Exploring The Mechanism Of Traditional Chinese Medicine Improving IVF Outcomes In PCOS Patients With Phlegm-dampness Based On Targeted Metabolomics

Objective:To evaluate the effect of traditional Chinese medicine Xiaonang Yusi Decoction on the clinical efficacy of in vitro fertilization-embryo transfer in patients with polycystic ovary syndrome of phlegm-dampness syndrome,and to explore its possible mechanism from the perspective of targeted metabolomics.Methods:A prospective cohort study method was used to select 96 patients who underwent IVF-ET due to infertility,and divided them into three groups:the experimental group(the phlegm-damp type PCOS traditional Chinese medicine Xiaonang Yusi Decoction intervention group)32 cases,the control group(Phlegm-damp type PCOS non-traditional Chinese medicine intervention group)32 cases and normal group(IVF-ET group simply due to male factors)32 cases.All three groups adopted the antagonist program for superovulation.The experimental group began to take the traditional Chinese medicine Xiaonang Yusi Decoction on the fourth day of the menstrual cycle of the previous month.The outcomes of IVF treatment(the number of oocytes retrieved,the number of 2PN,the number of available embryos,the number of high-quality embryos,the embryo implantation rate,and the clinical pregnancy rate)among the three groups were observed and compared,as well as the changes of TCM syndrome scores of phlegm-dampness syndrome in the experimental group before and after Chinese medicine intervention.In the experiment,ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-QTRAP MS)was used to conduct targeted metabolomic analysis on the follicular fluid retained on the day of oocyte retrieval in three groups of patients,to find out the difference in metabolite content among the three groups.Changes and related pathways.Results:1.The experiment was finally completed with 86 patients,including29 in the experimental group,28 in the control group,and 29 in the normal group.2.The TCM syndrome scores on HCG day in the experimental group were significantly lower than those before medication,and the difference was statistically significant(P<0.05).Compared with before treatment,the clinical symptoms of the experimental group in terms of BMI,menstrual cycle,abnormal menstrual volume and color quality,edema of limbs,stickiness in the mouth,fatigue of limbs,vaginal discharge,and acne were significantly improved,with statistical significance(P< 0.05),there was no statistical difference in the improvement of chest and abdomen fullness,hirsutism,acanthosis nigricans(P>0.05).There was a statistically significant difference in the total number of available embryos among the three groups(P<0.05),and the remaining IVF indicators showed a trend of improvement although there was no statistical significance(P>0.05).3.Targeted metabolomics analysis,compared with the control group,after the intervention of traditional Chinese medicine Xiaonang Yusi Decoction,Metabolites such as 1,4-Dihydronicotinamide adenine dinucleotide(NADH)、3-Chlorotyrosine、Acetamide、Choline、Epinephrine、Glutaric acid、Glycyl-L-leucine、Guanosine diphosphate、Malonic acid、NAcetyl-L-aspartic acid、Pyruvic acid、Taurohyodeoxycholic acid(THDCA)、Trimethylamine(TMA)、 Vanillic acid 、 xanthurenate 、 Dopamine2 were upregulated.Multiple metabolites such as b-Nicotinamide adenine dinucleotide、Alpha-N-Phenylacetyl-L-glutamine、2-Hydroxy-2-methylbutyric acid、Adipic acid、But-2-enoic acid、Elaidic Acid、L-Alanine、L-Homocitrulline、Sebacic acid、Tricosanoic acid、Palmitelaidic acid、L-Valine、Ketoleucine、L-Tryptophan、L-Tyrosine、Melatonin、Methylcysteine、Methylglutaric acid、Hippuric acid、Hydroxyphenyllactic acid、hydroxyproline、Indole-3-lactic Acid、Ortho-Hydroxyphenylacetic acid、Oxalic acid、Palmitelaidic acid、Palmitic acid、Suberic acid、Succinic acid、Tauro-a-muricholic acid、Taurob-muricholic acid(b-TMCA)、Ursocholic acid(UCA)、Vanillylmandelic acid、Vitamin B5 were down-regulated.The pathways involved include ABC transporters,Fox O signaling pathway,Glutathione metabolism,Amyotrophic lateral sclerosis(ALS),Non-alcoholic fatty liver disease(NAFLD),DGlutamine and D-glutamate metabolism,Aminoacyl-t RNA biosynthesis,etc.Conclusion:1.The traditional Chinese medicine Xiaonang Yusi Decoction can effectively improve the related TCM syndromes of PCOS patients with phlegmdampness type.2.Xiaonang Yusi Decoction can increase the number of oocytes retrieved,the number of 2PN,the number of available embryos,the number of high-quality embryos,the embryo implantation rate,the clinical pregnancy rate,and the IVF outcome of PCOS patients.3.Xiaonang Yusi Decoction can affect the expression of metabolites in the follicular fluid of PCOS patients with phlegm-dampness type.These metabolites can be used as potential biomarkers and therapeutic targets.The mechanism of action may be related to ABC transporters,Fox O signaling pathway,Glutathione It is related to pathways such as metabolism,Amyotrophic lateral sclerosis(ALS),Non-alcoholic fatty liver disease(NAFLD),D-Glutamine and Dglutamate metabolism,and Aminoacyl-t RNA biosynthesis.