Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with more than 2 million new cases in 2020. Its incidence and death rates have increased over the last three decades due to the change in risk factor profiles, better cancer registration, and cancer detection. Chemotherapy associated ovarian failure (COF) refers to disruption of both endocrine and reproductive ovarian function, after exposure to chemotherapy. It is defined as either the absence of regular menses in premenopausal female patients or as increased FSH levels (>40 IU/L). In 2006, the American Association of clinical oncology attempted to sort antineoplastic regimens, according to the associated fertility compromise risk. The exact mechanisms of ovarian toxicity have not been fully understood and depend on the type of drug and on the type of cell studied. Stroma and granulosa cells are generally more affected, but a direct toxicity of anticancer drugs (especially alkylating agents) on oocytes has also been described. The first observations focused on the consequences of radiation treatment, as irradiation was actually used to induce menopause as a form of endocrine treatment of breast cancer. Similar data were later obtained from the analysis of women included in trials of adjuvant treatment for breast cancer using alkylating agents and Cyclophosphamide. CPA is at present one of the most widely used agents in the adjuvant treatment of breast cancer: it is therefore not surprising that this probably is the most extensively studied agent. Its mechanism of action, after liver activation, consists in the formation double strand breaks in DNA. Actively proliferating cells are most sensitive to this agent, but this type of damage also affects oocytes. DNA damage results in apoptosis mediated by complex molecular mechanisms which may in part be reversed by protecting agents.