Effect of Intrauterine Administration of Autologous PBMC Modulated With IFNt on IVF Outcome

Effects of Intrauterine Administration of Autologous Peripheral Blood Mononuclear Cells (PBMC) Immunomodulated With Interferon Tau (IFNt) Prior to Embryo Transfer on IVF Outcome

The goal of this clinical trial is to test the effect of modulated specialised immune cells isolated from the patients' own blood when administered to the uterus before embryo transfer on the IVF outcome (implantation, pregnancy and live birth rates).

To achieve this, blood will be obtained from eligible participants. Target cells will be isolated and incubated with the tested modulator for 24h, and returned to the uterine cavity 1 day prior to embryo transfer.

Researchers will compare the reproductive outcome of the tested intervention to that of a control group who will not receive the investigated cell treatment prior to embryo transfer.

Study Overview

• Status: Recruiting
• Conditions: Infertility, Female; IVF
• Intervention / Treatment: Biological: PBMC immunomodulated with IFNt

Detailed Description

Female patients with no known uterine pathologies scheduled to undergo embryo transfer will be identified through patient records and invited to participate in the study. Five days after luteinizing hormone (LH) surge, peripheral blood mononuclear cells (PBMC) will be isolated from these patients' peripheral blood by density gradient centrifugation and suspended in culture medium. The obtained PBMC will be incubated with 500 IU/ml IFNt at 37˚C for 24 hours. This cell suspension will be carefully introduced in the uterine cavity by catheter on day 6 post LH surge. Embryo transfer will be performed the following day. A suitable age-matched control group will be recruited that will undergo embryo transfer but will not be administered immunomodulated PBMC prior to the transfer.

Reproductive outcomes in terms of rate of implantation, rate of clinical pregnancy and live birth rates will be recorded and compared between the two groups.

Data analysis will be performed by investigators blind to the patient group.

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

Contacts and Locations

• Study Contact: Name: Dimitar Parvanov, PhD; Phone Number: 359 885944618; Email: [email protected]

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1330
    • Recruiting
    • Nadezhda Women's Health Hospital
    • Contact: Georgi Stamenov, MD; Phone Number: 359 888269839; Email: [email protected]
    • Contact: Margarita Ruseva, MSc; Phone Number: 359 889150267; Email: [email protected]

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Participating in Assisted Reproduction Treatment
• Having primary infertility
• Having regular menstrual cycles
• Scheduled to undergo embryo transfer of euploid embryos only

Exclusion Criteria:

• Uterine pathologies
• Endometrial bacterial infections
• Active endometrial inflammation
• Polycystic ovary syndrome
• Presence of auto antibodies such as anti-TPO (thyroid peroxidase), anti-TG (thyroglobulin), ACA (anticentromere antibodies), APA (antiphospholipid antibodies), ANA (antinuclear antibodies), and anti-dsDNA
• Presence of mutations involving the coagulation system such as deficiency of factor XII, Pro C, Pro S
• Oncological condition
• Positive HIV (human immunodeficiency virus), HCV (hepatitis C virus) or HBV (hepatitis B virus) tests

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrauterine administration of PBMC immunomodulated with IFNt; Approximately 9 ml whole blood will be collected from each patient 5 days post 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. After washing the obtained PBMCs, they will be suspended in RPMI 1640 supplemented with 10% HSA (human serum albumin) and incubated in the presence of 500 IU/ml IFNt for 24 h at 37˚C. On day 6 after LH peak, this cultured cell suspension will be carefully introduced in the uterine cavity by catheter. The following day (LH+7), patients will undergo a standard embryo transfer (ET) procedure.	Biological: PBMC immunomodulated with IFNt; Autologous peripheral blood mononuclear cells (PBMC) isolated using a standard protocol will be cultured in the presence of interferon tau (IFNt) for 24 hours at 37 ˚C and administered in the uterine cavity of patients 1 day prior to embryo transfer.
No Intervention: Control Group; Participants will undergo standard embryo transfer procedure with no intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Implantation, %	Percentage of patients with positive hCG (human chorionic gonadotropin) test following ET	4 to 6 weeks post ET procedure
Clinical Pregnancy Rate, %	Percentage of patients with ultrasound confirmation of gestational sac or heartbeat following ET	6 weeks post ET procedure
Live Birth Rate, %	Percentage of patients with live birth following ET	up to 10 months post ET procedure

Collaborators and Investigators

• Sponsor: Nadezhda Women's Health Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 13, 2023
• Primary Completion (Anticipated): March 13, 2026
• Study Completion (Anticipated): April 28, 2026

Study Registration Dates

• First Submitted: March 7, 2023
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 20, 2023

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: implantation; live birth rate; clinical pregnancy; intrauterine PBMC; interferon tau
• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: 6/28022023

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