Study of nucleation status in the second cell cycle of human embryo and its impact on implantation rate

A retrospective study demonstrates the dynamics of embryo multinucleation in the first cell cycles and its effects on embryo viability.

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Volume 106, Issue 2, Pages 291-299


Jesus Aguilar, Ph.D., Irene Rubio, Ph.D., Elkin Muñoz, M.D., Ph.D., Antonio Pellicer, M.D., Ph.D., Marcos Meseguer, Ph.D.



To study nucleation status in two- and four-cell embryos and its effect on reproductive outcomes.


Retrospective cohort study.


University-affiliated private center.


A total of 1,679 embryos from 940 oocyte donation cycles from May 2012 to May 2014.



Main Outcome Measure(s)

Implantation, morphokinetics, and nucleation status restoration.


Multinucleation was present in 42.53% of embryos with known implantation data at the two-cell stage; it was present in approximately 14% of them at the four-cell stage. In all, 73.4% of the embryos were multinucleated at two cells and restored their nucleation status when they cleaved into four cells. Embryos with blastomeres multinucleated (more than two nuclei) at the four-cell stage showed a lower implantation rate. The average length of S-phase in the first embryo cell cycle in the positive known implantation data (KID+) embryos was longer than in KID− (15.50 hours vs. 14.38 hours) and slightly shorter in the second embryo cell cycle (8.35 hours in KID+ vs. 8.60 hours in KID−).


Multinucleation in two-cell-stage embryos is a frequent event, which is reversible in a high proportion of embryos, without impact on the implantation rate; and embryos with multinucleated blastomeres have a reduced outcome compared with those with binucleated blastomeres when multinucleation is present in four-cell-stage embryos.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.