Platelet-rich plasma (PRP) is also known as platelet-rich growth factors (GFs), platelet-rich fibrin (PRF) matrix, PRF, and platelet concentrate. The concept and description of PRP started in the field of hematology. Hematologists created the term PRP in the 1970s in order to describe the plasma with a platelet count above that of peripheral blood, which was initially used as a transfusion product to treat patients with thrombocytopenia. Ten years later, PRP started to be used in maxillofacial surgery as PRF. In the new millennium, the use of PRP has been boosted not only by research in maxillofacial surgery and hematology, but also by new applications in oral, orthopedics and sports medicine.
Fibrin had the potential for adherence and homeostatic properties, and PRP with its anti-inflammatory characteristics stimulated cell proliferation. Subsequently, PRP has been used predominantly in the musculoskeletal field in sports injuries.
The field of Regenerative Medicine is gaining ground stimulated by novel insights and the development of therapeutic biotechnologies, intending to restore tissue architecture and functionality. Regenerative Medicine technologies concern not only traumatic tissue injuries but also involve the biological manipulation of pathological conditions aiming to drive tissue circumstances to normal, i.e. the recovery of tissue homeostasis, therefore PRP found its place in other medical fields such as cardiac surgery, pediatric surgery, plastic surgery, ophthalmology, urology and gynecology.
Control mechanisms of cellular growth mainly consist of different growth factors. These factors are obtained from the patient’s own blood. In the ovaries, they control the production and growth of egg cells and the surrounding cells responsible for hormone production.
Main characteristics of Ovarian PLRP (platelet-rich plasma) rejuvenation is given below. Plasma contains platelets and lymphocytes, coagulation factors and proteins. Platelets are anuclear (nucleus- free) but contain around one thousand signal proteins, small granules (alfa, delta, and lambda). In 50 to 80 alfa granules per thrombocyte, there are almost 30 types of growth factors present (FR) connected with hemostasis, wound healing and repairing. In PRP the platelet concentration is 5 to 8 times higher than in physiological plasma. Platelet response is important for the initiation of wound repair. Besides the coagulative effect, they are an important source of growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor-b (TGF-b) 1 and 2, and vascular endothelial growth factor (VEGF). Adding calcium chloride and thrombin to PRP automatically activates alpha granules. This activation leads to the release of the above-mentioned biological growth factors, PDGF, TGF-b, VEGF, insulin-like growth factor I, epidermal growth factor (EGF) and epithelial cell growth factor.
Several studies have shown the important role of leukocytes in PRP. On one side, they are important for fighting infection, and on the other side, for immunoregulation. Leucocytes produce big amounts of VEGF. Considering that platelets are rich in VEGF stimulators, additional VEGF of leucocyte origin can be crucial for angiogenesis.
Ovarian rejuvenation is a procedure which involves several steps. Hormone, immunologic and infectious status is determined through blood tests. If the results are satisfactory, the procedure can be carried out.
- 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 prognosis, as well as the desired factor combination to be injected into the ovary. Separating platelet-rich plasma (PRP) and platelet poor plasma is performed in a closed system – in a completely automatized machine designed for that purpose. This machine can process from 40ml to 180ml of the entire blood extracted from a patient. In sterile conditions, the Angel system obtains 18 times higher platelet concentration in PRP than the basic measured value in a patient. In our case, the optimum concentration is between 6 and 8 which we can be specified and set on the machine.
- Second stage or lab stage includes applying complex technology which, using special separators and systems, divides and filters specific cells, prepare them and activates the growth factors inside them. At the end of this procedure, we get between 5-7 mL of active plasma which contains a large amount of growth factors, among which PDGF (platelet-derived growth factor), TGF-beta (transforming growth factor beta), VEGF (vascular endothelial growth factor), FGF(fibroblast growth factor), EGF (epithelial growth factor), PDAF and PAF and many others.
- Preparation for the next phase includes measuring ovarian volume and vascularization, identifying indices which help us plan for the next stage.
- Next phase, instillation, consists in colour Doppler ultrasound-guided injection of the active substance, obtained from the patient’s own blood, into the ovarian tissue, free of blood vessels. This intervention is carried under general or local anaesthesia.
TIMING OF THE PROCEDURE
Procedure is not related to the phase of the cycle.
Possible complications are related to the injection of blood elements into the ovary. The complication rate is less than 1% and can involve bleeding, puncturesor injuries to the surrounding organs and complication with anaesthesia. Serious complications requiring hospital treatment are significantly less frequent.
First results are to be expected in a few months and full effects are expected within 6 months. In the period following the treatment, standard in vitro fertility treatments are performed in a natural, modified, and stimulated cycle. We track all changes in hormonal, immunological and reproductive parameters and closely follow and assess the results of the treatment.
- Scott Sills E, Petersen JL et al, Regenerative effect of intraovarian injection of activated autologous platelet rich plasma: Serum anti-Mullerian hormone levels measured among poor-prognosis in vitro fertilization patients, International Journal of Regenerative Medicine 2020
- Scot Sills E, Xiang L et al, Metabolic and neurobehavioral response following intraovarian administration of autologous activated platelet rich plasma: First qualitative data, Neuro Endocrinology Letters 2019, 39(6):427-433
- Sfakianoudis K, Simopoulou M et al, Autologous Platelet-Rich Plasma Treatment Enables Pregnancy for a Woman in Premature Menopause, Journal of Clinical Medicine 2018, 8(1):1
- 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. Gynecological Endocrinology 2018, 34(9):756-760