Metabonomics Study on the Infertility Treated With Zishen Yutai Pills Combined With In Vitro Fertilization-embryo Transfer

Abstract

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, “Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial.” Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.

Metabolomic Analysis Reveals Association between Decreased Ovarian Reserve and In Vitro Fertilization Outcomes

“…Previous studies have shown that PUFA oxidation is an important energy source for oocyte maturation and division [ 52 , 55 , 56 ]. However, excessive PUFA oxidation can increase the level of reactive oxygen species (ROS), leading to dysfunction in the mitochondria and endoplasmic reticulum, ultimately impairing oocyte development [ 57 , 58 , 59 , 60 ]. The up-regulation of the three PUFA-related metabolic pathways suggests that DOR patients may experience more severe oxidative stress damage.…”

Effects of the Zishen Yutai Pill Compared With Placebo on Live Births Among Women in a Fresh Embryo Transfer Cycle

“…13 Metabonomic study also indicated the potential of the Zishen Yutai Pill in improving endometrial receptivity and oocytes quality. 15 It can be hypothesized that the Zishen Yutai Pill can maintain proper endometrial differentiation, improve uterine receptivity and oocytes quality, thus resulting in an elevation of implantation rates.…”

“…These metabolites may be involved in proliferation of endometrium, regulation of oxidative stress and lipid metabolism, and thus lead to improvements in endometrial receptivity and oocyte quality. 15 Clinically, a previous report demonstrates that using the Zishen Yutai Pill in luteal phase could improve pregnancy outcomes among patients undergoing in vitro fertilization-embryo transfer (IVF-ET). 16 However, the efficacy and safety of the Zishen Yutai Pill have not been demonstrated in any multicenter randomized controlled trial (RCT) among patients with infertility undergoing IVF or intracytoplasmic sperm injection (ICSI).…”

The Application of Complementary and Alternative Medicine in Polycystic Ovary Syndrome Infertility

“…In a double-blind, multicenter placebo, RCT with a sample size of 2265, administration of ZYP to infertile women undergoing IVF significantly increased the live birth rate compared to placebo before and after ovarian stimulation and ET (26.8% vs. 23.0% (rate ratio [RR], 1.16; 95% CI 1.01-1.34; P � .038) [46]. A metabolomic study suggested that ZYP may be involved in the regulation of endometrial proliferation, OS, and lipid metabolism, thus improving endometrial tolerance and oocyte quality and ultimately enhancing IVF live birth rates [140].…”