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Morphokinetic parameters of early embryo development via time lapse monitoring and their effect on embryo selection and ICSI outcomes: a prospective cohort study

  • Assisted Reproduction Technologies
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Abstract

Purpose

To compare the outcomes of embryos selected via time lapse monitoring (TLM) versus those selected with conventional methods of selection in subfertile women undergoing ICSI.

Methods

The study population (239 women) was classified into two groups, based on the monitoring method used: Group 1 (TLM) and Group 2 (conventional monitoring). Groups were compared according to the clinical and ICSI cycle characteristics and reproductive outcomes, while transfers were performed at day 2 or 3. Subgroup analyses were performed, in women of both groups according to age and clinical parameters, and in embryos of Group 1 based on their cellular events.

Results

There was a statistically significant difference between the two study groups with regard to the outcome parameters, favoring Group 1 and especially in women >40 years of age. No differences were found in subgroup analyses in participants of both groups, regarding the stimulation protocol used, number of the oocytes retrieved and type of subfertility, while in Group 1 the percentages of “in range” cellular events were higher in certain divisions in ages 35–40, non-smokers, and the GnRH-agonist group, and in embryos that resulted in pregnancy.

Conclusion

Morphokinetic parameters of early embryo development via TLM are related to the characteristics of subfertile patients and associated with ICSI outcomes.

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References

  1. Ferraretti AP, Goossens V, Kupka M, Bhattacharya S, de Mouzon J, Castilla JA, et al. Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE. Hum Reprod. 2013;28:2318–31.

    Article  CAS  PubMed  Google Scholar 

  2. 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 

  3. 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 

  4. Palmer GA, Traeger-Synodinos J, Davies S, Tzetis M, Vrettou C, Mastrominas M, et al. Pregnancies following blastocyst stage transfer in PGD cycles at risk for beta-thalassaemic haemoglobinopathies. Hum Reprod. 2002;17:25–31.

    Article  CAS  PubMed  Google Scholar 

  5. Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update. 2011;17:454–66.

    Article  CAS  PubMed  Google Scholar 

  6. Nel-Themaat L, Nagy ZP. A review of the promises and pitfalls of oocyte and embryo metabolomics. Placenta. 2011;32 Suppl 3:S257–63.

    Article  CAS  PubMed  Google Scholar 

  7. Swain JE. Could time-lapse embryo imaging reduce the need for biopsy and PGS? J Assist Reprod Genet. 2013;30:1081–90.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Simon A, Laufer N. Assessment and treatment of repeated implantation failure (RIF). J Assist Reprod Genet. 2012;29:1227–39.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Anifandis G. Temperature variations inside commercial IVF incubators. J Assist Reprod Genet. 2013;30:1587–8.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Zhang JQ, Li XL, Peng Y, Guo X, Heng BC, Tong GQ. Reduction in exposure of human embryos outside the incubator enhances embryo quality and blastulation rate. Reprod Biomed Online. 2010;20:510–5.

    Article  PubMed  Google Scholar 

  11. Calzi F, Papaleo E, Rabellotti E, Ottolina J, Vailati S, Vigano P, et al. Exposure of embryos to oxygen at low concentration in a cleavage stage transfer program: reproductive outcomes in a time-series analysis. Clin Lab. 2012;58:997–1003.

    CAS  PubMed  Google Scholar 

  12. 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 

  13. Conaghan J. Time-lapse imaging of preimplantation embryos. Semin Reprod Med. 2014;32:134–40.

    Article  PubMed  Google Scholar 

  14. Chen AA, Tan L, Suraj V, Reijo Pera R, Shen S. Biomarkers identified with time-lapse imaging: discovery, validation, and practical application. Fertil Steril. 2013;99:1035–43.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Hardarson T, Löfman C, Coull G, Sjögren A, Hamberger L, Edwards RG. Internalization of cellular fragments in a human embryo: time-lapse recordings. Reprod Biomed Online. 2002;5:36–8.

    Article  CAS  PubMed  Google Scholar 

  16. Rubio I, Kuhlmann R, Agerholm I, Kirk J, Herrero J, Escriba MJ, et al. Limited implantation success of direct-cleaved human zygotes: a time-lapse study. Fertil Steril. 2012;98:1458–63.

    Article  PubMed  Google Scholar 

  17. Athayde Wirka K, Chen AA, Conaghan J, Ivani K, Gvakharia M, Behr B, et al. Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development. Fertil Steril. 2014;101:1637–48.

    Article  PubMed  Google Scholar 

  18. 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 

  19. 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 

  20. Stecher A, Vanderzwalmen P, Zintz M, Wirleitner B, Schuff M, Spitzer D, et al. Transfer of blastocysts with deviant morphological and morphokinetic parameters at early stages of in-vitro development: a case series. Reprod Biomed Online. 2014;28:424–35.

