Vitrification of Ovarian Tissue for Fertility Preservation

Abstract

While 80 % of young patients currently survive their cancers, devastating side effects of chemo- or radiotherapies leave females facing infertility due to ovarian failure. Cryopreservation of embryos, oocytes, and ovarian tissue is available to preserve fertility in female patients with cancer. Both embryo and oocyte freezing are established methods, and ovarian tissue cryopreservation has emerged as a promising hope for future fertility for patients who are prepubertal, adolescent, lacking partners, or those who require immediate cancer therapy. Autografting of cryopreserved ovarian tissue to women restored ovarian endocrine function and resulted in live births, but this fertility preservation option is still considered experimental. All but two of the 60 reported human births have resulted from ovarian tissue cryopreserved using a slow-rate freezing protocol. The slower progress for clinical implementation of ovarian tissue vitrification is due to the lack of a uniform vitrification protocol, in contrast to slow-rate freezing, that demonstrates consistent outcome. Recent advances in embryo and oocyte cryopreservation have driven clinical practice in the United States almost exclusively to vitrification, with the vast majority of infertility clinics no longer having access to programmable freezers in their embryology laboratories. Thus, there is a current demand for an ovarian tissue vitrification method that could extend the ability of clinics to offer this option for fertility preservation. This chapter compares and contrasts slow-rate freezing with vitrification, discusses the facts and fallacies surrounding ovarian tissue vitrification, and summarizes the steps necessary for optimizing a method for ovarian tissue vitrification using a logical approach based on cryobiological principles. Advantages and disadvantages of various endpoints used for assessing the morphology and function of vitrified ovarian tissue are also described. Emerging studies in nonhuman primates, whose ovarian structure and function are similar to women, reveal the first evidence of in vivo function of vitrified-thawed ovarian tissue after transplantation including restoration of ovarian cyclicity as well as collection of healthy mature oocytes capable of early embryonic development in vitro. The first reports of live births in women who underwent heterotopic transplantation with vitrified-thawed ovarian tissue unequivocally demonstrate that vitrification is an effective method of human ovarian tissue cryopreservation that preserves ovarian function, including the fertile potential of this tissue. Ovarian tissue vitrification using optimized protocols underscored by best manufacturing methods for vitrification solutions along with successful clinical practice for transplantation is an immediate need for patients whose sole option for one day becoming parents is ovarian tissue cryopreservation.