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. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.