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

Sponsor

Nadezhda Women's Health Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05775198

Collaborator

(none)

300

Enrollment

Location

Arms

37.5

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility, Female IVF	Biological: PBMC immunomodulated with IFNt	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

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

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 13, 2023

Anticipated Primary Completion Date :

Mar 13, 2026

Anticipated Study Completion Date :

Apr 28, 2026

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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