    Article  PubMed  Google Scholar 

  21. Yang Z, Zhang J, Salem SA, Liu X, Kuang Y, Salem RD, et al. Selection of competent blastocysts for transfer by combining time-lapse monitoring and array CGH testing for patients undergoing preimplantation genetic screening: a prospective study with sibling oocytes. BMC Med Genomics. 2014;7:38.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Joergensen MW, Agerholm I, Hindkjaer J, Bolund L, Sunde L, Ingerslev HJ, et al. Altered cleavage patterns in human tripronuclear embryos and their association to fertilization method: a time-lapse study. J Assist Reprod Genet. 2014;31:435–42.

    Article  PubMed  Google Scholar 

  23. Munoz M, Cruz M, Humaidan P, Garrido N, Perez-Cano I, Meseguer M. The type of GnRH analogue used during controlled ovarian stimulation influences early embryo developmental kinetics: a time-lapse study. Eur J Obstet Gynecol Reprod Biol. 2013;168:167–72.

    Article  CAS  PubMed  Google Scholar 

  24. Bellver J, Mifsud A, Grau N, Privitera L, Meseguer M. Similar morphokinetic patterns in embryos derived from obese and normoweight infertile women: a time-lapse study. Hum Reprod. 2013;28:794–800.

    Article  CAS  PubMed  Google Scholar 

  25. Freour T, Dessolle L, Lammers J, Lattes S, Barriere P. Comparison of embryo morphokinetics after in vitro fertilization-intracytoplasmic sperm injection in smoking and nonsmoking women. Fertil Steril. 2013;99:1944–50.

    Article  PubMed  Google Scholar 

  26. 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 

  27. Wang Y, Moussavi F, Lorenzen P. Automated embryo stage classification in time-lapse microscopy video of early human embryo development. Med Image Comput Comput Assist Interv. 2013;16:460–7.

    PubMed  Google Scholar 

  28. Hlinka D, Kaľatová B, Uhrinová I, Dolinská S, Rutarová J, Rezáčová J, et al. Time-lapse cleavage rating predicts human embryo viability. Physiol Res. 2012;61:513–25.

    CAS  PubMed  Google Scholar 

  29. Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Thornton S. Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived from time-lapse imaging without PGS. Reprod Biomed Online. 2013;27:140–6.

    Article  PubMed  Google Scholar 

  30. 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 

  31. Meseguer M, Rubio I, Cruz M, Basile N, Marcos J, Requena A. Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study. Fertil Steril. 2012;98:1481–9.

    Article  PubMed  Google Scholar 

  32. Findikli N, Oral E. Time-lapse embryo imaging technology: does it improve the clinical results? Curr Opin Obstet Gynecol. 2014;26:138–44.

    Article  PubMed  Google Scholar 

  33. Cruz M, Gadea B, Garrido N, Pedersen KS, Martinez M, Perez-Cano I, et al. Embryo quality, blastocyst and ongoing pregnancy rates in oocyte donation patients whose embryos were monitored by time-lapse imaging. J Assist Reprod Genet. 2011;28:569–73.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Kirkegaard K, Kesmodel US, Hindkjaer 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 

  35. Kirkegaard K, Hindkjaer JJ, Grondahl ML, Kesmodel US, Ingerslev HJ. A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator. J Assist Reprod Genet. 2012;29:565–72.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Montag M. Morphokinetics and embryo aneuploidy: has time come or not yet? Reprod Biomed Online. 2013;26:528–30.

    Article  PubMed  Google Scholar 

  37. Ottolini C, Rienzi L, Capalbo A. A cautionary note against embryo aneuploidy risk assessment using time-lapse imaging. Reprod Biomed Online. 2014;28:273–5.

    Article  PubMed  Google Scholar 

  38. Veeck LL. An Atlas of Human Gametes and Conceptuses: An Illustrated Reference for Assisted Reproductive Technology. In: Preembryo grading and degree of cytoplasmic fragmentation. New York: Parthenon Publishing; 1999. p. 46–51.

    Google Scholar 

  39. 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  PubMed  Google Scholar 

  40. Ciray HN, Campbell A, Agerholm IE, Aguilar J, Chamayou S, Esbert M, et al. Time-lapse user group. Proposed guidelines on the nomenclature and annotation of dynamic human embryo monitoring by a time-lapse user group. Hum Reprod. 2014;29:2650–60.

    Article  PubMed  Google Scholar 

  41. 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 

  42. 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 

  43. Polanski LT, Coelho Neto MA, Nastri CO, Navarro PA, Ferriani RA, Raine-Fenning N, et al. Time-lapse embryo imaging for improving reproductive outcomes: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2014. doi:10.1002/uog.13428.

