Oncologic and fertility outcomes of progestin therapy for atypical hyperplasia and grade 1 cancer of the endometrium: Results of a specialized oncofertility program

Objective. This study describes the oncological and fertility outcomes of patients with atypical hyperplasia (AH) or low-grade endometrial cancer (EC) desiring fertility preservation, enrolled in a specialized oncofertility program. Methods. Patients referred between 2019 and 2024 were reviewed. This novel program provides integrated oncologic and reproductive endocrinology and infertility (REI) care, following standardized treatment pathways. Enrollment criteria include: AH/EC grade 1 histology, p53 wild-type status, no myometrial invasion or extrauterine disease, and desire to preserve fertility. Progestin intrauterine device was the main mode of treatment. Results. Of 206 patients initially seen, 119 (58 %) had AH and 87 (42 %) had EC. 170 patients were eligible for progestin treatment. Complete response (CR) rate was 69 % (AH 74 %; EC 60 %). The median time to CR was 8.3 months (AH 7.4; EC 10.4). The probability of CR for the whole cohort at 24 months was 86.6 % (95 %CI, 77.4-92.0). The AH group had a significantly higher probability of CR compared to the EC group, 91.6 % (95 % CI, 79.4-96.6) vs 78.4 % (95 %CI 59.8-88.4); p = 0.02, respectively. Despite continuous endometrial protection with progestin, recurrence probability at 24 months after CR was 32.8 % (95 %CI, 20.0-43.6), with no significant difference between AH and EC (36 % vs 27 %, p = 0.28). Sixty-four patients attempted to conceive, and majority underwent assisted reproductive treatment (98 %). Overall, 36 (56 %) patients conceived and 22 of these pregnancies resulted in a live birth (34 %; 22/64). Conclusion. Patients in a specialized oncofertility program had high rates of CR that continued up to 24 months suggesting that longer periods of treatment are feasible. (c) 2025 Published by Elsevier Inc.