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Endometrial receptivity enhancement with highly concentrated platelet-rich plasma/bio-regenerative fibrin.

The conception, development and birth of a healthy child depends on a series of very complex processes, with a large number of control mechanisms that coordinate the interactions of the embryo and the endometrium. The endometrium plays a very important role in establishing and maintaining pregnancy. In the natural menstrual cycle, the endometrium becomes receptive to embryo implantation approximately 6 days after ovulation, at the time the embryo reaches the blastocyst stage. Then there is a series of interactions between the blastocyst and the endometrium, culminating in the formation of a connection with the mother's vasculature. Successful implantation depends on the coordinated action between intrauterine factors and the embryo. Inadequate receptivity of the endometrium is one of the main reasons for the failure of IVF procedures.
Biological therapies, based on cells and their products, are used by various cells such as platelets/leukocytes in enriched plasma (PRP, PLRP), platelet-enriched fibrin (PRF) or leukocytes (L-PRF).

Highly concentrated Platelet-enriched plasma (eng. Platelet-rich Plasma (PRP) is a fraction of blood 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. After the activation, they release a great number of various growth factors, components which promote cell growth and regeneration. Bearing in mind that in PRP platelets are concentrated multiple times, therefore their effect is much more potent.
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 substrate.  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.  BRF serves as a scaffold for growth factor retention in the sub-endometrial layer. The effect of the BRF manifests in prolonging action and potentiating the local effects of the active principles of other biological therapies.
In addition to hcPRP/BRF, the addition of certain hormones, such as hCG, act by local endocrine mechanisms to increase receptivity.
The PRP administration, to improve receptivity, is becoming one of the foci of assisted reproductive techniques. Scientists have discovered that intrauterine administration of autologous PRR increases pregnancy and live birth rates, especially in patients with thin endometrium.
The procedure consists of two phases:

  • Blood withdrawal and PRP preparation

  • Intrauterine administration of PRP (flushing of the uterine cavity with the activated substrate; sub-endometrial injections under ultrasound guidance)

The whole procedure is completely painless and does not require hospitalisation. In this manner, the endometrium is enriched naturally - with autologous factors influencing endometrium receptivity. Peripheral blood components, such as thrombocytes, have a proven role in endometrium remodelling and positive coordination between the embryo and endometrium. This enables easier implantation and improves endometrium vascularisation.
Various studies have demonstrated that in women with thin endometrium undergoing infertility treatment, the result of intrauterine PRP application is endometrium thickening. This technique of improved endometrium receptivity may also be applied before fresh or frozen-thawed embryo transfer to increase the implantation rate.

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