated with increased risk of moderate-to-severe OHSS (OR 12.33; 95% CI 3.30-46.04), with consistently higher OHSS risk observed across hCG doses. Notably, no cases of OHSS were observed with the GnRHa-only trigger in either fresh or freeze-all cycles. Conclusion In high ovarian responders, dual trigger with low-dose hCG does not confer a reproductive benefit over GnRHa-only trigger but is associated with a higher observed incidence of moderate-to-severe OHSS. Because the included studies were limited in number and heterogeneous in embryo-transfer strategy, ovarian stimulation protocols, and hCG dosing, these findings should be interpreted with caution and regarded as hypothesis-generating. In particular, as fresh transfer cycles modify OHSS risk and subgroup analysis was not feasible, the applicability of these results to contemporary universal freeze-all practice remains uncertain.