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

Female Infertility Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05421364
• Other study ID #: 10/12042022
• Status: Recruiting
• Phase: N/A
• Start date: December 9, 2023
• Est. completion date: December 9, 2026

Study information

• Verified date: March 2024
• Source: Nadezhda Women's Health Hospital
• Contact: Georgi Stamenov, MD
• Phone: +359888269839
• Email: g.stamenov[@]abv.bg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 9, 2026
• Est. primary completion date: January 3, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Female Infertility
• Infertility
• Infertility, Female

Intervention

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.

Locations

Country	Name	City	State
Bulgaria	Medical diagnostic laboratory Imunovita	Sofia
Bulgaria	Nadezhda Women's Health Hospital	Sofia

Sponsors (2)

Lead Sponsor	Collaborator
Nadezhda Women's Health Hospital	Medical diagnostic laboratory ImunoVita

Country where clinical trial is conducted

Bulgaria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Embryo implantation rate	Defined as high levels of human chorionic gonadotropin (hCG) in the peripheral blood	Two weeks following embryo transfer
Secondary	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