PMA_PREPAIRE STUDY: Experimental Study on the Use of Intrauterine Infusion of Autologous Platelet-rich Plasma (PRGF-IUI) in Patients With Recurrent Implantation Failure and/or Refractory Thin Endometrium.

Endometrial receptivity plays a central role in the implantation process and the success of assisted reproductive technologies (ART). A receptive endometrium undergoes synchronized cellular proliferation, vascularization, stromal decidualization, and expression of specific cytokines and adhesion molecules at the time of embryo transfer. Thin endometrium, commonly defined as a transvaginal ultrasound-measured thickness of less than 7 mm, is frequently encountered in patients undergoing ART and is associated with lower implantation and clinical pregnancy rates.

Refractoriness of the endometrium to standard hormone replacement therapy (HRT) represents a persistent clinical challenge. Despite optimization of estrogen administration routes and doses, a significant subset of patients fails to achieve adequate thickness and functional receptivity. These patients often experience repeated implantation failure (RIF), defined by multiple unsuccessful implantation attempts despite transfer of high-quality embryos.

Platelet-Rich Plasma (PRP) is an autologous biological product obtained from peripheral blood through differential centrifugation. PRP contains a high concentration of platelets, which store a complex milieu of growth factors and cytokines, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). These bioactive molecules have mitogenic, angiogenic, and chemotactic properties that facilitate tissue repair and regeneration. The theoretical rationale for PRP application in reproductive medicine is based on its potential to augment stromal proliferation, enhance microvascular growth, and improve the structural and functional characteristics of the endometrium.

Preliminary evidence from observational and interventional clinical studies suggests that intrauterine infusion of autologous PRP may be associated with increased endometrial thickness, improved uterine hemodynamics, and enhanced reproductive outcomes, including implantation and clinical pregnancy rates. In retrospective cohort analyses, patients treated with PRP showed significant improvements in endometrial parameters and pregnancy outcomes compared to conventional therapy. Although variations exist in study designs, inclusion criteria, and infusion protocols, a recurring finding is the promising therapeutic effect of PRP on endometrial receptivity.

Despite these encouraging data, the current literature also highlights the lack of standardized protocols and high-quality, large-scale randomized controlled trials. Systematic reviews and meta-analyses have underscored the need for well-designed clinical trials to establish the reproducibility and clinical validity of PRP therapy in this context. Some guidelines and expert groups note that while the biological rationale is strong, PRP use cannot yet be universally recommended without further evidence from rigorously controlled studies.