Update on fertility restoration from prepubertal spermatogonial stem cells: How far are we from clinical practice?

Abstract

Fertility preservation in prepubertal boys facing gonadotoxic treatment is still at the experimental stage. Nevertheless cryopreservation of immature testicular tissue (ITT) obtained by small testicular biopsy is being increasingly proposed in reproductive care clinics for this purpose. Different approaches to in vivo or in vitro mature spermatogonial stem cells (SSCs) contained in ITT have been studied: autografting of testicular tissue pieces, transplantation of one's own purified germ cell suspensions, and in vitro maturation (IVM) for subsequent use of sperm for intra cytoplasmic sperm injection (ICSI). While complete spermatogenesis yielding fertile offspring has been achieved in a number of animal species after cell and tissue transplantation and IVM, no mature sperm has yet been obtained from human prepubertal SSCs. This review describes research conducted by our team and a number of others working on fertility restoration from SSCs, with special emphasis on debated concerns and progress made towards clinical application of different strategies.

Restoration of functional sperm production in irradiated pubertal rhesus monkeys by spermatogonial stem cell transplantation

“…If spermatogonial stem cells (SSCs) are completely lost after gonadotoxic therapy, the only way to preserve future fertility of pre‐pubertal males is by harvesting tissue or a cell suspension containing SSCs prior to therapy and cryopreservation. Indeed, it is the current clinical practice to cryopreserve the testicular tissues before gonadotoxic therapies in boys in various centers in the world 8‐11 hoping that a satisfactory technique will be developed to produce spermatozoa from the SSCs present in this tissue. SSC transplantation to the seminiferous tubules is one of the techniques that have the potential to restore spermatogenesis in vivo from an individual's own testis.…”

Fertility sparing strategies for pre- and peripubertal male cancer patients

“…Transplantation of SSCs in seminiferous tubules was first described by Brinster and Avarbock in mice [20]. Generation of offspring in a number of other animal species has also been reported (for review, see [21]) with sperm obtained from transplanted SSCs in non-human primates resulting in viable embryos [22]. With the perspective of translating the technique to humans, methods to perform transplantation of cell suspensions in larger testes were evaluated.…”

“…Successful transplantation of freeze-thawed murine testicular tissue with birth of offspring was first described in 2002 [29], with subsequent reports in a number of other species (for review see [21]). Very recently, an important milestone was reached with the generation of offspring from transplanted immature testicular tissue in macaques [30].…”

Cryopreservation- A Boon to Assisted Reproductive Technologies

“…Fertility restoration can be done by thawing the tissue at a later time, when the patient is ready to have a family, and sperm derived by either auto-transplantation to an orthotopic or heterotopic site or even be matured in vitro. 44 45 , chemotherapy or radiotherapy to treat cancer or other systemic diseases 46 and in women with chromosomal anomalies such as Turner's syndrome [45][46][47] , ovarian tissue cryopreservation or whole ovary cryopreservation can be offered. Though this procedure is still experimental in nature, it is a promising alternative to prevent fertility loss in the above mentioned group of patients.…”