Treatment options for impaired spermatogenesis: germ cell transplantation and stem-cell based therapy

Advances in infertility treatment had the most extraordinary breakthrough with the birth of the first in vitro fertilization baby in 1978. Fourteen years later, intracytoplasmic sperm injection has been introduced for the treatment of male factor infertility. Intra cytoplasmic sperm injection in combination with testicular sperm extraction has allowed men with azoospermia to father children. In fact, as long as a fully developed spermatozoon is identified, it can be utilized or can even be duplicated to inseminate several oocytes while providing information on its genomic content. There are, however, men who are suffering from spermatogenic arrest, where no post-meiotic germ cells are retrieved, and therefore, unable to generate their own offspring. More recently, the successful isolation and cultivation of spermatogonial stem cells has allowed the exploration of their biological characteristics and their application in therapeutic approaches following transplantation or in vitro maturation. Finally, men diagnosed with germ cell aplasia can only be treated by donor or de novo generated gametes. In the past several years, we have attempted to manufacture gametes by inducing haploidization of somatic cells and more recently, generating sperm-like cells through embryonic stem cell differentiation.