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

Oleksandra Dzyubak; Karen Glass; Megan Watts; Oishika Tarafdar; Andrea N Simpson; Manjula Maganti; Shima Deljoomanesh; Stephane Laframboise; Marcus Q Bernardini; Sara Pakbaz; Anjelica Hodgson; Blaise Clarke; Marjan Rouzbahman; Tanya Chawla; Tara Zad; Soyoun Rachel Kim; Sarah E Ferguson

doi:10.1016/j.ygyno.2025.06.015

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

Gynecol Oncol. 2025 Jun 30:199:72-78. doi: 10.1016/j.ygyno.2025.06.015. Online ahead of print.

Authors

Oleksandra Dzyubak¹, Karen Glass², Megan Watts¹, Oishika Tarafdar¹, Andrea N Simpson³, Manjula Maganti⁴, Shima Deljoomanesh¹, Stephane Laframboise¹, Marcus Q Bernardini¹, Sara Pakbaz⁵, Anjelica Hodgson⁶, Blaise Clarke⁶, Marjan Rouzbahman⁶, Tanya Chawla⁷, Tara Zad¹, Soyoun Rachel Kim¹, Sarah E Ferguson⁸

Affiliations

¹ Division of Gynecologic Oncology, University Health Network/Sinai Health Systems, Toronto, ON, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.
² Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada; CReATe Fertility Centre, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
³ Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada; Department of Obstetrics and Gynecology, St Michael's/Unity Health, Toronto, Ontario, Canada.
⁴ Department of Biostatistics, University Health Network, Toronto, Ontario, Canada.
⁵ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁶ Laboratory Medicine Program, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
⁷ Joint Department of Medical Imaging, University Health Network/Sinai Health Systems, Toronto, Ontario, Canada.
⁸ Division of Gynecologic Oncology, University Health Network/Sinai Health Systems, Toronto, ON, Canada; Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada. Electronic address: sarah.ferguson@uhn.ca.

PMID: 40592024
DOI: 10.1016/j.ygyno.2025.06.015

Abstract

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 extra-uterine 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.

Keywords: Atypical hyperplasia; Endometrial cancer; Fertility-preserving treatment; Progestin.