Effect of different trigger strategies on pregnancy outcomes in letrozole-stimulated and modified natural frozen-thawed embryo transfer cycles: a retrospective cohort study

This study evaluated the effects of different ovulation trigger strategies on pregnancy outcomes in letrozole-stimulated and modified natural frozen–thawed embryo transfer (L-FET and mNC-FET) cycles. A total of 2053 eligible cycles were retrospectively analyzed, including 773 L-FET and 1280 mNC-FET cycles. Participants were grouped by ovulation-triggering method: (1) dual trigger—0.1 mg gonadotropin-releasing hormone agonist (GnRHa) plus 2,000 IU of human chorionic gonadotropin (hCG); (2) hCG trigger—4,000–10,000 IU hCG alone, and (3) GnRHa trigger—0.1 mg GnRHa alone. In L-FET cycles, 105, 430, and 238 women received dual, hCG, and GnRHa triggers, respectively. In mNC-FET cycles, 914 women received hCG and 366 received GnRHa. Binary logistic regression identified independent predictors of pregnancy outcomes, and subgroup analyses were performed for L-FET cycles according to hCG trigger dose and serum luteinizing hormone (LH) levels on trigger day. In mNC-FET cycles, clinical pregnancy rates (CPR), pregnancy loss rates (PLR), and live birth rates (LBR) were comparable between the hCG and GnRHa trigger groups in both unadjusted and adjusted analyses. In L-FET cycles, after adjusting for confounders, both GnRHa (adjusted odds ratio [aOR] = 0.484, 95% confidence interval [CI], 0.244–0.962, P = 0.038) and hCG (aOR = 0.395, 95% CI 0.196–0.798, P = 0.010) triggers were associated with significantly lower miscarriage rates than the dual trigger group. CPR and LBR did not differ significantly among groups. Subgroup analysis revealed no significant differences in pregnancy outcomes across hCG trigger dose groups in L-FET cycles (P > 0.05). When stratified by LH level (< 20 IU/L vs. ≥20 IU/L), pregnancy outcomes were similar except for a higher PLR with the dual trigger in the LH surge (≥ 20 IU/L) subgroup (30.0% vs. 11.9%, P < 0.05). In mNC-FET, hCG and GnRHa triggering yielded similar pregnancy outcomes. In L-FET, dual triggering increased miscarriage risk, particularly in the LH surge group (≥ 20 IU/L). Routine dual trigger use in L-FET is therefore not recommended. Luteal support should be individualized, and a 4000 IU hCG trigger may represent a cost-effective alternative for patients undergoing L-FET.