New strategy for diagnosing embryo implantation potential by combining proteomics and time-lapse technologies

Fertil Steril. 2015 Oct;104(4):908-914. doi: 10.1016/j.fertnstert.2015.06.032. Epub 2015 Jul 18.


Objective: To develop a diagnostic tool for embryo implantation potential with the use of proteomic fingerprinting combined with time-lapse morphokinetic analysis.

Design: Retrospective cohort study.

Setting: University-affiliated private in vitro fertilization center.

Patient(s): Seventeen infertile patients undergoing intracytoplasmic sperm injection (ICSI) from our ovum donation program.

Intervention(s): 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.

Main outcome measure(s): 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.

Result(s): 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.

Conclusion(s): 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.

Keywords: Embryo kinetics; IL-6; blastocyst; implantation potential; proteomics; time lapse.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cells, Cultured
  • Embryo Culture Techniques
  • Embryo Implantation*
  • Embryo Transfer / methods
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / pathology
  • Female
  • Humans
  • Infertility, Female / pathology
  • Infertility, Female / therapy
  • Predictive Value of Tests
  • Pregnancy
  • Preimplantation Diagnosis / methods*
  • Prognosis
  • Proteomics / methods*
  • Retrospective Studies
  • Sperm Injections, Intracytoplasmic
  • Time-Lapse Imaging / methods*