Differential Impact of the Endometrial Immune Environment in Fresh Versus Frozen Embryo Transfer

Background: The endometrial immune environment regulates maternal immune tolerance and plays a key role in embryo implantation. We investigated whether its impact on reproductive outcomes differs between fresh and frozen embryo transfer (FET) cycles. Methods: In this prespecified secondary analysis of a prospective randomized study, 493 good-prognosis IVF patients underwent endometrial immune profiling before embryo transfer. Patients with a balanced profile received standard care, whereas those with immune dysregulation were randomized to conventional or immune-guided precision care. Live birth rates (LBRs) were analyzed according to immune status, transfer type, and treatment strategy. Results: A transfer type-specific effect was observed. In FET cycles, a balanced immune profile was associated with higher LBR compared with immune dysregulation (52.4% vs. 14.7%; adjusted OR 5.32 [95% CI 1.53–20.92]; ARD +37.7%). Precision care improved LBR compared with conventional management (48.6% vs. 14.7%; OR 5.03 [1.66–17.63]; ARD +33.9%). No significant association between immune status and reproductive outcomes was observed in fresh transfers. Conclusions: The impact of the uterine immune environment differed according to embryo transfer type and was predominantly observed in FET cycles. These findings suggest that endometrial immune competence may be particularly relevant to implantation success after frozen embryo transfer and warrants confirmation in larger prospective studies.