Fertility preservation in prepubertal boys: management and follow-up challenges

Survival after childhood cancer and severe haematological disorders has improved substantially, shifting clinical attention towards long-term quality-of-life outcomes. Preservation of male reproductive potential represents a major challenge, particularly in boys exposed to gonadotoxic therapies before the onset of spermatogenesis. While sperm cryopreservation is an established fertility preservation strategy for postpubertal males, no clinically validated option currently exists for prepubertal boys. Male fertility depends on the establishment and lifelong maintenance of a finite spermatogonial stem cell (SSC) pool within a specialized somatic microenvironment. Although the prepubertal testis lacks active spermatogenesis, it already contains the SSC populations required for future fertility and these are vulnerable to cytotoxic injury. Clinical and histological evidence shows that chemotherapy and radiotherapy, including conditioning regimens for haematopoietic stem cell transplantation, can deplete SSCs even when exposure occurs in early childhood, with consequences that may become apparent only at puberty or later in adulthood. Testicular tissue cryopreservation (TTC) has emerged as the only potential fertility preservation strategy for prepubertal boys at high risk of treatment-induced infertility. TTC aims to preserve immature testicular tissue containing SSCs for possible future use through experimental approaches. However, no human pregnancies have yet been achieved using tissue cryopreserved before puberty, and all current applications remain experimental. This review summarizes current practice for TTC in prepubertal boys, with a particular focus on the issues most relevant to paediatric endocrinologists involved in the long-term follow-up and management of these patients.