Effects Of Abnormal Lipid Metabolism On The Development Of Oocytes And Embryos In Women With Polycystic Ovary Syndrome

Background and ObjectivePolycystic ovary syndrome(PCOS)is a common reproductive endocrine disease,affecting women aged 19-45.PCOS can cause lack of ovulation and infertility with heterogeneity and complexity of metabolism.Application of lifestyles improvement,medications and assisted reproductive technology(ART)can increase the pregnancy rate of PCOS patients,but still face problems such as high cycle cancellation rate,low fertilization rate and high early abortion rate,which suggests that the oocyte and embryo development may be impaired.Recent study suggests that altered lipid metabolism which may affect the oocyte development,fertilization and embryo quality has a higher incidence rate in PCOS,especially for patients with obesity.This study uses LC/MS non-targeted metabolomics technology to detect lipid profile in follicular fluid of PCOS patients,which is helpful to explore the causes and mechanisms of the reduced quality of PCOS oocytes and embryos,and provide a theoretical basis for individualized and standardized treatment of PCOS patients.Materials and methodsWe recruited 40 PCOS patients and 20 control patients who were under 35 years old and had no insulin resistance who had undergone IVF/ICSI at the Reproductive Medicine Center of Henan Provincial People's Hospital from June 2018 to October 2019.Patients were grouped according to body mass index,including PCOS overweight or obese patients(PO group),PCOS normal weight patients(P group)and control normal weight patients(C group).This study was approved by the Henan Provincial People 's Hospital Ethics Committee and informed consent of all patients were obtained.The basic data and clinical indicators of patients were collected.The first tube of clear and blood free follicular fluid collected on the day of oocyte retrieval was centrifuged and the supernatant was separately packed in EP tubes and stored in-80 ? refrigerator.All samples were tested by LC/MS non-targeted metabolomics.The differential metabolites were screened by multivariate statistical analysis and t-test.The metabolic pathways was enriched and analyzed by KEGG annotation.Pearson correlation analysis was used to find the lipid metabolites related to ART clinical indicators.Using SPSS 22.0 statistical software,measurement data are expressed by x s?(mean ± standard deviation),the differences of measurement data of normal distribution were compared with independent sample t-test;measurement data of non-normal distribution were analyzed by non-parametric rank sum test;count data was expressed as a percentage,and chi-square test was carried out;Pearson method was used for correlation analysis;P <0.05 indicated statistically significant.Results1.Clinical data analysis found that PCOS patients have a decreased rate of D3 high-quality embryos;PCOS combined with obesity factors may affect the follicular output rate and MII rate.2.Through LC/MS metabolomics analysis,23 lipid differential metabolites were detected in PCOS normal weight patients and control normal weight patients;29 lipid differential metabolites were detected in PCOS overweight or obese patients and PCOS normal weight patients;There were 7 intersections of lipid differential metabolites in the three groups.3.Through the KEGG annotations,the altered metabolic pathways of lipid differential metabolites in PCOS normal weight patients and control normal weight patients include glycerophospholipid metabolism,fat digestion and absorption,insulin resistance,aldosterone synthesis and secretion,sphingolipid metabolism and linoleic acid metabolism.The altered metabolic pathways of lipid differential metabolites in PCOS overweight or obese patients and PCOS normal weight patients include primary bile acid biosynthesis,fat digestion and absorption,glycerophospholipid metabolism,insulin resistance,sphingolipid metabolism and linoleic acid metabolism.4.Pearson correlation analysis of lipid differential metabolites and ART-related clinical indicators found that in the lipid differential metabolites in PCOS normal weight patients and control normal weight patients,pregnenolone was positively correlated with the follicular output rate of PCOS normal weight patients.Diglyceride(18: 1(9Z)/ 16: 0/0: 0)was significantly positively correlated with AMH of PCOS normal weight patients;pregnenolone was positively correlated with AMH of control normal weight patients.In the lipid differential metabolites in PCOS overweight or obese patients and PCOS normal weight patients,glycocholic acid was positively correlated with the 2PN rate of PCOS overweight or obese patients;2-Deoxycastrosterone was negatively correlated with the 2PN rate and D3 available embryo rate of PCOS overweight or obese patients;DL-acetylcarnitine was positively correlated with the rate of D3 high-quality embryos of PCOS overweight or obese patients;Tylosin was negatively correlated with BMI and AFC of PCOS normal weight patients;diglyceride(18: 1(9Z)/ 16: 0/0: 0)and lactosylceramide(d18: 1/16: 0)was positively correlated with AMH of PCOS normal weight patients;Scilliroside was negatively correlated AFC of PCOS normal weight patients.Conclusion1.Compared with control normal weight patients,PCOS normal weight patients have significant changes in fatty acyls,glycerophospholipids,sphingolipids,sterol lipids,steroids and steroids derivatives,glycerolipids,and prenol lipids;PCOS overweight or obese patients also have differences in lipid metabolism compared with PCOS normal weight patients.2.PCOS and combined obesity factors may affect ovarian responsiveness,oocyte fertilization and embryo development potential through fat digestion and absorption,glycerophospholipid metabolism,sphingolipid metabolism,insulin resistance,aldosterone synthesis and secretion,linoleic acid metabolism and primary bile acid biosynthesis pathways.