Reproductive function in male childhood cancer survivors

Abstract: Childhood cancer (CC) survival rate has increased over the last couple of decades, today approaching 80%. Therefore more attention has been paid to late effects. One important issue for CC survivors (CCS) is impaired reproductive function. CC per se and/or its treatment can impair the reproductive ability by affecting sperm production, as well as by damaging sperm DNA. This is a matter of concern, since subsequent use of assisted reproduction can cause transmission of genetic abnormalities to the offspring. Another, relatively uncovered issue is the question of androgen deficiency in CCS. To improve the counselling and management of CCS, the aim of this thesis was to investigate reproductive function in a group of male CCS (n=151). The specific aims were: • to investigate the magnitude of risk for hypogonadism in relation to diagnosis- and treatment; • to determine to which extent CC treatment is associated with the risk of azoospermia and to whether genetic polymorphisms, hormonal levels and ? or testicular size could predict its risk; • to assess the impact of the disease, or the treatment, on sperm DNA integrity. We found that: • hypogonadism was almost 7 times more common in CCS than in controls, which should be acknowledged in the long-term follow up of CCS. None of the clinical predictors, except hormone analysis was sufficiently reliable in diagnosing androgen deficiency; • most childhood cancer diagnoses are associated with an increased risk of azoospermia, especially in CCS receiving testicular irradiation, high doses of alkylating drugs, and other types of cytotoxic treatment, if combined with irradiation. Inhibin B, FSH and testicular volume can, to a limited degree be used as predictors for the risk of azoospermia; • sperm DNA integrity is slightly impaired in CCS, not treated with chemotherapy. This sperm DNA damage may be associated with the disease per se rather than the treatment and may have negative consequences in relation to fertility and health of the offspring; • a genetic variant of the Estrogen Receptor ? was associated with an increased risk of azoospermia, a finding demonstrating the potential of genetic analysis in future selection of boys to whom preservation of testicular tissue prior to cancer therapy should be offered.