Abstract
Objective: This retrospective study aims to investigate the effects of immunosuppressive therapy on the expression of regulatory T (Treg) cells, natural killer (NK) cells, and natural killer T (NKT) cells in patients with recurrent embryo implantation failure (RIF). Materials and Methods: In vitro fertilization and embryo transplantation (IVF-ET) at Jinhua Municipal Central Hospital from July 2013 to November 2015 of 30 RIF patients were enrolled into RIF group, and peripheral blood Treg, NK, and NKT were detected before entering the embryo transfer cycle. Meanwhile, 20 normal non-pregnant women were enrolled into control group. Twenty-four patients in RIF group were administered prednisone; Treg, NK, and NKT cell contents were detected twice before and after the embryo transfer cycle, respectively. The remaining six patients with high NK cell contents were treated with gamma globulin via intramuscular injection, and Treg, NK, and NKT cell contents were detected twice before the embryo transfer cycle and after treatment. Results: Treg cell content was significantly lower in RIF group than in control group, while NK cell proportion was significantly higher in RIF group than in control group before treatment. There was no statistical difference in NKT cells. After treatment, expression rate of Treg in RIF group was 7.1 ± 1.8%, which compared with that before treatment (2.8±1.6%) was significantly higher (p < 0.01). In addition, NK cell proportion was significantly lower than pretherapy (20.9 ± 3.6% vs. 38.6 ± 8.1%, p < 0.05) and NKT cell percentage did not present the obvious difference before and after treatment. Conclusion: The occurrence of RIF may be related to the decrease in Treg expression and increase of NK cells. Immunotherapy can upregulate the expression of Treg and decrease NK cell proportion, thereby regulating maternal fetal immune tolerance and reducing the rejection effect of NK cells on fetal foreign bodies, which are conducive to embryo implantation.
Highlights
Recurrent implantation failure (RIF) in assisted reproductive technology has been a very challenging problem for reproductive scientists and embryologists
Studies have suggested that RIF and recurrent spontaneous abortion (RSA) may be caused by the same kind of immune dysfunction, and that immune factors play an important role in its pathogenesis [1]
Studies have confirmed that CD4+CD25+ regulatory T cells (CD4+CD25+Treg) play an important role in maternal immune tolerance [2], and natural killer (NK) cells play a key role in graft rejection
Summary
Recurrent implantation failure (RIF) in assisted reproductive technology has been a very challenging problem for reproductive scientists and embryologists. Studies have suggested that RIF and recurrent spontaneous abortion (RSA) may be caused by the same kind of immune dysfunction, and that immune factors play an important role in its pathogenesis [1]. Since the 1980s, many studies on the effects of lymphocytes on immune tolerance in immune-induced women in pregnancy have been carried out, while immunotherapy has been successfully applied to cure RSA patients. Studies have confirmed that CD4+CD25+ regulatory T cells (CD4+CD25+Treg) play an important role in maternal immune tolerance [2], and natural killer (NK) cells play a key role in graft rejection. Treg, NK, and NKT percentage in peripheral blood of patients before and after immunotherapy treatment were examined using flow cytometry, in order to investigate the application of immunotherapy in RIF, and its effect on pregnancy
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