Reproductive Toxicities of Anticancer Drugs in Females: A Systematic Review of Mechanisms, Consequences, Clinical Implications, and Oncofertility Care

With the advances in molecular diagnostics and newer treatment approaches, the overall survival and quality of life of patients have increased significantly. However, many anticancer drugs often cause ovarian damage or toxicity, leading to premature ovarian insufficiency, infertility, and serious long-term psychosocial issues, making oncofertility an unmet need in current oncology practice. This manuscript addresses questions such as, "What are the molecular pathways of anticancer drug-induced ovarian toxicity in reproductive-aged females and their clinical applications?" and "How do oncofertility care models and regulation frameworks support fertility preservation in clinical oncology?" Our goal is to provide a clear, comprehensive understanding of how major classes of anticancer drugs cause ovarian damage and to identify potential interventions to improve overall quality of life. From 2770 records, 52 studies were included. Mechanistic evidence shows distinct pathways: alkylating agents trigger oocyte apoptosis through TAp63α activation; platinum drugs and anthracyclines cause mitochondrial dysfunction and oxidative stress; and taxanes interfere with oocyte meiotic spindles. Clinically, this results in measurable loss of ovarian reserves like anti-Mullerian hormone (AMH) and antral follicle count (AFC), and decreased oocyte quality. Existing fertility preservation strategies, such as oocyte/embryo and ovarian tissue cryopreservation, are effective, and gonadotropin-releasing hormone (GnRH) agonists may offer additional protection. Ovarian toxicity from anticancer drugs represents a significant, drug-specific survivorship challenge. Understanding these mechanisms is crucial for risk assessment. To minimize the long-term impact on patients' quality of life, it is essential to incorporate proven fertility-preservation techniques into routine oncology care.