The Effects of Cancer Immunotherapy on Fertility: Focus on Hematological Malignancies

Abstract

In recent years, cancer management has benefitted from new effective treatments, including immunotherapy. While these therapies improve cancer survival rates, they can alter immune responses and cause long-term side effects, of which gonadotoxic effects and the potential impact on male and female fertility are growing concerns. Immunotherapies, such as immune checkpoint inhibitors, immunomodulators, monoclonal antibodies, and CAR-T, can lead to elevated levels of proinflammatory cytokines and immune-related adverse events that may exacerbate fertility problems. Immunotherapy-related inflammation, characterized by cytokine imbalances and the activation of pathways such as AMPK/mTOR, has been implicated in the mechanisms of fertility impairment. In men, hypospermatogenesis and aspermatogenesis have been observed after treatment with immune checkpoint inhibitors, by direct effects on the gonads, particularly through the inhibition of cytotoxic T lymphocyte antigen-4. In women, both damage to ovarian reserves, recurrent pregnancy loss, and implantation failure have been documented, secondary to a complex interplay between immune cells, such as T cells and uterine NK cells. In this review, the impact of immunotherapy on fertility in patients with hematological cancers was analyzed. While this area is still underexplored, fertility preservation methods remain crucial. Future studies should investigate immunotherapy’s effects on fertility and establish standardized preservation protocols.