Impacts of oncological treatments on fertility: A systematic review

Cancer is a leading cause of death worldwide, affecting individuals of reproductive age. Although conventional treatments are essential for cure and survival improvement, they adverse effects on male and female fertility. This systematic review, registered in PROSPERO (CRD42024538296) and conducted according to PRISMA guidelines, aimed to evaluate the impact of these treatments on the reproductive system of murine animal models. A literature search across PubMed, Scopus, Web of Science, and Embase yielded 30 included studies. Most studies used C57BL/6 J and Wistar rats. The most frequently drugs were cyclophosphamide, cisplatin, and doxorubicin, which were mainly administered intraperitoneally at varying doses. Assessed outcomes included sperm analysis, ovulation rate, reproductive efficiency, histological alterations, and gene expression. Alkylating agents caused significant testicular degeneration and follicular toxicity, severely impairing fertility. Antimetabolites and antineoplastic antibiotics induced severe reproductive damage in both sexes. Topoisomerase and microtubule inhibitors demonstrated relevant reproductive toxicity, although data are limited. In women, alterations in ovarian and uterine functions are observed, and in men, the effects range from dysfunctions of the hypothalamic-pituitary-gonadal axis to alterations in the structural and functional integrity of gametes. Both radiotherapy and chemotherapy target cellular DNA; however, they act through distinct mechanisms. Most studies are with males, and studies with females, when present, often lacked comprehensive evaluation. The methodological quality assessment shows a lack of blinding and allocation concealment. In general, the studies focused on doses, treatment regimens, and experimental protocols. Therefore, conventional treatments negatively affect fertility in murine models, highlighting need for fertility preservation strategies in cancer patients.