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Early compaction at day 3 may be a useful additional criterion for embryo transfer

  • Sébastien Le Cruguel
  • Véronique Ferré-L’Hôtellier
  • Catherine Morinière
  • Sophie Lemerle
  • Pascal Reynier
  • Philippe Descamps
  • Pascale May-Panloup
ASSISTED REPRODUCTION TECHNOLOGIES

Abstract

Purpose

The reduction of the number of embryos transferred while maintaining a satisfactory rate of pregnancy (PR) with in vitro fertilization calls for a refined technique of embryonic selection. This prospective study investigates the significance of early embryonic compaction at day 3 as a marker of the chances of implantation.

Methods

We examined 317 transfers and their outcome involving 509 embryos including 91 compacted embryos.

Results

Early compaction seems linked with the ovarian response to stimulation and embryonic quality. The PR is significantly increased when the embryonic cohort contains at least one compacted embryo (44 % versus 29.5 %, p = 0.01), and when at least one compacted embryo is transferred (44 % versus 31 %, p < 0.05). The analysis of our single embryo transfers shows that the implantation rates are significantly better for compacted embryos (50 % versus 30 %, p < 0.05) (OR 2.98; CI 1.02–5.28).

Conclusion

Thus, early compaction, sometimes observed at day 3, may serve as a useful additional criterion for selecting the embryos transferred.

Keywords

Early compaction Cleavage stage Embryonic selection Transfer at day 3 

Notes

Acknowledgments

We thank Ms. C. Douillard, M. Guezenec, S. Lehais and C. Moyon, technicians at the In Vitro Fertilization Laboratory of the University Hospital of Angers, for their participation in the classification of embryos. We thank P. Saulnier for his help in the statistical analysis. We are grateful to Kanaya Malkani for his critical reading and comments on the manuscript.

