ESPE Yearbook of Paediatric Endocrinology

Brief summary: This multicentre retrospective cohort study evaluated testicular structure in 101 boys aged <14 years with solid tumors, CNS tumors, leukemia/lymphoma, or non-malignant hematological disorders, who were admitted for a fertility preservation programme between 2002 and 2018.

The aim of the study was to clarify a possible role of the disease itself on the risk of infertility, independently of cancer therapies. Clinical data, testicular volume and histological staining of testicular biopsies were obtained at cryopreservation and before treatment, in order to evaluate the number of spermatogonia per tubular cross-section, tubular fertility index, and the most advanced germ cell type before cancer treatment. Control data were extrapolated by previously published studies reporting testicular characteristics in healthy prepubertal boys.

Histological data showed a reduced number of spermatogonia in prepubertal patients with childhood cancer or hematological disorders, compared to healthy controls (48.5% versus 31.0%). The highest proportion of patients with impaired spermatogonial quantity was found in the CNS tumor and hematological disorder groups (56.7% and 55.6%, respectively), including patients with sickle cell disease pre-treated with hydroxyurea (58.3%) as well as those not exposed to hydroxyurea (50%). The disease had also a detrimental effect on spermatogonial distribution and differentiation. The most relevant spermatogonial quantity reduction was observed in patients <7 years of age, regardless of disease, and probably reflects the effects of cancer onset during a sensitive period of testicular development.

Although treatment effects on germ cells have been extensively investigated, limited data are still available regarding the effects of the disease on the prepubertal male gonad. This study suggests that cancer itself, especially CNS tumors, and severe hematological disorders can affect spermatogonial reserve in prepubertal boys. The mechanisms behind these effects are variable and only partially known. Certain mechanisms can be hypothesised. The function of the hypothalamus–pituitary gonadal axis could be negatively affected by hydrocephalus in patients with CNS tumours. Tumour dissemination in solid tumours, pro-inflammatory cytokines or impaired oxygen and nutrient supply to target organs in blood cancer, vaso-occlusion and hydroxyurea treatment in sickle cell disease could disrupt testicular environment and cause germline mutations.

Regardless of the mechanisms involved, appropriate counselling about side effects of the disease itself and its treatment on the reproductive system is mandatory for patients and parents, even before treatment, when the attention is predominantly focused on cancer diagnosis and staging.