In Vitro Spermatogenesis: How Far from Clinical Application?

Male infertility affects 7 % of the male population, and 10 % of infertile men are azoospermic. In these instances, using microsurgical testicular sperm extraction (m-TESE) and intra-cytoplasmic sperm injection (ICSI) helps a significant number of patients. However, in vitro differentiation of diploid germ cells to mature haploid germ cell has the potential to benefit many others, including pediatric cancer survivors who have previously cryopreserved their immature testicular tissue prior to starting gonadotoxic cancer treatment as well as men with spermatogenic arrest. This systematic review evaluates and summarizes half a century of researchers' efforts towards achieving in vitro spermatogenesis in mammalian species. A myriad of experimental assays and approaches has been developed using whole testis tissue or separated single cells from testis in two- or three-dimensional cell culture systems (2D versus 3D). Recent advances in the mammalian in vitro spermatogenesis, particularly in murine and nonhuman primate systems, hold promise towards translating the availability of in vitro spermatogenesis models in the human clinical setting in the near future.