Biological therapies use autologous components, that originate from the patient himself and lead to improved patient health, quality of life, and rejuvenation of tissues and cells, as well as increasing the success of treatment of infertility by IVF, and the outcome of pregnancy and delivery.
Biological IVF refers to IVF procedures that use the patient's own cells or their products to increase the chance of success. These cells and their products are processed with state-of-the-art technology that leads to changes in concentration, activity and function. Various autologous substrates are used (such as stem cells, exosomes, growth factors, regenerative fibrin, etc.) which alone or in combination stimulate reproductive ability, acting positively on ovarian and testicular function, endometrial susceptibility to embryonic implantation, as well as the quality of cells and embryos, overall increasing the success of the IVF procedure. Biological therapies are based on cells and their products, such as platelets/leukocytes in enriched plasma (PRP, PLRP), bio-regenerative platelet (BRF) or leukocytes (L-BRF) enriched fibrin, cells with regenerative potential, like mesenchymal Stem cells (mSC).
Highly concentrated Platelet-enriched plasma (hc PRP) is a blood fraction obtained by a special automatised centrifugation process that contains from 4 to 8 times the concentration of platelets compared to full blood. Platelets are blood elements that play a fundamental role in blood coagulation and the healing process of injured tissues. They contain numerous growth factors that support cell proliferation, improve vascularization and exhibit an immunomodulatory effect. Bearing in mind that in PRP platelets are concentrated multiple times, by concentrating platelets in hcPRP, we are concentrating the growth factors that are released from platelets, therefore their effect is much more potent.
Growth factors are cellular products that locally support the growth of cells or tissues. The application of autologous growth factors from activated platelets is one of the most modern techniques for the regeneration of ovarian tissue. Local application of PRP in the ovary has a regenerative effect and stimulates the process of follicle growth, growth of eggs as well and surrounding cells responsible for the production of hormones. In addition to the regeneration of ovarian tissue, hcPRP has been shown to enhance the growth of inadequate endometrium. Inadequate receptivity of the endometrium is one of the main reasons for the failure of IVF procedures. Intrauterine application of autologous hcPRP increases the rate of pregnancy and live births, especially in patients with a thin endometrium, stimulating the growth (thickening) of the endometrium. Endometrial growth disorder can also be treated with the use of stem cells.
Bioregenerative Fibrin (BRF)
Bioregenerative fibrin is an autologous product that is obtained from the blood plasma by multiple filtrations during which the proteins necessary for blood clotting are concentrated. BRF is a biodegradable component whose positive effect on the outcomes of surgical procedures is reflected in improving hemostasis, reducing blood loss, and additionally reducing postoperative complications.
PRP can be applied alone or in combination with autologous BRF, which retains growth factors locally in the tissue and serves as a scaffold. These products play an important role in intercellular communication and modulation of the immune response, thus contributing to the regenerative effect, improving ovarian function and regulating hormonal status.
Since it is an autologous product, the administration of BRF does not lead to the initiation of an inflammatory response and there is no risk of getting infections. The newly formed fibrin mesh is an ideal autologous biological scaffold. This autologous scaffold retains the material that is applied to the ovaries and prevents, i.e. reduces entry into the circulation system. The effect of the BRF manifests in prolonging action and potentiating the local effects of the active principles of other biological therapies.
Cells with regenerative potential – Stem cells
Stem cells are undifferentiated cells that can self-renew and differentiate into different types of cells. Stem cells have different origins, and when treating different conditions, adult stem cells are used, which can be isolated from various sources: adipose tissue, bone marrow and peripheral blood. Due to its easy accessibility, multipotence and low immunogenicity, mesenchymal stem cells (mSC) are a very important therapeutic approach for the treatment of various conditions. They have several local positive effects on existing stem cells and other differentiated cells. Intraovarian autologous stem cell injection is another of the new methods of regeneration of ovarian tissue. In tissues with altered function, they interact with existing cells and tissues, improving the conditions for the development and maturation of eggs. This type of therapy represents a new level of treatment of the ovaries whose function has declined due to disease, adverse environmental influences or ageing. Furthermore, mSC may also improve the implantation capacity of the endometrial receptivity, if injected into the sub-endometrial region.
In vitro maturation of eggs (IVM)
In vitro maturation of eggs is the process of taking immature eggs from small immature follicles or ovarian tissue of patients and then maturing them in laboratory (in vitro) conditions. The procedure is used in reproductive medicine in women who have undergone infertility treatment or these cells can undergo freezing so that they can be used later. This technique is usually applied in cases of impaired final stages of cell maturation, and the process is controlled by hormone therapy that stimulates the natural processes of egg maturation. This technology has been developed to avoid overreaction to drugs. Autologous HC PRP can be added to specific maturation media. As an effective method of treatment, IVM can be used to treat patients with ovarian hyporeactivity, patients with an inability to create mature and quality cells, as well as embryos, and is also used to preserve the fertility of cancer patients.
Bio-IVF is intended for patients who have multiple failed attempts, whether due to lack or poor quality of eggs and/or sperm, lack of fertilization, improper development of embryos, as well as dysfunctional implantation. Furthermore, the second group of patients are those with a lower chance, such as advanced reproductive age, early ovarian function ingestion, or poor response to stimulation. Bio-IVF is used in several programs in the IVF procedure: