or-o : Ovarıan rejuvenatıon organısatıon

PROJECT: OR-O (OVARIAN REJUVENATION ORGANISATION)

Combined use of adipose tissue and blood-derived regenerative cells for optimal results in ovarian rejuvenation

OUR HYPOTHESIS QUESTION : Can optimal regenerative cell therapy be used to restore impaired ovarian reserve and function depending on age and different factors, and to increase endometrial receptivity to ensuresuccessful fertility and normal ovarian function?

Ovarian insufficiency (OI) is characterised by deficient ovarian sex hormones and decreased ovarian reserve, which together lead to an accelerated reduction in ovarian function and could lead to early onset of menopause. OI is a medical condition in which ovarian follicles are depleted and cease to function normally both as reproductive organs and endocrine organs in women under 40 years of age.

This condition often results in subfertility or infertility, as it is associated with hypoestrogenism, which causes menstrual irregularities and pregnancy failures. The decrease in estrogen secretion also causes a myriad of menopausal symptoms, such as hot flashes, night sweats, and insomnia. In addition, long-term consequences of premature loss of ovarian function increase the lifetime risk of skeletal fragility and cardiovascular and neurocognitive disorders. Spontaneous pregnancies are extremely scarce in patients with OI. Women experiencing OI have menstrual irregularities that hinder their fertility. Some patients with idiopathic OI present an intermittent ovarian function and hence, their chance of conceiving spontaneously and having an uneventful pregnancy course is approximately 5%.

Unfortunately, there is still no accepted successful treatment for ovarian insufficiency. Although hormone replacement therapy is performed pharmacologically, it has many side effects. In recent years, regenerative treatments have also been tried. Platelet Reach Plasma (PRP) and Stromal Vascular Fraction (SVF) applications are present in published literature with different results. Even though mesenchymal and other stem cell applications have been reported, they have not been included in routine clinical applications. Regenerative therapy is proving to be a very promising branch of medicine. This kind of therapy has already been proven to be effective in orthopedic conditions and skin rejuvenation.

The main aim of this project is to document the changes in biochemical/hormonal parameters, bone densitometry, physical and mental health status and hormonal status in peri-menopausal and early post-menopausal women and non-Turner's premature ovarian failure using an optimal regenerative approach. and to demonstrate changes in clinical symptomatology. The ORO Project will also show whether the quality and/or quantity of follicles are affected. PRP is a very common and simple regenerative application. The aim is to apply platelet- derived cytokines and growth factors for regenerative purposes in the treatment of many clinical conditions. It has also been reported that PRP is applied with different success rates in ovarian rejuvenation. When all regenerative cell sources are examined, the most effective of these is adipose tissue. Adipose tissue has the largest number and diversity of stromal cells in the body. It is also very easy to obtain and apply. Stromal cells originating from adipose tissue are obtained by two methods: enzymatic and mechanical methods. Obtaining stromal cells by enzymatic methods has been accepted by regulatory authorities (such as EMA, FDA) as a kind of biological drug production. Mechanical methods have become very popular. Such methods have many advantages over enzymatic methods. They are much easier, cheaper, do not require complicated devices and equipment and take less time. Studies have shown that 10 times more stromal cells can be obtained by mechanical methods. However, the most important difference is that the extracellular matrix (ECM) is preserved in mechanical methods. This is the most important requirement to achieve the desired effect. The enzyme destroys both ECM and parenchymal cells and some cytokines. Prof Copcu's most recent study at the beginning of 2023 described a new classification for obtaining stromal cells from adipose tissue, this being a mechanical method.

The mechanical methods using the ultra-sharp blade system were named and presented for the first time by Copcu and Oztan as “mechanical stromal-cell transfer” (MEST). Again, these authors have defined a new approach for the application of a broader spectrum of regenerative cells, namely the optimal regeneration: Supercharged MEST. Although the use of PRP and fat-derived stromal cells is not a new practice, cutting PPP with concentrated fat with sharp blades and obtaining stromal cells is a new and revolutionary practice. Fibrin in PPP can attain approximately 5 times more stromal cells, and it also ensures that it adheres to the desired place in the target tissue since fibrin is the natural glue in plasma. The main reason for the failure in ovarian regenerative applications to date is the failure of the fluid or cells to remain in the ovary due to the pressure and application technique in the applications made to the ovary. However, in the protocol described in this project, the fibrin in the PPP will allow adherence of stromal cells in the ovary and optimal regeneration.

In this project, supercharged MEST will be applied to provide optimal regeneration in cases with ovarian insufficiency and/or endometrial rejuvenation participating in the study. The cases will be included in the study by evaluating pre-op, clinical, biochemistry, and hormone aspects. PRP and PPP will be obtained from 27 cc of whole blood taken from the peripheral vein under local anesthesia/sedation, and condensed fat will be obtained by centrifugation from 20 cc of fat taken from the abdomen. The condensed oil will be mixed with PPP at a ratio of 1:1 and cut using a special kit with a sharp blade system of 2400, 1200, 600 and 400 microns, respectively (this is called adinizing) and then centrifuged to obtain TOST. Optimal regeneration will be achieved by adding PRP to the obtained TOST and applying it to the ovary and, if necessary, to the endometrium with a special probe by vaginal ultrasound. With this project, optimal regeneration will be ensured by both cell number and diversity, as well as allowing the cells to adhere to the fibrin ovary and endometrium in the PPP in the application and to achieve the desired effect.

for more information : ProjectORO@gmail.com , ecopcu@gmail.com