Embryo multinucleation at the two-cell stage is an independent predictor of intracytoplasmic sperm injection outcomes

Transfers of non-multinucleated embryos at the twocell stage improve implantation and birth rates.

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Volume 107, Issue 1, Pages 97-103


Laurent Desch, M.D., Céline Bruno, M.D., Maxime Luu, M.D., Julie Barberet, Pharm.D., Cécile Choux, M.D., Marjorie Lamotte, M.D., Emeline Schmutz, M.D., Paul Sagot, M.D., Patricia Fauque, M.D., Ph.D.



To determine the prognostic impact of the nuclear status at the two-cell stage on intracytoplasmic sperm injection (ICSI) outcomes.


Retrospective study.




Only ICSI cycles with time-lapse monitoring of transferred embryos with known implantation/delivery data from November 2012 to December 2014 were included. A total of 2,449 embryos were assessed for multinucleation rates at the two- and four-cell stage, and 608 transferred embryos were studied for ICSI outcomes.



Main Outcome Measure(s)

Implantation rate (IR) and live birth rate (LBR) according to the number of multinucleated blastomeres at the two-cell stage: none (Without-MNB2cell), one (MNB1/2cell), and two (MNB2/2cell); morphokinetics of MNB2cellembryos.


Embryos with MNB1/2cell led to lower IR (27.7%) and LBR (22.7%) than embryos Without-MNB2cell (33.4% and 29.8%, respectively). The MNB2/2cell embryos led to significantly lower IR (18.3%) and LBR (13.4%) than embryos Without-MNB2cell. This difference remained significant in multivariate analysis for implantation (odds ratio 0.57; 95% confidence interval 0.34–0.94) and birth (odds ratio 0.46; 95% confidence interval 0.26–0.80), independently of the other significant parameters (women's age, time of two-cell formation, and multinucleation at the four-cell stage). Among implanted MNB2cell, if cleavage into four cells occurred later than 37 hours after insemination, embryos were significantly more likely to lead to birth.


The presence of multinucleation at the two-cell stage and more specifically in both blastomeres had a significant negative impact on birth potential. Thus, embryo multinucleation at the two-cell stage should be used as an additional noninvasive criterion for embryo selection.

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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.