title: New strategy for diagnosing embryo implantation potential by combining proteomics and time-lapse technologies.
abstract: OBJECTIVE
  To develop a diagnostic tool for embryo implantation potential with the use of proteomic fingerprinting combined with time-lapse morphokinetic analysis.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  University-affiliated private in vitro fertilization center.
  
  
  METHODS
  Seventeen infertile patients undergoing intracytoplasmic sperm injection (ICSI) from our ovum donation program.
  
  
  METHODS
  No patient intervention. We examined morphokinetic data and proteomic data from the spent media of 16 embryos that implanted and 12 embryos that did not implant.
  
  
  METHODS
  We analyzed seven proteins in the embryo spent media-SCF, TNFR1, PIGF-1, IFN-α2, IL-6, CXCL13, and GM-CSF-with the use of a bead-based multiplexing technology and combined this data with the exact timing (in hours) of cell cycle duration (cc2), blastomere synchrony (s2), and 5-blastomere cleavage (t5) with the use of an incubator equipped with time-lapse videography.
  
  
  RESULTS
  Logistic regression analysis with the use of the forward-step likelihood selection method revealed that the presence/absence of interleukin (IL) 6 and the duration of cc2 were the most relevant embryo features for embryo selection. We combined these two parameters to obtain a hierarchic model that established four categories (A/B/C/D), based on the presence of IL-6 and a cc2 range of 5-12 hours. A direct relationship was observed between the morphologic categories and implantation rates: Those with the presence of IL-6 and 5-12 h cc2 had significantly higher implantation rates.
  
  
  CONCLUSIONS
  The strategy we report here combines time-lapse and proteome analysis to improve embryo selection while minimizing handling and monitoring by the embryologist. Our results describe the utility of a combined biochemical/morphokinetic approach to select embryos for transfer according to their implantation potential. Clinical validation with larger sample sizes is mandatory to confirm the effectiveness of this initial study.
authors.affiliation: Fundacion Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain; INCLIVA Biomedical Research Institute, Valencia, Spain INCLIVA, Valencia, Spain. Electronic address: francisco.dominguez@ivi.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Dominguez
authors.affiliation: INCLIVA Biomedical Research Institute, Valencia, Spain INCLIVA, Valencia, Spain; IVI Valencia, Valencia, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Meseguer
authors.affiliation: IVI Valencia, Valencia, Spain.
authors.forename: Belen
authors.initials: B
authors.lastname: Aparicio-Ruiz
authors.affiliation: IVI Valencia, Valencia, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Piqueras
authors.affiliation: Fundacion Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Quiñonero
authors.affiliation: Fundacion Instituto Valenciano de Infertilidad (FIVI), Instituto Universitario IVI (IUIVI), Valencia, Spain; INCLIVA Biomedical Research Institute, Valencia, Spain INCLIVA, Valencia, Spain; IVI Valencia, Valencia, Spain; Department of Obstetrics and Gynecology, Stanford University, Stanford, California.
authors.forename: Carlos
authors.initials: C
authors.lastname: Simón
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D004624:Embryo Transfer / Q000379:methods; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D012189:Retrospective Studies; D020554:Sperm Injections, Intracytoplasmic; D059008:Time-Lapse Imaging / Q000379:methods*
keywords: Embryo kinetics; IL-6; blastocyst; implantation potential; proteomics; time lapse