The increasing survival rates among paediatric and adolescent cancer patients has increased attention on long-term consequences of chemotherapy, particularly male fertility. This review addresses age- and dose-dependent gonadotoxicity and drug type on reproductive potential. It further investigates the damage, including disruption of the hypothalamic-pituitary-gonadal axis and epigenetic alterations that may pose transgenerational risks. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted for studies from database inception to April 2025. Inclusion criteria included paediatric and adolescent male cancer patients or adult survivors of childhood cancer and reported chemotherapy-related effects on fertility. Preclinical animal models were included to elucidate epigenetic changes. Due to heterogeneity of study designs, a narrative synthesis was performed to categorize findings into hormonal, cellular, and clinical outcomes. Chemotherapy-induced infertility is highly dependent on the developmental stage and specific regimen. Alkylating agents and platinum-based therapies were consistently associated with impaired spermatogenesis, hormonal disruption, and azoospermia or oligospermia. Chemotherapy and cranial irradiation were altered hormonal system that regulates male reproduction and persists epigenetic changes in germ cells. Fertility preservation for postpubertal males is through sperm cryopreservation, while prepubertal boys relied on experimental strategies such as testicular tissue cryopreservation and in vitro spermatogenesis. Chemotherapy induces epigenetic after-effects, including altered DNA methylation patterns that persist even after spermatogenesis recovers. Chemotherapy compromises male fertility through cytotoxic damage and potential long-term genomic instability. The findings highlight that reproductive recovery does not guarantee genomic recovery (epigenetically intact sperm). Consequently, oncofertility care must adapt a reproductive health model that prioritizes early, customized counselling and use of biomarkers to better predict and preserve fertility in young survivors. Although sperm banking remains a standard approach for postpubertal, promising experimental may expand fertility options for prepubertal boys in future.
Sundaram et al. (Wed,) studied this question.