| Objective : To evaluate the clinical efficacy of Traditional Chinese Medicine(TCM)“Xiaoyi Yusi Decoction”in the treatment of IVF-ET for patients with endometriosis of Kidney deficiency and blood stasis type,and to explore its possible targets and pathways from tryptophan metabolism pathway of follicular fluid.Methods:In the clinical study part,a prospective randomized controlled method was implemented,we selected a total of 93 cases of infertility patients who underwent IVF-ET in the reproductive center of Affiliated hospital of Shandong University of Traditional Chinese Medicine,of which including 62 patients with EMs of Kidney deficiency and blood stasis type.The latter were randomly divided into TCM“Xiaoyi Yusi Decoction”intervention group(TCM group:31 cases)and non-intervention group(NON group:31 cases).In addition,there were 31 women in the normal control group because of solely male factors(CON group:31 cases).The three groups were treated with fixed Gonadotropin-releasing hormone(Gn RH)antagonist protocol for ovarian stimulation treatment.The TCM intervention group was treated from the menstrual cycle before ovulation induction to the day trigger.That the changes of TCM syndrome scores before and after treatment in TCM intervention group and non-intervention group were compared.The IVF treatment outcomes of the three groups were observed including Gn usage time(days),Gn dosage(IU),E2 level of HCG day(pg/m L),P level of HCG day(ng/m L),LH level of HCG day(IU/L),the number of eggs,normal fertilized eggs number,normal fertilization rate,portable embryo number,high-quality embryo number,high-quality embryo rate,positive pregnancy rate,clinical pregnancy rate,pregnancy loss rate,ectopic pregnancy rate,cumulative pregnancy rate.In the experimental study,the three groups’ follicular fluid of HCG day were analysed with targeted metabonomics of MRM method for tryptophan metabolism pathway.Significant differences metabolites were extracted by univariate statistical analysis and clustering analysis method.KEGG pathways was used to annotate and analyse related metabolic pathways.Results: 1.Finally,a total of 89 patients completed the clinical study,including 30 cases in TCM group,29 cases in NON group and 30 cases in CON group.2.The baseline characteristics among the three groups showed there was no significant statistical difference(P>0.05);Compared with NON group and before treatment,the kidney deficiency and blood stasis syndrome in TCM group were all improved significantly(P<0.05).3.That Gn usage time,Gn dosage,E2 and P levels of HCG day were significantly different among the three groups(P<0.05).The E2 and P levels of HCG day in TCM group were significantly higher than those in NON group;The number of portable embryo,high-quality embryo number and high-quality embryo rate in TCM group were significantly higher than those in NON group(P<0.05);There was the increasing trend in the number of eggs in TCM group compared to NON group(P>0.05);The cumulative pregnancy rate was significantly different among the three groups(P<0.05);Compared with NON group,there was the increasing trend in TCM group(P>0.05).4.A total of 85 follicular fluid samples were selected in the experimental study.The results showed that a total of 19 tryptophan metabolites were identified in the three groups.In NON and CON groups’ follicular fluid,six differential metabolites were found.Five metabolites were up-regulated including tryptophan,kynurenate,indole-3-carboxaldehyde,indole-3-acetaldehyde,indole-3-lactic acid;whereas N-formyl-kynurenine was down-regulated.5.We found four differential metabolites after intervention of TCM “Xiaoyi Yusi Decoction”including cinnavalininate,tryptophan,indole-3-carboxaldehyde,3-Hydroxyanthranilic acid,among which tryptophan was expressed adversely in both NON group.CON group and TCM group vs.NON group.KEGG analysis showed that those differential metabolites participate in tryptophan metabolism pathway、glycine,serine and threonine metabolism pathway、phenylalanine,tyrosine and tryptophan biosynthesis pathway 、 purine metabolism pathway.Conclusion:1.TCM “Xiaoyi Yusi Decoction”can effectively improve the clinical symptoms of infertility patients with EMs of Kidney deficiency and blood stasis type and the outcome of IVF treatment.2.Those metabolites relating to inflammation or oxidative stress including tryptophan,kynurenate,indole-3-carboxaldehyde,indole-3-acetaldehyde,indole-3-lactic acid,N-formyl-kynurenine maybe biomarkers of EMs of Kidney deficiency and blood stasis type.Tryptophan may be the main target of TCM “Xiaoyi Yusi Decoction”.In addition to the tryptophan metabolism pathway,the effect of TCM may have some connections with glycine,serine and threonine metabolism、phenylalanine,tyrosine and tryptophan biosynthesis、purine metabolism. |
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