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

NCT ID: NCT05095597

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-22
• Study Completion Date: 2025-01-27

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.

Detailed Description

Phase II clinical trial, designed as a pilot study, single-center and open-label, which aims to study the efficacy of platelet-rich plasma from umbilical cord after injection into a pathological endometrium (thin endometrium, Asherman's Syndrome, endometrial atrophy).

This treatment will be applied to patients with the aforementioned endometrial pathologies (group B), as well as to patients with premature ovarian failure (group A), which will serve to study its clinical value in greater detail. Plasma samples as well as endometrial biopsies will be analyzed to try to understand what molecular events are triggered in the endometrial tissue after the application of the treatment under study.

Conditions

Asherman Syndrome; Endometrial Atrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Umbilical cord PRP donors

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.

Group Type: OTHER

Umbilical cord blood collection

Intervention Type: 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.

Group B- Asherman with PRP treatment and estrogen therapy

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.

Group Type: EXPERIMENTAL

Injection of hUC-PRP by hysteroscopy

Intervention Type: 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.

Oestraclin

Intervention Type: DRUG

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

Endometrial biopsy

Intervention Type: 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

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.

Group Type: OTHER

Injection of hUC-PRP by hysteroscopy

Intervention Type: 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.

Oestraclin

Intervention Type: DRUG

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

Endometrial biopsy

Intervention Type: 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 A2- POI with estrogen therapy

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

Group Type: OTHER

Oestraclin

Intervention Type: DRUG

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

Endometrial biopsy

Intervention Type: 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 A3- POI without PRP treatment nor estrogen therapy

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.

Group Type: OTHER

Endometrial biopsy

Intervention Type: 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.

Interventions

Injection of hUC-PRP by hysteroscopy

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.

Intervention Type: PROCEDURE

Oestraclin

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

Intervention Type: DRUG

Umbilical cord blood collection

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.

Intervention Type: PROCEDURE

Endometrial biopsy

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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).

• 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.

Exclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 48 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fundación IVI

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mónica Romeu Villaroya, MD., PhD.

Role: PRINCIPAL_INVESTIGATOR

Hospital La Fe

Irene Cervelló Alcaráz, PhD.

Role: STUDY_DIRECTOR

IVI Foundation/ IIS La Fe

Locations

Hospital la Fe

Valencia, Valencia, Spain

Countries

Spain

Other Identifiers

2020-005717-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2001-FIVI-002-IC

Identifier Type: -

Identifier Source: org_study_id