Clinical trial NCT05775211: Effects of Intrauterine Administration of Autologous PBMC Modulated With IFNt on Endometrial Cell Populations
Official title: Effects of Intrauterine Administration of Autologous Peripheral Blood Mononuclear Cells (PBMC) Modulated With Interferon Tau (IFNt) on Endometrial Cell Populations
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Infertility
Keywords: intrauterine PBMC
interferon tau
endometrium
endometrial cell populations
window of implantation
Lead sponsor: Nadezhda Women's Health Hospital
Sponsor class: OTHER
First posted: 2023-03-20
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants will undergo the same procedures.
Primary purpose: TREATMENT

Brief summary: The aim of this clinical trial is to investigate the change in endometrial composition during the window of implantation following intrauterine administration of PBMC immunomodulated with IFNt.

Patients seeking assisted reproductive therapy will be invited to participate. Two endometrial biopsies will be obtained from each patient during mid-secretory phase of two consecutive menstrual cycles. The first biopsy will be obtained one month before the intervention, and the second one - a day after intrauterine administration of the tested cell treatment which will take place the following month.

Immunohistochemistry analysis of the cell composition of the endometrium will be performed.

Detailed description: Female patients with no known uterine pathologies and good general health undergoing treatment for unexplained infertility will be identified and invited to participate in the study. Endometrial biopsy will be obtained seven days after luteinizing hormone (LH) surge during a natural cycle. The following month, 5 days after LH surge, peripheral blood mononuclear cells (PBMC) will be isolated from patients' peripheral blood by density gradient (1.077g/ml) centrifugation and suspended in culture medium. The obtained PBMC will be incubated with 500 IU 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. A second biopsy will be obtained the following day (LH+7).

Immunohistochemistry evaluation of endometrial tissue will be performed in terms of quantities and spatial distribution of various cell types.

Eligibility criteria: Inclusion Criteria:

* Participating in Assisted Reproduction Treatment
* Having primary infertility
* Having regular menstrual cycles
* Having signed informed consent

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

Primary outcomes:
measure: Change in the numbers of certain endometrial cell populations (immune cells, stem cells, senescent cells) from their levels one month prior to intrauterine administration of immunomodulated PBMC
timeFrame: One month prior to and one day following intrauterine administration of cell treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Nadezhda Women's Health Hospital
Study officials:
References: