Study On The Metabonomics Mechanism Of Traditional Chinese Medicine Intervening In Senile IVF Outcome Of Kidney Qi Deficiency Type

Objective:To analyze the follicular fluid of senile patients in vitro fertilization and embryo transplantation with kidney qi deficiency after intervention of the Chinese medicine used for tonifying kidney by using the method of quasi target metabllomics,and excavate the biomarkers of kidney qi deficiency syndrome in elderly patients.The mechanism of different metabolites and related metabolic pathways should be clarified,and the metabolic mechanism of Chinese herbs for tonifying the kidney should be discussed giving a thinking to improve the outcome of IVF treatment in elderly infertile women.Method:Clinical studies used prospective study to analyze the clinical data of 95 patients with IVF-ET due to infertility.The subjects were divided into three groups:the first was called treatment group in 34 cases(the senile patients with kidney qi deficiency after the intervention of Chinese medicine),the second was control group in 31 cases(the senile patients with kidney qi deficiency of no intervention of Chinese medicine)and the third one was normal group in 30 cases.All the patients in these three groups were treated with long regimen hyperstimulation of ovulation,and the treatment group were treated with Qizi Yusi decoction from the day of lowering adjustment to the day of HCG.The outcome of IVF treatment between the observation 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 score of deficiency of kidney qi before and after treatment were observed.The experimental study was carried out by using MetaboAnalyst group analysis software to analyze the quasi 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 metabolites content and related metabolic pathways among the three groups.Result:1.In the treatment group,the syndrome integral of deficiency of kidney qi was obviously improved,and the score of single symptom of deficiency of kidney qi after treatment was lower than that before treatment,the difference was statistically significant(P<0.01).2.Compared with the control group,the rate of available embryos and seeding in the treatment group was significantly higher than that in the latter group(P<0.05).There was no significant difference in other indexes,but there was a tendency to improve to the normal group.3.The results of quasi-targeted metabonomics statistical analysis showed that the follicular fluid samples of the senile group of treatment and the normal group were aggregated,and the two groups of the treatment group and the control group were also separated to a certain extent.A total of 12 metabolites changed significantly.After the intervention of traditional Chinese medicine,the content of the components has been lowered,such as Progesterone,Indoleacrylic acid,2-Propenyl 1-(1-propenylsulfinyl)propyl disulfide,N-acetyltryptophan,Decanoylcamitine,20a-Dihydroprogesterone,Testosterone Acetate,Eicosatrienoic acid,1 H-Indole-3-carboxaldehyde,Choline,Phosphorylcholine and tryptophan.By Pathway analysis,glycerol phospholipid metabolism pathway,fatty acid metabolism pathway,steroid hormone synthesis pathway,tryptophan metabolic pathway,glycine,serine and threonine metabolism were found in senile patients with kidney qi deficiency after intervention with Chinese medicine.The metabolic pathway of linoleic acid is regulated.Conclusion:1.Qizi Yusi decoction can effectively improve the symptoms of kidney vital energy deficiency,oocyte quality and embryo availability in senile patients with IVF,and then improve embryo implantation potential.2.Significant changes have taken place in follicular fluid metabolites in senile infertile women with Kidney qi deficiency,involving hormones(progesterone,20a-dihydroprogesterone,testosterone acetate),carnitine(decyl carnitine),choline(choline,choline phosphate).Fatty acids(eicosatrienoic acid)and so on,they are closely related to the aging of women and oocyte quality.It is speculated that these substances may be a potential biomarker of kidney vital energy deficiency syndrome in old age.3.The opportunity of improving the outcome of IVF treatment with traditional Chinese Medicine for tonifying Kidney.It may be related to steroid hormone synthesis,fatty acid metabolism,glycerol phospholipid metabolism,glycine,serine and threonine metabolism and linoleic acid metabolic pathway.