Adverse effects of chemotherapeutic drugs on female reproduction

Chemotherapeutic drugs such as cyclophosphamide (CP) and ifosfamide (IF), despite their main use in treating diseases such as ovarian cancer, and their derivatives (e.g. acrolein, phosphoramide mustard) can also cause infertility by either directly damaging the ovaries or depleting the ovarian reserve, which can stop ovarian function. Even mesna, an adjuvant to CP and IF commonly used to manage their side effects, has also demonstrated similar effects. Other than through cancer treatment, women may also be exposed to these metabolites such as acrolein through a variety of other sources including cigarette smoke, industrial, and environmental exposure. Our research has shown that exposure to CP, its derivatives, and mesna damage oocytes and embryos at the genetic level and generates highly harmful reactive oxygen species (ROS). ROS have been demonstrated to cause extensive damage to oocyte and embryo DNA, enzyme production and balance, lipid metabolism, oocyte cell structure, protein production, cell growth, and mitochondria, and even activate cell death. In particular, mitochondrial damage is responsible for a series of further events that damage the oocyte and embryo, including calcium dysregulation, antioxidant depletion, and further overproduction of ROS. Our research also shows some possibilities for reprieve from these debilitating events, such as use of antioxidant therapy and/or acrolein scavengers, which may help offset some of these effects and help women undergoing chemotherapeutic treatment.