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Deconstructing the myth of poor prognosis for fast-cleaving embryos on day 3. Is it time to change the consensus?

  • Assisted Reproduction Technologies
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To determine the developmental competence of fast-cleaving D3 embryos.

Methods

Retrospective study including 4028 embryos from 513 PGT-A cycles performed between July 2014 and June 2017. Embryos were cultured in time-lapse incubators and biopsied at blastocyst stage. Embryos were classified in groups according to the number of cells on D3 (from 2-cell to ≥13 -cell and compacted). A generalized linear mixed model adjusted for confounding factors was performed to assess the chance to give rise to an euploid blastocyst in each group compared with the chance of 8-cell embryos. Implantation and live birth rates were also analyzed.

Results

The statistical analysis showed that embryos with 9 to 11 cells had a slightly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.77 (0.61–0.96)) while embryos with more than 11 cells were found to be just as likely to give rise to an euploid blastocyst as the 8-cell embryos (OR (95% CI) 1.20 (0.92–1.56)). Conversely, slow-cleaving embryos had a significantly lower euploid blastocyst rate than 8-cell embryos (OR (95% CI) 0.31 (0.24–0.39)). Moreover, euploid blastocysts derived from fast-cleaving embryos and from 8-cell embryos exhibit similar live birth rates. No significant differences were found in the chance to give rise a live birth between 8-cell and 9- to 11-cell embryos (OR (95% CI) 1.23 (0.70–2.15)) and > 11-cell embryos (OR (95% CI) 1.09 (0.57–2.09)).

Conclusions

Embryos with more than 11 cells exhibit similar developmental competence to 8-cell embryos. Their poor prognosis should be reconsidered.

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References

  1. Racowsky C, Jackson KV, Cekleniak NA, Fox JH, Hornstein MD, Ginsburg ES. The number of eight-cell embryos is a key determinant for selecting day 3 or day 5 transfer. Fertil Steril. 2000;73:558–64.

    Article  CAS  Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. Cuevas Saiz I, Pons Gatell MC, Cuadros Vargas M, Delgado Mendive A, Rives Enedáguila N, Moragas Solanes M, et al. The embryology interest group: updating ASEBIR’s morphological scoring system for early embryos, morulae and blastocysts. Med Reprod Embriol Clín. 2018;5:42–54.

    Google Scholar 

  4. Racowsky C, Stern JE, Gibbons WE, Behr B, Pomeroy KO, Biggers JD. National collection of embryo morphology data into Society for Assisted Reproductive Technology Clinic Outcomes Reporting System: associations among day 3 cell number, fragmentation and blastomere asymmetry, and live birth rate. Fertil Steril. 2011;95:1985–9.

    Article  Google Scholar 

  5. Shapiro BS, Harris DC, Richter KS. Predictive value of 72-hour blastomere cell number on blastocyst development and success of subsequent transfer based on the degree of blastocyst development. Fertil Steril. 2000;73:582–6.

    Article  CAS  Google Scholar 

  6. Langley MT, Marek DM, Gardner DK, Doody KM, Doody KJ. Extended embryo culture in human assisted reproduction treatments. Hum Reprod. 2001;16:902–8.

    Article  CAS  Google Scholar 

  7. Luna M, Copperman AB, Duke M, Ezcurra D, Sandler B, Barritt J. Human blastocyst morphological quality is significantly improved in embryos classified as fast on day 3 (>or=10 cells), bringing into question current embryological dogma. Fertil Steril. 2008;89:358–63.

    Article  Google Scholar 

  8. Kong X, Yang S, Gong F, Lu C, Zhang S, Lu G, et al. The relationship between cell number, division behavior and developmental potential of cleavage stage human embryos: a time-lapse study. PLoS One. 2016;11:e0153697.

    Article  Google Scholar 

  9. Magli MC, Gianaroli L, Ferraretti AP, Lappi M, Ruberti A, Farfalli V. Embryo morphology and development are dependent on the chromosomal complement. Fertil Steril. 2007;87:534–41.

    Article  Google Scholar 

  10. Finn A, Scott L, O’Leary T, Davies D, Hill J. Sequential embryo scoring as a predictor of aneuploidy in poor-prognosis patients. Reprod BioMed Online. 2010;21:381–90.

    Article  CAS  Google Scholar 

  11. Kroener LL, Ambartsumyan G, Pisarska MD, Briton-Jones C, Surrey M, Hill D. Increased blastomere number in cleavage-stage embryos is associated with higher aneuploidy. Fertil Steril. 2015;103:694–8.

    Article  Google Scholar 

  12. Barri PN, Martinez F, Coroleu B, Tur R. The role of GnRH antagonists in assisted reproduction. Reprod BioMed Online. 2002;5(Suppl 1):14–9.

    Article  Google Scholar 

  13. Gardner DK, Schoolcraft WB. In vitro culture of human blastocyst. Jansen R Mortimer Eds Reprod certain Infertil genet 1999. Carnforth: Parthenon Press; 1999. p. 378–388.

