HCG/GnRHa support improves outcomes after GnRH antagonist dual trigger and the predictive role of mid-luteal estradiol ratio: a case control study

Background Optimal luteal phase support after fresh transfer remains a clinical challenge in GnRH antagonist IVF/ICSI cycles triggered with dual trigger. HCG/GnRha supports may improve outcomes, but its safety and ideal application remain uncertain. To investigate the effectiveness and safety of strengthened luteal phase support in fresh embryo transfer cycles following GnRH antagonist protocols with dual trigger, and further to identify patients who best most as well as clinical indicators. Methods This retrospective cohort study included all fresh embryo transfer cycles after dual-trigger oocyte retrieval between January 2020 and May 2024 at a single center. Patients were grouped based on LPS strategy: routine support (RT) or strengthened support (ST) using hCG (S-hCG), GnRHa (S-GnRHa), or both (S-Double). Pregnancy and neonatal outcomes and safety profiles were compared before and after propensity score matching. Subgroup analyses and mid-luteal estradiol ratio (E2 ratio) assessment were performed. Results ST was associated with significantly higher clinical pregnancy (48.2% vs 37.1%) and live birth rates (43.2% vs 34.3%) than RT (P < 0.001) without additional risks including OHSS, birth defects and maternal complications. Subgroup analyses showed benefits across diverse populations, including women ≥ 35 years, those with diminished ovarian reserve, and patients receiving suboptimal embryos. Among ST regimens, hCG supplementation achieved the best outcomes, and patients with a low mid-luteal E2 ratio (< 0.15) derived the greatest benefit. Conclusions Enhanced luteal support improves pregnancy outcomes in antagonist-dual trigger cycles. hCG appears most effective, but individualized strategies using biomarkers such as E2 ratio merit further investigation. Trial registration: Not applicable.