Fertility-preserving treatment for endometrial atypical hyperplasia and endometrial cancer: a systematic review and meta-analysis

Abstract Objective The incidence of endometrial cancer is rising, especially among younger women. Given the strong need to preserve fertility, robust evidence is required to evaluate the effectiveness of progestin-based fertility-preserving treatment regimens. We conducted a systematic review and meta-analysis to summarize the oncological and reproductive outcomes of patients with endometrial cancer (EC) and endometrial atypical hyperplasia patients (EAH) undergoing progestin-based therapies, and to compare outcomes across different fertility-preserving treatment regimens. Methods We searched PubMed and EMBASE to identify relevant studies published online up to 2 Apr 2025. This proportional meta-analysis was performed using a random-effects model to combine the data. A checklist based on the Newcastle-Ottawa Scale and the Methodological Index for Non-randomized Studies was used for quality assessment. The primary outcomes for this meta-analysis were complete response, pregnancy rate, and live birth rate following fertility-preserving treatment in patients with EC or AH. The secondary outcomes are was the recurrence rate (RR). Cochran’s Q test and I 2 were used to evaluate the degree of heterogeneity of eligible studies. Sensitivity analyses were performed with the leave-one-out strategy. Publication bias was assessed using funnel plots and Egger’s test. Results Of 1332 identified studies, 54 were included in the final analysis. Including 2148 patients with endometrial cancer and 1418 with endometrial atypical hyperplasia. For patients with EC, 78% achieved complete response (CR). Patients treated with LNG-IUD alone had the highest CR rate (85%). Among patients who achieved CR and contempt to conceive, 60% achieved clinical pregnancy and 57% achieved live delivery. While about 1/3 patients will undergoing relapse (33%). For patients with EAH, 87% achieved CR, 48% achieved pregnancy and 37% achieved live delivery, while approximately one-fifth experienced relapse (22%). Sensitivity analysis demonstrated robust results. Conclusion Different progestin-based therapy regimens are effective for fertility preservation in patients with EC and EAH. The results of this meta-analysis may inform clinical management and support personalized treatment decisions.