Fertility Outcomes in Leukemia Survivors by Treatment Modality: A Systematic Review and Meta-Analysis

Introduction: Leukemia is the most common childhood malignancy. Treatment requires urgent polychemotherapy and may escalate to hematopoietic stem cell transplantation (HSCT) with or without total body irradiation (TBI). Due to the frequently young age at diagnosis, time limitations and unpredictable course, fertility preservation (FP) is especially challenging and may not be feasible prior to treatment, particularly in females. Methods: We conducted a systematic review and meta-analysis of fertility outcomes in leukemia survivors using MEDLINE, Embase, and Cochrane databases (search date: 13 June 2024). Results: Forty-two studies with 2048 patients were included. Overall infertility was 37% (95% CI 23-54%) with substantial heterogeneity. The highest infertility rates were observed after HSCT (68%) and after testicular irradiation (92%) or TBI ≥ 10-12 Gy (66%). Chemotherapy alone was associated with lower infertility (4%). Sex-specific differences were noted, with higher infertility in males following chemotherapy-only regimens (18% vs. 6% in females), while females were more affected after HSCT (70% vs. 59% in males). Subfertility affected about one-fifth of survivors. Conclusions: While standard chemotherapy is associated with relatively low gonadotoxicity, HSCT and irradiation confer substantial risk. These findings support individualized fertility counseling and long-term reproductive follow-up based on treatment exposure.