Serum Metabolomic Signature Predicts Ovarian Response to Controlled Stimulation

Abstract Introduction In in vitro fertilization (IVF) cycles, some patients fail to adequately respond to ovarian stimulation. Finding novel biomarkers predicting ovarian response in advance would be meaningful.Objective To identify serum metabolomics predicting the growth of follicles after controlled ovarian stimulation (COS).Methods Blood samples were collected at the start of pituitary downregulation and on the fifth day after controlled ovarian stimulation. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods were used to quantify metabolites. Demographic data were calculated with SPSS version 22.0 software. Multivariate statistics were used to analyze metabolomics dataset. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic model.Results The number of retrieved oocytes was higher in the group of Follicle-to-oocyte index (FOI) ≥ 1 group. Analyses revealed 50 different metabolomics between the pre- and post- COS groups. Compared with baseline, amino acids increased significantly following COS. At baseline, acetylglycine was more abundant in the FOI <1 group, while glycine and lipids were more abundant in the FOI ≥1 group. After COS, glycine, N-acetyl-L-alanine, D-alanine, and 2-aminomuconic acid were increased in those with FOI ≥1, but L-glutamine was increased in those with FOI <1. ROC curves indicated that the combination of glycine, acetylglycine and lipids predicts different responses to controlled ovarian stimulation (AUC =0.866).Conclusion Serum metabolism might reflect the response to ovarian stimulation. Higher glycine and PC may be a good predictor for response to COS.