Pregnacy Outcome Of Women With Normal Thyroid Function And Thyroid Autoimmunity Undergoing In Vitro Fertilization/intracytoplasmic Sperm Injection And Different Protein Expression Patterns In Their Follicular Fluid

Background: Autoimmune diseases are plaguing many women of childbearing age,and the most common one is autoimmune thyroiditis.Its main characteristic is that thyroid autoantibodies,including thyroid peroxidase antibodies and globulin antibodies,are positive.The positive rates of TPOAb and TgAb in infertile women was significantly higher than that in normal women.Recent studies have found that pregnant women with positive thyroid autoantibodies have a higher risk of adverse pregnancy outcomes such as spontaneous miscarriage and premature birth even though their thyroid hormone levels are within the normal range.The mechanism of its occurrence is currently not clear.Objectives: 1.To investigate the effect of thyroid autoantibodies on the outcome of IVF/ICSI;2.Using proteomics to screen for differentially expressed proteins in the follicular fluid of thyroid autoantibody-positive and negative infertile women and to explore the mechanism of the influence of thyroid autoantibodies on the outcome of the assisted reproductive technology,and searching for suitable markers for assessing the oocyte quality.Methods: 1.Collection: Samples were taken from June 2015 to January 2017 in women undergoing IVF/ICSI at the endocrine reproductive center of the Second Affiliated Hospital of Chongqing Medical University.There were 49 cases of thyroid autoantibody positive group and 63 cases of control group.2.Proteomic analysis: After protein extraction and enzymolysis of follicular fluid,peptides were labeled with TMT and fractionated by HPLC,followed by liquid chromatography-mass spectrometry analysis.Secondary mass spectrometry data were searched in the SwissProt Human database using Maxquant(v1.5.2.8)to screen differential proteins.3.Bioinformatics analysis: Using the UniProt-GOA database for Gene Ontology analysis and the KEGG pathway database for Protein pathways,and enriched for both.Results: 1.The abortion rate of assisted reproduction of thyroid autoantibody-positive group was significantly higher than that of the control group,and the clinical pregnancy rate and the rate of holding baby was significantly lower than that of the control group;2.The proteins with a difference of more than 1.2 times were identified by proteomic analysis.Among them,31 were up-regulated and 18 were down-regulated.3.Bioinformatics analysis showed that the differential proteins identified were associated with reproduction and fertilization,cell adhesion and movement,signal transduction and regulation,and hormones and stimulation.The response,tissue regeneration and remodeling are related to many important biological processes,and involves multiple biological regulatory pathways such as hsa04921,hsa04512 and hsa04611.Conclusions: 1.Positive thyroid autoantibodies can reduce the clinical pregnancy rate and are associated with adverse pregnancy outcomes such as miscarriage;2.Abnormal expression of many proteins in follicular fluid of thyroid autoantibody-positive women may be closely related to oocyte quality and development,which partially explains the mechanism of the influence of thyroid autoantibodies on pregnancy.