The effect of chemotherapy and radiotherapy on the human reproductive system

Cancer in childhood is rare, with approximately 1400 new cases per year in the UK, and a cumulative risk of around 1 in 500 by the age of 15 in resource-rich countries. With long-term survival rates approaching 73%, it has been estimated that by the year 2010 about 1 in 715 of the adult population will be a long-term survivor of childhood cancer [1]. Cancer is more common after puberty during the reproductive life span of men and women [2, 3], and many of these patients will be cured by combination treatment with surgery, chemotherapy and radiotherapy. Long-term survivors are nevertheless at risk of developing a number of late sequelae [4], including impaired fertility, adverse pregnancy outcomes and health problems in offspring [5–7]. Loss of fertility is one of the most devastating consequences of radio- or cytotoxic therapy for these young patients who, having overcome their disease, have expectations of a normal reproductive life. Normal ovarian development and follicular depletion Current understanding of human ovarian reserve presumes that the ovary establishes several million non-growing follicles (NGFs) during the second half of intrauterine life, which is followed by a decline to the menopause when approximately 1000 remain at an average age of 50–51. With approximately 450 ovulatory monthly cycles in the normal human reproductive life span, this progressive decline in NGF numbers is attributed to follicle death by apoptosis.