(Future) Fertility after treatment for childhood Hodgkin lymphoma

Childhood Hodgkin lymphoma (HL) and its treatment has significant impact on pediatric patients and their families. Even after successful treatment, (late) adverse effects of treatment can continue to affect the quality of life during survivorship. Depending on the state of disease and received treatment, newly diagnosed HL patients and survivors can be at risk of in- or subfertility, related to impaired spermatogenesis in males and damage to ovarian follicle pool, potentially affecting the fertility life span and leading to premature ovarian insufficiency (POI) in females. The objective of the present thesis was to improve knowledge on gonadotoxicity of childhood HL treatment and the incidence of fertility impairment during survivorship. In addition, this thesis aimed to briefly assess current fertility counseling and the use of fertility-preserving treatments in childhood HL patients. These data are useful to improve future childhood HL treatment and fertility care for newly diagnosed patients and survivors. Over the past decades, efforts have been made to minimize late effects without comprising effectivity of treatment. Overall exposure to alkylating agents and radiotherapy dose and -field have gradually been reduced, which are all associated with risk of infertility. Within the most recent European treatment protocol for childhood HL, the EuroNet-PHL-C2 treatment protocol, standard use of radiotherapy is further reduced in an effort to reduce risk of secondary malignancies. However, to compensate, chemotherapy is intensified, resulting in an 25% increased alkylating agent exposure. Studies conducted within this dissertation revealed a gonadotoxic effect of current HL treatment, with impaired reproductive markers observed in both boys and girls during treatment and the first years of follow-up, especially in patients treated for advanced stage disease. However, recovery rates and clinical outcomes of childhood HL patients treated according to the current EuroNet-PHL-C2 treatment protocol remain unknown, thus additional long-term studies are still needed. Hopefully, we will continue to make significant process in identifying and reducing gonadotoxic treatments, ideally resulting in effective treatments without adverse late effects. Patients and their families should be well informed about the potential impact of HL disease and its treatment on (future) fertility, and personalized fertility care should be offered at diagnosis and during survivorship.