Male Fertility in the Era of Modern Oncology: Chemotherapy, Tyrosine Kinase Inhibitors, Immunotherapy, and Antibody-Drug Conjugates
Year: 2026
Type: article
Abstract: Background: Cancer diagnoses among males of reproductive age are increasing, yet male fertility preservation remains underutilized. Systemic cancer therapies differentially affect spermatogenesis, testosterone production, and sexual function, with substantial drug-class-specific variability. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Embase, Cochrane Library, and Scopus using standardized terms related to male fertility, spermatogenesis, gonadotoxicity, sperm banking, and testicular toxicity, combined with chemotherapy, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and antibody–drug conjugates (ADCs). Guidelines of the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the European Association of Urology (EAU), and the National Comprehensive Cancer Network (NCCN) were also reviewed. Records from database inception to July 2026 were searched, with emphasis on studies published since 2000, including prospective cohorts, semen analyses, seminal-fluid pharmacokinetic studies, and preclinical reproductive toxicology. The certainty of evidence for each drug class was graded with an approach adapted from the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: Chemotherapy causes dose-dependent spermatogonial depletion, with alkylating agents associated with the greatest risk of severe and potentially permanent azoospermia. Platinum agents and taxanes demonstrate intermediate gonadotoxicity, with recovery potentially requiring 1–5 years. TKIs show variable reproductive toxicity; imatinib, dasatinib, and nilotinib have demonstrated preclinical testicular effects, while limited clinical data suggest predominantly transient abnormalities. The labels of several TKIs recommend male contraception during and after treatment. Evidence of direct ICI spermatotoxicity is of very low certainty (one prospective cohort of 26 men showed a non-significant decline in sperm output), but ICIs may indirectly impair the hypothalamic–pituitary–gonadal axis through immune-mediated endocrinopathies. ADCs lack human fertility data, although payload-dependent testicular toxicity has been observed in animals. Conclusions: Fertility preservation should be integrated into the care of reproductive-age men receiving systemic anticancer therapy, with sperm cryopreservation offered before potentially gonadotoxic treatment. For TKIs, ICIs, and ADCs, this offer rests on low- to very-low-certainty evidence and precaution, which should be stated explicitly during counseling. Drug-class-specific counseling regarding fertility risks, recovery, and paternal safety is essential. Prospective studies and paternal outcome registries for TKIs, ICIs, and ADCs are needed.
Source: Sci
DOI: 10.3390/sci8110354
Author: Walid Shalata
Institutions: Ben-Gurion University of the Negev, Soroka Medical Center
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,448
OpenAlex ID: W7225658315