Clinical and Genetic Determinants of the Impact of Childhood Cancer on Reproductive Health

Over the past five decades, survival of childhood cancer has improved throughout Europe, with survival rates now approximating 80% as a result of improved treatment strategies. Despite this accomplishment, around 75% of the resulting growing population of long-term childhood cancer survivors (CCS) develops at least one long-term complication as a result of their cancer treatment. Major effects on reproductive health include gonadal function damage and pregnancy complications. The general aim of research described in this thesis was to evaluate the impact of cancer on clinical and genetic aspects of reproductive health. In this thesis, we demonstrate that gonadal function is impaired already prior to cancer treatment, and show that gonadal function is further decreased in both boys and girls by childhood cancer treatment. However, as gonadal function markers can show recovery, we conclude that evaluation of gonadal function markers within the first year after end of treatment is unreliable. In adult CCS, the decline of gonadal function markers was not accelerated as compared to the physiological decline of AMH levels in healthy women of the same age. A genetic variation possibly modifies the association between chemotherapy and reduced ovarian function, making girls with cancer with this particular genetic variation more sensitive for the adverse effects of chemotherapy on their ovarian function. We conclude with addressing obstetric outcomes in CCS. Especially after radiotherapy on the uterus, CCS are more at risk for miscarriages, premature delivery and giving birth to a child with a low birth weight. We present recommendations for counseling and surveillance of obstetric risks for CCS resulting from our worldwide collaborative effort to harmonize these recommendations.

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