RESUMO
ObjectiveTo evaluate the effect of Wenshen Yangxue prescription （WSYX） on the outcome of in vitro fertilization-embryo transfer （IVF-ET） in poor ovarian responders and the safety. MethodA total of 116 eligible patients who were admitted to Beijing Obstetrics and Gynecology Hospital in June 2016-June 2019 were randomized into the experimental group and the control group with random number table method （58 in either group）. Conventional controlled ovarian hyperstimulation （COH） was directly implemented in the control group， while the experimental group was intervened with WSYX for 3 menstrual cycles before the COH. The pregnant patients were observed till childbirth and the non-pregnant patients for 12 months. Gonadotropins （Gn） dosage and the days of use were recorded. Serum levels of follicle-stimulating hormone （FSH）， basal FSH （bFSH）， basal luteinizing hormone （bLH）， and basal estrogen （bE2）， endometrial thickness， and antral follicle count （AFC） before and after treatment were measured. The serum levels of estrogen （E2）， progesterone （P）， and luteinizing hormone （LH） on the day of human chorionic gonadotropin （HCG） injection， and levels of FSH， LH， E2， testosterone （T）， and P in follicular fluid 36 h after HCG injection were determined. Number of fertilization， rate of fertilization， number of high-quality embryos， cycle cancellation rate， clinical pregnancy rate， and live birth rate were evaluated. The traditional Chinese medicine （TCM） syndrome scores before and after treatment were recorded. Liver and kidney functions were detected before and after treatment， and adverse reactions during treatment were recorded. ResultCompared with the control group， the experimental group showed the decrease in the days of Gn use and dosage of Gn （P<0.05）， endometrium thickening （P<0.05）， and increase in oocytes obtained， levels of E2 and LH on the day of HCG injection， and ovarian reserve function. Moreover， in follicular fluid 36 h after HCG injection， the reduction in level of FSH （P<0.05）， rise of levels of LH and E2 （P<0.05）， and insignificant changes in levels of T and P in the experimental group were observed as compared with those in the control group. In addition， larger number of fertilization， more available embryos， and higher rate of high-quality embryos were observed in the experimental group than in the control group （P<0.05）. The experimental group demonstrated improvement in quality of oocytes， decrease in cycle cancellation rate ， and increase in clinical pregnancy rate and live birth rate compared with the control group. The TCM syndrome score in experimental group was decreased after treatment compared with that before treatment （P<0.05）. No serious adverse reactions occurred in two groups during treatment and the safety indexes before and after treatment were all within the normal ranges. ConclusionWSYX can reduce the use duration and dosage of Gn in infertile patients receiving IVF-ET， improve the quality of oocytes， increase the rate of high-quality embryos， and improve the pregnancy outcome of IVF-ET patients.
RESUMO
Objective:To explore the effective components， targets， and possible mechanisms of Wenshen Yangxue prescription in improving endometrial receptivity of aged female mice based on network pharmacology and experimental verification. Method:Based on Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM） and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine， the components and targets of Wenshen Yangxue prescription were retrieved， and the targets of ovulatory dysfunctional infertility were collected from the Online Mendelian Inheritance in Man （OMIM） and GeneCards with "anovulatory sterility" and "anovulatory infertility" as keywords. The protein-protein interaction （PPI） network was constructed based on STRING and the core targets of Wenshen Yangxue prescription against ovulatory dysfunctional infertility were screened by Cytoscape， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the core targets in DAVID database. Then， the "medicinal-component-target-pathway" network was established and the core targets were verified by animal experiment. Result:A total of 253 components and 326 targets of Wenshen Yangxue prescription， 819 disease targets， and 74 common targets were screened out. The common targets were mainly involved in the biological processes such as positive regulation of nitric oxide biosynthetic process， positive regulation of cell proliferation， response to estradiol， aging， response to oxidative stress， and angiogenesis. The GO term of response to oxidative stress and five of the top 20 KEGG pathways were analyzed. According to the "medicinal-component-target-biological process/pathway" network， 41 chemical components in 20 medicinals participated in hypoxia inducible factor-1 （HIF-1） signaling pathway， tumor necrosis factor （TNF） signaling pathway， forkhead box O （FOXO） signaling pathway， Toll-like receptor （TLR） signal pathway， and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway by affecting 35 targets. The results of animal experiment showed that the prescription could increase the expression of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， forkhead box O3A （FoxO3A）， and phosphorylated FoxO3A （p-FoxO3A） in uterus of aged female ICR mice. Conclusion:Wenshen Yangxue prescription interferes with oxidative stress and PI3K/Akt/FoxO3A signaling pathway by influencing Akt1， dual oxidase 2 （DUOX2）， epidermal growth factor receptor （EGFR）， heme oxygenase-1 （HMOX1）， myeloperoxidase （MPO）， and other targets， thereby improving endometrial receptivity of aged female mice.