Persistent endometrial dysfunction after fertility-sparing treatment for endometrial carcinoma: insights from donor oocyte cycles

Pierfrancesco Greco, Ermanno Greco, Maria Teresa Varricchio, Manuel Maria Ianieri, Valeria Masciullo, Flavia Costanzi

Background Fertility-sparing treatment (FST) is an accepted option for selected women with endometrial carcinoma (EC) or atypical endometrial hyperplasia (AEH) wishing to preserve fertility. However, the impact of FST on subsequent endometrial function remains poorly understood. Oocyte donation (OD) offers a unique model to evaluate endometrial receptivity independently of oocyte quality. We assessed reproductive outcomes after OD in women aged ≥40 years with a history of FST for EC or AEH. Methods This retrospective case series included women aged ≥40 years with histologically confirmed Endometrioid endometrial carcinoma (EEC) or AEH who achieved complete response after FST and subsequently underwent blastocyst transfer through OD. All cycles involved vitrified-warmed donor oocytes, intracytoplasmic sperm injection, blastocyst culture, and elective single embryo transfer. The primary outcome was live birth rate (LBR) per embryo transfer. Results Sixteen patients underwent 27 embryo transfer cycles. Median age at first transfer was 45.5 years. Embryological outcomes were excellent, with a 96.8% oocyte survival rate and 80.4% top-quality blastocysts. Despite adequate endometrial preparation in all cases, reproductive outcomes were poor. The cumulative LBR per embryo transfer was 18.5% (5/27), while the cumulative LBR per patient was 31.2% (5/16). Patients with disease recurrence showed lower live birth rates than those without recurrence. Endometrial thickness was not associated with implantation outcomes. Conclusion Women aged ≥40 years undergoing OD after FST for EC or AEH experience reduced reproductive success despite optimal embryo quality. These findings are consistent with the hypothesis of persistent endometrial dysfunction after FST and highlight the need for improved assessment of endometrial receptivity and timely integration of assisted reproductive treatment following complete response.