Mechanism-Driven Evolution of Fertility-Sparing Treatment and Precision Management of Special Populations in Endometrial Cancer: A Review

Abstract

Simple Summary Endometrial cancer is increasingly affecting individuals who have not yet completed childbearing. For carefully selected patients with early-stage, low-risk disease, fertility-sparing treatment can preserve the uterus while the disease is closely monitored. However, responses to conventional progestin therapy vary, particularly among patients with obesity, polycystic ovary syndrome, abnormal glucose metabolism, Lynch syndrome, mismatch repair-deficient tumors, persistent disease, or recurrent disease. This review describes how fertility-sparing treatment has expanded from oral progestin therapy alone to include local intrauterine therapy, hysteroscopic lesion resection, metabolic interventions, combined endocrine therapy, and selected molecularly guided strategies. It also summarizes the patient populations most likely to benefit from each approach, their limitations, and the circumstances in which fertility-sparing treatment should be discontinued. Integrating pathological, metabolic, molecular, treatment-response, and reproductive factors may help clinicians better balance oncologic safety with the opportunity for future pregnancy.