Study On The Correlation Between Obesity And Polycystic Ovary Syndrome,IVF Outcomes

Background: Obesity refers to the abnormal or excessive accumulation of adipose tissue caused by the imbalance between energy intake and consumption of the body,and is a chronic metabolic disease.Polycystic ovary syndrome(PCOS)is a group of reproductive endocrine disorders and abnormal metabolic syndromes that occur in women of reproductive age.It is often combined with obesity,insulin resistance(IR),infertility and increased pregnancy complications,which seriously affects female reproductive health.It is commonly believed that obesity and PCOS are closely related and can be a vicious circle that leads to worse reproductive outcomes.The mechanisms underlying the association between the two are not yet fully understood.Both obesity and PCOS are epigenetically related,and genome-wide association studies have verified the existence of genetic correlations and common genetic loci,but less research has been done to explore the genes and pathways associated with obesity and PCOS.On the other hand,the assessment of obesity in clinical practice usually uses anthropometric parameters.In recent years,new body fat indices,lipid accumulation product(LAP)and visceral adiposity index(VAI),which combine anthropometric parameters and metabolic indices,have been proposed to investigate the effects of insulin resistance and abnormal lipid metabolism on PCOS.However,existing studies have focused less on the infertility population,and it is unclear whether the new body fat index in infertile women is associated with the prevalence of PCOS and whether it is associated with assisted reproductive outcomes in this group of patients.Therefore,this study aims to explore the genes and possible pathways related to obesity and PCOS from both theoretical and clinical perspectives,as well as to explore the correlation between the new body fat index as an obesity assessment indicator and the onset and assisted reproductive outcomes of PCOS.The aim is to verify the genetic correlation between obesity and PCOS,provide new gene targets for early diagnosis and treatment of PCOS.We hope to identify and intervene in PCOS as early as possible to achieve more ideal assisted reproductive outcomes.Part I: Screening key genes associated with obesity and polycystic ovary syndrome.Purpose:1.To screen out genes that are co expressed between obesity and PCOS,analyze their possible biological processes,and explore whether there is a genetic level correlation between the two diseases;2.To screen out key genes that are co expressed between obesity and PCOS,and verify the predictive value of key genes for PCOS disease.Method:1.We have downloaded the "Series Matrix File(s)" files for obesity related datasets GSE25402 and PCOS related datasets GSE54250,GSE80432,GSE137684,GSE168404,and GSE145461 from the GEO database;2.We have used the R package "limma" for data preprocessing;3.We have used the R package "lima" to analyze the differentially expressed genes of GSE25402 and GSE54250,the intersection was obtained to obtain the differentially expressed genes of obesity and PCOS.Verify the expression amount of co expressed differential genes in GSE80432,GSE137684,GSE168404,and GSE145461.4.We have used the Metacap database to conduct GO and KEGG enrichment analysis on co expressed differential genes to obtain the main functions and participating pathways of the genes.5.We have used the STRING database to establish protein interaction networks that co express differential genes,and using the Cyto Hubba plug-in to obtain key genes.6.We have screened miRNAs of key genes in miRDB and Target Scan databases,and constructing miRNA interaction networks by using the Cytoscape software;7.We have used the R package "p ROC" to draw ROC curves for PCOS disease,and compare the predictive value of key gene expression levels for PCOS disease.Result:1.In GSE25402,we screened 1989 differential genes,including 662 up-regulated genes and 1327 down-regulated genes.In GSE54250,we screened 491 differential genes,including 248 up-regulated genes and 243 down-regulated genes.56 differentially expressed genes were screened,including 31 up-regulated genes and 25down-regulated genes.2.The co-expressed differential genes are mainly concentrated in metabolism,immunity,and inflammatory reactions.3.We screened 10 key genes: ITGAM,IL1 B,PTPRC,CCR1,CD14,FCGR2 A,CD163,MMP9,CCL3,and AIF1.4.We screened 32 miRNAs,and the most frequently interacting miRNAs were hsa-miR-5692 a and hsa-miR-3613-3p.5.The genes that have predictive value for PCOS are CCR1 and CD163,and the diagnostic and predictive efficiency of CCR1 is higher than that of CD163.Conclusion:1.Obesity and PCOS are genetically related.56 genes related to obesity and PCOS were screened in this study,which are mainly involved in the biological processes of metabolism,immune and inflammatory responses of the body.2.In this study,10 key genes were identified: ITGAM,IL1 B,PTPRC,CCR1,CD14,FCGR2 A,CD163,MMP9,CCL3 and AIF1,which have potential as future therapeutic targets for obesity and PCOS.Among the key genes,CCR1 and CD163 had predictive value for PCOS disease.These genes have the potential to serve as early diagnostic and therapeutic targets for obesity and PCOS in the future.Part II: Exploring the correlation between the new body fat indexes and IVF outcomes.Purpose:1.To explore the predictive value of the new body fat indexes for the prevalence of PCOS in infertile women.2.To compare the clinical outcomes of IVF between different levels of the new body fat indexes and analyze the correlation between the new body fat indexes and IVF outcomes in infertile patients.Methods: A retrospective study was conducted to include 510 infertile patients who underwent IVF for the first time at the Reproductive