Study On Pathogenesis Factors Of Unexplained Recurrent Spontaneous Abortion

Purpose:According to the latest expert consensus on the diagnosis and treatment of spontaneous abortion and combined with clinical practice,the related risk factors of URSA(unexplained recurrent spontaneous abortion)were discussed,so as to provide theoretical basis for the clinical diagnosis,treatment and management of recurrent abortion.Materials and Methods:Case data of 543 URSA patients admitted to the Department of Reproductive Medicine,the Second Hospital of Lanzhou University from September2019 to May 2021 were collected.It mainly included general clinical data(age,gestational history,menstrual history,gynecological disease and surgical history,gestational week of previous abortion),blood routine,thyroid function,coagulation correlation(DIC,thrombus elasmogram),autoimmune correlation(dsDNA,ANA,ANA spectrum,RF,immunoglobulin C3,C4,<s:2>,λ,),homocysteine(HCY),25-hydroxyvitamin D,erythrocyte precipitation(ESR),glucose metabolism,blood lipid,liver function,kidney function,anti-phospholipid syndrome(APS)related antibodies(anti-cardiolipin three quantitative,anti-β2 glycoprotein antibody 1quantitative,lupus anticoagulant),alloimmunorelated(irregular antibody,blocking antibody,interleukin,gamma-interferon,tumor necrosis factor-α,NK,Treg cells).According to the nature of abortion,they were divided into primary unknown cause abortion group(n=447)and secondary unknown recurrent abortion group(n=96).According to the number of abortion,the patients were divided into two groups of unexplained recurrent abortion(n=371)and two or more groups of unexplained recurrent abortion(n=172).After sorting out the above data,statistical analysis was carried out:(1)(1)The above factors were analyzed in different groups,and statistically significant indicators were selected for comparison within the group;(2)ROC curve was used to analyze the diagnostic value of the above indexes in unexplained recurrent abortion.(3)Multivariate Logistic regression analysis of the risk factors leading to the occurrence of unexplained recurrent abortion.Results:(1)The positive rates of IL-2,IFN-γ,TNF-α and blocking antibody in the secondary unknown recurrent abortion group were higher than those in the primary group;The levels of IL-6,IL-10 and Treg(CD25+FOXP3)were lower than those in the primary group.(2)IL-2,IL-6,IL-10,IFN-γ,TNF-α,Treg(CD25+FOXP3)and positive blocking antibody were all risk factors associated with unexplained recurrent abortion,and the difference was statistically significant(P<0.05).ROC curve showed that positive IL-2,IL-6,IL-10,IFN-γ,TNF-α,Treg(CD25+FOXP3)and blocking antibody had high diagnostic value in secondary recurrent abortion of unknown cause.(3)Baseline clinical data(age,gestational week of the last abortion),endocrine-related indexes(T3,T4,FT3,FT4,TSH,thyroglobulin,thyroglobulin antibody,thyroid peroxidase antibody,fasting blood glucose,fasting insulin,fasting C-peptide,2h blood glucose and 2h insulin)of the two groups of patients with primary and secondary unexplained recurrent abortion,2h C peptide,CHO,TG,HDL,LDL),coagulation related indicators(PT,PT%,pt-R,INR,APTT,FIB,TT,AT-Ⅲ,D-dimer,FDP,R,K,Angle,MA,LY30,EPL,Cl),autoimmune related indicators(ANA,dsDNA,AN A spectrum,anti-nucleosome antibody,RF-IgG,RF-IgA,RF-IgM,Anti-CCP,complement C3,complement C4,light chain κ,light chain γ),blood routine,renal function,HCY,25-hydroxyvitamin D,erythrocyte precipitation,anti-cardiolipin three quantitative(ACA-IgA,ACA-IgG,ACA-IgM),anti-β2 There was no significant difference between glycoprotein antibody 1(β2GP1-IgA,IgG,IgM,protein C,protein S),lupus anticoagulant screening(LA1,LA2,LA1/LA2)and alloimmune factor(IL-4,NK cells,irregular antibody)levels(P>0.05).(4)The positive rates of IFN-γ,TNF-α and blocking antibody in the group with more than two unexplained recurrent abortions were higher than those in the group with two unexplained recurrent abortions;The levels of IL-10 and Treg(CD25+FOXP3)in the group with more than two unexplained recurrent abortions were lower than those in the group with two unexplained recurrent abortions.(5)IL-10,IFN-γ,TNF-α,Treg(CD25+FOXP3)and positive blocking antibody were all important factors leading to unexplained recurrent abortion,and the difference was statistically significant(P<0.05).ROC curve showed that positive IL-10,IFN-γ,TNF-α,Treg(CD25+FOXP3)and blocking antibody had high diagnostic value for more than two unexplained recurrent abortion.(6)Clinical baseline data,endocrine related indexes,coagulation related indexes,autoimmune related indexes,blood routine,renal function,HCY,25-hydroxyvitamin D),erythrocyte precipitation,anti-cardiolipin three quantifications,anti-β2 glycoprotein antibody 1 quantifications,lupus anticoagulant screening,and the same in the two groups of unexplained recurrent abortion for two or more times There was no significant difference in the levels of immune factors(IL-2,IL-4,IL-6,NK cells and irregular antibody)(P>0.05).Conclusion:(1)Among the disease-related factors included in this study,isoimmune factors had the most obvious relationship with URSA.Alloimmunity may be an important risk factor for recurrent abortion,especially for unexplained recurrent abortion,which should be paid full attention to and further studied in clinic.(2)The levels of alloimmunorelated factors were different in URSA patients with different nicities: the positive rates of IL-2,IFN-γ,TNF-α and blocking antibody in secondary URSA patients were higher than those in primary Ursa patients.IL-6,IL-10 and Treg(CD25+FOXP3)were lower than those in primary URSA group.(3)The levels of isoimmunorelated factors were different in patients with different times of URSA: The positive rates of IL-2,IL-6,IFN-γ,TNF-α and blocking antibody in the group with more than two unexplained recurrent abortions were higher than those in the group with two unexplained recurrent abortions,while the levels of IL-10 and Treg(CD25+FOXP3)were lower than those in the group with two unexplained recurrent abortions.(4)Other included indicators in this study no statistical significance in the incidence of unexplained recurrent abortion of different nature or different frequency.