    PubMed  Google Scholar 

  44. Kovacs P, Matyas S, Forgacs V, Sajgo A, Rarosi F, Pribenszky C. Time-lapse embryo selection for single blastocyst transfer-results of a multicenter, prospective, randomized clinical trial. Fertil Steril. 2013;100:S90.

    Article  Google Scholar 

  45. Kahraman S, Cetinkaya M, Pirkevi C, Yelke H, Kumtepe Y. Comparison of blastocyst development and cycle outcome in patients with eSET using either conventional or time lapse incubators. A prospective study of good prognosis patients. J Reprod Stem Cell Biotechnol. 2013;3:55–61.

    Google Scholar 

  46. 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;102:1287–94.

    Article  PubMed  Google Scholar 

  47. Aparicio B, Cruz M, Meseguer M. Is morphokinetic analysis the answer? Reprod BioMed Online. 2013;27:654–63.

    Article  CAS  PubMed  Google Scholar 

  48. Muñoz M, Cruz M, Humaidan P, Garrido N, Pérez-Cano I, Meseguer M. Dose of recombinant FSH and oestradiol concentration on day of HCG affect embryo development kinetics. Reprod BioMed Online. 2012;25:382–9.

    Article  PubMed  Google Scholar 

  49. Wissing ML, Hoest T, Mikkelsen AL. Slower early embryo development in women with polycystic ovary syndrome (PCOS) compared to regularly cycling women (controls). Fertil Steril. 2012;98 Suppl 3:S109.

    Article  Google Scholar 

  50. Davies S, Christopikou D, Tsorva E, Karagianni A, Handyside AH, Mastrominas M. Delayed cleavage divisions and a prolonged transition between 2-and 4-cell stages in embryos identified as aneuploid at the 8-cell stage by array CGH. Hum Reprod. 2012;27 Suppl 2:ii84.

    Article  Google Scholar 

  51. Mercader A, Garcia-Velasco JA, Escudero E, Remohi J, Pellicer A, Simon C. Clinical experience and perinatal outcome of blastocyst transfer after coculture of human embryos with human endometrial epithelial cells: a 5-year follow-up study. Fertil Steril. 2003;80:1162–8.

    Article  PubMed  Google Scholar 

  52. 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 

  53. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. <http://handbook.cochrane.org/> (2011). Accessed on 31 Dec 2014.

  54. Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011;26:1768–74.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank the clinical, paramedical and laboratory team of Mitera Assisted Reproduction Unit. There was no finding for the current work. The study is a part of the Msc thesis of the second author.

Conflict of interest

All authors declare no conflict of interest.

Authors’ roles

CS: Study design, interpretation of findings and manuscript preparation.

MAK: Study design, data collection and data analysis.

AM: Data collection, data analysis and manuscript preparation.

AS, MB: Clinical embryology, data acquisition and interpretation of results.

GS, GM: data acquisition and interpretation of results.

GAP: Study concept and design, clinical embryology, data acquisition, data analysis and interpretation.

All authors critically reviewed and approved the final version of the manuscript.

Author information

Authors and Affiliations

  1. Assisted Reproduction Unit, 3rd Department of Obstetrics and Gynecology, University of Athens, Rimini 1, Chaidari, Athens, Greece, 12642

    Charalampos Siristatidis & George Salamalekis

  2. Assisted Reproduction Unit, MITERA Hospital, Erythrou Stavrou 6, Marousi, Athens, Greece, 15123

    Maria Aggeliki Komitopoulou, Andreas Makris, Afrodite Sialakouma, Mitrodora Botzaki & Giles Anthony Palmer

  3. 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece

    George Mastorakos

  4. First Unit of Obstetrics and Gynecology, Department of Biomedical Sciences and Human Oncology, University “Aldo Moro”, 70124, Bari, Italy

    Stefano Bettocchi

Authors
  1. Charalampos Siristatidis
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  2. Maria Aggeliki Komitopoulou
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  3. Andreas Makris
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  4. Afrodite Sialakouma
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  6. George Mastorakos
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  7. George Salamalekis
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  8. Stefano Bettocchi
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  9. Giles Anthony Palmer
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Corresponding author

Correspondence to Charalampos Siristatidis.

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Capsule

This prospective cohort study showed that the morphokinetic parameters of early embryo development observed via time lapse monitoring in subfertile women undergoing ICSI are related to the special characteristics of these women and are associated with ICSI outcomes.

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Siristatidis, C., Komitopoulou, M.A., Makris, A. et al. Morphokinetic parameters of early embryo development via time lapse monitoring and their effect on embryo selection and ICSI outcomes: a prospective cohort study. J Assist Reprod Genet 32, 563–570 (2015). https://doi.org/10.1007/s10815-015-0436-z

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  • DOI: https://doi.org/10.1007/s10815-015-0436-z

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