Skip to main content
Log in

Morphokinetic parameters using time-lapse technology and day 5 embryo quality: a prospective cohort study

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

Abstract

Purpose

The aims of this prospective study were to evaluate whether time-lapse parameters can aid in the prediction of day 5 embryo quality and also to assess their discriminatory capacity.

Methods

In this prospective cohort study, we used time-lapse technology to record specific timings of key events for 380 day 5 blastocysts (originating from 108 patients). Generalized estimating equation regression models were used to evaluate the capacity of these markers to identify a top-quality blastocyst. Multivariable regression models were also constructed, aiming to identify the model with the highest capacity to predict a top-quality blastocyst. The discriminatory capacity of single predictors or composite models was assessed with the use of receiver operating characteristic (ROC) analyses.

Results

Eight significant predictive parameters of a top-quality blastocyst were identified: s3, t6, t7, t8, tM, tSB, tB and tEB. A ROC analysis of the identified parameters found s3 (area under the curve—AUC 0.585, 95 % CI 0.534–0.635) to have the best individual discriminatory capacity to predict a top-quality blastocyst prior to embryo compaction. The parameter tEB (AUC 0.727, 95 % CI 0.675–0.775) was the best predictor regardless of embryo stage. A model containing s3, t8 and tEB showed a slightly increased discriminatory capacity for top-quality blastocyst prediction (AUC 0.748, 95 % CI 0.697–0.794).

Conclusions

The identified morphokinetic parameters and their cutoffs, albeit of limited clinical value, add to the increasing knowledge concerning the potential predictive markers of a top-quality blastocyst. Additional evidence is necessary before validated time-lapse parameters can be used for embryo selection in IVF laboratories.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Edwards RG, Purdy JM, Steptoe PC, Walters DE. The growth of human preimplantation embryos in vitro. Am J Obstet Gynecol. 1981;141:408–16.

    CAS  PubMed  Google Scholar 

  2. Cummins JM, Breen TM, Harrison KL, Shaw JM, Wilson LM, Hennessey JF. A formula for scoring human embryo growth rates in in vitro fertilization: its value in predicting pregnancy and in comparison with visual estimates of embryo quality. Journal of In Vitro Fertilization and Embryo Transfer: IVF. 1986;3:284–95.

    Article  CAS  PubMed  Google Scholar 

  3. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73:1155–8.

    Article  CAS  PubMed  Google Scholar 

  4. Balaban B, Yakin K, Urman B. Randomized comparison of two different blastocyst grading systems. Fertil Steril. 2006;85:559–63.

    Article  PubMed  Google Scholar 

  5. Ahlstrom A, Westin C, Reismer E, Wikland M, Hardarson T. Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. Hum Reprod. 2011;26:3289–96.

    Article  CAS  PubMed  Google Scholar 

  6. Pool TB. An update on embryo culture for human assisted reproductive technology: media, performance, and safety. In: Seminars in reproductive medicine. Copyright© 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA., 2005:309-18.

  7. Gardner DK. Dissection of culture media for embryos: the most important and less important components and characteristics. Reprod Fertil Dev. 2007;20:9–18.

    Article  Google Scholar 

  8. Sundvall L, Ingerslev HJ, Breth Knudsen U, Kirkegaard K. Inter- and intra-observer variability of time-lapse annotations. Hum Reprod. 2013;28:3215–21.

    Article  PubMed  Google Scholar 

  9. Lemmen JG, Agerholm I, Ziebe S. Kinetic markers of human embryo quality using time-lapse recordings of IVF/ICSI-fertilized oocytes. Reprod Biomed Online. 2008;17:385–91.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  PubMed  Google Scholar 

  11. Wong CC, Loewke KE, Bossert NL, Behr B, De Jonge CJ, Baer TM, et al. Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat Biotechnol. 2010;28:1115–21.

