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

Reduced intercellular contact in four-cell stage human embryos leads to compromised subsequent development and implantation potential. Implantation rates could be improved by not selecting embryos showing abnormal cleavage patterns.


Yanhe Liu, M.Sc., Vincent Chapple, M.B., B.S., F.R.A.N.Z.C.O.G., Katie Feenan, M.Sc., Peter Roberts, Ph.D., Phillip Matson, Ph.D.

Volume 103, Issue 6, Pages 1485-1491



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.


Retrospective cohort study.


Private IVF center.


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).



Main Outcome Measure(s):

Morphologic score on day 3, embryo morphokinetic parameters, incidence of abnormal biological events, and known implantation results.


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%).


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.

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