  14. Veiga A, Sandalinas M, Benkhalifa M, Boada M, Carrera M, Santaló J, et al. Laser blastocyst biopsy for preimplantation diagnosis in the human. Zygote. 1997;5:351–4.

    Article  CAS  Google Scholar 

  15. Kuwayama M, Vajta G, Ieda S, Kato O. Comparison of open and closed methods for vitrification of human embryos and the elimination of potential contamination. Reprod BioMed Online. 2005;11:608–14.

    Article  Google Scholar 

  16. MacKenna A, Crosby J, Zegers-Hochschild F. Embryo early cleavage, number of blastomeres and morphology at day three as factors to predict blastocyst development. JBRA Assist Reprod. 2013;17:158–61.

    Article  Google Scholar 

  17. Meseguer M, Herrero J, Tejera A, Hilligsøe KM, Ramsing NB, Remohí J. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod. 2011;26:2658–71.

    Article  Google Scholar 

  18. Motato Y, de los Santos MJ, Escriba MJ, Ruiz BA, Remohí J, Meseguer M. Morphokinetic analysis and embryonic prediction for blastocyst formation through an integrated time-lapse system. Fertil Steril. 2016;105:376–384.e9.

    Article  Google Scholar 

  19. Giorgetti C, Terriou P, Auquier P, Hans E, Spach JL, Salzmann J, et al. Embryo score to predict implantation after in-vitro fertilization: based on 957 single embryo transfers. Hum Reprod. 1995;10:2427–31.

    Article  CAS  Google Scholar 

  20. Ziebe S, Petersen K, Lindenberg S, Andersen AG, Gabrielsen A, Andersen AN. Embryo morphology or cleavage stage: how to select the best embryos for transfer after in-vitro fertilization. Hum Reprod. 1997;12:1545–9.

    Article  CAS  Google Scholar 

  21. Petersen BM, Boel M, Montag M, Gardner DK. Development of a generally applicable morphokinetic algorithm capable of predicting the implantation potential of embryos transferred on day 3. Hum Reprod Oxf Engl. 2016;31:2231–44.

    Article  Google Scholar 

  22. Carrasco B, Arroyo G, Gil Y, Gómez MJ, Rodríguez I, Barri PN, et al. Selecting embryos with the highest implantation potential using data mining and decision tree based on classical embryo morphology and morphokinetics. J Assist Reprod Genet. 2017;34:983–90.

    Article  Google Scholar 

  23. Sunde A, Brison D, Dumoulin J, Harper J, Lundin K, Magli MC, et al. Time to take human embryo culture seriously. Hum Reprod. 2016;31:2174–82.

    Article  Google Scholar 

  24. Rubio I, Galán A, Larreategui Z, Ayerdi F, Bellver J, Herrero J, et al. Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope. Fertil Steril. 2014;102:1287–1294.e5.

    Article  Google Scholar 

  25. Kovacic B, Vlaisavljević V. Influence of atmospheric versus reduced oxygen concentration on development of human blastocysts in vitro: a prospective study on sibling oocytes. Reprod BioMed Online. 2008;17:229–36.

    Article  CAS  Google Scholar 

  26. Kirkegaard K, Hindkjaer JJ, Ingerslev HJ. Effect of oxygen concentration on human embryo development evaluated by time-lapse monitoring. Fertil Steril. 2013;99:738–744.e4.

    Article  Google Scholar 

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Acknowledgements

This work was performed under the auspices of “Càtedra d’Investigació en Obstetricia i Ginecologia” of Department of Obstetrics, Gynaecology and Reproductive Medicine; Hospital Universitari Dexeus, Universitat Autònoma de Barcelona.

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Authors and Affiliations

  1. Reproductive Medicine Service, Dexeus Mujer, Hospital Universitari Dexeus, Gran Via Carles III, 71-75, 08028, Barcelona, Spain

    Maria Carme Pons, Beatriz Carrasco, Mònica Parriego, Montserrat Boada, Iñaki González-Foruria, Sandra Garcia, Buenaventura Coroleu, Pedro N. Barri & Anna Veiga

  2. Barcelona Stem Cell Bank, Centre of Regenerative Medicine in Barcelona, Hospital Duran i Reynals, Gran Via de l’ Hospitalet 199, 08908, Hospitalet de Llobregat, Spain

    Anna Veiga

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  1. Maria Carme Pons
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  4. Montserrat Boada
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  9. Anna Veiga
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Contributions

M.C.P. and B.C. designed the study, interpreted the data, and wrote the manuscript. M.P., M.B., and A.V. edited and reviewed the manuscript. S.G. conducted the statistical analysis. I.G-F, B.C., and P.B. reviewed the manuscript. All authors approved the final version of the manuscript.

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Correspondence to Maria Carme Pons.

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Pons, M.C., Carrasco, B., Parriego, M. et al. Deconstructing the myth of poor prognosis for fast-cleaving embryos on day 3. Is it time to change the consensus?. J Assist Reprod Genet 36, 2299–2305 (2019). https://doi.org/10.1007/s10815-019-01574-y

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