The effect of peripheral blood mononuclear cells (PBMC) on pregnancy outcomes in patients with recurrent implantation failure (RIF)

Abstract

In recent years, the involvement of immune-related factors in the development of endometrium and endometrial receptiviry and then increasing of implantation rate, have been reported. We aimed to investigate the effect of intrauterine administration of peripheral blood mononuclear cells (PBMCs) in recurrent implantation failure (RIF) women with low helper T(Th)17/ regulatory T (Treg) cell ratio. Matherial and method: 248 women with the history of implantation failure volunteered to receive PBMC-therapy. After immunologic consultation and doing flow cytometry analysis, 100 women with at least three IVF/ET failure who had low Th-17/Treg ratio in comparison with healthy control were enrolled in this study. These 100 patients divided randomly in to two group, 50 patients received PBMC and 50 patients as control group received PBS. Five days before the embryo transfer, blood samples were taken from patients and the PBMCs were isolated by Ficol 1.077 and cultured in the presence of hCG for 48 hours. Cultured PBMCs were administered into the uterine cavity by embryo transfer catheter, two days before embryo transfer (ET). PBS was inseminated into uterine cavity of control group instead of PBMC. The concentration of inflammatory cytokines was examined in supernatant of cultured PBMCs 2, 24 and 48 hour after incubation by ELISA. After getting positive pregnancy test, the success of implantation and clinical pregnancy were appraised using ultrasound after 5-6 weeks. Live birth rate and miscarriage rate was also examined. Results: The frequency of Th-17 and Treg was significantly lower in women enrolled in our study than the healthy control (P < 0.0001, P = 0.0338; respectively) The Th-17/Treg ratio was also significantly lower in women enrolled in our study than the healthy control (P < 0.0001). The secretion of inflammatory cytokines (TNF-α, IL-1β and INF-γ) was significantly higher after 48 hours than 2 and 24 hours (P < 0.0001). The pregnancy and live birth rate was significantly increased in women undergoing PBMC-therapy when compared with control group receiving PBS (P = 0.032 and P= 0.047 respectively). The miscarriage rate was significantly lower in PBMC-therapy group than the PBS-injecting group (P = 0.029).