Study On The Correlation Between Lipid Metabolomics Of Follicular Fluid And Oocyte Quality And Embryo Development Potential In Women With Polycystic Ovary Syndrome

Polycystic ovary syndrome(PCOS)is a common metabolic dysfunction and endocrine disorders in women of childbearing age.The incidence of PCOS is about 5% to 10%,and 30% of infertile couples is caused by PCOS.In clinical practice,metabolic disorders are common in PCOS patients,the occurance of glucose metabolism,abnormal glucose tolerance and insulin resistance is about50%-70%.Meanwhile,disorders of lipid metabolism,obesity or weight gain are occurred in 30%-75% of patients.Previous studies have shown that obese occurred accompany with infertility.The quality of their germ cells is reduced,and pregnancy rates are significantly lower than those of normal weight.And we also obsered,PCOS patients were prone to occure ovulation dysfunction.The oocyte quality is declined in PCOS patients,which leads to increased of infertility rates.PCOS is leading to a variety of adverse pregnancy outcomes,such as lower fertilization rate,cleavage rate and implantation rate,and higher abortion rate.Oocyte quality is regulated by many factors,including the microenvironment.As an important part of the microenvironment of oocytes development,follicular fluid is mainly composed of secretions produced by surrounding granulosa cells and serum diffused by local capillaries.It also contains plasma components that cross the follicular blood barrier and active products secreted by granulosa cells and membrane cells.The metabolic status of maternal follicular fluid is the determinant of oocyte and embryo quality,and it controls oocyte development,especially meiosis,epigenetics,and organelles.Since most PCOS women have abnormal lipid metabolism,they are prone to suffer from abnormal blood glucose and lipids.To assess oocyte quality in patients with PCOS,lipid metabolism in follicular fluid is of concern.In the existing studies,there are few studies on the follicular fluid metabolome of PCOS patients,and this field needs to be improved urgently.Therefore,the following studies were carried out in this study: Firstly,the oocyte quality and embryo development of infertility patients with PCOS and oviduct factors after ovulation induction were analyzed,and the clinical observation was made.Secondly,the follicular fluid of tubal infertility patients and PCOS patients was collected to detect the difference of lipid metabolism group.Finally,the lipid metabolism factors related to oocyte and embryo quality were expected to be evaluated,so as to provide theoretical basis and ideas for clinical oocyte quality prediction.Part I: Analysis of oocyte quality and embryo development of PCOS patients using IVF.Objective: To study the oocyte quality and embryo development of PCOS patients after hyperovulation induction,and to analyze the long-term pregnancy outcome of PCOS patients.Methods:According to the definition of infertility and diagnostic criteria of PCOS in 2018,patients with infertility factors of PCOS were selected as the research group.The method of propensity score was used to compare the control group(infertile patients with tubal factor)matching to PCOS patients.To investigate the number of oocytes,oocytes maturity,normal fertilization rate,available embryo rate,and blastocyst formation rate of each group.Moreover,The differences in long-term pregnancy outcomes in each group were analyzedResults: To compare with the control group,the number of oocytes in the PCOS group was 14.73 ± 6.47 and the Control group was 12.47 ± 3.75.The mature oocyte count in the PCOS group was 12.37 ± 5.53 and the control group was11.03 ± 3.38.The differences between them were statistically significant(P<).However,the oocyte maturity rate of patients(the PCOS group: 84.66 ± 12.71%;the Control group: 89.10 ± 10.01%),the oocyte fertilization rate(the PCOS group : 79.74 ± 15.14%;the Control group: 84.25 ± 11.66%),the normal oocyte fertilization rate(the PCOS group: 66.86 ± 18.58%;the Control group: 70.32 ±13.97%),the embryo cleavage rate(the PCOS group: 96.40 ± 10.72%;the Control group: 97.55 ± 5.64%),available embryo rate(the PCOS group: 68.78 ±24.68%;the Control group: 76.97 ± 18.52%)and blastocyst formation rate(the PCOS group: 38.16 ± 35.46%;the Control group: 54.02 ± 35.33%)were significantly lower than the control group(P< 0.05),and the number of oocytes obtained by PCOS patients was significantly higher than that of the control group.However,the oocyte maturity,normal fertilization rate of oocytes,available embryo rate and blastocyst formation rate of PCOS patients all decreased significantly,and the above differences were statistically significant.The clinical outcome of the fresh cycle was analyzed in the two groups,excluding the lost follow-up cycle.The results showed that there was no statistical difference in clinical pregnancy rate,ectopic pregnancy rate and abortion rate between the two groups.However,compared with the live birth rate of the two groups,the live birth rate of the PCOS group was significantly lower than that of the control group(PCOS group: 104(46.81%)).Control group: 487(58.53%)),the difference was statistically significant(P < 0.05).Conclusion: Although the number of oocytes obtained in PCOS patients increased,the results showed that oocyte quality decreased and the number of mature oocytes significantly decreased,which may lead to a significant decrease in the normal fertilization rate of oocytes,the rate of available embryos and the rate of blastocyst formation.The main reasons and the specific mechanism needs further study.Although there was no difference in clinical pregnancy rate,ectopic pregnancy rate and abortion rate in PCOS patients,their long-term live birth rate was significantly lower than that in the control group.Part II: Study on the correlation between metabolomics of female follicular fluid and oocyte quality and embryo development potentialObjective: To detect the lipid metabolites in follicular fluid and to explore whether they can be used as an index to predict oocyte quality and lipid metabolites in early development.Methods: According to the classification standard of BMI in China,the subjects were divided into four groups: lean control(LC),overweight(OW),lean PCOS(LP)and overweight PCOS(OP).Our purpose is compare with the lipid metabolites in the follicular fluid between the four groups.Results:Compared with the LC group,the fertilization rate of the OP group decreased obviously.A total of 236 metabolites were identified and quantified by metabolomics,of which 69 metabolites had statistical differences between the PCOS subgroup and healthy women.Compared with the LC group,the levels of19 metabolites and 50 metabolites and 66 metabolites in the OW,LP,and OP groups were significantly changed.Compared with the OW group,the levels of24 metabolites in the LP group and 43 metabolites in the OP group were significantly changed.Furthermore,compared with the LP group,the levels of 26 metabolites in the OP group showed statistical changes.Further analysis of 236 metabolites in follicular fluid levels affect oocyte fertilization rate and embryo rate,and the result shows that there are seven kinds of follicular fluid metabolites and oocyte fertilization rate,there are five kinds of follicular fluid metabolites associated with high-quality embryo rate several metabolites of all patients have a significant correlation with the rate of fertilization rate and embryo quality.Conclusion: Fertilization rates in obese PCOS women dropped significantly.There were significant differences in follicular fluid metabolites between PCOS patients and healthy women,and they were more significant in obese PCOS women.Egg fertilization rate is related to embryo rate and various lipid metabolites in follicular fluid,among which lysophospholipin is positively correlated with PCOS oocyte mass,which can be used as a potential candidate marker to predict oocyte mass.The changes of metabolic markers may be closely related to oocyte quality.Whether it can be used as a marker of oocyte quality still needs further study.