Influence of autologous in vitro activation of ovaries by stem cells and growth factors on endocrine and reproductive function of patients with ovarian insufficiency

Objective: Premature ovarian failure (POF) can be find in 1% of women, in age 35-40, mostly of unknown cause. Many genetic and external factors cause the interruption of the Hippo signaling pathway and the termination of follicular growth, while the pathway of phosphatidylinositol-3-kinase/protein kinase B (PI3K-Akt) plays a key role in cellular responses to cell proliferation. PI3K-Akt signaling is associated with ovarian function and growth of primordial follicles. In this study, we examined the effect of autologous in vitro ovarian activation with stem cells and autologous growth factors on reproductive and endocrine function in patients with ovarian impairment. Materials and methods: The study included 50 patients (between 30 and 50 years) with a diagnosis of POF and infertility. The study was performed at Jevremova Special Hospital in Belgrade, Sant James Hospital (Malta), and Remedica Skoplje Hospital, between 2015-2018. All patients went through the numerous laboratory testing, including hormonal status. The autologous bone marrow mesenchymal stem cells (BMSCs) and growth factors were used in combination for activation of ovarian tissue before its retransplantation. The software package SPS 20.0 was used for statistical analysis of the results. Results: Differences in FSH, LH, E2, and PG hormone concentrations before and after 3, 6, and 12 months after transplantation were tested in correlation with the volume of transplanted ovarian tissue. A significant correlation (p = 0.029) was found between the change in E2 level after 3 months and the volume of retransplanted tissue. Also after re-transplantation, 64% of patients had follicle resulting in aspiration of oocytes in 25% of positive women with follicle. Conclusion: The SEGOVA method in the future could solve many problems in human reproduction due to the large number of patients diagnosed with POF, as well as the possibility of delaying menopause, thus improving the quality of life and general health.