Fertility sparing strategies for pre- and peripubertal male cancer patients

Genetic parenthood following cancer therapy is considered to be a major factor of quality of life. Given the rising proportion of patients surviving cancer due to improved therapeutic protocols, it is an issue of growing importance. Hence, the efforts to preserve fertility have motivated researchers to develop options for the paediatric population facing fertility-threatening cancer therapies. In prepubertal boys who do not yet produce sperm, cryo-banking of testicular tissue containing spermatogonial stem cells (SSCs) is the only viable option for future fertility preservation. While proposed in a number of clinics worldwide, however, this strategy remains still experimental. Transplanting the SSCs, or testicular tissue containing SSCs, back to the cured patient appears the most promising strategy. However, experiments performed with human testicular tissue in mice models reveal spermatogonial loss after transplantation, indicating the need for further optimisation of the transplantation procedure. The approach further poses the risk of reintroducing tumour cells back to the patient. In cases of haematological and blood-metastasising malignancies, in vitro generation of sperm combined with assisted reproductive technologies (ART), is the only possibility, avoiding reintroducing cancer cells. Although xenotransplantation would allow to recover sperm cells for ART being thus on the safe side with regard to cancer cells, the risk of infections with xeno-microbiological agents makes this option incompatible with clinical application. So far, offspring from in vitro matured sperm has only been achieved in mice. While human haploid germ cells, showing specific morphological features, expression of post-meiotic markers, as well as DNA and chromosome content, as well as fertilisation and development capacity, have been obtained by culturing spermatogonia or immature testicular tissue, the functionality of these cells still needs to be demonstrated. Despite the promising results obtained in recent years, further research is urgently warranted to establish a clinical tool offering these boys a fertility restoration option in the future. This mini-review will focus on current achievements and future challenges of fertility preservation in young boys and underscore the next steps required to translate experimental strategies into clinical practice.