hcg-activated pbmc-therapy in rif patients

Conditions: Recurrent Implantation Failure

Summary: despite the many research done in the field of infertility and in vitro fertilization (ivf), more than half of the embryos transmitted in the ivf and intracytoplasmic sperm injection (icsi) do not implant successfully. currently, pregnancy failure following at least three ivf/et cycle, so that one or two high-quality embryos transmitted in each cycle is defined as recurrent implantation failure (rif). maternal and fetal factors can be a reason for implantation failure; maternal factors include endometrial receptivity, uterine anatomic abnormalities, and immunologic factors. implantation failure with embryonic reasons includes genetic abnormalities and any factor that affects the implantation and growth of the embryo within the uterus. in recent years, the involvement of immune-related factors mainly natural killer cells (nk), dendritic cells (dcs), macrophages (mq), regulatory t cells (treg) and th-1, in the endometrial differentiation and development and endometrial receptivity, as well as induction of immunological tolerance to the fetus, have been reported.

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 into two groups, 50 patients received pbmc and 50 patients as the control group received pbs. pbmcs were obtained from patients themselves five days before embryo transfer (et) and were cultured with hcg for 48 hours. frothy-eight hours later, pbmcs were then administered into the uterine cavity of that patient from the study group two days before et. pbs was inseminated into the uterine cavity of the control group instead of pbmc. the concentration of inflammatory cytokines was examined in the supernatant of cultured pbmcs 2, 24 and 48 hour after incubation by elisa. the pregnancy occurrence was confirmed 12 days after et through positive pregnancy test (β-hcg test). the success of implantation and the occurrence of clinical pregnancy were evaluated by ultrasound through the observation of the number and the location of gestational sacs at 5-6 weeks and confirming the embryo heart pulsation.

Eligibility criteria:
all patients were evaluated in accordance with the following inclusion and exclusion criteria; inclusion criteria: 1. having at least three implantation failures following ivf 2. having primary infertility 3. age under 45 years old 4. having regular menstrual cycles 5. bmi under 30 exclusion criteria: 1. having polycystic ovary syndrome 2. the presence of uterine pathology; 3. poor ovarian reserve 4. having chromosomal abnormalities 5. presence of auto anti-bodies such as anti-tpo, anti-tg, aca, apa, ana, and anti-dsdna 6. presence of mutations involving the coagulation system such as deficiency of factor xii, pro c, pro s 7. positive hiv, hcv or hbv tests

Keywords: recurrent implantation failure peripheral blood mononuclear cell human chorionic gonadotropin