Evaluating the Effectiveness of Platelet Rich Plasma Therapy in Enhancing Endometrial Receptivity for Women with Infertility: A Narrative Review.

Infertility, one of the most prevalent human problems, has long had an adverse effect on families’ or couples’ social and psychological well-being. Infertility affects 10% to 15% of couples globally, and its prevalence increased in recent years.[ 1 ] The causes of infertility could have affected either males or females or both. Disorders that interfered with the normal function of the reproductive organs (extragenital etiology), innate or acquired conditions influencing genital etiology, or psychological variables could have all impeded female reproductive function.[ 2 ] Poor endometrial receptivity was a significant cause of embryo implantation failure and was critical for a successful pregnancy. Several methods were investigated to increase endometrial thickness in females with a normal uterine cavity and a persistently thin lining. These methods included the use of exogenous estrogens, vaginal sildenafil, low-dose acetylsalicylic acid, and granulocyte-colony stimulating factor.[ 3 ] The results showed that with the progression of the disease, the endometrial thickness increased, but the pregnancy rate was also higher. Several investigations have determined that an endometrial thickness of at least 7 mm is required for embryo transfer.[ 4 ] For several years, platelet-rich plasma (PRP) was used in clinical research. Its application in other medical specialties, such as plastic surgery, orthopedics, and dermatology, was predicated on clinical experience and served as a recommendation for additional research. During the operation, the patient’s peripheral blood was pushed to produce a platelet concentrate.[ 5 ] An individual’s whole blood was drawn via a peripheral venipuncture, and autologous PRP was made by spinning a mixture to separate the red blood cell concentration.[ 6 ] The sample was taken from peripheral veins and contained many growth factors involved in growth and proliferation, including vascular endothelial growth factor (VEGF), transforming growth factor (TGF), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF).[ 7 ] A case was recommended as RIF if a woman under 40 years old was not pregnant after the transfer of four or fewer viable embryos in three fresh or fewer embryo transfer rounds. Even though multifactorial mechanisms were involved in the pathophysiology of repeated implantation failure (RIF), uterine and embryonic disorders were considered the major ones. Prior interventions, notably hysteroscopy for adhesions, polyps, intracavitary fibroid or septum resection, had some efficacy in raising the probability of conception by improving endometrial receptiveness.[ 8 ] Many implantation failures were termed RIF due to endometrial, embryonic, and immunological causes.[ 9 ] Chronic endometritis might have downregulated the endometrium by making it less receptive and functional.[ 10 11 ] The ability of the endometrium to allow the embryo to implant and later be invaded was referred to as endometrial receptivity, which was an aspect of implantation.[ 12 ] The window of implantation (WOI), the time in the menstrual cycle when this receptive state was reached, was normally between 19 and 23 days in a 28-day cycle. Several changes occurred in the endometrium during the WOI due to hormonal variations, especially from the hormone’s progesterone and estrogen. Thus, improving implantation rates in RIF patients appeared to depend on enhancing endometrial receptivity through hormone adjustment or other treatment approaches.[ 13 ] Based on the amount of fibrin and leukocytes present, the Dohan Ehrenfest classification (2009) categorized the platelet preparations into three types: The preparation containing leukocytes and minimal fibrin with a sparse meshwork upon activation was called pure platelet-rich plasma (P-PRP) or leukocyte-depleted PRP. Liquid or activated gel PRP products may be used in this area. They can be directly applied to skin wounds, injuries, or oversutured areas. In the leukocyte-platelet-rich plasma (L-PRP) preparations, citrate tubes on activation comprised leukocytes with low-density fibrin networks. L-PRP products could also be liquid or gel, and L-PRP products were acceptable for a wound or suture as with P-PRP. Both compounds were prepared with dense fibrin meshwork and minimal or no leukocytes; P-PRF contained a higher fibrin concentration than PRF. P-PRF products could not be injected as they were in the form of activated gels. Because of the characteristics of the fibrin matrix, it was possible to consider it as a solid formation and thus provide the conditions for cell movement and developing tissue.[ 14 ] Another evolution in the field of reproduction was PRP intrauterine injection that improved the endometrial permeability and treated pathologies like Asherman syndrome, chronic endometritis, and thin endometrium.[ 15 ] To arrive at PRP from the patient blood sample, the sample was undergone through the process of centrifugation. Under local anesthesia, PRP was directly injected into the uterine cavity using a catheter, and it contained many growth factors such as PDGF, TGF-β, and VEGF. This procedure was normally done around midcycle to prepare the endometrium for embryo implantation.[ 7 ] These growth factors were useful to implantation and pregnancy by facilitating the formation of new blood vessels, tissue remodeling, and cell division at the implantation site. Some clinical studies have shown the enhancement of endometrial thickness and the higher implantation rates during this procedure; however, more studies with better methods, repeatability, and additional effects on the endometrium and the fetus’s long-term safety were needed.