GnRH Agonist-Aromatase Inhibitor Pretreatment Before Frozen Embryo Transfer in Patients with Endometriosis, Adenomyosis or Both

Research Question Does pretreatment with a GnRH agonist and an aromatase inhibitor (PRET) improve live birth rates in individuals with endometriosis, adenomyosis or both undergoing frozen embryo transfer (FET) after one or more prior failed conventional cycles? Design Multicentre retrospective cohort study of FET cycles performed between 2018 and 2024 at Northwestern University (USA), University Fertility Clinic (Skive, Denmark), and IVI Rome (Italy). Eligible individuals had endometriosis and/or adenomyosis and ≥1 prior failed conventional FET. The intervention (PRET-FET) consisted of 2 months of GnRH agonist treatment concomitant with or followed by aromatase inhibitor treatment before endometrial preparation. The primary outcome was live birth per cycle. Generalized estimating equation models were fitted with an exchangeable correlation structure to account for multiple cycles per patient; selected models adjusted for prespecified covariates (including site and embryo quality). Weighted analyses used inverse weights proportional to the total number of reported cycles per patient. Results Fifty-one patients across 3 centres (Northwestern n=22; University Fertility Clinic n=17; IVI Rome n=12) contributed 217 FET cycles: 159 conventional FET cycles and 58 PRET-FET cycles. Most conventional cycles used an HRT-FET protocol (119/159, 75%). PRET-FET was associated with significantly higher odds of live birth compared with conventional FET (OR 26.7, 95% CI 9.48–75.0; p<0.001). Conclusions GnRH agonist–aromatase inhibitor pretreatment was associated with significantly higher live birth odds among individuals with endometriosis, adenomyosis or both undergoing FET after one or more prior failed conventional cycles. Prospective studies are needed to confirm efficacy and define ideal candidates for this protocol.