Limited Implantation Success of Direct Cleaved Human Zygotes A Time Lapse Study

In a multicenter retrospective study, embryos with direct cleavage from two to three cells (5 hours) had a statistically significantly lower implantation rate than embryos with a normal cleavage pattern.

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Irene Rubio, Ph.D., Reidun Kuhlmann, Inge Agerholm, Ph.D., John Kirk, M.D., Javier Herrero, Ph.D., Maria-José Escriba, Ph.D., José Bellver, M.D., Marcos Meseguer, Ph.D.

Volume 98, Issue 6, Pages 1458-1463, December 2012



To evaluate embryos with direct cleavage (≤ 5 hrs) from two to three cells (DC2-3) and correlate this morphokinetic parameter to implantation and ongoing pregnancy.


Clinical multicenter retrospective study.


Private in vitro fertilization centers.


From three clinics, a total of 979 treatments including 5,225 embryos using autologous or donated oocytes, of which 1,659 embryos were transferred.



Main outcome measurements:

Clinical pregnancy confirmed by ultrasound in week 7.


Of the total embryo cohort, 715 (13.7%) underwent direct cleavage from two to three cells, 1659 embryos were transferred to recipients and 109 of the transferred embryos cleaved directly from two to three cells (6.6%). Only one DC2-3 embryo was known to result in a clinical pregnancy (1%) and 80 (73.4%) DC2-3 embryos did not implant. Of the 1550 embryos transferred not showing DC2-3, 203 embryos were from treatments with 100% implantation (13.1%), and 804 (51.8%) embryos did not implant. The known implantation rate of DC2-3 embryos was significantly lower than for embryos with a normal cleavage pattern (1.2% vs. 20.2%, respectively).


Embryos with DC2-3 had a significantly lower implantation rate than embryos with a normal cleavage pattern, suggesting that rejection of these embryos for transfer could improve the implantation rate.

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Fertility and Sterility

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