Clinical significance of intercellular contact at the four-cell stage of human embryos, and the use of abnormal cleavage patterns to identify embryos with low implantation potential: a time-lapse study

Fertil Steril. 2015 Jun;103(6):1485-91.e1. doi: 10.1016/j.fertnstert.2015.03.017. Epub 2015 Apr 22.


Objective: To investigate the clinical significance of intercellular contact point (ICCP) in four-cell stage human embryos and the effectiveness of morphology and abnormal cleavage patterns in identifying embryos with low implantation potential.

Design: Retrospective cohort study.

Setting: Private IVF center.

Patient(s): A total of 223 consecutive IVF and intracytoplasmic sperm injection treatment cycles, with all resulting embryos cultured in the Embryoscope, and a subset of 207 cycles analyzed for ICCP number where good-quality four-cell embryos were available on day 2 (n = 373 IVF and n = 392 intracytoplasmic sperm injection embryos).

Intervention(s): None.

Main outcome measure(s): Morphologic score on day 3, embryo morphokinetic parameters, incidence of abnormal biological events, and known implantation results.

Result(s): Of 765 good-quality four-cell embryos, 89 (11.6%) failed to achieve six ICCPs; 166 of 765 (21.7%) initially had fewer than six ICCPs but were able to establish six ICCPs before subsequent division. Embryos with fewer than six ICCPs at the end of four-cell stage had a lower implantation rate (5.0% vs. 38.5%), with lower embryology performance in both conventional and morphokinetic assessments, compared with embryos achieving six ICCPs by the end of four-cell stage. Deselecting embryos with poor morphology, direct cleavage, reverse cleavage, and fewer than six ICCPs at the four-cell stage led to a significantly improved implantation rate (33.6% vs. 22.4%).

Conclusion(s): Embryos with fewer than six ICCPs at the end of the four-cell stage show compromised subsequent development and reduced implantation potential. Deselection of embryos with poor morphology and abnormal cleavage revealed via time-lapse imaging could provide the basis of a qualitative algorithm for embryo selection.

Keywords: Embryo; abnormal cleavage; intercellular contact; in vitro fertilization; time lapse.

MeSH terms

  • Adult
  • Cells, Cultured
  • Cleavage Stage, Ovum / cytology*
  • Cleavage Stage, Ovum / physiology
  • Cohort Studies
  • Cytokinesis
  • Embryo Implantation, Delayed / physiology*
  • Embryo Transfer / methods*
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / physiology*
  • Embryonic Development
  • Female
  • Fertilization in Vitro
  • Humans
  • Microscopy / methods*
  • Retrospective Studies
  • Time-Lapse Imaging / methods*