LETTER TO THE EDITOR REPLY OF THE AUTHORS: Despite the promise of the ‘‘omic’’ approach in embryo selection, its actual use on a daily basis is still impending. Therefore, we embryologists need to rely on other noninvasive alternatives mainly focused on embryo morphology, which is the unique, tangible, and noninvasive tool for selecting embryos in IVF, and the search for new phenotypes that help to select the best embryos for transfer. More than 10 years ago, early cleavage (EC) was considered to be the warrant of promising phenotypes associated with both embryo quality and live birth (1), but it required performing additional embryo assessments at the time that the first mitotic division was expected to occur, requiring additional removals of the embryos from the incubators at a delicate time of the cellular cycle comprising G2 and mitosis phases. EC has been associated with embryo quality and implantation rates; however, the benefit of checking for EC is not sufficiently clear. As a matter of fact, the Istanbul Consensus Group leaves to the laboratory the decision of whether or not to include the EC variable in embryo selection (2). In our prospective multicenter study, we saw that selecting embryos by morphology (number of blastomeres, symmetry, fragmentation, multinucleation, etc.) on day 2 or 3 is actually a better model for implantation than EC. Most of the embryos that undergo mitosis at 25–27 hours after insemination are actually embryos with a good morphology on day 2 or day 3, in both egg donation cycles and cases with own oocytes. Therefore, observing EC does not add any benefit at all and actually may add more laboratory workload and more distortion to the embryo culture conditions. Considering the era of time-lapse technology, when it is easier to combine an enormous variety of morphologic

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assessments with specific kinetic parameters throughout the entire embryo development, revisiting an old parameter such as EC may be meaningless. Time-lapse technology gives us a universe of information to explore and the possibility to build new algorithms without disturbing embryo culture conditions. Interestingly, though, many of the algorithms do not find EC to be a strong predicting embryo phenotype for implantation, which agrees with the perspective we defend in this letter (3). When the time comes that this technology is accessible to all IVF laboratories, this suggestion could be helpful and should be taken into account. In response to the question of whether EC should be assessed in routine practice, I would say that there is no need to do the same job twice. Looking at day 3 embryo morphology would be sufficient for selecting embryos for cleavage-stage embryo transfers. Maria Jose de los Santos, Ph.D. IVF Laboratory, IVI Valencia, Valencia, Spain February 27, 2014 http://dx.doi.org/10.1016/j.fertnstert.2014.02.053

REFERENCES 1. 2.

3.

Lundin K, Bergh C, Hardarson T. Early embryo cleavage is a strong indicator of embryo quality in human IVF. Hum Reprod 2001;16:2652–7. Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod 2011;26:1270–83. Meseguer M, Herrero J, Tejera A, Hilligsoe KM, Ramsing NB, Remohi J. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod 2011;26:2658–71.

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