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

Summary

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.

Conditions

• Recurrent Implantation Failure
• Endometrial Receptivity Disorders
• Embryo Implantation
• Platelet-Rich Plasma
• Platelet-rich Plasma (PRP)
• Infertility, Female

Interventions

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.

Sponsors & Collaborators

• Azienda Sanitaria Locale di Asti

  lead OTHER_GOV

Principal Investigators

• ELISABETTA DOLFIN, PI · ASL AT

• SANDRO MACCHI, CO-PI · ASL AT

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-01

Primary Completion

2027-05-01

Completion

2027-12-31