Optimizing fertility preservation in prepubertal boys Focus on spermatogonia

This PhD thesis, titled "Optimizing Fertility Preservation in Prepubertal Boys: Focus on Spermatogonia," addresses the critical challenge of safeguarding future fertility for young male patients facing gonadotoxic treatments. Because prepubertal boys do not yet produce mature sperm, they rely on the experimental cryopreservation of testicular tissue containing spermatogonial stem cells (SSCs) for future fertility restoration. The research is divided into two primary parts: clinical decision-making and tissue biology. In the first part, comprehensive normative reference values for spermatogonial quantity in healthy boys were established, providing a benchmark to evaluate the impact of disease and treatment. Using these normative values, it was found that cancers (particularly CNS tumors) and severe hematological disorders (such as sickle cell disease) can significantly reduce spermatogonial quantity even before treatment is initiated. In boys with leukemia, exposure to alkylating agents, specifically at doses exceeding 4 g/m², was found to lead to a severe depletion of the spermatogonial pool. In the second part, a new membrane exclusive biomarker for human spermatogonia was identified and validated. Finally, the evidence base for international clinical guidelines is strengthened by this work, and early fertility counseling and personalized preservation strategies based on a patient's specific diagnosis, age, and treatment plan are advocated.