Oncological and Reproductive Outcomes for Gonadotropin-Releasing Hormone Agonist Combined with Aromatase Inhibitors or Levonorgestrel-releasing Intrauterine System Fertility-Sparing Treatment in Women with Endometrial Cancer or Atypical Endometrial Hyperplasia: A single-center retrospective analysis of 179 cases

Abstract Purpose: To evaluate the efficacy and safety of gonadotropin-releasing hormone agonist (GnRHa) combined with levonorgestrel-releasing intrauterine system (LNG-IUS) or aromatase inhibitor (AI) in women with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) who wish to preserve their fertility.Methods: 179 EC/AEH patients who were contra-indicated or unsuitable for high-dose oral progestin were included in our study. Patients were treated with the combination of GnRHa with LNG-IUS (group GLI: GnRHa IH every 4 weeks and LNG-IUS insertion constantly) or combination of GnRHa with AI (group GAI: GnRHa IH every 4 weeks and oral letrozole 2.5mg, daily). Histological evaluation was performed every 3-4 months. After achieving complete remission (CR), maintenance treatments including LNG-IUS, cyclical oral contraceptives or low-dose cyclic progestin were recommended until they began attempting to conceive. Results: Overall, 169 (94.4%) patients achieved CR, 96.7% in AEH and 93.3% in EC patients. The CR rate in GLI and GAI was 93.5% and 95.8%, respectively. The median time to CR was 6 (3-18) months, 4 (3-10) months in AEH and 8 (3-18) months in EC patients. After a median follow up of 27.5 months, 41 (24.3%) women developed recurrence with the median recurrence time of 17 (6-77) months. Of the patients with CR, 134 cases desired to conceive, 42 (32.3%) women became pregnant, 24 (17.9%) of them successfully delivered and 5 (3.7%) were in pregnancy, while 13 of them miscarried.Conclusion: GnRHa combined treatment achieved good oncological and reproductive outcomes. Future larger multi-institutional studies should be designed to confirm these preliminary findings.