title: Discovery of biomarkers of endometrial receptivity through a minimally invasive approach: a validation study with implications for assisted reproduction.
abstract: OBJECTIVE
  To determine whether a minimally invasive approach to sampling endometrial cells that can be applied during an active conception cycle can generate robust biomarker candidates for endometrial receptivity by genomewide gene expression profiling.
  
  
  METHODS
  Longitudinal study comparing gene expression profiles of cells isolated from uterine aspirates collected during the prereceptive and receptive phases of a natural cycle.
  
  
  METHODS
  University-affiliated hospital.
  
  
  METHODS
  Healthy volunteers, ≤40 years of age, with regular menstrual cycles and no history of infertility.
  
  
  METHODS
  One menstrual cycle monitored with urinary kits to identify the luteinizing hormone (LH) surge; uterine aspirations collected at LH + 2 days (LH + 2) and at LH + 7; endometrial biopsy obtained on LH + 7; RNA extraction from the cellular material for gene expression profiling, and differential gene expression validated by NanoString assay and cross-validated against a publically available data set.
  
  
  METHODS
  Differentially expressed genes between LH + 2 and LH + 7 samples.
  
  
  RESULTS
  NanoString assay validated 96% of the 245 genes found differentially expressed at LH + 7. Unsupervised hierarchical clustering of aspiration and biopsy samples demonstrated the concordance of the sampling methods. A predictor gene cassette derived by a shrunken centroid class prediction technique correctly classified the receptive phase within an external data set.
  
  
  CONCLUSIONS
  Uterine aspiration, which can be performed during an active conception cycle, identified robust candidate biomarkers of endometrial receptivity, and will enable their validation by direct correlation with clinical outcomes.
authors.affiliation: Department of Obstetrics and Gynaecology University of Toronto, Toronto, Ontario, Canada. cryssie.chan@mail.utoronto.ca
authors.forename: Crystal
authors.initials: C
authors.lastname: Chan
authors.forename: Carl
authors.initials: C
authors.lastname: Virtanen
authors.forename: Neil A
authors.initials: NA
authors.lastname: Winegarden
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Colgan
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Brown
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Greenblatt
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001707:Biopsy, Needle / Q000379:methods; D010064:Embryo Implantation / Q000235:genetics*; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008137:Longitudinal Studies; D046228:Microarray Analysis; D019060:Minimally Invasive Surgical Procedures; D011247:Pregnancy; D027724:Reproductive Techniques, Assisted; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers
keywords: Endometrium; gene expression profiling; implantation; menstrual cycle; uterine aspiration