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.

The PMA_PREPAIRE study was designed to address the current lack of robust clinical evidence regarding the use of intrauterine autologous platelet-rich plasma (PRP) in patients with refractory thin endometrium undergoing assisted reproductive technology (ART) treatments.

The study prospectively evaluates the efficacy and safety of intrauterine PRP infusion in a controlled clinical setting, comparing reproductive and endometrial outcomes between patients treated with HRT plus PRP and a prospective control group receiving standard HRT alone.

The trial design aims to combine real-world clinical applicability with methodological rigor through:

• predefined inclusion and exclusion criteria; standardized PRP preparation and infusion procedures; prospective and structured data collection; controlled comparison between study groups.

Primary and secondary outcomes include:

• changes in endometrial thickness (EMT); achievement of EMT ≥7 mm; implantation rate; clinical pregnancy rate; safety and tolerability endpoints. By integrating clinical practice with a structured interventional research framework, the PMA_PREPAIRE study aims to generate high-quality prospective evidence and contribute to the future development of standardized clinical recommendations regarding the use of PRP in reproductive medicine and refractory thin endometrium.

Inclusion criteria

• Female patients aged 18 to 45 years
• Body mass index (BMI) between 18 and 30 kg/m
• Undergoing assisted reproductive technology (ART) cycle with hormone replacement therapy
• Endometrial thickness < 7 mm after at least 10 days of hormone replacement therapy
• History of at least one failed embryo transfer
• Normal hematologic and biochemical laboratory results
• Ability to understand and sign written informed consent

Exclusion criteria

• Endometrial hyperplasia or uterine malignancy
• Active pelvic inflammatory disease or untreated sexually transmitted infection
• Coagulation disorders or platelet abnormalities
• Thrombocytopenia (<100,000/mm³)
• Chronic anticoagulant therapy
• Active systemic infection or immunodeficiency
• Contraindications to intrauterine procedures