Umbilical Cord Plasma for Treating Endometrial Pathologies (Thin Endometrium / Asherman's Syndrome/ Endometria Atrophy)

NCT05095597 | Completed Phase 2

• 2 other identifiers: 2001-FIVI-002-IC2020-005717-40
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

In the last years, platelet-rich plasma (PRP) has emerged as a promising alternative to treat endometrial pathologies affecting the endometrial lining. Different studies have tried this therapeutic approach in human patient, but results are not conclusive at all. Also, in the last years, different studies have suggested the umbilical cord blood has a stronger reservoir of growth factors and other pro-regenerative molecules than the adult peripheral blood. That is the reason why the present study aims to evaluate if using platelet-rich plasma obtained from umbilical cord blood is able to increase endometrial thickness and prepare the endometrium for an embryo transference. However, due to the novelty of this approach, the investigators have considered to include a 'proof of concept' group (women with premature ovarian insufficiency) to obtain a deeper understanding of the clinical value of this blood derivative.

Conditions

Asherman Syndrome; Endometrial Atrophy

Keywords

Endometrial pathology; Platelet-rich plasma; Umbilical cord blood; Regenerative medicine

Outcome Measures

Primary Outcomes (1)

• Study of endometrial regeneration and/or improvement in patients with endometrial pathologies (thin endometrium/Asherman's syndrome/endometrial atrophy) treated with platelet-rich plasma from the umbilical cord by endometrial thickeness.

  Improvement will be studied in form of tissue thickening (mm), comparing endometrial thickness before and after PRP injection

  An average of 3 months

Secondary Outcomes (3)

• Proof-of-concept in POI patients by improvement endometrial thickeness.

  An average of 3 months

• Gene and protein level evaluation of the endometrial biopsies collected.

  An average of 3 years

• Study of the molecular composition of the different plasma fractions obtained from collected umbilical cord samples.

  An average of 3 years

Study Arms (5)

Umbilical cord PRP donors

OTHER

Women who are going to give birth to a healthy live newborn at the Hospital Universitario y Politécnico La Fe. Donors will donate their umbilical cord blood to obtain the hUC-PRP. A total of 30±15 donors will be recruited.

Procedure: Umbilical cord blood collection

Group B- Asherman with PRP treatment and estrogen therapy

EXPERIMENTAL

Women with thin endometrium/endometrial atrophy and/or Asherman's syndrome with fertility problems and reproductive desires, desires that could be achieved by their participation in the present study. A total of 15 patients will be included; all of them will receive the investigational treatment as well as estrogen therapy.

Procedure: Injection of hUC-PRP by hysteroscopy; Drug: Oestraclin; Procedure: Endometrial biopsy

Group A1- POI with PRP treatment and estrogen therapy

OTHER

Women with premature ovarian failure (POI). A total of 10 patients will be included. All of them will receive the investigational treatment as well as estrogen therapy.

Procedure: Injection of hUC-PRP by hysteroscopy; Drug: Oestraclin; Procedure: Endometrial biopsy

Group A2- POI with estrogen therapy

OTHER

Women with premature ovarian failure (POI). A total of 10 patients will be included. All of them will receive the estrogen therapy.

Drug: Oestraclin; Procedure: Endometrial biopsy

Group A3- POI without PRP treatment nor estrogen therapy

OTHER

Women with premature ovarian failure (POI). A total of 10 patients will be included. None of them will receive either the investigational treatment nor estrogen therapy.

Procedure: Endometrial biopsy

Interventions

Injection of hUC-PRP by hysteroscopy PROCEDURE

PRP previously frozen at -80ºC (6±2 mL) will be defrozen after checking donor-receptor compatibility and viral safety study. PRP (4±2 mL) will be activated with 5% CaCl2 and immediately injected (4±2 mL) in the sub-endometrial wall via hysteroscopy.

