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.
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.


METHODS
Retrospective cohort study.


METHODS
Private IVF center.


METHODS
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).


METHODS
None.


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


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%).


CONCLUSIONS
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.
Fertility North, Joondalup Private Hospital, Joondalup, Western Australia, Australia; School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia. Electronic address: yanhe.liu@fertilitynorth.com.au.
Yanhe
Y
Liu
Fertility North, Joondalup Private Hospital, Joondalup, Western Australia, Australia.
Vincent
V
Chapple
Fertility North, Joondalup Private Hospital, Joondalup, Western Australia, Australia.
Katie
K
Feenan
School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
Peter
P
Roberts
Fertility North, Joondalup Private Hospital, Joondalup, Western Australia, Australia; School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
Phillip
P
Matson
D000328:Adult; D002478:Cells, Cultured; D002970:Cleavage Stage, Ovum / Q000166:cytology* / Q000502:physiology; D015331:Cohort Studies; D048749:Cytokinesis; D010065:Embryo Implantation, Delayed / Q000502:physiology*; D004624:Embryo Transfer / Q000379:methods*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000502:physiology*; D047108:Embryonic Development; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D008853:Microscopy / Q000379:methods*; D012189:Retrospective Studies; D059008:Time-Lapse Imaging / Q000379:methods*
Embryo; abnormal cleavage; intercellular contact; in vitro fertilization; time lapse