Effects of Intrauterine Administration of Autologous PBMC on the Endometrial Cells Populations

Effects of Intrauterine Administration of Autologous Peripheral Blood Mononuclear Cells (PBMC) on the Endometrial Cells Populations

The behaviour of the endometrium during its receptive phase is highly dependent on the endometrial cell type composition. Each cell type has its role in the endometrial preparation for the invading embryo. Alteration in the immune cells dialogue could be the main reason for unsuccessful implantation in certain patients. Immune cell homeostasis is often improved by intrauterine administration of autologous PBMC.

There have been numerous reports on the positive effects of the intrauterine administration of autologous PBMC on the IVF outcomes (embryo implantation and ongoing pregnancy success). However, there is little data on the direct effect of the PBMC administration on the cell composition of the endometrium. This study will focus on the changes in the endometrial cell populations by PBMC treatment that could lead to IVF outcome improvement.

The aim of this project is to analyze the effect of intrauterine administration of autologous PBMC on the endometrial cell populations and on the IVF outcome parameters (implantation and ongoing pregnancy success as IVF outcome variables).

Study Overview

• Status: Recruiting
• Conditions: Female Infertility
• Intervention / Treatment: Biological: Intrauterine administration of autologous peripheral blood mononuclear cells (PBMC)

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Georgi Stamenov, MD; Phone Number: +359888269839; Email: g.stamenov@abv.bg
• Study Contact Backup: Name: Rumiana Ganeva, MSc; Phone Number: +359898484825; Email: rum.ganeva@gmail.com

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1373
    • Recruiting
    • Nadezhda Women's Health Hospital
    • Contact: Georgi Stamenov, MD; Phone Number: +359888269839; Email: g.stamenov@abv.bg
    • Contact: Rumiana Ganeva, MSc; Phone Number: +359898484825; Email: rum.ganeva@gmail.com
  • Sofia, Bulgaria, 1373
    • Recruiting
    • Medical diagnostic laboratory Imunovita
    • Contact: Daniela Baltadzhieva, Professor; Phone Number: +359888823290; Email: baltadjievad@yahoo.com
    • Contact: Petya Boneva, MSc; Phone Number: +359898569702

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participating in Assisted Reproduction Treatment
• Presenting altered endometrial immune profile
• Having primary infertility
• Having regular menstrual cycles
• Embryo transfer of euploid embryos

Exclusion Criteria:

• Uterine pathologies
• Endometrial Bacterial infections
• Active endometrial inflammation
• Polycystic ovary syndrome
• Presence of auto anti-bodies such as anti-TPO, anti-TG, ACA, APA, ANA, and anti-dsDNA
• Presence of mutations involving the coagulation system such as deficiency of factor XII, Pro C, Pro S
• Cancer diagnostics
• Positive HIV, HCV or HBV tests

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Endometrial cell composition; The cell composition and their quantities will be compared before and after intrauterine administration of PBMC in the endometrial biopsies.

Biological: Intrauterine administration of autologous peripheral blood mononuclear cells (PBMC); Approximately 9 ml blood from each patient will be collected on the day of the LH peak by peripheral venipuncture using a 21G butterfly catheter affixed via vacutainer to negative pressure receiving tubes (BD vacutainer acid-citrate-dextrose (ACD-A), REF:366645). PBMC will be isolated by density gradient centrifugation in room-temperature centrifuge set to 400 g for 25 min. PBMCs (1x106cells/ml) suspended in RPMI 1640 supplemented with 10% HSA will be incubated in the presence of 10 IU/ml hHCG for 48 h. On day 2 after LH peak, fresh PBMCs (1x107 cells) will be also obtained from the same patients, these fresh PBMCs will be immediately combined with the 2-day cultured PBMC and suspended in PBS (2x107 cells/200µl). This cell suspension will be carefully introduced in the uterine cavity by catheter on day 2 after LH peak.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the numbers of certain ednometrial cell populations (immune cells, stem cells, senescent cells) from their levels one month prior intrauterine PBMC administration	Immunohistochemical analysis	One month following intrauterine PBMC administration
Change in the percentages of the immune cells in the endometrial stroma from their levels one month prior intrauterine PBMC administration	Flowcytometric analysis	One month following intrauterine PBMC administration
Change in the distance between the endometrial immune cells, stem cells and senescent cells in the endometrial stroma from their initial distances one month prior intrauterine PBMC administration	Spatial analysis with Visual analysis software	One month following intrauterine PBMC administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Embryo implantation rate	Defined as high levels of human chorionic gonadotropin (hCG) in the peripheral blood	Two weeks following embryo transfer
Clinical pregnancy rate	Defined as number of gestational sacs with fetal heart beat, shown by ultrasound in gestational week 6 per number of embryo transferred.	Six to 8 weeks of gestation

Collaborators and Investigators

• Sponsor: Nadezhda Women's Health Hospital
• Collaborators: Medical diagnostic laboratory ImunoVita

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2023
• Primary Completion (Estimated): January 3, 2026
• Study Completion (Estimated): December 9, 2026

Study Registration Dates

• First Submitted: June 6, 2022
• First Submitted That Met QC Criteria: June 13, 2022
• First Posted (Actual): June 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Endometrium; Female infertility; Peripheral blood mononuclear cells (PBMC); Endometrial cell populations
• Additional Relevant MeSH Terms: Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Infertility; Infertility, Female
• Other Study ID Numbers: 10/12042022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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