Enhancement of Vascularization and Ovarian Follicle Survival Using Stem Cells in Cryopreserved Ovarian Tissue Transplantation-A Systematic Review

Simple Summary Increases in survival rates from malignant diseases has introduced the need to ensure fertility preservation treatment for cancer patients. Cryopreservation of ovarian tissue is a relatively new technology in which fragments of ovarian tissue are sampled and cryopreserved in order to be re-transplanted into the patient after completion of treatment. The main shortcoming of this method is tissue re-transplantation without the formation of vascular anastomoses, which limits the blood flow and oxygen supply to the transplanted tissue until a novel vascular network is established. In this systematic review, we have gathered reports that study how co-transplantation of mesenchymal cells together with thawed ovarian tissue contributes to the process of revascularization and, consequently, the preservation of follicles and ovarian tissue. The conclusion that stem cells contribute to ovarian tissue preservation was drawn from histological analysis of ovarian tissue, the detection of factors that contribute to vascular formation and analysis of sex hormone levels which indirectly indicate the resumption of ovarian function.Abstract The increase in cancer survival rates has put a focus on ensuring fertility preservation procedures for cancer patients. Ovarian tissue cryopreservation presents the only option for prepubertal girls and patients who require immediate start of treatment and, therefore, cannot undergo controlled ovarian stimulation. We aimed to provide an assessment of stem cells' impact on cryopreserved ovarian tissue grafts in regard to the expression of growth factors, angiogenesis promotion, tissue oxygenation, ovarian follicle survival and restoration of endocrine function. For this systematic review, we searched the Scopus and PubMed databases and included reports of trials using murine and/or human cryopreserved ovarian tissue for transplantation or in vitro culture in combination with mesenchymal stem cell administration to the grafting site. Of the 1201 articles identified, 10 met the criteria. The application of stem cells to the grafting site has been proven to support vascular promotion and thereby shorten the period of tissue hypoxia, which is reflected in the increased number of remaining viable follicles and faster recovery of ovarian endocrine function. Further research is needed before implementing the use of stem cells in OT cryopreservation and transplantation procedures in clinical practice. Complex ethical dilemmas make this process more difficult.