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• W2796711823 abstract "The title of this commentary tries to commit to memory the popular sentence from Shakespeare, that even those who are not native English speakers, like us, know very well; “to be, or not to be, that is the question”. What are the big questions in embryology today? Should more genetic screening be offered? Well, at least for us (the authors of this commentary) we are in front of two options: increase the number of cases in which pre-implantation genetic screening (PGS) is offered to our patients or offer an alternative, in those cases without a clinical indication, by noninvasive continuous embryo monitoring. The first option is extremely popular between the clinics and patients in North America, even offered for those cycles of oocyte donation, in which the indication could be questionable. But, the situation in Europe is completely different; it is quite difficult for an oocyte donation cycle to be accepted for PGS. Here, the clinical indications are probably stricter and maybe the costs are taken into consideration more as the public resources, which finance an important proportion of the cycles, are limited and in consequence are not able to afford such huge costs linked with trophoectoderm biopsy, additional blastocyst vitrification, and chromosomal analysis. And what about the second choice? It is definitely more popular in Europe than North America. Time-lapse microscopy (TLM) unquestionably made life in the laboratory more comfortable, apparently even for the embryo, but mostly for the embryologist. However, it did not make things more comfortable for the clinicians that may not understand its outstanding contribution to embryology. At the present time, we face opposition from those completely against TLM, gynecologists and embryologists that have never used this technology, with absolutely no idea of its applications, daily routine work, or clinical experience. Instead their opinions are based on a few words read in some of the latter reviews or meta-analyses. Maybe this affirmation is exaggerated, but anyone without experience and only a small number of concepts taken from the scientific literature cannot become an opinion leader of any technology or specialty and even more make decisions related to groups of clinics or national societies. Then, what else can experts do? We can keep working hard and provide more convincing data. We may be partially agreed in affirming that TLM remained in search of an indication. In the last few years, many authors decided to investigate whether application of TLM reveals new algorithms related with embryo selection. This research started with a deep analysis of the fertilization process moving forward to the cleavage stage, including multinucleation, symmetry or synchrony, being those potentially able to predict embryo quality at latter stages of development. But even more, the analysis of the final steps of development (blastulation) may reveal important features that could condition the outcome as collapse, expansion, inner cell mass diameter or even final blastocyst diameter. A great reply to the question in this commentary comes from the work published by Desai et al. this month's Fertility and Sterility (1Desai N. Goldberg J.M. Austin C. Falcone T. Are cleavage anomalies, multinucleation or specific cell cycle kinetics observed with time lapse imaging predictive of embryo developmental capacity or ploidy?.Fertil Steril. 2018; 109: 665-674Abstract Full Text Full Text PDF Scopus (66) Google Scholar). Excellent science will always come from the Cleveland group from which we have become used to reading high quality scientific papers related to TLM technology. The authors determined if cleavage anomalies, multinucleation and specific cellular kinetic parameters available from TLM imaging were predictive of developmental capacity or blastocyst chromosomal status. The study is a retrospective analysis of prospectively collected data. The sample size is quite important, close to 1500 zygotes and over 700 blastocysts with Trophectoderm biopsy with an euploidy proportion over 40% (which reveals a population with low incidence of chromosomal abnormalities and a wide indication). Surprisingly, individual dysmorphisms such as multinucleation, reverse cleavage, irregular chaotic division, or direct uneven cleavage were not associated with aneuploidy, but this may be due to direct uneven cleavage and irregular chaotic division embryos exhibiting lower developmental potential as has been extensively described before (2Zhan Q. Ye Z. Clarke R. Rosenwaks Z. Zaninovic N. Direct unequal cleavages: embryo developmental competence, genetic constitution and clinical outcome.PLoS One. 2016; 11: e0166398Crossref PubMed Scopus (69) Google Scholar). Interestingly. the presence of two or more dysmorphisms was associated with an overall lower euploidy rate close to 15%. The most relevant data extracted from the Desai et al. (1Desai N. Goldberg J.M. Austin C. Falcone T. Are cleavage anomalies, multinucleation or specific cell cycle kinetics observed with time lapse imaging predictive of embryo developmental capacity or ploidy?.Fertil Steril. 2018; 109: 665-674Abstract Full Text Full Text PDF Scopus (66) Google Scholar) paper is that chromosomal status was correlated significantly with start time of blastulation, expansion, and the start time of blastulation-expansion interval with differences again, around 15%. The relevance of these results in the actual context can be recapitulated by the following points. In contrast with the view of many non-expert opinion leaders, morphokinetics and more specifically timing of the main important events of embryo development are objective markers of quality and optimal ranges may help in embryo selection. Recent studies reflect that TLM, although not a substitute for a clinical indication of PGS (advanced maternal age, repeated implantation failure, and recurrent miscarriage) may help reduce the risk of transferring an aneuploid embryo (3Carmen Nogales M. Bronet F. Basile N. Martínez E.M. Liñán A. Rodrigo L. et al.Type of chromosome abnormality affects embryo morphology dynamics.Fertil Steril. 2018; 107: 229-235Abstract Full Text Full Text PDF Scopus (53) Google Scholar). It should be noted that this study is moving forward previous studies on the relationship between euploidy and morphokinetics in which the biopsy was performed on cleavage rather than blastocyst stage embryos (4Basile N. Nogales Mdel C. Bronet F. Florensa M. Riqueiros M. Rodrigo L. et al.Increasing the probability of selecting chromosomally normal embryos by time-lapse morphokinetics analysis.Fertil Steril. 2014; 101: 699-704Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar). We now appreciate that early kinetic markers were not as predictive of normal chromosomal content when blastulation is analyzed as most of the early parameters are related with the ability to initiate blastulation and form expanded blastocysts. This is bringing us to a new era of TLM research in which extended time in culture can itself serve to deselect many aneuploid embryos by late parameter analysis. We must take into consideration the conflicting data from the publications reported until now. They were coming from different laboratories, and serve to emphasize the fact that many patient and laboratory variables affect embryo kinetics. Selection algorithms may require extensive testing by different laboratories and in-house refinement, a new question that remains to be elucidated. The authors also pointed out the need for prospective validation studies with day 5/6 blastocysts selected for transfer based on kinetic endpoints, but, those studies are extremely difficult to be undertaken. Cost, patient recruiting, and ethical issues are hurdles in front of a researcher seeking answers to the big questions concerning TLM and reproductive medicine. Finally, the most important issue is the big difference in the use of PGS around the world. Many aspects are affecting this: our regulatory topics, the economic environment, the patient acceptance of the technique (influenced by social, political and religious issues), and finally the availability of laboratory resources and experienced embryologists. Then, answering our own question, to invade or to observe, why not both? Are all the questions related with viability linked with chromosome content? We may know the chances of implantation of an euploid embryo by analyzing their morphokinetics. In an environment of increased PGS demand, in which more euploid embryos will become suitable for transfer, TLM will provide more chances to select the perfect euploid blastocyst. Are cleavage anomalies, multinucleation, or specific cell cycle kinetics observed with time-lapse imaging predictive of embryo developmental capacity or ploidy?Fertility and SterilityVol. 109Issue 4PreviewTo determine whether cleavage anomalies, multinucleation, and specific cellular kinetic parameters available from time-lapse imaging are predictive of developmental capacity or blastocyst chromosomal status. Full-Text PDF Open Access" @default.
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• W2796711823 title "To invade, or to observe, that is the question" @default.
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