Gonadotrophin releasing hormone agonist-aromatase inhibitor pretreatment before frozen embryo transfer in patients with endometriosis, adenomyosis, or both

Francone NO, Nicolás O. Francone, Serdar E. Bulun, Bulun Se, Yangruijue Ma, Ma Y, Bahar Yilmaz, Yilmaz B, Olamide O. Akin-Olugbade, Olamide Akin Olugbade, Olugbade OA, Bernardi LA, Lia A. Bernardi, Emily S. Jungheim, Jungheim ES, Eve C. Feinberg, Feinberg EC, Christina E Boots, Boots CE, Christina Boots, Masha Kocherginsky, Masha Kocherginsky PhD, Kocherginsky M, Peter Humaidan, Humaidan P, Cozzolino M, Mauro Cozzolino
Reproductive BioMedicine Online · 2026 · vol. 53(6) , pp. 105982 · doi:10.1016/j.rbmo.2026.105982 · PMID:42892070 · W7213894576
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A multicentre retrospective study found that GnRH agonist–aromatase inhibitor pretreatment significantly increased live birth odds compared with conventional frozen embryo transfer in patients with endometriosis, adenomyosis, or both who had prior failed cycles.

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Abstract

RESEARCH QUESTION: Does pretreatment with a gonadotrophin releasing hormone (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 previously failed conventional cycles? DESIGN: Multicentre retrospective cohort study of FET cycles conducted between 2018 and 2024 at Northwestern University, USA, University Fertility Clinic, Skive, Denmark and IVI Rome, Italy. Eligible individuals had endometriosis, adenomyosis and one or more previously failed conventional FET, or all. 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 pre-specified 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 three 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 a hormone replacement therapy, controlled or programmed cycle protocol (119/159 [75%]). Compared with conventional FET, PRET-FET was associated with significantly higher odds of live birth (OR 26.7, 95% CI 9.48 to 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 previously failed conventional cycles. Prospective studies are needed to confirm efficacy and define ideal candidates for this protocol.

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