Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation

Abstract

BACKGROUND Female cancer patients are offered 'banking' of gametes before starting fertility-threatening cancer therapy. Transplants of fresh and frozen ovarian tissue between healthy fertile and infertile women have demonstrated the utility of the tissue banked for restoration of endocrine and fertility function. Additional methods, like follicle culture and isolated follicle transplantation, are in development. METHODS Specialist reproductive medicine scientists and clinicians with complementary expertise in ovarian tissue culture and transplantation presented relevant published literature in their field of expertise and also unpublished promising data for discussion. As the major aims were to identify the current gaps prohibiting advancement, to share technical experience and to orient new research, contributors were allowed to provide their opinioned expert views on future research. RESULTS Normal healthy children have been born in cancer survivors after orthotopic transplantation of their cryopreserved ovarian tissue. Longevity of the graft might be optimized by using new vitrification techniques and by promoting rapid revascularization of the graft. For the in vitro culture of follicles, a successive battery of culture methods including the use of defined media, growth factors and three-dimensional extracellular matrix support might overcome growth arrest of the follicles. Molecular methods and immunoassay can evaluate stage of maturation and guide adequate differentiation. Large animals, including non-human primates, are essential working models. CONCLUSIONS Experiments on ovarian tissue from non-human primate models and from consenting fertile and infertile patients benefit from a multidisciplinary approach. The new discipline of oncofertility requires professionalization, multidisciplinarity and mobilization of funding for basic and translational research.

Quality and functionality of human ovarian tissue after cryopreservation using an original slow freezing procedure

“…Therefore, the efficiency of a cryopreservation protocol has to be evaluated not only by the analysis of the follicles but also of other cells contained in cortical ovarian tissue. In vitro culture of thawed ovarian tissue provides a complementary approach to xenograft for appreciating the functionality of ovarian tissue after thawing [42]. Hence, with the aim to further evaluate the efficiency of our original slow freezing procedure, we analyzed the quality of the different cortical ovarian elements (follicles, stroma cells and vascular system) before and after freezing.…”

Whole sheep ovary cryopreservation: evaluation of a slow freezing protocol with dimethylsulphoxide

“…Attention is now focused on fertility preservation/restoration methods in young cancer patients and ovarian cortex cryopreservation, followed by avascular autotransplantation, has resulted in a small number of live-births [5]. In general, the function of these transplanted ovarian cortical grafts persist up to 3-4 years [6].…”

Detection of Non-Hodgkin’s Lymphoma in ovarian cortex pieces during the process of cryopreservation

“…One approach is the re-implantation of isolated follicles from the ovarian tissue [39]. Indeed, isolated human preantral follicles can survive and grow in vitro, that represents a lot of hope for the future [40][41][42][43].…”