Hysteroscopic Injections of Autologous Endometrial Cells and Platelet-rich Plasma in Patients With Thin Endometrium

Hysteroscopic Injections of Autologous Endometrial Cells and Platelet-rich Plasma in Patients With Thin Endometrium - a Pilot Study

The investigation is devoted to the study of the effect of the introduction of autologous platelet-rich plasma (PRP) on the thickness of the endometrium. It was found that the injection of PRP and endometrial cells resuspended in PRP into the endometrium of patients with thin endometrium leads to an increase in the proliferation of endometrial cells, and as a result, to an increase in its thickness.

Study Overview

• Status: Completed
• Conditions: Thin Endometrium
• Intervention / Treatment: Procedure: Conservative therapy; Biological: PRP injection; Biological: Injection of PRP after conservative therapy; Biological: Injection of PRP with endometrial cells

Detailed Description

The study enrolled 115 patients with thin endometrium (<7 mm at implantation window) and infertility. The cohort was divided into groups based on the treatment regimen.

Group 1 (the control, n=30) underwent conservative therapy. Group 2 (n=42) received intraendometrial injections of autologous PRP instead of the conservative therapy. Group 3 (n=38) received identical injections after conservative therapy. Group 4 (n=5) received injections of the minimally manipulated autologous endometrial cells suspended in autologous PRP.

Injections of PRP and endometrial cells suspended in autologous PRP into basal layer of endometrium facilitate the reconstitution by enhancing cell proliferation and angiogenesis.

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 117997
    • Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age 18-40 years
• Normal karyotype
• Normal karyotype of the partner
• Regular ovulatory and menstrual cycle
• Endometrium <7 mm thick as measured at implantation window
• Availability of ≥2 vitrified blastocysts of good quality
• History of implantation failure and/or embryo transfer (ET) cancellation due to insufficient endometrial thickness

Exclusion Criteria:

• Pathospermia in partner
• Use of donor gametes
• Premature ovarian failure
• Internal genital anomalies
• Systemic blood diseases and coagulopathy
• Hemoglobin <100 g/L
• Platelets <100×109/L
• Antiplatelet/anticoagulant therapy recipient status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Conservative therapy; This is Group 1, whose patients received electrical impulse therapy using a BTL-4000 Premium G device (BTL Medical Technologies, Czech Republic) starting from day 5-7 of menstrual cycle for 10-12 days daily.	Procedure: Conservative therapy; Conservative therapy to which the patients were subjected was the effect of an electrical impulse
EXPERIMENTAL: PRP injection; This is Group 2, whose patients received single intraendometrial injections of autologous PRP during proliferative phase (day 6-9) of menstrual cycle.	Biological: PRP injection; This intervention consisted of injecting platelet-rich plasma (PRP) into the endometrium
EXPERIMENTAL: Injection of PRP after conservative therapy; This is Group 3, whose patients received electrical impulse therapy identically with Group 1 during the first menstrual cycle. In the second cycle, the patients received autologous PRP injections identically with Group 2.	Biological: Injection of PRP after conservative therapy; This intervention consisted of conducting conservative therapy with an electrical impulse and then injecting PRP inside the endometrium
EXPERIMENTAL: Injection of PRP with endometrial cells; This is Group 4, whose patients received single intraendometrial injections of the minimally manipulated autologous endometrial cells suspended in autologous PRP during proliferative phase (day 6-9) of menstrual cycle.	Biological: Injection of PRP with endometrial cells; This intervention consisted of injecting endometrial cells suspended in prp

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in endometrial thickness after treatment compared with control.	Ultrasonography measurements of endometrial thickness before and after the therapy and compare the thickness. Endometrial thickness measured in mm.	Baseline and 2 month
The Doppler-assisted detection of the uterine spiral arteries	The number of identified vessels is counted and the percentage of detection frequency is calculated accordingly, adjusted for the McNemar's binomial test. Compare the rates of visualization of the uterine spiral arteries after therapy in all groups of patients.	1 month
Study of the effect of therapy on the onset of pregnancy	Investigation of the rates of clinical pregnancies and live births in all groups. After therapy, the number of clinical pregnancy and the number of live births were calculated.	9 months
The content of growth factor in autologous PRP	Investigation of the content of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF) in autologous PRP. Relative levels of PDGF-BB and VEGF are normalized to the total protein content.	3 month
Phenotyping of cells isolated from endometrial biopsies	Investigation of cellular composition in endometrial biopsy. The percentage of cells positive for markers of mesenzymal stromal cells, epithelial and endothelial cells, lymphocytes is calculated and the determination of the phenotype of cells in endometrial biopsy.	3 month

Collaborators and Investigators

• Sponsor: Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare
• Collaborators: Sechenov University
• Investigators: Study Director: Inna Apolikhina, MD, FSBI "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov" Ministry of Healthcare of the Russian Federation; Principal Investigator: Zulfiia Efendieva, PhD, FSBI "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov" Ministry of Healthcare of the Russian Federation

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ACTUAL): January 11, 2021
• Study Completion (ACTUAL): March 1, 2021

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: July 8, 2022
• First Posted (ACTUAL): July 13, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 8, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: infertility; platelet-rich plasma; endometrial cells
• Other Study ID Numbers: №10-18/11.2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No