Fertility Outcomes in Leukemia Survivors by Treatment Modality: A Systematic Review and Meta-Analysis.
This systematic review and meta-analysis of 42 studies encompassing 2,048 leukemia survivors reports substantially higher infertility after HSCT, testicular irradiation, and high-dose TBI than after chemotherapy alone, supporting treatment-exposure-based fertility counseling and follow-up.
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This systematic review and meta-analysis of 42 studies encompassing 2,048 leukemia survivors reports substantially higher infertility after HSCT, testicular irradiation, and high-dose TBI than after chemotherapy alone, supporting treatment-exposure-based fertility counseling and follow-up.
Research significance
Evidence from the pooled observational literature indicates that infertility risk differs markedly by treatment exposure; it is reasonable—but not directly tested here—to hypothesize that early risk stratification and modality-specific fertility-preservation pathways could reduce avoidable reproductive harm or improve reproductive planning.
Source abstract
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.