[ 16 ] In the authors’ words, “PRP therapy was considered rather safe and most likely a highly effective technique for patients with refractory infertility problems since it originated from the patients” own blood and, therefore, excluded immunogenic reactions or infections.[ 17 ] An increasing amount of research conducted in the last 10 years revealed that injecting PRP directly into the ovary might have improved folliculogenesis and egg production. This methodology was used in one of the earliest research projects.[ 18 ] An innovative treatment strategy meant to boost ovarian function and maybe improve reproductive results was intraovarian platelet-rich plasma (PRP) therapy. Rich in growth factors and cytokines, PRP was created from the patient’s own blood. When administered into the ovaries, it was suggested to stimulate ovarian tissue, promoting follicular growth and regeneration.[ 19 ] This technique may be helpful for women undergoing IVF procedures, those with poor ovarian reserve, and those with early ovarian insufficiency. Women with poor ovarian reserve (POR), a pathological disorder affecting the ovarian reserve that typically results in infertility, may find PRP treatment appealing. POR is characterized by low oocyte production and poor quality. The disease’s impact on assisted reproductive technology (ART), including IVF and other reproductive treatments, made it even more difficult to treat. PRP therapy involves infusing the patient’s blood into the ovaries to restore function, combined with a concentrated platelet solution.[ 20 ] Growth factors and cytokines found in platelets, which encourage tissue repair, angiogenesis, and cellular proliferation, were the basis for the processes by which platelets assisted in ovarian rejuvenation. By enhancing the ovarian environment and drawing dormant follicles, these components may raise the quality of the oocytes.[ 21 ] An essential first step in the therapeutic course of autologous PRP infusion in the endometrial cavity was PRP preparation. At the start of the procedure, five milliliters of the patient’s venous blood were taken; typically, this was done in tubes that contained anticoagulants to prevent blood clotting. The collected blood was first slowly spin to create the three layers. The layers containing red blood cells were the lowest, buffy coat, an intermediate layer of white blood cells, and the highest layer containing platelet-rich plasma and white blood cells. The innermost buffy coat layer, along with the plasma layer directly above it, was carefully transferred into a separate tube and subjected to a second centrifugation at a higher G-force to further concentrate the platelet-rich plasma.[ 7 16 ] In this stage, the platelets were further concentrated by removing the upper platelet-poor plasma. The final product, a platelet-rich pellet, was formed at the bottom of the tube. The PRP was then ready for therapeutic use, containing concentrated platelets, growth factors, and cytokines. This double centrifugation method ensured the most efficient and desired level of platelet separation and concentration, which was necessary for the success of PRP therapy.[ 7 ] As shown in Figure 1 . Steps of formation of PRP However, before the prepared PRP could be delivered to the specified site in the patient’s body, several processes were followed to ensure that the process of PRP infusion into the endometrial cavity was safe and efficient.[ 22 ] The patient underwent transvaginal ultrasound-guided techniques to introduce PRP into the endometrial cavity from the collected and processed blood sample. The positioning of the patient was similar to that of a standard gynaecological examination, which made the cervix discernible due to the introduction of a sterile speculum.[ 4 ] Under ultrasound guidance, a catheter was then passed through the cervix into the uterine cavity. The endometrial cavity was then gradually filled with the prepared PRP using a catheter. Endometrial receptivity was a critical factor in successful embryo implantation and pregnancy. It explained the stage at which the endometrium, or lining of the uterus, was prepared to receive and support an embryo. This stage, often called the “window of implantation,” typically begins six to 10 days following ovulation.[ 23 ] The endometrium’s molecular environment and structure changed during this period due to hormones like progesterone and estrogen. Some of these changes that aided in embryo attachment and implantation were increased blood flow, the production of adhesion molecules, and the secretion of essential proteins.[ 24 ] However, certain women may experience implantation failure and infertility due to issues with endometrial receptivity. Conditions including endometriosis, irregular hormone levels, or insufficient endometrial thickness may impair receptivity.

Autologous PRP improved the implantation efficacy of embryo-endometrium synchronization in patients with RIF, as shown by a fluctuating WOI. Female infertility was a prevalent issue, and increasing the responsiveness of the endometrium was crucial for successful implantation and conception. Clinical trials involving PRP interventions also demonstrated improved outcomes for endometrial features and pregnancy. PRP, along with growth factors and cytokines, promoted the regeneration of injured tissue and supported angiogenesis to address endometrial receptivity issues. There are no conflicts of interest.