Study On The Metabonomics Mechanism Of Traditional Chinese Medicine Intervening In IVF Outcome Of PCOS Patients With Kidney Yang Deficiency

Objective:To analyze the follicular fluid of polycystic ovary syndrome(PCOS)patients in vitro fertilization and embryo transplantation with kidney yang deficiency after intervention of traditional Chinese medicine and placebo by using the method of target metabllomics,and excavate the biomarkers of kidney yang deficiency syndrome in PCOS patients.Combined with the clinical therapeutic effect,we can excavate the biomarkers of PCOS with kidney yang deficiency,clarify the mechanism of differential metabolites and related metabolic pathways,and explore the metabonomics mechanism of the therapeutic effect of kidney tonifying Chinese medicine(Yougui capsule),so as to provide ideas for improving the IVF treatment outcome of PCOS with kidney yang deficiency.Method:The clinical data of 95 patients with IVF-ET due to infertility were analyzed by prospective,randomized,double-blind and controlled study.The subjects were divided into three groups:treatment group(32 cases of PCOS patients with kidney yang deficiency after the intervention of Chinese medicine),placebo group(33 cases of PCOS patients with kidney yang deficiency after the intervention of placebo)and normal group(30 cases).All the patients in the three groups were treated with short-acting long regimen to do ovarian hyperstimulation.The treatment group was given Yougui capsule from the day of lowering adjustment to the day of HCG,and the placebo group was given placebo from the day of lowering adjustment to the day of HCG.The outcome of IVF treatment between the obse rvation groups(number of eggs obtained,MⅡoocyte rate,IVF 2PN fertilization rate,ICSI 2PN fertilization rate,2PN cleavage rate,usable embryo rate,excellent embryo rate,implantation rate,clinical pregnancy rate)and the changes of syndrome scare of deficiency of kidney yang before and after treatment were observed.The experimental study was carried out by using MetaboAnalyst analysis software to analyze the target metabolomics of follicular fluid collected from three groups of patients on the day of egg collection.Partial least squares discriminant analysis(PLS-DA)was used to analyze the data.Explore the changes of the contents of different metabolites and the related metabolic pathways among the three groups.Result:1.Compared with placebo group,the rate of oocyte acquisition and the number of MⅡ oocytes in the treatment group were higher than those in the placebo group,the difference was statistically significant(P<0.05).2.Compared with placebo group,the score of kidney yang deficiency syndrome in treatment group was significantly improved,and the score of single symptom of kidney yang deficiency was lower after treatment than before treatment,the difference was statistically significant(P<0.01).The results of targeted metabonomics statistical analysis showed that the follicular fluid samples of the treatment group of treatment and the normal group were aggregated,and the two groups of the treatment group and the placebo group were also separated to a certain extent.A total of 20 metabolites changed significantly.After the intervention of traditional Chinese medicine,the content of the components has been lowered,such as phytosphingosine、phosphorylcholine、O-phospho-L-homoserine、LysoPC181、L-threonine、Linoleic acid、Linoleic acid-2、Leucine-2、Lactate、Dimethylglycine、Creatine、Choline、Betaine Aldehyde、Uric acid、sn-Glycero-3-phosphocholine、sarcosine;the other content of the components has been rised,such as Decanoylcarnitine、2-acyl-sn-glycero-3-phosphocholine-、3-Sulfopyruvic acid、progesterone.By Pathway analysis,the glycerol phospholipid metabolic pathway and the glycine,serine and threonine metabolic pathway in PCOS patients with kidney yang deficiency were regulated.Conclusion:1.Yougui Capsulecan effectively improve the symptoms of kidney yang deficiency in PCOS patients with kidney yang deficiency,improve the quality of oocyte and the rate of oocyte acquisition,and then improve the final cumulative pregnancy rate.2.In PCOS patients with kidney yang deficiency,the metabolites in follicular fluid changed significantly,involving amino acids:L-threonine,Phosphohomoserine,Leucine,Sarcosine,Dimethylglycine;Organic acids:Linoleic acid,Linoleic acid-2,Creatine,Uric acid,Lactate,3-sulfopyruvic acid;hormone:Progesterone;alkaloids:Decanoylcarnitine,Phosphorylcholine,Choline,Betaine Aldehyde;lipid:LysoPC(18:1),Phytosphingosine,sn-glycero-3-phosphocholine,2-Acyl-sn-glycero-3-phosphocholine.3.The mechanism of kidney tonifying Chinese medicine intervention in IVF treatment outcome of PCOS patients with kidney yang deficiency may be related to the glycerol phospholipid metabolic pathway and the glycine,serine and threonine metabolic pathway.