STEM CELL THERAPY

Stem cell therapy (with stem cells obtained from the patient’s own body) aims to create new or incite existing non-differentiated ovarian stem cells – which are to be developed into new egg cells and hormone- producing cells.

The ‘no new eggs’ doctrine has a long history. In 1951, the influential anatomist Solly Zuckerman, at the University of Birmingham, UK, performed an in-depth analysis of evidence available at the time. He concluded that female mammals stop producing oocytes after birth. It was from this limited “bank account” of egg cells, the understanding went, that a woman would “drawdown” with each ovulation, and from which she would also lose viable eggs due to genetic and other ageing damage. When her egg cell “bank balance” fell below some limit, the loss of crosstalk amongst egg cells, follicles, and the regulatory centres in the brain would cause her follicles to atrophy and stop producing estrogen, leading to the symptoms of menopause.

However, recent studies are showing that female germline stem cells still exist in mammalian ovaries after birth. In 2004, animal studies showed that the ovaries possess rare female germ line or oogonial stem cells (OSCs), which could generate oocytes and offspring.
Moreover, cases were being reported of women who had regained their fertility after having had it destroyed by cancer therapy: months or years after being rendered infertile and suffering with menopausal symptoms, women who had received bone marrow transplants would spontaneously begin cycling again, with several cases of spontaneous pregnancies reported.

WHERE WERE THE EGGS COMING FROM?

There were two possibilities
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One was that factors in the bone marrow transplants were contributing growth factors and other molecules that were resuscitating follicles that had been inactivated by the chemotherapy, allowing them to release a supply of egg cells that were secretly lying dormant within them. The other, even more, exciting possibility: the transplanted cells were coming into the follicles and regenerating their capacity to produce completely new egg cells. The OSC lie dormant in ageing women, waiting to be revitalized with the right cocktail of cells or signalling factors.

Stem cells are undifferentiated cells with unlimited capacity to divide. Within our bodies we have sources of stem cells which can further develop in any given cell type. Bone marrow stem cells are used for ovarian rejuvenation. Stem cell therapy has contributed greatly to regenerative medicine and it is used in orthopaedics, cardiovascular medicine, dentistry, maxillofacial, plastic and aesthetic surgery and other medical branches.

Anti-ageing is the biggest field of research for stem cell application, and in our case, it is significant for fertility treatments. This treatment aims to create new eggs using the intrinsic capacity of the ovarian tissue. Injecting bone marrow stem cells into the ovary stimulates follicles and egg growth. This growth can be caused by the factors present in the bone marrow which activate and assist growth factors and other molecules inside the ovarian tissue. Another possibility is that transplanted cells restore capacity of the ovarian tissue to produce completely new eggs.

Stem cell technology leads to improved ovarian hormone function. Hormones are not produced by the eggs, but by the surrounding cells. Growth factors and other factors induced by the stem cell ovarian revitalization increase the activity of these cells and increase the level of hormones produced by the ovary. Application of SCOR (Stem Cell Ovarian Revitalization) technology has significant advantages compared to hormone replacement therapy – HRT, which has been the base treatment for postmenopausal women for decades. Although HRT alleviates unpleasant menopausal symptoms and decreases bone mass loss, it can increase the risk of stroke and some cancers. Ovarian rejuvenation and revitalization restore ovarian hormone function under natural body regulation mechanisms and does not have dangerous side effects.

PROCEDURE DESCRIPTION

Preparation for the procedure consists in analysing patient’s overall state and confirming the normal appearance of the ovaries. Hence, hormone, immunologic and infectious status is determined, and tumour markers are checked through blood tests. If all conditions are fulfilled, the procedure can be performed, and it involves several steps.

  1. In the first phase, bone marrow cells are extracted, usually, from the tibia, the lower leg bone. This procedure is carried out under general or local anaesthesia.
  2. During the next phase stem cells are prepared, identified, and differentiated (these cells are of Mesenchymal origin, as are ovarian cells).
  3. Preparation for the next phase includes measuring ovarian volume and vascularization, identifying indices which help us plan for the next stage.
  4. Last phase, instillation, consists of laparoscopic-guided injection of stem cells in specific parts of the ovaries where the eggs are being produced. To do so, we map blood vessel. This intervention is carried out under general or local anaesthesia.

If we combine SCOR treatment with PLRP ovarian rejuvenation (intra-ovarian injection of platelet-rich plasma- PLRP), we need to prepare the PLRP before the last phase of SCOR, after we have obtained stem cells. The first step of PLRP is to obtain an adequate amount of blood, depending on the patient’s built and the assessed ovarian insufficiency, clinical picture, and diagnosis, as well as the desired growth factor combination. Second stage or lab stage includes applying special technology which, using special separators and systems, divides and filters specific cells, prepares them and activates the growth factors inside them.

