Research Of The Expression Of Th1/Th2, Th17/Treg Cytokines And Lymphocyte Immunotherapy With Repeated Implantation

Objectives:1. to explore potential immunological etiology of repeated implantation failure by analyzing the difference of Th1/Th2 and Th17/Treg cytokines levels between RIF and normal female.2,to explore the clinical values of lymphocyte immunotherapy with repeated implantation failure;3, to explore the immune regulation mechanism of lymphocyte immunotherapy by analyzing the changes of Th1/Th2 and Th17/Treg cytokines after lymphocyte immunotherapy with repeated implantation failure.Methods:Object: 1, 214 cases who was engaged in the IVF-ET with RIF was enrolled in the Department of reproductive medicine of Second of Affiliated Hospital of Kunming Medical University from January 2014 to December 2016,and divide them into LIT group (97 cases ) and control group(117 cases) by whether lymphocyte immunotherapy were used before ET. 2, 48 cases who was engaged in the IVF-ET were enrolled in the Department of reproductive medicine of Second of Affiliated Hospital of Kunming Medical University from May 2016 to December 2016,28 cases with repeated implantation failure as the RIF group; and 20 cases who was clinical pregnant in the the first cycle of classic long protocol ovulation induction then transplantation of fresh as pregnancy group.Pregnancy group (28 cases)and RIF group( 20 cases) collect samples on the day before the first GnRHa administration (GnRHa day); LIT group collect samples before treatment and after 2 weeks of LIT treatment a period (4-6times). All serum samples were detected IL-10, IL-17, IFN-γ, TGF-β1 cytokine levels by ELASE. IL-10,IL-17, IFN-γ, TGF-β1 cytokine levels and IFN-γ/IL-10 and IL-17/TGF-β1 ratios was comparised between pregnancy group and RIF group. The embryo implantation rate,clinical pregnancy rate and early abortion rate was comparised between LIT group and control group. Discuss the changes of IL-10, IL-17, IFN-γ, TGF-β1 cytokine levels and IFN-γ/IL-10 and IL-17/TGF-β1 ratios after LIT treatment.SPSS22.0 software package was used for date processing, measurement data were expressed as mean ± standard deviation x±s),t test was used between two groups.paired t test was used between paired groups, the classification count data uesed chi-square test( X2), using bilateral alpha =0.05 as the test level.Results:1. IL-17, IFN-γ, IFN-γ/IL-10 and IL-17/TGF-β1 ratios in RIF group were higher than pregnancy group (22.63 ± 9.42) vs (17.56 ± 3.36),(399.70 ± 117.40) vs (338.72 ±54.48),(0.06 ± 0.02) vs (0.04 ± 0.01),(1.71 ± 0.54) vs (1.31 ± 0.34),the differences were statistically significant (P<0.05). IL-10, TGF-β1 was lower than the pregnancy group (406.19 ± 73.95) vs (426.01 ± 126.11),(240.90 ± 61.79) vs (274.87± 76.79),but the differences were not statistically significant (P>0.05).2.The implantation rate, clinical pregnancy rate of LIT group was significantly higher than the control group (58/239 24.3%) vs 47/301 (15.6%), 43/97 (44.3%) vs 36/107(30.8%), the differences were statistically significant (P<0.05).The abortion rate of LIT group was lower than the control group 5/43 (10.4%) VS 8/36 (22.2%), but the differences were not statistically significant (P>0.05).3. IL-17, IFN-γ,IFN-γ/IL-10 was decreased after the treatment of LIT (22.23 ± 4.94)VS (20.01 ± 4.68),(399.85 ± 77.74) VS (360.40 ± 85.47),(1.70 ± 0.31) VS (1.45 ±0.44), the differences were statistically significant(P>0.05).IL-10 and TGF-β1 was increased after treatment of LIT(403.38 ± 78.47) VS (427.71 ± 78.87),(239.18 ±45.50) VS (264.50 ± 87.23),IFN- gamma /IL-10 ratio was decreased (0.06 ± 0.01) VS(0.05 ± 0.02),but the differences were not statistically significant (P>0.05).Conclusions:1. There are higher level of IL-17, IFN-γ, IFN-γ/IL-10 and IL-17/TGF-β1 ratios to repeated implantation failure patients.2. There are Th1 and Th17 dominant of balance of Th1/Th2 and Th17/Treg to repeated implantation failure patients.3. Repeated implantation failure patients can benefit from,it can improve the implantation rate, clinical pregnancy rate, but can not reduce the abortion rate.4. lymphocyte immunotherapy throughing down-regulation of IL-17, IFN-γand Th17/Treg cytokines IL-17/TGF-β1 ratios to convert Th17 dominant to the Treg immune tolerance.5.lymphocyte immunotherapythe regulate Thl was more significantly, but it was not obvious to Th2.