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

Not Applicable

Recruiting

• Conditions: Infertility, Female; IVF
• Interventions: Biological: PBMC immunomodulated with IFNt

• Registration Number: NCT05775198
• Lead Sponsor: Nadezhda Women's Health Hospital

Brief Summary

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.

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 Timeline

• Study Start: 2023-03-01
• Study First Submitted: 2023-03-07
• Study First Submitted QC: 2023-03-07
• Study First Posted: 2023-03-20
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-21
• Primary Completion: 2026-03-13
• Study Completion: 2026-04-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 300

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intrauterine administration of PBMC immunomodulated with IFNt	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.

Primary Outcome Measures

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

Trial Locations

Locations (1)

Nadezhda Women's Health Hospital; 🇧🇬 Sofia, Bulgaria