# Intrauterine Administration of PBMC Modulated with IFN-τ Before Embryo Transfer Improves Clinical Outcomes of IVF Patients—A Randomized Control Trial

## TL;DR

This study found that giving IVF patients a treatment involving immune cells activated with a specific protein before embryo transfer improves their chances of successful implantation and live birth.

## Contribution

The novel contribution is demonstrating that IFN-τ-modulated PBMCs improve clinical outcomes in IVF patients when administered before embryo transfer.

## Key findings

- Implantation rates were significantly higher in the IFN-τ-modulated PBMC group (38.3% vs. 27.7%).
- Live birth rates were significantly higher in the treatment group (28.7% vs. 17.6%).
- No serious adverse events were reported in the treatment group.

## Abstract

Objective: The aim of this study was to evaluate whether intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated with interferon tau (IFN-τ) before embryo transfer improves implantation and pregnancy outcomes in IVF patients. Methods: This single-center, prospective, randomized, controlled trial was conducted at Nadezhda Women’s Health Hospital (Approval No.: 6/28022023). The study was registered at ClinicalTrials.gov (NCT05775198). Randomization was computer-generated with allocation concealed via sealed envelopes. Participants and statisticians were blinded to group assignment; clinicians were not. Women aged 21–50 undergoing frozen–thawed embryo transfer with euploid embryos were included. Exclusion criteria included uterine anomalies, autoimmune, oncologic conditions, infections, or use of immunosuppressants. Participants (n = 340) were randomized 1:1 to receive either intrauterine infusion of autologous PBMCs activated in vitro with IFN-τ or standard IVF care without PBMC treatment. PBMCs were cultured with recombinant IFN-τ, washed, and infused 24 h prior to single euploid blastocyst transfer. A total of 14 patients were excluded from analysis because of early dropout, leaving 326 (n = 167; n = 159) patients for modified intention-to-treat analysis. Primary outcomes included implantation rate (elevated urinary or blood hCG), clinical pregnancy (fetal heartbeat at 6–8 weeks), and live birth rates. Miscarriage rate and safety were secondary objectives. Patients were followed up until 6 weeks post pregnancy resolution. Results: In the intervention group, 38.3% of patients achieved implantation, compared to 27.7% in the controls (OR 1.6, 95% CI: 1.0–2.6, p = 0.04). Live birth rates were also significantly higher in the IFN-τ-modulated PBMC group (28.7% vs. 17.6%, OR 1.9, 95% CI: 1.1–3.2; p = 0.02). While the clinical pregnancy rate was higher, it did not reach statistical significance (34.7% vs. 25.8%, p = 0.08). There was no difference between the groups in terms of miscarriage (p = 0.4). No serious adverse events were reported after treatment, during pregnancy or in the postnatal period. Conclusions: Intrauterine treatment with IFN-τ-activated PBMCs before ET significantly improves implantation and live birth rates in IVF patients.