title: Noninvasive metabolomic profiling of embryo culture media using Raman and near-infrared spectroscopy correlates with reproductive potential of embryos in women undergoing in vitro fertilization.
abstract: OBJECTIVE
  To determine if metabolomic profiling of embryo culture media correlates with reproductive potential of individual embryos.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  An academic and a private assisted reproduction program; a university research center.
  
  
  METHODS
  Women undergoing assisted reproduction treatment.
  
  
  METHODS
  Sixty-nine spent media samples from 30 patients with known outcome (0 or 100% sustained implantation rates) were individually collected after embryo transfer on day 3 and were evaluated using Raman and/or near-infrared spectroscopy. The spectra obtained from each instrument were separately analyzed using a wavelength selective genetic algorithm to determine regions predictive of pregnancy outcome. Viability indices reflective of reproductive potential were calculated for each sample. To avoid random correlations, a leave-one-out cross-validation was used. Sensitivity and specificity of predicting viability (described as implantation and delivery) were calculated.
  
  
  METHODS
  Metabolomic profile of culture media and embryo viability.
  
  
  RESULTS
  Viability indices calculated by Raman or near-infrared spectroscopy were higher for embryos that implanted and resulted in a delivery, compared with those that failed to implant. Raman spectroscopy predicted viability of individual embryos with a sensitivity of 86% and a specificity of 76.5%; near-infrared provided a sensitivity of 75% and a specificity of 83.3%.
  
  
  CONCLUSIONS
  Rapid, noninvasive metabolomic profiling of human embryo culture media using Raman or near-infrared spectroscopy combined with bioinformatics correlates with pregnancy outcome.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA. emre.seli@yale.edu
authors.forename: Emre
authors.initials: E
authors.lastname: Seli
authors.forename: Denny
authors.initials: D
authors.lastname: Sakkas
authors.forename: Richard
authors.initials: R
authors.lastname: Scott
authors.forename: Shing C
authors.initials: SC
authors.lastname: Kwok
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rosendahl
authors.forename: David H
authors.initials: DH
authors.lastname: Burns
mesh_terms: D003470:Culture Media / Q000032:analysis / Q000378:metabolism*; D046149:Embryo Culture Techniques; D004624:Embryo Transfer / Q000379:methods*; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D006801:Humans; D054315:Oocyte Retrieval / Q000379:methods; D011446:Prospective Studies; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013059:Spectrum Analysis, Raman / Q000379:methods*
chemical_list: D003470:Culture Media