    Article  CAS  PubMed  Google Scholar 

  12. Cruz M, Garrido N, Herrero J, Perez-Cano I, Munoz M, Meseguer M. Timing of cell division in human cleavage-stage embryos is linked with blastocyst formation and quality. Reprod Biomed Online. 2012;25:371–81.

    Article  PubMed  Google Scholar 

  13. Hashimoto S, Kato N, Saeki K, Morimoto Y. Selection of high-potential embryos by culture in poly(dimethylsiloxane) microwells and time-lapse imaging. Fertil Steril. 2012;97:332–7.

    Article  PubMed  Google Scholar 

  14. Kirkegaard K, Kesmodel US, Hindkjær JJ, Ingerslev HJ. Time-lapse parameters as predictors of blastocyst development and pregnancy outcome in embryos from good prognosis patients: a prospective cohort study. Hum Reprod. 2013;28:2643–51.

    Article  CAS  PubMed  Google Scholar 

  15. Azzarello A, Hoest T, Mikkelsen AL. The impact of pronuclei morphology and dynamicity on live birth outcome after time-lapse culture. Hum Reprod. 2012;27:2649–57.

    Article  CAS  PubMed  Google Scholar 

  16. Dal Canto M, Coticchio G, Mignini Renzini M, De Ponti E, Novara PV, Brambillasca F, et al. Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation. Reprod Biomed Online. 2012;25:474–80.

    Article  PubMed  Google Scholar 

  17. VerMilyea MD, Tan L, Anthony JT, Conaghan J, Ivani K, Gvakharia M, et al. Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: a blinded, multi-centre study. Reprod Biomed Online. 2014;29:729–36.

    Article  PubMed  Google Scholar 

  18. Kaser DJ, Racowsky C. Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review. Hum Reprod Update. 2014;20:617–31.

    Article  PubMed  Google Scholar 

  19. Conaghan J, Chen AA, Willman SP, Ivani K, Chenette PE, Boostanfar R, et al. Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial. Fertil Steril. 2013;100:412–9.

    Article  PubMed  Google Scholar 

  20. Best L, Campbell A, Duffy S, Montgomery S, Fishel S. Session 57: does one model fit all? Testing a published embryo selection algorithm on independent time-lapse data. Hum Reprod. 2013;28:i87–90.

    Article  Google Scholar 

  21. Freour T, Le Fleuter N, Lammers J, Splingart C, Reignier A, Barriere P. External validation of a time-lapse prediction model. Fertility and Sterility 2015.

  22. Kilani S, Chapman MG. The use of polarized light microscopy in IVF. 2011.

  23. Blake DA, Farquhar CM, Johnson N, Proctor M. Cleavage stage versus blastocyst stage embryo transfer in assisted conception. The Cochrane Database of Systematic Reviews 2007: CD002118.

  24. Kallen B, Finnstrom O, Lindam A, Nilsson E, Nygren KG, Olausson PO. Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome? Fertil Steril. 2010;94:1680–3.

    Article  PubMed  Google Scholar 

  25. Dar S, Librach CL, Gunby J, Bissonnette F, Cowan L. IVFDGotCF. ASobot. Increased risk of preterm birth in singleton pregnancies after blastocyst versus day 3 embryo transfer: Canadian ART Register (CARTR) analysis. Hum Reprod. 2013;28:924–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors wish to thank all of the IVF Australia nurses involved in patient recruitment as well as the embryology team at IVF Australia—Eastern Suburbs for their continued support.

Compliance with ethical standards

The authors declare that they have no conflict of interest. Consent was obtained from all individual participants included in the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ashleigh Storr.

Additional information

Capsule

Morphokinetic parameters using time-lapse technology can predict the quality of day 5 embryos, although their clinical usefulness might be limited.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Storr, A., Venetis, C.A., Cooke, S. et al. Morphokinetic parameters using time-lapse technology and day 5 embryo quality: a prospective cohort study. J Assist Reprod Genet 32, 1151–1160 (2015). https://doi.org/10.1007/s10815-015-0534-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-015-0534-y

Keywords

Navigation