References

  1. 1.
    Aboulghar MM, Aboulghar MA, Mansour RT, Serour GI, Amin YM, Abou-Setta AM. Pregnancy rate is not improved by delaying embryo transfer from days 2 to 3. Eur J Obstet Gynecol Reprod Biol. 2003;107:176–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Bahceci M, Ulug U, Ciray HN, Akman MA, Erden HF. Efficiency of changing the embryo transfer time from day 3 to day 2 among women with poor ovarian response: a prospective randomized trial. Fertil Steril. 2006;86:81–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Blondel B, Kaminski M. Trends in the occurrence, determinants, and consequences of multiple births. Semin Perinatol. 2002;26:239–49.PubMedCrossRefGoogle Scholar
  4. 4.
    Blondel B, Kogan MD, Alexander GR, Dattani N, Kramer MS, Macfarlane A, et al. The impact of the increasing number of multiple births on the rates of preterm birth and low birthweight: an international study. Am J Public Health. 2002;92:1323–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Bolton VN, Braude PR. Development of the human preimplantation embryo in vitro. Curr Top Dev Biol. 1987;23:93–114.PubMedCrossRefGoogle Scholar
  6. 6.
    Braude P, Bolton V, Moore S. Human gene expression first occurs between the four- and eight-cell stages of preimplantation development. Nature. 1988;332:459–61.PubMedCrossRefGoogle Scholar
  7. 7.
    Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences. Endocr Rev. 2009;30:465–93.PubMedCrossRefGoogle Scholar
  8. 8.
    Chason RJ, Csokmay J, Segars JH, DeCherney AH, Armant DR. Environmental and epigenetic effects upon preimplantation embryo metabolism and development. Trends Endocrinol Metab. 2011;22:412–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Desai NN, Goldstein J, Rowland DY, Goldfarb JM. Morphological evaluation of human embryos and derivation of an embryo quality scoring system specific for day 3 embryos: a preliminary study. Hum Reprod. 2000;15:2190–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Ebner T, Moser M, Shebl O, Sommergruber M, Gaiswinkler U, Tews G. Morphological analysis at compacting stage is a valuable prognostic tool for ICSI patients. Reprod Biomed Online. 2009;18:61–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Embryology A. S. i. R. M. a. E. S. I. G. o. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26:1270–83.CrossRefGoogle Scholar
  12. 12.
    Feenan K, Herbert M. Can ‘abnormally’ fertilized zygotes give rise to viable embryos? Hum Fertil (Camb). 2006;9:157–69.CrossRefGoogle Scholar
  13. 13.
    Fernandez-Gonzalez R, Moreira P, Bilbao A, Jimenez A, Perez-Crespo M, Ramirez MA, et al. Long-term effect of in vitro culture of mouse embryos with serum on mRNA expression of imprinting genes, development, and behavior. Proc Natl Acad Sci U S A. 2004;101:5880–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Glujovsky D, Blake D, Farquhar C, Bardach A. Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology. Cochrane Database Syst Rev. 2012;7:CD002118.PubMedGoogle Scholar
  15. 15.
    Gosden R, Trasler J, Lucifero D, Faddy M. Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet. 2003;361:1975–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Huisman GJ, Alberda AT, Leerentveld RA, Verhoeff A, Zeilmaker GH. A comparison of in vitro fertilization results after embryo transfer after 2, 3, and 4 days of embryo culture. Fertil Steril. 1994;61:970–1.PubMedGoogle Scholar
  17. 17.
    Ivec M, Kovacic B, Vlaisavljevic V. Prediction of human blastocyst development from morulas with delayed and/or incomplete compaction. Fertil Steril. 2011;96:1473–8. e2.PubMedCrossRefGoogle Scholar
  18. 18.
    Kanka J. Gene expression and chromatin structure in the pre-implantation embryo. Theriogenology. 2003;59:3–19.PubMedCrossRefGoogle Scholar
  19. 19.
    Kligman I, Benadiva C, Alikani M, Munne S. The presence of multinucleated blastomeres in human embryos is correlated with chromosomal abnormalities. Hum Reprod. 1996;11:1492–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Laverge H, De Sutter P, Van der Elst J, Dhont M. A prospective, randomized study comparing day 2 and day 3 embryo transfer in human IVF. Hum Reprod. 2001;16:476–80.PubMedCrossRefGoogle Scholar
  21. 21.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    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.PubMedCrossRefGoogle Scholar
  23. 23.
    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.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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. e10.PubMedCrossRefGoogle Scholar
  26. 26.
    Mio Y, Maeda K. Time-lapse cinematography of dynamic changes occurring during in vitro development of human embryos. Am J Obstet Gynecol. 2008;199:660. e1–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Pantos K, Makrakis E, Chronopoulou M, Biba M, Perdikaris A, Dafereras A. Day 4 versus day 3 embryo transfer: a prospective study of clinical outcomes. Fertil Steril. 2008;89:573–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Puissant F, Van Rysselberge M, Barlow P, Deweze J, Leroy F. Embryo scoring as a prognostic tool in IVF treatment. Hum Reprod. 1987;2:705–8.PubMedGoogle Scholar
  29. 29.
    Rijnders PM, Jansen CA. The predictive value of day 3 embryo morphology regarding blastocyst formation, pregnancy and implantation rate after day 5 transfer following in-vitro fertilization or intracytoplasmic sperm injection. Hum Reprod. 1998;13:2869–73.PubMedCrossRefGoogle Scholar
  30. 30.
    Schultz RM. From egg to embryo: a peripatetic journey. Reproduction. 2005;130:825–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Seli E, Robert C, Sirard MA. OMICS in assisted reproduction: possibilities and pitfalls. Mol Hum Reprod. 2010;16:513–30.PubMedCrossRefGoogle Scholar
  32. 32.
    Shahine LK, Milki AA, Westphal LM, Baker VL, Behr B, Lathi RB. Day 2 versus day 3 embryo transfer in poor responders: a prospective randomized trial. Fertil Steril. 2011;95:330–2.PubMedCrossRefGoogle Scholar
  33. 33.
    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.PubMedCrossRefGoogle Scholar
  34. 34.
    Shen S, Rosen MP, Dobson AT, Fujimoto VY, McCulloch CE, Cedars MI. Day 2 transfer improves pregnancy outcome in in vitro fertilization cycles with few available embryos. Fertil Steril. 2006;86:44–50.PubMedCrossRefGoogle Scholar
  35. 35.
    Skiadas CC, Jackson KV, Racowsky C. Early compaction on day 3 may be associated with increased implantation potential. Fertil Steril. 2006;86:1386–91.PubMedCrossRefGoogle Scholar
  36. 36.
    Tao J, Tamis R, Fink K, Williams B, Nelson-White T, Craig R. The neglected morula/compact stage embryo transfer. Hum Reprod. 2002;17:1513–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Tsai YC, Chung MT, Sung YH, Tsai TF, Tsai YT, Lin LY. Clinical value of early cleavage embryo. Int J Gynaecol Obstet. 2002;76:293–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Vajta G, Rienzi L, Cobo A, Yovich J. Embryo culture: can we perform better than nature? Reprod Biomed Online. 2010;20:453–69.PubMedCrossRefGoogle Scholar
  39. 39.
    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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sébastien Le Cruguel
    • 1
  • Véronique Ferré-L’Hôtellier
    • 1
  • Catherine Morinière
    • 2
  • Sophie Lemerle
    • 2
  • Pascal Reynier
    • 3
    • 4
  • Philippe Descamps
    • 2
  • Pascale May-Panloup
    • 1
    • 4
  1. 1.Laboratoire de Biologie de la ReproductionCentre Hospitalier Universitaire d’AngersAngers cedex 9France
  2. 2.Service de Gynécologie-ObstétriqueCentre Hospitalier Universitaire d’AngersAngers cedex 9France
  3. 3.Laboratoire de Biochimie et Biologie MoléculaireCentre Hospitalier Universitaire d’AngersAngers cedex 9France
  4. 4.UMR CNRS 6214-INSERM U771Angers cedex 9France

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