How to Advise Female Patients to Avoid Pregnancy When You Administer Ovotoxic or Genotoxic Pharmaceuticals

Abstract

Many of oncology pharmaceuticals have ovotoxicity and/or genotoxicity. Ovarian reserve, numbers of healthy oocytes in the ovary, gradually decreases in aging, but abruptly decreases when young female cancer patients are exposed to ovotoxic pharmaceuticals. Therefore increasing number of young patients undergo fertility preservation in which oocytes or ovarian tissue are retrieved and cryopreserved before chemotherapy. The deterioration of the quality of oocytes in aging is called “oocyte aging”, and the function of DNA repair in the oocytes are known to be deteriorated in aging. Similar to those from U. S. Food and Drug Administration and European Medicines Agency, labeling guidance in Japan recommends “5×T_1/2+6 months” of contraception period after the cessation of genotoxic pharmaceuticals, based on mouse model experiments which suggested that early fertilization soon after the administration of ovotoxic pharmaceuticals can result in a high rate of pregnancy failure and high malformation rate. However, the teratogenicity of pharmaceuticals has been generally found when administered during the 4th to 10th weeks of pregnancy, and healthy children were born even when they originated from the oocytes or ovarian tissue which had been retrieved immediately after chemotherapy. All healthcare professionals, especially obstetricians and pharmacists, should carefully provide information and counseling to the female patients and their partners who get unexpectedly pregnant during the above-mentioned contraception period.