Impact of immunotherapy and small molecule cancer therapy on fertility: a narrative review of current evidence, mechanisms and future directions.
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With increasing cancer incidence among individuals of reproductive age, preserving fertility has become a critical aspect of cancer care. This narrative review explores the impact of contemporary cancer therapies, including immunotherapies and targeted agents, on reproductive health, highlighting clinical fertility outcomes and underlying biological mechanisms. We outline the epidemiology and treatment strategies for malignancies common in adolescents and young adults (AYAs), including breast, melanoma, lung, gynaecologic, colorectal cancers and haematologic malignancies. Basic reproductive physiology in males and females is reviewed, including the hypothalamic-pituitary-gonadal axis, ovarian follicle and oocyte development, and spermatogenesis. Clinical data related to fertility and reproductive outcomes in patients receiving immunotherapy or targeted therapy are summarised, along with proposed mechanisms of gonadotoxicity from both conventional chemotherapy and newer drug classes. Special emphasis is placed on immunotherapy, such as checkpoint inhibitors, cell-based therapies (eg, chimeric antigen receptor T cells, tumour-infiltrating lymphocytes) and monoclonal antibodies, and small-molecule inhibitors, including kinase inhibitors (eg, BRAF, MEK, epidermal growth factor receptor), poly (ADP-ribose) polymerase inhibitors, epigenetic modifiers and apoptosis promoters (eg, BCL-2 inhibitors). Despite their growing use, these therapies are poorly studied in terms of reproductive safety, with available evidence being limited, heterogeneous and often lacking baseline fertility assessments or long-term follow-up. This uncertainty complicates counselling and decision-making, requiring a precautionary approach to fertility preservation. Multidisciplinary collaboration incorporating oncology, reproductive medicine, psychology and ethics is essential for individualised, ethically sound care. Emerging technologies such as organ-on-chip systems and induced pluripotent stem cell models offer promising avenues for mechanistic insight. To advance the field, future efforts must focus on prospective cohort studies, robust preclinical models and interim clinical guidelines to support informed fertility-related care for cancer patients.