Bckground: Premature ovarian insufficiency (POI) occurs in 1% of cases in women aged 35–40 years and a large number of women of this age are faced with the problem of reduced reproductive ability or losing reproductive ability and a number of other symptoms affecting overall health and quality of life. It has been proven that many genetic and external factors lead to the Hippo signal pathway disruption and follicle growth disruption, resulting in amenorrhea and menopause.
Methods: Our study provides concise summary of published data about experimental evidences for the restoration of reproductive ovarian function in women with compromised reproductive health. The database used was Pubmed where full text articles and English-written reviews published between 2004 and 2018 were preferred. The MeSH (Medical Subject Headings) terms used were ‘ovarien rejuvenation’, ‘ovarien follicle activation’, ‘female germline stem cells’, ‘stem cell therapy’ and ‘ovarien insufficiency’, either alone or in combination. The references of the articles were also considered when searching for the most relevant articles.
Results: Exposure of ovarian tissues to autologous concentrated growth factors and autologous stem cells results in the Hippo signal path disruption and stimulation of revived follicle growth and improvement of ovarian reproductive function. In vitro ovarian activation represents autologous genetic treatment of the gonadal tissue to restore reproductive and endocrine ovarian function. Among the sleepy follicles, ~ 0.1% of the follicles were selected for activation. Since patients with POIs (primary ovarian insufficiencies) have <1,000 residual follicles, growth factors and maternal cells can activate sleepy follicles. SEGOVA acts on the intracellular signaling system. The use of the SEGOVA method (ovarian in vitro activation by autologous growth factors and autologous stem cells) leads to regeneration and improvement of the reproductive function of the ovaries.
Conclusion: In vitro ovarian activation represents autologous genetic treatment of gonadal tissue to restore reproductive and endocrine ovarian function. Oogenesis depends on the proper genetic control. Ovarian function is achieved by the formation of ovarian cells, which is associated with a specific hormone activity. The primitive status of primordial follicles is characterized by communication with the surrounding granulocyte cells and numerous mechanical and chemical factors that control the progression of their cell cycle. Autologous growth factors and autologous stem cell therapy activate genetic pathways, initiate, and promote the development and differentiation of ovarian cells, resulting in improved endocrine status and ovarian function.
Johnson J, Canning J, et al. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004;428:145–150. DOI: 10.1038/nature02316.
White YA, Woods DC, et al. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med 2012;18:413–421. DOI: 10.1038/nm.2669.
Sánchez F, Smitz J. Molecular control of oogenesis. Biochim Biophys Acta 2012;1822:1896–1912. DOI: 10.1016/j.bbadis.2012.05.013.
Lawson KA, Hage JW. Clonal analysis of the origin of primordial germ cells in the mouse. Ciba Found Symp 1994;182:68–84.
Albanese A, Licata ME, et al. Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration. Immun Ageing 2013;10:23. DOI: 10.1186/1742-4933-10-23.
Zhang N, Wu YP, et al. Research progress in the mechanism of effect of PRP in bone deficiency healing. Sci World J 2013;134582. DOI: 10.1155/2013/134582.
Callejo J, Salvador C, et al. Live birth in a woman without ovaries after autograft of frozen-thawed ovarian tissue combined with growth factors. J Ovarian Res 2013;6:33. DOI: 10.1186/1757-2215-6-33
Hosseini L, Shirazi A, et al. Platelet-rich plasma promotes the development of isolated human primordial and primary follicles to the preantral stage. Reprod Biomed Online 2017;35:343–350. DOI: 10.1016/j.rbmo.2017.04.007.
Scott Sills E, Rickers NS, et al. First data on in vitro fertilization and blastocyst formation after intraovarian injection of calcium gluconate-activated autologous platelet rich plasma. Gynecol Endocrinol 2018;34(9):756–760. DOI: 10.1080/09513590.2018.1445219.
Pellicer A. IVI achieves four pregnancies in women with ovarian failure thanks to ovarian rejuvenation. IVI Press release, 2017.
White YAR, Woods DC, et al. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med 2012;18:413–421. DOI: 10.1038/nm.2669.
Woods DC, Tilly JL. An evolutionary perspective on adult female germline stem cell function from flies to humans. Semin Reprod Med 2013;31:24–32. DOI: 10.1055/s-0032-1331794.
Woods DC, Tilly JL. Isolation, characterization and propagation of mitotically active germ cells from adult mouse and human ovaries. Nat Protoc 2013;8:966–988. DOI: 10.1038/nprot.2013.047.
Hayashi K, Ogushi S, et al. Offspring from oocytes derived from in vitro primordial germ cell-like cells in mice. Science 2012;338(6109): 971–975. DOI: 10.1126/science.1226889.
Li J, Kawamura K, et al. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A 2010;107:10280–10284. DOI: 10.1073/pnas.1001198107.
Suzuki N, Yoshioka N, et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod 2015;30:608–615. DOI: 10.1093/humrep/ deu353.
Ljubiæ A, Abazoviæ Dž, et al. Autologous ovarian in vitro activation with ultrasound-guided orthotopic re-transplantation. Am J Clin Exp Obstet Gynecol 2017;4:51–57.
Sittadjody S, Saul JM, et al. Engineered multilayer ovarian tissue that secretes sex steroids and peptide hormones in response to gonadotropins. Biomaterials 2013;34:2412–2420. DOI: 10.1016/ j.biomaterials.2012.11.059.
Liu C, Xia X, et al. An ovarian cell microcapsule system simulating follicle structure for providing endogenous female hormones. Int J Pharm 2013;455:312–319. DOI: 10.1016/j.ijpharm.2013. 07.004.
Lai RC, Chen TS, et al. Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med 2011;6:481–492. DOI: 10.2217/rme.11.35.
Paliwal S, Chaudhuri R, et al. Regenerative abilities of mesenchymal stem cells through mitochondrial transfer. J Biomed Sci 2018;25:31. DOI: 10.1186/s12929-018-0429-1.