Hysteroscopic Resection Shows Promise for Fertility Preservation in Progestin-Resistant Endometrial Hyperplasia and Cancer

A prospective clinical trial evaluating hysteroscopic resection (HR) for progestin-resistant atypical hyperplasia (AH) or grade 1 endometrioid endometrial cancer (EC) found high remission rates and successful pregnancies, offering a potential alternative to hysterectomy for select patients. Researchers presented their results at the Society of Gynecologic Oncology 2025 Annual Meeting on Women’s Cancer in Seattle, WA.

High-dose progestin therapy is the standard fertility-sparing treatment for patients with AH or grade 1 EC, but treatment failure occurs in 30% to 40% of cases, often necessitating hysterectomy. This study evaluates HR as an alternative fertility-preserving intervention for patients with progestin-resistant disease.

Researchers conducted a prospective clinical trial (NCT04362046) using a standardized treatment protocol that included oral megestrol acetate (160 mg daily) with or without a levonorgestrel IUD for at least 6 months. Disease monitoring was performed via endometrial biopsies and/or hysteroscopic assessment at 3- to 6-month intervals. Patients with persistent disease who met inclusion criteria—age 18-40 years, minimal myometrial invasion (<1/3), limited endometrial cavity involvement, and MRI-confirmed localized disease—were offered HR. The multidisciplinary treatment team included specialists in gynecologic oncology, minimally invasive gynecology, pathology, reproductive endocrinology, and radiology.

Among 43 screened patients, 33 followed the standardized medical management protocol, with 11 (33%) having grade 1 EC and 22 (67%) having AH. Of these, 22 achieved complete remission with medical management (MM) alone (16/22, 73%), and 10 of the 16 patients attempting to conceive had a live birth (63%). Eleven patients with progestin-resistant disease underwent HR. Two were excluded from analysis due to more advanced disease. Compared with the MM group, more patients in the HR group had grade 1 EC (7/11 vs 4/22; P = .02). Disease remission was achieved in 7/9 patients in the HR group (78%), with two showing no residual disease on pathology. Among the four patients attempting conception following HR, two (50%) achieved pregnancy via assisted reproduction. Four patients who underwent HR ultimately had a hysterectomy. No perioperative complications were reported, with only one case of minimal intrauterine scarring. There were no deaths or adverse cancer-related outcomes.

“This multidisciplinary protocol holds promise as a safe and effective fertility-sparing approach for the treatment of grade 1 EC or AH,” the authors concluded. “Hysteroscopic assessment helps direct the diagnosis and monitoring of AH/EC in this setting and guides patient selection for HR.”

Reference
Carey M. Endomyometrial resection for fertility preservation in patients with progestin-resistant atypical hyperplasia or grade 1 endometrioid endometrial cancer. Paper presented at: Society of Gynecologic Oncology 2025 Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Accessed March 11, 2025. https://www.sgo.org/events/annual-meeting/