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Background  Human follicular fluid (FF) is a unique biological fluid in which the oocyte develops in vivo, and presents an optimal source for non-invasive biochemical predictors. Oocyte quality directly influences the embryo development and hence, may be used as a predictor of embryo quality. Peptide profiling of FF and its potential use as a biomarker for oocyte quality has never been reported.    Methods  This study screened FF for peptide biomarkers that predict the outcome of in vitro fertilization (IVF). Potential biomarkers were discovered by investigating 2 training datasets, consisting both of 17 samples and validating on an independent experiment containing 32 samples. Peptide profiles were acquired by nano-scale liquid chromatography coupled to tandem mass spectrometry (nano LC-MS/MS).    Results  From the training datasets 53 peptides were found as potential biomarker candidates, predicting the fertilization outcome of 24 out of the 32 validation samples blindly (81.3% sensitivity, 68.8% specificity, AUC = 0.86). Seven potential biomarker peptides were identified. They were derived from: insulin-like growth factor binding protein-5, alpha-2-antiplasmin, complement component 3, inter-alpha-trypsin inhibitor heavy chain H1, serum albumin, protein diaphanous homolog 1 and plastin-3.    Conclusions  The MS-based comprehensive peptidomic approach carried out in this study, established a novel panel of potential biomarkers that present a promising predictive accuracy rate in fertilization outcome, and indicates FF as an interesting biomarker resource to improve IVF clinic routine.    Electronic supplementary material  The online version of this article (doi:10.1186/s12953-016-0106-9) contains supplementary material, which is available to authorized users.

Follicular fluid biomarkers for human in vitro fertilization outcome: Proof of principle