Study On The Mechanism Of Bu-Shen-Huo-Xue Recipe In Treating Repeated Implantation Failure Based On Metabolomics

Background:In recent years,the increasing maturity of assisted fertility technology has brought great benefits to infertility patients and significantly increased their clinical pregnancy rate,especially for women under 35 years old.However,there are still some patients with multiple embryo transfer failures,which are seriously harmful to their physical and mental health and brings great financial burden on their couples.In clinical practice,its treatment is mainly based on improving the uterine cavity environment through hysteroscopic operations,regulating maternal immunity with immune preparations,alleviating maternal hypercoagulability with small doses of anti-platelet aggregation drugs,and improving embryo quality with laboratory techniques.However,its related treatments have different degrees of side effects,such as the appearance of subcutaneous hard nodules,affecting liver and kidney functions,and some operations are relatively expensive.However,under the academic thought of "the kidney collects the essence and is the master of reproduction",Traditional Chinese medicine has achieved certain efficacy in the treatment of Repeated Implantation Failure(RIF)by tonifying the kidney and invigorating the blood.Objective:Based on the previous clinical observation that Bu-Shen-Huo-Xue Recipe(BSHXR)was effective in treating multiple embryo implantation failures,this study further investigated the mechanism of BSHXR in treating RIF based on non-targeted metabonomics.Methods:1.Forty patients with RIF who met the inclusion criteria were divided into two groups,the Western medicine group(the pre group)was treated with western medicine(aspirin enteric soluble tablet 25mg/tablet,one tablet once,three times a day,and prednisone tablet 5mg/tablet,one tablet once,once a day),and the Chinese medicine + Western medicine group(the post group)was treated with western medicine combined with BSHXR.In both groups,the intervention was started one week before the next transfer after repeated failed embryo transfers,and the medication was administered until 1 month after the transfer and ultrasound indicated:early intrauterine pregnancy.Another twenty normal pregnant women without abortion history were selected as the normal group(the control group).2.General information on all subjects participating in the experiment was recorded in detail,including age,BMI,and number of failed transfers.3.The serum were collected from three groups of patients and metabolites in each group were detected through HILIC-UPLC-Q-TOF/MS technique.The differential metabolites were selected using a combination of multidimensional and unidimensional statistical analysis.The STEM algorithm was used to perform trend clustering analysis on the differential metabolites among the three groups,and the obtained differential metabolites were imported into KEGG online database for metabolic pathway analysis,which was used to investigate the metabolites and metabolic pathways associated with RIF treated with BSHXR.Results:1.A total of 61 potential biomarkers were screened between the post and pre groups,mainly focusing on the significant changes of lipids,amino acids and bile acids.2.Trend cluster analysis showed that the control group was taken as the reference standard of metabolite expression,and the metabolites with the same baseline level between the post and control groups,and significant difference from the pre group,that is,the metabolite expression reached the normal level after treatment with traditional Chinese medicine,were found to be mainly concentrated in lipids,amino acids and bile acids.3.Four major metabolic pathways were detected between the post and pre groups,including Bile acid anabolic pathway,Glycerophospholipid metabolism pathway,Linoleic acid metabolic pathway and Protein digestion and absorption pathway.Conclusion:BSHXR can effectively call back some serum lipids,amino acids and bile acid metabolites in patients with RIF.It is preliminarily considered that the mechanism of BSHXR in intervening RIF may be related to the regulation of some metabolic disorders.