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The Science

Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less.

Marie Curie

The Medicine Behind Ovarian Rejuvenation

Female infertility is a global health issue with significant medical and psychological suffering among women throughout the world. It is a disease condition in which the female counterpart of a couple fails to achieve pregnancy in 12 months of unprotected sexual relationship without using any contraceptives.[1] According to a study published in 2007, 72.4 million women aged between 20-44 years suffered from primary or secondary infertility worldwide.[2] Defective ovulation, transport, and implantation are the three broadly categorized causes of female infertility by the Center for Disease Control (CDC).[3] However, the defect or complete cessation of ovarian function such as ovulation is the leading cause of female infertility.

Premature Ovarian Failure, which is also referred to as Ovarian Insufficiency, is the condition in which the ovaries cease to produce eggs and observe the decline in follicle count has the main influence on rendering infertility.[4-5] It was believed that women have a limited number of eggs that emerge from a finite number of primordial follicles produced during fetal development. Only these follicles were thought to develop to the grafian stage, in which the eggs ovulate. However, the revolutionary work of Dr. Tilly and his colleagues proved contrary to the landmark discovery of Female Germline Stem Cells (FGSCs) in postnatal mammalian ovaries.[6]. Notably, these undifferentiated FGSCs were shown to differentiate and form oocytes or egg cells which challenged the belief of limited Ovarian Reserve. [7]. Secondly, ovarian aging disrupts the ovulation cycle that leads to hormonal disparity and establishes the basis of female infertility. Moreover, the increased follicle-stimulating hormone (FSH) level > 25 IU/l is an important diagnostic factor for premature ovarian failure. Consequently, Premature Ovarian Failure and Menopause cause a decline in the overall wellbeing of women aged 35 and above 40 years respectively.

The  program in conjunction with our affiliates consists of a comprehensive treatment plan for infertility involving baseline blood testing, evaluation, mononuclear cell treatment, energy mitochondria boosting, extracellular vesicle therapy, and Ovarian In-Vitro activation.

This extracellular vesicle/mononuclear cell treatment uses the autologous injection of mesenchymal stem cells derived from the patient’s own body to the ovaries to promote the differentiation of germline stem cells into healthy follicles. The autologous nature minimizes any chances of infections and has the potential to restores ovarian function. [8-9] The mesenchymal stem cells have been proven to restore fertility through the reduction of apoptosis in stromal and oocytes, promote folliculogenesis and improve the ovarian microenvironment.[10]

Energy mitochondrial boosting involves High Intensity Interval Training, a specific anaerobic fitness regime that boosts mitochondrial energy production in gonadal cells. [11] as well as proprietary supplementation. 

Procedure

This is a multi-phase procedure, and it is carried out after a complete examination of possible patterns of omission of the ovarian function, treatment of hereditary, hormonal and immunological factors.

The first phase involves the extraction of an adequate amount of bone marrow which depends on the patient’s constitution and the degree of oxygen deprivation, clinical picture, and prognosis, as well as the desired composition of the factors that are injected into the ovary.

The second phase, laboratory, implies the application of complex technology, by which special systems are separated and purified by the corresponding cells, prepared and then activated.

The third stage involves inserting an active substance, derived from its own blood by a special treatment method, into the tissue of the ovary, outside the blood vessels.

The effects relate to the growth of follicles and the production of egg cells in a spontaneous and stimulated cycle, as well as repairing the hormonal function of the ovaries. This allows for their fertilization and could leads to more pregnancies. The first effects are expected in a month or two. For the next six months, the standard procedures of IVF in a natural, modified and stimulated cycle are carried out. Spontaneous pregnancy may also be attempted without IVF intervention.

Case Results

The sample of 73 patients with sonographic follow-ups, and 50 patients who finished one-year hormone change monitoring showed that the procedure has a favorable effect on the endocrine status and on the reproductive outcome of patients in post-menopause.

The results show that the first effects of the intervention on FSH levels could be seen after 6 months when FSH starts significant declining (25.8%). (Table 1) The effects of the intervention on LH could be seen already after 3 months, when its concentration starts declining, while a decrease is the most pronounced at six months post-intervention (25%).

The rise in estradiol (E2) levels were recorded at 3 months post-intervention (26.6%). The decrease in progesterone levels was recorded at 3 months post-intervention, being the most pronounced at six months (56.2%).

The total results of ultrasonography for 73 patients that completed the one-year follow-up show during 12 months period after the re-transplantation 64% of patients had the presence of a follicle. Attempts to perform oocyte retrieval resulted in aspirated oocytes in 39.1% follicle positive women (24.6% out of the total number of patients). The fertilization rate of the aspirated oocytes was 83 %, resulting in embryos in 20.54 % of women out of the total number of patients. Embryo transfers were performed in 60 % embryo positive women (12.32% out of the total number of patients), while 66.6% embryo positive women had vitrified embryos (13.69% out of the total number of patients had embryos vitrified). Two patients spontaneously conceived after transplantation, while two pregnancies were conceived with IVF (one of them Gemelli pregnancy), resulting in 5 newborns. 

References

  1. Gurunath S, Pandian Z, Anderson RA, Bhattacharya S. Defining infertility—a systematic review of prevalence studies. Human reproduction update. 2011 Apr 14;17(5):575-88.

  2. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care.

  3. Human reproduction. 2007 Jun 1;22(6):1506-12.
    Centers for Disease Control and Prevention. Infertility FAQs. 2013. 

  4. Fortuño C, Labarta E. Genetics of primary ovarian insufficiency: a review. Journal of assisted reproduction and genetics. 2014 Dec 1;31(12):1573-85.

  5. Rudnicka E, Kruszewska J, Klicka K, Kowalczyk J, Grymowicz M, Skórska J, Pięta W, Smolarczyk R. Premature ovarian insufficiency–aetiopathology, epidemiology, and diagnostic evaluation. Menopause Review/Przegląd Menopauzalny.;17(3):105-8.

  6. Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004 Mar;428(6979):145.

  7. White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nature medicine. 2012 Mar;18(3):413.

  8. Fazeli Z, Abedindo A, Omrani MD, Ghaderian SM. Mesenchymal stem cells (MSCs) therapy for recovery of fertility: a systematic review. Stem Cell Reviews and Reports. 2018 Feb 1;14(1):1-2.

  9. Sheikhansari G, Aghebati-Maleki L, Nouri M, Jadidi-Niaragh F, Yousefi M. Current approaches for the treatment of premature ovarian failure with stem cell therapy. Biomedicine & Pharmacotherapy. 2018 Jun 1;102:254-62.

  10. Fu XF, He YL, Xie CH, Liu W. Bone marrow mesenchymal stem cell transplantation improves ovarian function and structure in rats with chemotherapy-induced ovarian damage. Cytotherapy. 2008 Jan 1;10(4):353-63.

  11. Ndlovu P, Ackerman SA, Davis WH, Wise A. The effect of high intensity interval training and detraining on the health-related outcomes of young women.