Center of the First Hospital of Lanzhou University from January 2020 to August 2021.The patients were divided into a PCOS group(238 cases)and a control group(272 cases)with tubal infertility.The differences between the two groups in basic indicators and obesity assessment indicators were compared.The predictive value of obesity assessment indicators on the prevalence of PCOS was compared using univariate and multivariate binary logistic regression and ROC curves.Subsequently,all the subjects were divided into high LAP group(216 cases)and normal LAP group(294 cases)using the diagnostic cut-off points of LAP and VAI as the cut-off values;High VAI group(296 cases)and normal VAI group(215 cases).Compare ovulation induction,embryo laboratory results,and pregnancy outcomes among the corresponding groups of patients.Result:1.The menstrual cycle,HOMA-IR,total AFC,RBC,HGB,UA,LH,P,AMH,TG,and HDL-C of the PCOS group were higher,while the age and FSH of the female were lower,with a statistically significant difference(P<0.05).2.The BMI,WC,HC,WHR,WHt R,LAP,and VAI in the PCOS group were significantly higher than those in the control group(P<0.05).3.There was no statistically significant correlation between age and BMI,WC,HC,WHR,WHt R,LAP,VAI in the overall study object and PCOS group(P>0.05).The age of patients in the control group was positively correlated with BMI,WC,HC,WHR,WHt R,LAP,and VAI(P<0.05).4.Age can be an independent influencing factor for the prevalence of PCOS.After adjusting for age,all obesity assessment indicators included are independent risk factors for PCOS.In multivariate analysis,BMI,WC,LAP,and VAI can be used as influencing factors for predicting the prevalence of PCOS.When the LAP value increases by 1,the risk of PCOS increases by 1.652 times;For every 0.1 increase in VAI,the risk of PCOS is 0.808 times higher.5.The age of the woman and various obesity assessment indicators alone or partially combined diagnosis have certain predictive value for the prevalence of PCOS,among which LAP combined with VAI,LAP,VAI,HC,and WC have good predictive value for PCOS.In single factor diagnosis,LAP had the highest efficacy,with an AUC of 0.886.The diagnostic efficacy of VAI is second only to LAP and higher than other indicators,with an AUC of 0.796.If considering multi factor combined diagnosis,LAP combined with VAI can achieve the maximum diagnostic efficiency,with an AUC of0.887,which is higher than any single factor diagnosis.6.LAP and VAI were positively correlated with HOMA-IR(P>0.05).7.The menstrual cycle,BMI,WC,HC,WHR,WHt R,VAI,HOMA-IR,total AFC,WBC,RBC,PLT,HGB,UA,AMH,TC,TG,HDL-C,LDL-C in the high LAP group were higher than those in the normal LAP group,while FSH,E2,PRL,and P were lower,with a statistically significant difference(P<0.05).The menstrual cycle,BMI,WC,HC,WHR,WHt R,LAP,HOMA-IR,total AFC,WBC,RBC,PLT,UA,AMH,TG,and LDL-C in the high VAI group were higher,while FSH,E2,PRL,P,and HDL-C were lower,with a statistically significant difference(P<0.05).8.The number of Gn days,total Gn amount,Gn initial dose,and HCG daily target follicles used during ovulation induction in the high LAP and high VAI groups were significantly higher than those in the normal group(P<0.05).9.The levels of LAP and VAI in patients were positively correlated with the number of Gn days,Gn total amount,Gn initial dose,and HCG daily target follicle count during ovulation induction(P<0.05).10.The high LAP group had a higher number of oocytes retrieved and MⅡ oocytes,but a lower rate of oocytes retrieved,MⅡ oocytes obtained,2PN fertilization rate,D3high-quality embryos obtained,D3 high-quality embryos obtained,transferable blastocysts obtained,high-quality blastocysts obtained,and egg utilization rate(P<0.05).The number of oocytes retrieved,MⅡ oocytes,2PN oocytes,lower rate of oocytes retrieved,MⅡ oocytes rate,2PN fertilization rate,D3 high-quality embryos rate,transplantable blastocysts rate,high-quality blastocysts rate,high-quality blastocysts rate,and egg utilization rate in the high VAI group were higher than those in the normal VAI group,with a statistically significant difference(P<0.05).11.The level of LAP in patients was positively correlated with the number of oocytes retrieved,MⅡ oocytes,2PN oocytes,D3 transferable embryos,transferable blastocysts,and high-quality blastocysts(P<0.05),but negatively correlated with the rate of oocytes retrieved,MⅡ oocytes,2PN fertilization rate,D3 high-quality embryos,D3 high-quality embryos,high-quality blastocysts,and egg utilization rate(P<0.05).The VAI level of patients was positively correlated with the number of oocytes obtained,MⅡ oocytes,2PN oocytes,D3 transferable embryos,transferable blastocysts,and highquality blastocysts(P<0.05),while negatively correlated with MⅡ oocyte rate,2PN fertilization rate,D3 high-quality embryos rate,high-quality blastocysts rate,and egg utilization rate(P<0.05).12.The clinical pregnancy rate,embryo implantation rate,early abortion rate,and live birth rate in the high LAP group were significantly lower than those in the normal LAP group(P<0.05).The clinical pregnancy rate,embryo implantation rate,early abortion rate,multiple pregnancy rate,and live birth rate of patients in the high VAI group were significantly lower than those in the normal LAP group(P<0.05).Conclusion:1.The predictive value of the novel body fat index for the prevalence of PCOS is higher than that of the traditional indexs,and the diagnostic efficacy of LAP is higher than that of VAI,with the highest diagnostic efficacy when the two are combined.2.LAP and VAI are associated with IVF outcomes,and their elevated levels reduce quality of oocytes and embryos,interfere with embryo implantation,reduce clinical pregnancy rate and live birth rate,increase early miscarriage rate,and bring negative impact on IVF outcomes.