Journal of Assisted Reproduction and Genetics

, Volume 32, Issue 12, pp 1811–1815 | Cite as

Irregular cleavage of early preimplantation human embryos: characteristics of patients and pregnancy outcomes

  • Miriam AlmagorEmail author
  • Yuval Or
  • Sheila Fieldust
  • Zeev Shoham
Embryo Biology



This is a retrospective analysis of the morphokinetics, prevalence, and implantation potential of embryos with irregular first and second cleavages as identified by time-lapse microscopy.


The study included 253 women who underwent 387 assisted reproduction treatments with intracytoplasmic sperm injection (ICSI). Each patient was assigned to one of three groups based on embryo cleavage results. In group I, one to two embryos per cycle showed irregular cleavage; group II, at least three embryos with abnormal cleavage; and in group III (the control group), all embryos cleaved normally. The number of embryos that cleaved from 1 to ≥3 cells or from 2 to ≥5 cells for each patient was recorded. Their prevalence and association with women’s characteristics and pregnancy outcome were evaluated.


The prevalence of irregular cleavage was 15.6 % among 1772 ICSI embryos. In 101 cycles, 1–2 embryos per cycle showed irregular cleavage (group I). In 32 cycles, at least 3 embryos showed abnormal cleavage (group II). In 254 cycles, all embryos cleaved normally (group III). The average age of the women in group II was significantly lower in comparison with groups I and III (32.5 ± 4.2 vs. 35.1 ± 4.9 and 35.5 ± 5.1, respectively, p < 0.02). In comparison of groups I and II, the odds ratio for ≥3 embryos with irregular cleavage in women younger than 35 was 3.48 (95 % CI, 1.28 to 9.46). Embryos with irregular cleavage were transferred in 16 women. Three live births were achieved following the transfer of single blastocysts derived from embryos with irregular cleavage from two to five cells.


Early embryos with irregular cleavage are significantly more prevalent in younger women. When these embryos develop to the blastocyst stage, they may have normal implantation potential, leading to the birth of healthy babies.


Embryo development Implantation Irregular cleavage Pregnancy Time-lapse 




Conflict of interest

The authors declare that they have no competing interests.

Ethics approval

Study approval was obtained from the Kaplan Medical Center Institutional Review Board.


  1. 1.
    Kirkegaard K, Agerholm IE, Ingerslev HJ. Time-lapse monitoring as a tool for clinical embryo assessment. Hum Reprod. 2012;27:1277–85.CrossRefPubMedGoogle Scholar
  2. 2.
    Chen AA, Tan I, Suraj V, Reijo Pera R, Shen S. Biomarkers identified with time-lapse imaging: discovery, validation and practice application. Fertil Steril. 2013;99:1035–43.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Herrero J, Meseguer M. Selection of high potential embryos using time-lapse imaging: the era of morphokinetics. Fertil Steril. 2013;99:1030–34.CrossRefPubMedGoogle Scholar
  4. 4.
    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.CrossRefPubMedGoogle Scholar
  5. 5.
    Wirka KA, 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.CrossRefGoogle Scholar
  6. 6.
    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.CrossRefPubMedGoogle Scholar
  7. 7.
    Yang ST, Shi JX, Gong F, Zhang SP, Lu CF, Tan K, et al. Cleavage pattern predicts developmental potential of day 3 human embryos produced by IVF. Reprod Biomed Online. 2015;30:625–34.CrossRefPubMedGoogle Scholar
  8. 8.
    Somfai T, Inaba Y, Aikawa Y, Ohtake M, Kobayashi S, Konishi K, et al. Relationship between the length of cell cycles, cleavage pattern and developmental competence in bovine embryos generated by IVF or parthenogenesis. J Reprod Dev. 2010;56:200–7.CrossRefPubMedGoogle Scholar
  9. 9.
    Kola I, Trounson A, Dawson G, Rogers P. Tripronuclear human oocytes: altered cleavage pattern and subsequent kariotypic analysis of embryos. Biol Reprod. 1987;37:395–401.CrossRefPubMedGoogle Scholar
  10. 10.
    Chavez SL, Loewke KE, Han J, Moussavi F, Colls P, Munne S, et al. Dynamic blastomere behavior reflects human embryo ploidy by the four cell stage. Nat Commun. 2012;2249:1–12.Google Scholar
  11. 11.
    Taylor TH, Gitlin SA, Patrick JL, Crain JL, Wilson JM, Griffin DK. The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans. Hum Reprod Update. 2014;4:571–81.CrossRefGoogle Scholar
  12. 12.
    Wells D, Delhanty JD. Comprehensive chromosomal analysis of human preimplantation embryos using whole genome amplification and single cell comparative genomic hybridization. Mol Hum Reprod. 2000;6:1055–62.CrossRefPubMedGoogle Scholar
  13. 13.
    Mertzanidou A, Wilton L, Cheng J, Spits C, Vanneste E, Moreau Y, et al. Microarray analysis reveals abnormal chromosome complements in over 70% of 14 normally developing human embryos. Hum Reprod. 2013;28:256–64.CrossRefPubMedGoogle Scholar
  14. 14.
    Chow JFC, Yeung WSB, Lau EYL, Lee VCY, Ng EHY, Ho PC. Array comparative genomic hybridization analyses of all blastomeres of a cohort of embryos from young IVF patients revealed significant contribution of mitotic errors to embryo mosaicism at the cleavage stage. Reprod Biol Endocrinol. 2014;12:105–14.PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Miriam Almagor
    • 1
    • 2
    Email author
  • Yuval Or
    • 1
  • Sheila Fieldust
    • 1
  • Zeev Shoham
    • 1
  1. 1.Reproductive Medicine and IVF UnitKaplan Medical Center, Rehovot, Israel, affiliated with the Hadassah Medical School, the Hebrew UniversityJerusalemIsrael
  2. 2.Department of Obstetrics and Gynecology, Reproductive Medicine and IVF UnitKaplan Medical CenterRehovotIsrael

Personalised recommendations