Influence of Autologous In Vitro Activation of Ovaries by Stem Cells and Growth Factors on Endocrine and Reproductive Function of Patients with Ovarian Insufficiency-A Clinical Trial Study

Document Type : Original Article


1 Department of Gynecology, Polyclinic, Korak do Života, Tuzla, Bosnia and Herzegovina

2 Department of Regenerative Medicine, Remedika Hospital, Belgrade, Serbia

3 Department of Gynecology, MediGroup Hospital, Belgrade, Serbia

4 Faculty of Medicine, Military Medical School, Belgrade, Serbia

5 Department of Gynecology and Obstetrics, Medical School, University of Belgrade, Belgrade, Serbia

6 Department of Medical Biology and Human Physiology, Sarajevo Medical School, University Sarajevo School of Science and Technology, Sarajevo, Bosnia and Herzegovina

7 Department of Histology, Medical School, University of Tuzla, Tuzla, Bosnia and Herzegovina

8 Department of Gynecology, Dubrovnik International University, Dubrovnik, Croatia


Premature ovarian failure (POF) can be found in 1% of women at the age of 35-40, mostly due to unknown
causes. PI3K-Akt signaling is associated with both ovarian function and growth of primordial follicles. In this
study, we examined the effects 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 longitudinal prospective observational study included 50 patients (between 30 and 50
years) with a diagnosis of POF and infertility. This multicenter study was performed at Jevremova Special Hospital in
Belgrade, Saint James Hospital (Malta), and Remedica Skoplje Hospital, between 2015 and 2018. All patients went
through numerous laboratory testings, 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 re-transplantation.
The software package SPSS 20.0 was used for statistical analysis of the results.

Differences in follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone
(PG) hormone concentrations before and after 3, 6, and 12 months post-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 re-transplanted tissues. Also after re-transplantation, 64% of the patients
had follicles resulting in aspiration of oocytes in 25% of positive women with follicles.

The SEGOVA method could potentially solve many human reproductive problems in the future due to
the large number of patients diagnosed with POF, as well asthe possibility of delaying menopause, thus improving
the quality of life and general health (Registration number: NCT04009473).