Preparation for the next phase includes measuring ovarian volume and vascularization, identifying indices which help us plan for the next stage. In the final phase of the combined SCOR and PLRP procedure, stem cells with growth factors are injected into specific parts of the ovaries.

TIMING OF THE PROCEDURE

Procedure is not related to the phase of the cycle.

POSSIBLE COMPLICATIONS

Possible complications are related to the injection of SC and PLRP into the ovary. The complication rate is less than 1% and can involve bleeding, punctures or injuries to the surrounding organs and complications with anaesthesia. Serious complications requiring hospital treatment are significantly less frequent.

TREATMENT EFFECTS

Full effects are expected within 6 months. If the desired effect is a reproduction, in the period following SCOR/PLRP treatment, standard in vitro fertility treatments are performed in a natural, modified, and stimulated cycle. We track all changes in the hormonal, immunological and reproductive parameters and closely follow and assess the results of the treatment

REFERENCES:

  1. Ahmadian S, Mahdipour M et al, Effectiveness of Stem Cell Therapy in the Treatment of Ovarian Disorders and Female Infertility: A Systematic Review, Current Stem Cell Research & Therapy 2020, 15(2):173-186 https://www.ncbi.nlm.nih.gov/pubmed/?term=Effectiveness+of+Stem+Cell+Therapy+in+the+Treatment+of+Ovarian+Disorders+and+Female+Infertility%3A+A+Systematic+Review.+Curr+Stem+Cell+Res+Ther.+2020
  2. Herraiz S, Pellicer N et al, Treatment potential of bone marrow-derived stem cells in women with diminished ovarian reserves and premature ovarian failure. Current Opinion in Obstetrics & Gynecology 2019, 31(3):156-162 https://www.ncbi.nlm.nih.gov/pubmed/?term=Treatment+potential+of+bone+marrow-derived+stem+cells+in+women+with+diminished+ovarian+reserves+and+premature+ovarian+failure.+Curr+Opin+Obstet+Gynecol.+2019
  3. Telfer EE, Anderson RA, The existence and potential of germline stem cells in the adult mammalian ovary. Climacteric 2019, 22(1):22-26 https://www.ncbi.nlm.nih.gov/pubmed/?term=The+existence+and+potential+of+germline+stem+cells+in+the+adult+mammalian+ovary.+Climacteric.+2019
  4. Silvestris E, D`Oronzo S et al, In Vitro Generation of Oocytes from Ovarian Stem Cells (OSCs): In Search of Major Evidence, International Journal of Molecular Sciences 2019, 20(24). pii: E6225 https://www.ncbi.nlm.nih.gov/pubmed/?term=In+Vitro+Generation+of+Oocytes+from+Ovarian+Stem+Cells+(OSCs)%3A+In+Search+of+Major+Evidence.+Int.+J.+Mol.+Sci.+2019
  5. Sheikhansari G, Aghebati-Maleki L et al, Current approaches for the treatment of premature ovarian failure with stem cell therapy, Biomedicine & Pharmacotherapy 2018, 102:254-262 https://www.ncbi.nlm.nih.gov/pubmed/?term=Current+approaches+for+the+treatment+of+premature+ovarian+failure+with+stem+cell+therapy.
  6. Herraiz S, Romeu M et al, Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders, Fertility Sterility 2018, 10(3):496-505.e https://www.ncbi.nlm.nih.gov/pubmed/?term=Autologous+stem+cell+ovarian+transplantation+to+increase+reproductive+potential+in+patients+who+are+poor+responders.+Fertil+Steril.+2018
  7. Herraiz S, Buigues A et al, Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion, Fertilty Sterility 2018, 109(5):908-918.e2 https://www.ncbi.nlm.nih.gov/pubmed/?term=Fertility+rescue+and+ovarian+follicle+growth+promotion+by+bone+marrow+stem+cell+infusion.+Fertil+Steril.+2018
  8. Gupta S, Lodha P et al, Role of autologous bone marrow-derived stem cell therapy for follicular recruitment in premature ovarian insufficiency: Review of literature and a case report of world’s first baby with ovarian autologous stem cell therapy in a perimenopausal woman of age 45 year, Journal of  Human Reproductive Sciences 2018, 11(2):125-130 https://www.ncbi.nlm.nih.gov/pubmed/30158807