Effect Of Female Genital Tuberculosis On Ovarian Reserve Function Based On Metabonomics Analysis

Objective:To explore whether female genital tuberculosis（FGTB）and latent and genital tuberculosis（LGTB）affect ovarian reserve function,and to preliminarily explore the interaction between changes in endogenous metabolites and ovarian reserve function in FGTB and LGTB patients through serum and follicular fluid metabonomics analysis.In order to further study the mechanism of FGTB and LGTB affecting ovarian reserve function.To provide ideas for predicting the quality of oocytes in this population and improving the outcome of in vitro fertilization and embryo transfer（IVF-ET）treatment.Methods:A total of 19 FGTB patients,16 LGTB patients,and 16 healthy women in the control group（infertile due to male factors）who were treated with IVF assisted pregnancy at the Reproductive Medicine Centre of the Affiliated Hospital of Inner Mongolia Medical University from September 2021 to December 2022 were selected.First of all,collect basic information and clinical data of subjects.Basic information:age,body mass index（BMI）and infertility years;Basic clinical data:basic follicle-stimulating hormone（FSH）,anti-mullerian hormone（AMH）and antral follicular count（AFC）;The clinical data of the ovulation process of the united use of the antagonist protocol:the total amount of gonadotropin（Gn）,Gn time,Estradiol（E₂）on the day of injection of human chorionic gonadotropin（h CG）and number of retrieved oocytes.Using statistical methods to analyze whether ovarian reserve function and ovarian responsiveness during IVF are affected in FGTB and LGTB patients.Secondly,the venous blood and follicular fluid of the subjects were collected at 7am on the day of oocytes collection.Finally,the serum and follicular fluid were detected and analyzed by liquid chromatography-mass spectrometry（LC-MS）.Through univariate statistical analysis and multi-dimensional statistical analysis,we screened out the significant difference metabolites of FGTB and LGTB patients compared with the control group,and analyzed the relevant metabolic pathways with the help of the Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway database.Results:1.Comparison of basic information and clinical data:FGTB group was significantly lower in AMH,AFC,E₂on the day of injection of h CG,and number of retrieved oocytes than the control group,but significantly higher in basic FSH,Gn time and the total amount of Gn than the control group（P<0.05）.LGTB group was significantly lower in AFC,E₂on the day of injection of h CG,and number of retrieved oocytes than the control group,but significantly higher in basic FSH and Gn time than the control group（P<0.05）.No significant difference in other values（P>0.05）。2.Compared with the control group,the FGTB group screened 18 serum differential metabolites,among which phosphatidylethanolamine,glycerol phosphatidylethanolamine,dimethyl phosphatidylethanolamine,diglyceride,estrone glucoside,estrone 3-sulfate and pregnenolone sulfide were down-regulated,and 3-hydroxyanthranilic acid and L-glutamine were up-regulated.Twelve different metabolites of follicular fluid,including phosphatidylcholine,phosphatidylinositol,lysophosphatidylinositol,estrone gluconate,estrone 3-sulfate,pregnenolone sulfide,cortisol,linolenic acid,chenodeoxycholic acid and glutathione,were down-regulated,and D-galactose and D-glucose were up-regulated.The metabolic pathways involved are glycerophosphate metabolism,glyceride metabolism,steroid hormone biosynthesis,unsaturated fatty acid biosynthesis,cholesterol metabolism,tryptophan metabolism,glutamic acid metabolism,and glucose metabolism.3.Compared with the control group,the LGTB group screened 9 serum differential metabolites,among which phosphatidylethanolamine,phosphatidylserine,pregnenolone sulfide and chenodeoxycholic acid were down-regulated,while anthranilic acid and melatonin were up-regulated.Eleven different metabolites of follicular fluid,including lysophosphatidylcholine,pregnenolone sulfide,cortisol,linolenic acid,oleic acid,glycylcholic acid,glutathione and pipecolic acid,were down-regulated,and2-hydroxycinnamic acid was up-regulated.The metabolic pathways involved include glycerophosphate metabolism,steroid hormone biosynthesis,unsaturated fatty acid biosynthesis,cholesterol metabolism,tryptophan metabolism,glutamic acid metabolism,lysine degradation,and phenylalanine metabolism.The metabolic pathways involved include glycerophosphate metabolism,steroid hormone biosynthesis,unsaturated fatty acid biosynthesis,cholesterol metabolism,tryptophan metabolism,glutamic acid metabolism,lysine degradation,and phenylalanine metabolism.Conclusion:The ovarian reserve function and ovarian responsiveness during IVF in FGTB and LGTB patients have decreased.Further analysis based on metabolomics revealed that the adverse effects of FGTB and LGTB on ovarian reserve function may be related to changes in serum and follicular fluid metabolites that induce changes in oocytes,which mainly involve pathways such as lipid metabolism,steroid hormone biosynthesis,amino acid metabolism,and glucose metabolism.