title: Noninvasive metabolomic profiling of human embryo culture media using Raman spectroscopy predicts embryonic reproductive potential: a prospective blinded pilot study.
abstract: OBJECTIVE
  To determine if metabolomic profiling of embryonic development was associated with implantation rates in IVF.
  
  
  METHODS
  Prospective blinded.
  
  
  METHODS
  University-affiliated assisted reproductive technology program.
  
  
  METHODS
  Unselected assisted reproductive technology population.
  
  
  METHODS
  None.
  
  
  METHODS
  Raman-based biospectroscopic metabolomic profiling of spent culture media and delivery rates.
  
  
  RESULTS
  Forty-one spent media samples from 19 patients with known reproductive potential (0 or 100% delivery rates of each embryo that implanted) were evaluated. Raman-based metabolomic profiling was used to calculate a viability index for each sample. On day 3, the spent media of embryos with proven reproductive potential (n = 33) demonstrated higher viability indices (0.875 +/- 0.12) than those that failed to implant (0.56 +/- 0.09). Similar findings were present in spent media from embryos transferred on day 5 (n = 8) (-0.40 +/- -0.21 vs. -0.81 +/- -0.08). Receiver operating characteristic curve analyses were used to select thresholds with the greatest ability to discriminate outcomes. Overall diagnostic accuracy for predicting delivery or a failed implantation was 80.5%.
  
  
  CONCLUSIONS
  There is a clear relationship between the reproductive potential of human embryos and their modification of their culture media as detected by Raman biospectroscopy-based metabolomic profiling. This technology offers great potential for development as a tool to allow rapid noninvasive assessment of embryonic reproductive potential before transfer.
authors.affiliation: Reproductive Medicine Associates of New Jersey, Morristown, New Jersey, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Scott
authors.forename: Emre
authors.initials: E
authors.lastname: Seli
authors.forename: Kathy
authors.initials: K
authors.lastname: Miller
authors.forename: Denny
authors.initials: D
authors.lastname: Sakkas
authors.forename: Katherine
authors.initials: K
authors.lastname: Scott
authors.forename: David H
authors.initials: DH
authors.lastname: Burns
mesh_terms: D016022:Case-Control Studies; D003470:Culture Media / Q000378:metabolism*; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011247:Pregnancy; D018873:Pregnancy Rate; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D013059:Spectrum Analysis, Raman; D013997:Time Factors
chemical_list: D003470:Culture Media