title: Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome.
abstract: OBJECTIVE
  To investigate the prevalence, developmental potential, chromosomal constitution and clinical outcome of embryos with direct unequal cleavages (DUC).
  
  
  METHODS
  A retrospective observational study.
  
  
  METHODS
  Academic Institution.
  
  
  METHODS
  21,261 embryos from 3,155 cycles cultured in EmbryoScope®.
  
  
  RESULTS
  The total incidence of DUCs per embryo occupying the first three cleavages were 26.1%. Depending of the cell stage, DUC rate was 9.8% at first cleavage (DUC-1), 9.1% at second cleavage (DUC-2), and 3.7% at third cleavage (DUC-3) with 3.6% of embryos exhibiting multiple DUCs (DUC-Plus). The occurrence of DUCs was not correlated with female gamete age or source. The incidence of DUC-1 was significantly higher in embryos fertilized by epididymal and testicular sperm (13.6% and 11.4%, respectively) compared to ejaculated sperm (9.1%, all p<0.05). The total incidences of DUCs were strongly correlated with the onset of blastomere multinucleation (MNB) during the first three divisions. In MNB embryos, DUCs incidence are two to three times more likely to develop when compared to non-MNB embryos (OR = 3.11, 95% CI [2.64, 3.67] at 1-cell stage, OR = 2.64, 95% CI [2.39, 2.91] at 2-cell stage and OR = 2.51, 95% CI [1.84, 3.43] at 4-cell stage). The blastocyst formation rates gradually decreased from 61.0% in non-DUC to 40.2% in DUC-3, 18.8% in DUC-2, 8.2% in DUC-1 and 5.6% in multiple DUC embryos (DUC-Plus). The known implantation rates (FH) for day 3 (D3) transfers were 12.42% (n = 3172) in Non-DUC embryos, 6.3% (n = 127) in DUC-3, and 2.7% (n = 260) in DUC-2 embryos. No live births resulted from either DUC-1 (n = 225) or DUC-Plus (n = 100) embryo transfers. For blastocyst transfers, lower implantation rates (33.3%) but similar live birth (LB) rates (40%) were observed if DUC blastocysts were transferred. Comparatively rates in Non-DUC blastocyst were 45.2% and 34.8%, respectively. The euploid rate gradually increased from DUC-1, -2, -3 to Non-DUC (13.3%, 19.5%, 33.3%, 45.6%, p<0.001) for D3 biopsied embryos. Interestingly, the trend of decreased euploidy disappeared in DUC D5/6 biopsied embryos and similar rates were exemplified in DUC (D5 56.3%, D6 35.6%) vs. non-DUC (D5 51.4%, D6 33.8%) embryos.
  
  
  CONCLUSIONS
  Blastocyst formation, implantation potential and euploid rate were significantly reduced in DUC embryos. DUC embryos should be deselected for D3 transfers, but should be culture to blastocyst stage for possible ET.
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Qiansheng
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Clarke
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Zev
authors.initials: Z
authors.lastname: Rosenwaks
authors.affiliation: Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medicine, New York, New York, United States of America.
authors.forename: Nikica
authors.initials: N
authors.lastname: Zaninovic
mesh_terms: D000328:Adult; D001755:Blastocyst; D001757:Blastomeres / Q000378:metabolism; D002970:Cleavage Stage, Ovum / Q000378:metabolism / Q000473:pathology*; D004624:Embryo Transfer; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D050498:Live Birth; D008297:Male; D009865:Oocytes / Q000254:growth & development*; D011247:Pregnancy; D018873:Pregnancy Rate; D020554:Sperm Injections, Intracytoplasmic