Can we really protect the ovary from chemotherapy damage?

Future alternatives to current fertility preservation methods such as pharmacological strategies to prevent chemotherapy-induced ovarian damage in female cancer patients are of growing interest. Chemotherapeutic agents, especially alkylating agents, cause DNA damage and apoptosis in ovarian follicles, significantly reducing ovarian reserve. To mitigate this gonadotoxicity, various emerging strategies are being explored, including kinase inhibitors, PI3K/Akt/mTOR pathway inhibitors, antioxidants, miRNAs and GnRH agonists. These treatments work by preventing follicular apoptosis or excessive activation of primordial follicles. Although promising results have been observed in vitro and in vivo in rodent models, further investigations to bypass their limitations are needed to confirm their efficacy and safety. These challenges include the non-interference with anti-tumoral effect of chemotherapy and the specificity of fertoprotective agents to ovaries.