Intrauterine Autologous PBMC Therapy: Effects on Endometrial Immunity and IVF Success in Repeated Implantation Failure

Nearly 10% of IVF patients experience repeated implantation failure (RIF). Although several meta-analyses report improved outcomes following peripheral blood mononuclear cell (PBMC) administration, the uterine mechanisms remain poorly understood. We first analyzed PBMC composition and cytokine secretion in a preliminary cohort (n = 18), followed by endometrial immune profiling in a larger cohort (n = 70) before and after PBMC treatment. Embryo transfer was performed in 41 women, enabling the assessment of associations between immune profiles and implantation success. Successful implantation occurred in 16 of 41 embryo transfers (39%). PBMCs were predominantly composed of lymphocytes (60.7%), with T helper cells as the predominant T cell subset (Th/cytT ratio 1.44). Cytokine assays confirmed secretion of TNF-α, IL-6, IL-4, and IL-10. C-reactive protein levels remained below the threshold for systemic inflammation and were unaffected by PBMC administration. In the full cohort, PBMC infusion significantly enriched stromal macrophages and T helper cells, reflected by higher Th/T, Th/MΦ, and Th/cytotoxic T cell ratios and a reduced cytotoxic T/T cell ratio (all p ≤ 0.001). Importantly, women with successful implantation exhibited a significantly higher macrophage/T cell ratio (1.15 vs. 0.74; p = 0.024). These findings suggest that PBMC administration reshapes the endometrial immune landscape and that the macrophage/T cell ratio may serve as a promising biomarker of treatment efficacy.