REJUVENATION OF PREMATURE OVARIAN FAILURE WITH STEM CELLS

Rejuvenation of Premature Ovarian Failure With Stem Cells

Premature ovarian failure (POF) is defined as hypergonadotropic ovarian failure occurring prior to age 40 . It is surprisingly common and affects approximately 1% of women below the age of 40. The incidence is 10% to 28% in women with primary amenorrhea and 4% to 18% in women with secondary amenorrhea . The clinical manifestations include amenorrhea and abnormally high levels of luteinizing (LH) and follicle stimulating hormone (FSH). The etiology of POF is unknown in most cases. It can be caused by combination of inherited conditions, immune disorders, environmental toxins and iatrogenic injury. The majority of patients with POF are considered to have idiopathic premature ovarian failure because usually no cause can be identified . POF has been shown to be associated with an increased incidence of other conditions, including Alzheimer’s, cardiovascular and immune system diseases, metabolic syndrome, osteoporosis, diabetes and cancer of reproductive organs. POF is characterized by loss of secondary follicles, arrested folliculogenesis, decreased estrogen production, and infertility . The mechanism of ovarian failure is most likely accelerated follicular atresia but detailed pathogenesis is yet to be fully understood .

In women younger than 40, at least two menopausal FSH levels (≥40 IU/L) will be sufficient for the diagnosis of POF. It is not essential to have amenorrhea for the diagnosis of POF, because spontaneous menstrual cycles can sometimes be seen after the diagnosis as well. Resumption of normal ovarian function, albeit temporary, in patients with normal karyotypes has been documented in 10 to 20% of patient; thus, resumption of fertility is possible .

No presently available therapeutic intervention has been proven effective in restoring normal fertility in patients with POF. Various attempts at ovarian stimulation are usually unsuccessful. Therefore, the diagnosis of POF can cause great physical and mental suffering among patients. Thus, there is critical need to develop novel effective approaches for the treatment of POF.

Throughout life, there is an ongoing physiological level of atresia of oocytes. A decreased germ cell endowment combined with an increased rate of germ cell destruction can explain POF . The current concept that the ovary has a static ovarian reserve is entirely at odds with the germ cell dynamics. Current research supports the concept that the ovary continues to produce new germ cells into adult life, however if this occurs in humans is not universally accepted yet. Recent research suggests that diminished ovarian reserve is a result of the aging of the niche rather than a defect in germ cell. Emerging evidence suggests that bone marrow-derived mesenchymal stem cells (BMSCs) could restore the structure and function of injured tissues. During embryologic development, cells of the mesodermal layer give rise to multiple mesenchymal tissue types including bone, cartilage, tendon, muscle, fat and marrow stroma . These precursor cells, also present in the postnatal organism, are referred to as mesenchymal stem cells. These stem cells have been shown to retain their developmental potential following extensive subcultivation in vitro. Implantation of culture-expanded mesenchymal stem cells has been demonstrated to effect tissue regeneration in a variety of animal models and depends on local factors to stimulate differentiation into the appropriate phenotype .

Recent studies suggest that stem cell therapy holds promise in treatment of variety of diseases including reproductive dysfunction. In a recent investigation  bone marrow stem cell (BMSC) treated animals revealed recovered ovarian function. Post bone marrow nucleated cell transplantation, treated animals revealed resumption of estrogen production and folliculogenesis . In another investigation by Lui et al (2014), granulosa cell apoptosis induced by cisplatin was reduced when BMSCs were migrated to granulosa cells in vitro. In this study, chemotherapy-induced POF rats were injected with BMSCs. The BMSCs treatment group’s antral follicle count and estradiol levels increased after 30 days, compared with untreated POF group . In a recent clinical trial in Egypt, Edessy et al evaluated the therapeutic potential of autologous mesenchymal bone marrow stem cells transplantation in women with POF. Ten patients with POF were selected and their ovaries were injected with autologous BMSC via laparoscopy. The results revealed resumption of menstruation in one case after 3 months; two cases showed focal secretory changes after having atrophic endometrium . According to these results, BMSC seem to have the ability to revive prematurely failed ovaries both in its hormonal and follicular development abilities.

Based on our research CD34 Stem cells from mesenchymal origin no matter bone marrow or fat tissue can be used for ovarian rejuvenation although the results still needs to be analyzed.we can provide stem cell ovarian rejuvenation in Dubai in our center based on patient request and with signed consent that they acknowledge that this method still is under research and there is no guarantee .If you have any question regarding this treatment please feel free to contact with Dr Roya P through ; info@royamc.com
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