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

NCT07455773 | Not Yet Recruiting DMC

• 1 other identifier: PMA_PREPAIRE STUDY ASL AT
• Study Type: interventional
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief 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

Keywords

Endometrial receptivity; Recurrent implantation failure; Assisted reproductive technology; Platelet-rich plasma; Intrauterine infusion; Autologous biological therapy

Outcome Measures

Primary Outcomes (1)

• Endometrial Thickness ≥ 7 mm After PRP Treatment

  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.

Study Arms (2)

Autologous platelet-rich plasma (PRP) Group

EXPERIMENTAL

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; Drug: Hormone Replacement Therapy (HRT)

External Control

ACTIVE COMPARATOR

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)

Interventions

Intrauterine Platelet-Rich Plasma (PRP) Infusion PROCEDURE

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.

Autologous platelet-rich plasma (PRP) Group

Hormone Replacement Therapy (HRT) DRUG

Standard estrogen therapy used for endometrial preparation.

Autologous platelet-rich plasma (PRP) Group; External Control

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Sanitaria Locale di Asti: lead

Related Publications (5)

• Yahyaei A, Madani T, Vesali S, Mashayekhi M. Intrauterine infusion of autologous platelet rich plasma can be an efficient treatment for patients with unexplained recurrent implantation failure. Sci Rep. 2024 Oct 29;14(1):26009. doi: 10.1038/s41598-024-77578-1.

  PMID: 39472511 BACKGROUND

• Mouanness M, Ali-Bynom S, Jackman J, Seckin S, Merhi Z. Use of Intra-uterine Injection of Platelet-rich Plasma (PRP) for Endometrial Receptivity and Thickness: a Literature Review of the Mechanisms of Action. Reprod Sci. 2021 Jun;28(6):1659-1670. doi: 10.1007/s43032-021-00579-2. Epub 2021 Apr 22.

  PMID: 33886116 BACKGROUND

• Nazari L, Salehpour S, Hosseini S, Sheibani S, Hosseinirad H. The Effects of Autologous Platelet-Rich Plasma on Pregnancy Outcomes in Repeated Implantation Failure Patients Undergoing Frozen Embryo Transfer: A Randomized Controlled Trial. Reprod Sci. 2022 Mar;29(3):993-1000. doi: 10.1007/s43032-021-00669-1. Epub 2021 Oct 14.

  PMID: 34651260 BACKGROUND

• Chang Y, Li J, Chen Y, Wei L, Yang X, Shi Y, Liang X. Autologous platelet-rich plasma promotes endometrial growth and improves pregnancy outcome during in vitro fertilization. Int J Clin Exp Med. 2015 Jan 15;8(1):1286-90. eCollection 2015.

  PMID: 25785127 BACKGROUND

• Kasius A, Smit JG, Torrance HL, Eijkemans MJ, Mol BW, Opmeer BC, Broekmans FJ. Endometrial thickness and pregnancy rates after IVF: a systematic review and meta-analysis. Hum Reprod Update. 2014 Jul-Aug;20(4):530-41. doi: 10.1093/humupd/dmu011. Epub 2014 Mar 23.

  PMID: 24664156 BACKGROUND

MeSH Terms

Conditions

Infertility, Female

Interventions

Hormone Replacement Therapy

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• ELISABETTA DOLFIN, PI

  ASL AT

  STUDY DIRECTOR

• SANDRO MACCHI, CO-PI

  ASL AT

  STUDY CHAIR

Central Study Contacts

ELISABETTA DOLFIN, PRINCIPAL INVESTIGATOR

CONTACT

+39 3381787959; edolfin@asl.at.it

MANUELA CANICATTI', Clinical Trials Coordinator

CONTACT

+39 3297278131; sperimentazionicliniche@asl.at.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This study uses a Parallel Assignment intervention model. Participants are prospectively allocated to one of two study groups according to clinical indication and informed consent: \- an intervention group receiving intrauterine infusion of autologous platelet-rich plasma (PRP) in addition to standard hormone replacement therapy (HRT); a control group receiving standard HRT alone without PRP. The study is conducted as a prospective, controlled, non-randomized interventional clinical trial. Both groups follow predefined clinical protocols and undergo the same prospective clinical, ultrasonographic, and reproductive outcome assessments. This design was selected to allow a controlled prospective evaluation of the efficacy and safety of intrauterine PRP infusion while reducing the methodological limitations and potential biases associated with retrospective historical controls.

Study Record Dates

• First Submitted: March 3, 2026
• First Posted: March 6, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 14, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share