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 (PMA_PREPAIRE)

May 12, 2026 updated by: Azienda Sanitaria Locale di Asti

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 is a key determinant of success in assisted reproductive technology (ART). A significant proportion of patients experience repeated implantation failure despite euploid embryos and adequate laboratory conditions. Thin endometrium, often defined as ultrasound-measured thickness <7 mm at embryo transfer, is frequently refractory to estrogen therapy and associated with low implantation and clinical pregnancy rates.

Platelet-Rich Plasma (PRP), obtained from autologous blood by double centrifugation, is rich in growth factors capable of stimulating cell proliferation, angiogenesis, and tissue regeneration, suggesting potential benefits for endometrial function. Preliminary studies indicate improved endometrial thickness and reproductive outcomes following intrauterine PRP infusion, but standardized protocols and systematic data are lacking.

The PMA_PREPAIRE study is a prospective, single-center, controlled, non-randomized interventional clinical trial conducted at the Reproductive Medicine Center of Cardinal Massaia Hospital, Asti. The study aims to evaluate the efficacy and safety of intrauterine infusion of autologous platelet-rich plasma (PRP), in association with hormone replacement therapy (HRT), in improving endometrial receptivity and reproductive outcomes in women with thin or refractory endometrium. The study includes a prospective control group treated with standard HRT alone.

Eligible women will be treated with standard clinical care, with PRP infusion offered to those with insufficient response to HRT. Inclusion criteria include age 18-45, BMI 18-30 kg/m², history of ≥1 failed embryo transfer, EMT <5 mm after ≥10 days of HRT, and normal routine lab tests. Exclusion criteria include endometrial disease, recent gynecological infection, and systemic conditions such as thrombocytopenia or coagulopathies.

Procedures include standard HRT from cycle days 1-2, serial ultrasound monitoring of endometrial thickness from days 6-8, intrauterine PRP infusion if EMT ≤7 mm (up to three infusions per cycle), embryo transfer once EMT ≥7 mm, and follow-up through pregnancy testing and confirmatory ultrasound.

Collected data will be analyzed using descriptive statistics, paired and unpaired comparative analyses, and multivariate logistic regression models to evaluate predictors of treatment response and reproductive outcomes (significance level p < 0.05).

A sample size of 34 patients per group was estimated to detect a 1.5 mm difference in endometrial thickness (EMT) with 90% statistical power. Considering an anticipated dropout rate of 15%, a total of 40 patients per group will be enrolled.

The study includes:

an intervention group consisting of 40 patients treated with HRT plus intrauterine PRP infusion; a prospective control group consisting of 40 patients with refractory thin endometrium treated with standard HRT alone, without PRP.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: ELISABETTA DOLFIN, PRINCIPAL INVESTIGATOR
  • Phone Number: +39 0141 9525 +39 3381787959
  • Email: edolfin@asl.at.it

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Autologous platelet-rich plasma (PRP) Group
Autologous platelet-rich plasma (PRP) is prepared from peripheral venous blood collected from the participant and processed using a standardized double-centrifugation technique to obtain a platelet-concentrated plasma fraction. Participants in this arm receive a standard hormone replacement therapy (HRT) protocol combined with intrauterine infusions of autologous platelet-rich plasma (PRP). HRT begins on cycle days 1-2, with serial ultrasound monitoring of endometrial thickness. If endometrial thickness (EMT) is ≤ 7 mm, one to three intrauterine PRP infusions are administered according to protocol. Participants proceed to embryo transfer once EMT ≥ 7 mm. Follow-up includes β-hCG testing and confirmatory ultrasound to assess clinical pregnancy outcomes. This arm represents the sole prospective intervention group in the study, with outcomes compared to a retrospective control group from historical data.
Procedure: Intrauterine Platelet-Rich Plasma (PRP) Infusion
Autologous platelet-rich plasma (PRP) is prepared from peripheral venous blood collected from the participant and processed using a standardized double-centrifugation technique to obtain a platelet-concentrated plasma fraction. The PRP is administered via intrauterine infusion using a sterile flexible catheter in an outpatient setting without anesthesia. Up to three infusions may be performed within a treatment cycle based on endometrial response. The procedure is performed in addition to standard hormone replacement therapy (HRT) for endometrial preparation.
Drug: Hormone Replacement Therapy (HRT)
Standard estrogen therapy used for endometrial preparation.
Active Comparator: External Control

This arm consists of a prospective control cohort of patients treated at the same center during the study period. Patients meet eligibility criteria comparable to the intervention group, including refractory thin endometrium (<7 mm after at least 10 days of HRT) and history of failed embryo transfer.

Participants receive standard hormone replacement therapy (HRT) alone without intrauterine PRP infusion. Clinical, ultrasonographic, and reproductive outcome data are collected prospectively using the same monitoring schedule applied to the intervention group, including endometrial thickness, implantation rate, clinical pregnancy, and adverse events.

This control group allows prospective comparison between HRT + PRP and standard HRT while reducing the methodological limitations associated with retrospective historical controls.
Drug: Hormone Replacement Therapy (HRT)
Standard estrogen therapy used for endometrial preparation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endometrial Thickness ≥ 7 mm After PRP Treatment
Time Frame: Up to 14 days after initiation of hormone replacement therapy within the treatment cycle.
Proportion of participants achieving endometrial thickness (EMT) ≥ 7 mm after intrauterine infusion of autologous platelet-rich plasma during hormone replacement therapy.
Up to 14 days after initiation of hormone replacement therapy within the treatment cycle.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Sanitaria Locale di Asti

Investigators

  • Study Director: ELISABETTA DOLFIN, PI, ASL AT
  • Study Chair: SANDRO MACCHI, CO-PI, ASL AT

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

May 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

March 3, 2026

First Submitted That Met QC Criteria

March 3, 2026

First Posted (Actual)

March 6, 2026

Study Record Updates

Last Update Posted (Actual)

May 14, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PMA_PREPAIRE STUDY ASL AT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The individual participant data (IPD) collected in this study will not be shared outside the sponsoring institution. Data contain sensitive health information and are stored within the secure institutional database of ASL AT in compliance with GDPR regulations. Aggregate study results will be published, but access to de-identified individual-level data is not planned.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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