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

Phase 2

Completed

• Conditions: Endometrial Atrophy; Asherman Syndrome
• Interventions: Procedure: Umbilical cord blood collection; Procedure: Injection of hUC-PRP by hysteroscopy; Drug: Oestraclin; Procedure: Endometrial biopsy

• Registration Number: NCT05095597
• Lead Sponsor: Fundación IVI

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.

Study Timeline

• Study First Submitted: 2021-09-30
• Study First Submitted QC: 2021-10-15
• Study First Posted: 2021-10-27
• Study Start: 2022-04-22
• Primary Completion: 2025-01-27
• Study Completion: 2025-01-27
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 15

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).

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

Inclusion Criteria:

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Umbilical cord PRP donors	Umbilical cord blood collection	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 A1- POI with PRP treatment and estrogen therapy	Oestraclin	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 A2- POI with estrogen therapy	Endometrial biopsy	Women with premature ovarian failure (POI). A total of 10 patients will be included. All of them will receive the estrogen therapy.
Group B- Asherman with PRP treatment and estrogen therapy	Injection of hUC-PRP by hysteroscopy	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 B- Asherman with PRP treatment and estrogen therapy	Endometrial biopsy	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 B- Asherman with PRP treatment and estrogen therapy	Oestraclin	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 A1- POI with PRP treatment and estrogen therapy	Injection of hUC-PRP by hysteroscopy	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 A1- POI with PRP treatment and estrogen therapy	Endometrial biopsy	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 A2- POI with estrogen therapy	Oestraclin	Women with premature ovarian failure (POI). A total of 10 patients will be included. All of them will receive the estrogen therapy.
Group A3- POI without PRP treatment nor estrogen therapy	Endometrial biopsy	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.

Primary Outcome Measures

Name	Time	Method
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.	An average of 3 months	Improvement will be studied in form of tissue thickening (mm), comparing endometrial thickness before and after PRP injection

Secondary Outcome Measures

Name	Time	Method
Proof-of-concept in POI patients by improvement endometrial thickeness.	An average of 3 months	Improvement will be studied in form of tissue thickening (mm), comparing endometrial thickness before and after PRP injection.
Study of the molecular composition of the different plasma fractions obtained from collected umbilical cord samples.	An average of 3 years	Different molecular assays will be performed with the blood samples obtained.
Study of implantation, pregnancy, miscarriage and live newborn rates after injection of the investigational drug (platelet-rich plasma from umbilical cord) by questionnaire at different visits.	Through study completion, an average of 1 year	If the thickness is good enough, patients will undergo embryo transfer and implantation, pregnancy, miscarriage or live newborn rates will be asked in subsequent visits.
Gene and protein level evaluation of the endometrial biopsies collected.	An average of 3 years	Different molecular and histological assays will be performed with the biopsies from all the groups.

Trial Locations

Locations (1)

Hospital la Fe; 🇪🇸 Valencia, Spain