Fertility-Sparing Treatments in Endometrial Cancer: A Comprehensive Review on Efficacy, Oncological Outcomes, and Reproductive Potential

Endometrial cancer (EC) affects 3–14% of women under 40 who wish to preserve their fertility. The standard treatment for EC is a hysterectomy with salpingo-oophorectomy. However, for those desiring fertility preservation, oral progestogens such as medroxy-progesterone acetate (MPA) or megestrol acetate (MA) are the most common therapies in Fertility-Sparing Treatment (FST). Other treatments include gonadotropin-releasing hormone agonist (GnRHa), levonorgestrel-releasing intrauterine system (LNG-IUS), and metformin plus progestin. This comprehensive review evaluates the best FST options for women with reproductive potential. PubMed, EMBASE, and Scopus were searched in June 2023 using specific keywords. Studies included in the review focused on patients with EC undergoing FST, with outcomes such as complete response rate (CRR), recurrence rate (RR), pregnancy rate (PR), and live birth rate. Eighteen studies met the inclusion criteria, involving 23,976 patients. In only-oral progestin trials, CRR ranged from 18% to 100%; RR ranged from 0% to 81.8%; Death Rate ranged from 0% to 3.6%. In studies combining oral progestin with LNG-IUS, CRR ranged from 55% to 87.5%; RR ranged from 0% to 41.7%; Death Rate was 0%. Most patients with Stage IA EC received MPA or MA. Fertility-related outcomes were reported in 15 studies. PR ranged from 4 to 44 patients in trials involving only oral progestins. When combining oral progestin with LNG-IUS, PR ranged from 1 to 46 patients. Progestin therapy, including oral MPA and MA, is considered safe and effective, with limited evidence supporting the use of LNG-IUS.