Group A1- POI with PRP treatment and estrogen therapy; Group B- Asherman with PRP treatment and estrogen therapy

Oestraclin DRUG

Patients will receive estrogenic therapy, based on estradiol, for 10±2 days (oestraclin, topical cream, 5µg daily for 10±2 days).

Group A1- POI with PRP treatment and estrogen therapy; Group A2- POI with estrogen therapy; Group B- Asherman with PRP treatment and estrogen therapy

Umbilical cord blood collection PROCEDURE

The SCU will be collected using a blood collection bag containing anticoagulant. This step will be performed by the medical and nursing staff of the obstetrics service of the HUP La Fe. The blood collection bags will be the following, or similar: Cord Blood Collection Bags from MACOPHARMA; CPD Umbilical Cord Bag from GRIFOLS.

Umbilical cord PRP donors

Endometrial biopsy PROCEDURE

Biopsies will be taken by specialized medical personnel by aspiration with an intrauterine cannula (pipelle or cornier). Samples will be collected in 15 mL tubes (or in a larger capacity container if needed) containing PBS or RNA later until frozen at -80ºC, at the IVI Foundation facilities. Prior to freezing (in a 1.8-2 mL cryotube) the PBS will be removed and the sample cleaned in a Petri dish if needed.

Group A1- POI with PRP treatment and estrogen therapy; Group A2- POI with estrogen therapy; Group A3- POI without PRP treatment nor estrogen therapy; Group B- Asherman with PRP treatment and estrogen therapy

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient information sheet and signed informed consent.
• Female, acting voluntarily, aged between 18 and 48 years at the time of recruitment.
• BMI ≥ 18 kg/m2 and ≤ 35 kg/m2.
• Patients with premature ovarian failure (amenorrhea prior to 40 years of age and FSH \> 40 IU/L).

You may not qualify if:

• Active genital infection proven at the time of recruitment; chronic endometritis.
• Known endometrial pathology.
• Psychological disorder that may hinder study follow-up.
• Positive results after viral safety analysis (HBsAg, HBcAb, HCV, HIV1, HIV2, syphilis).
• Presenting any syndrome or condition that, from the principal investigator's point of view, could pose a risk to the study or to the patient.
• Any significant clinical anomaly detected during the recruitment process; simultaneous participation in another clinical study that could affect the objectives of the present study or previous participation in this same study.
• GROUP B
• Information and signed informed consent.
• female, acting voluntarily, aged between 18 and 48 years at the time of recruitment.
• body mass index (BMI): ≥ 18 kg/m2 and ≤ 35 kg/m2.
• Patients undergoing an assisted reproduction cycle.
• Endometrial thickness \< 5mm despite estrogen administration for more than 10 days and/or evidence of Asherman's Syndrome.
• Active genital infection proven at the time of recruitment; chronic endometritis.
• Known endometrial pathology.
• Psychological disorder that may hinder study follow-up.

Sponsors & Collaborators

• Fundación IVI: lead

Study Sites (1)

Hospital la Fe

Valencia, Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Gynatresia

Condition Hierarchy (Ancestors)

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

Study Officials

• Mónica Romeu Villaroya, MD., PhD.

  Hospital La Fe

  PRINCIPAL INVESTIGATOR

• Irene Cervelló Alcaráz, PhD.

  IVI Foundation/ IIS La Fe

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Recruitment period: * Umbilical cord donors: throughout the study. Although the aim is to recruit the maximum number of umbilical cord samples during the first 10±3 months of the study. 30±15 donors will be recruited. * Patients (group A and B): from month 4 of the first year until the end of the study. * Expected duration of treatment per patient: * Group A (arms 1 and 2): 22±8 days (visit 2 to visit 3). * Group B: 22±8 days (visit 2 to visit 3).

Study Record Dates

• First Submitted: September 30, 2021
• First Posted: October 27, 2021
• Study Start: April 22, 2022
• Primary Completion: January 27, 2025
• Study Completion: January 27, 2025
• Last Updated: September 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)