Male fertility restoration: in vivo and in vitro stem cell-based strategies using cryopreserved testis tissue
Childhood cancer survival rates have increased substantially in the past few decades, with over 80% of survivors reaching adulthood thanks to modern treatment regimens. Many prepubertal patients with cancer are facing gonadotoxic treatments such as chemotherapy or gonadal radiation, which poses a significant threat to their future fertility. Prepubertal males have no option to preserve fertility by traditional sperm cryopreservation; for these patients, the only fertility preservation strategy is cryopreservation of immature testis tissue (ITT). Fertility restoration is increasingly becoming a concern, with the focus shifting toward continuation of care after successful cancer treatment and securing quality of life for childhood cancer survivors who wish to become biologic parents in adulthood. Some centers also offer testis tissue cryopreservation for selected young boys with cryptorchidism who have a high risk of infertility. A growing number of centers worldwide now offer routine cryopreservation of ITT with the aim of advancing spermatogonial stem cell (SSC)–based treatments to a clinical stage to provide opportunities for fertility restoration.
Fertility has a profound impact on our quality of life. Male fertility restoration is currently a dynamically evolving field including a broad range of strategies such as surgical and in vitro approaches to achieve restoration of fertility from prepubertally cryopreserved testis tissue. Meanwhile, the current evidence for fertility restoration strategies has not yet been systematically synthesized, leading to a potential lack of structured research cooperation across different disciplines. Thus, this topic lends itself to a scoping approach to map and assess the extent of the evolving heterogeneous literature and identify gaps in knowledge. This review aimed to examine the current evidence and clinical applicability of the different strategies for fertility restoration using ITT as well as identify future research questions that will accelerate the expected implementation of therapy options in clinical medicine. Furthermore, potential barriers in the development of clinically relevant therapies are identified.
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