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01-12-2017 | Gynecologic Endocrinology and Reproductive Medicine

Time-lapse imaging provides further evidence that planar arrangement of blastomeres is highly abnormal

Authors: Thomas Ebner, Alexandra Höggerl, Peter Oppelt, Elisabeth Radler, Simon-Hermann Enzelsberger, Richard B. Mayer, Erwin Petek, Omar Shebl

Published in: Archives of Gynecology and Obstetrics | Issue 6/2017

Abstract

Purpose

Recently, guidelines on the annotation of dynamic human embryo monitoring recommended screening for the presence of planar blastomere arrangement at the 4-cell stage. This observational study was set up in order to analyze whether developmental kinetics of planar human embryos are different from tetrahedral ones.

Methods

Therefore, embryos of 115 consecutive ICSI patients (showing 32 planar and 554 tetrahedral embryos) were cultured in a new time-lapse system (Miri TL) and their embryos were annotated for morphokinetic development and screened for irregular cleavages and morphological dysmorphisms.

Results

Significantly less planar embryos reached blastocyst stage and showed worse quality as compared to regular tetrahedral embryos. The rate of bi- and/or multinucleation was also significantly higher in the affected group. Irregular cleavages, particularly embryo rolling, were more often seen in planar embryos. Morphokinetics between planar and tetrahedral were distinguishable up to 4-cell stage (t2–t4), thereafter the observed delay in planar embryos (t8) was more likely the result of a higher rate of arrested embryos in the planar group.

Conclusions

Planar embryos are associated with both a significant increase in irregular cleavage as well as a delay in preimplantation development. This indicates that planar embryos are rather abnormal and should only be considered for transfer if no other embryos are available.

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Wirleitner B, Schuff M, Stecher A, Murtinger M, Vanderzwalmen P (2016) Pregnancy and birth outcomes following fresh or vitrified embryo transfer according to blastocyst morphology and expansion stage, and culturing strategy for delayed development. Hum Reprod 31:1685–1695CrossRefPubMed

Ajduk A, Zernicka-Goetz M (2015) Polarity and cell division orientation in the cleavage embryo: from worm to human. Mol Hum Reprod 22:691–703CrossRefPubMed

Erenus M, Zouves C, Rajamahendran P, Leung S, Fluker M, Gomel V (1991) The effect of embryo quality on subsequent pregnancy rates after in vitro fertilization. Fertil Steril 56:707–710CrossRefPubMed

Giorgetti C, Terriou P, Auquier P, Hans E, Spach SL, Salzmann J et al (1995) Embryo score to predict implantation after in vitro fertilization: based on 957 single embryo transfers. Hum Reprod 10:2427–2431CrossRefPubMed

De Cássia Savio Figueira R, Souza Setti A, Paes De Almeida Ferreira Braga D, Iaconelli A Jr, Borges E Jr (2010) Blastomere multinucleation: contributing factors and effects on embryo development and clinical outcome. Hum Fertil (Camb) 13:143–150CrossRef

Hardarson T, Hanson C, Sjögren A, Lundin K (2001) Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation. Hum Reprod 16:313–318CrossRefPubMed

Alikani M, Cohen J, Tomkin G, Garrisi GJ, Mack C, Scott RT (1999) Human embryo fragmentation in vitro and its implications for pregnancy and implantation. Fertil Steril 71:836–842CrossRefPubMed

Ebner T, Shebl O, Moser M, Sommergruber M, Tews G (2008) Developmental fate of ovoid oocytes. Hum Reprod 23:62–66CrossRefPubMed

Ebner T, Tews G, Sommergruber M, Moser M (2005) Cytoplasmic pitting has a negative influence on implantation outcome. J Assist Reprod Genet 22:239–244CrossRefPubMedPubMedCentral

10.

Alpha Scientists in Reproductive Medicine, ESHRE Special Interest Group of Embryology (2011) The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Reprod Biomed Online 22:632–646

11.

Rhenman A, Berglund L, Brodin T, Olovsson M, Milton K, Hadziosmanovic N et al (2015) Which set of embryo variables is most predictive for live birth? A prospective study in 6252 single embryo transfers to construct an embryo score for the ranking and selection of embryos. Hum Reprod 30:28–36CrossRefPubMed

12.

Lundin K, Bergh C, Hardarson T (2001) Early embryo cleavage is a strong indicator of embryo quality in human IVF. Hum Reprod 16:2552–2557CrossRef

13.

Moriwaki T, Suganuma N, Hayakawa M, Hibi H, Katsumata Y, Oguchi H et al (2004) Embryo evaluation by analyzing blastomere nuclei. Hum Reprod 19:152–156CrossRefPubMed

14.

Saldeen P, Sundström P (2005) Nuclear status of four-cell preembryos predicts implantation potential in in vitro fertilization treatment cycles. Fertil Steril 84:584–589CrossRefPubMed

15.

Lemmen JG, Agerholm I, Ziebe S (2008) Kinetic markers of human embryo quality using time-lapse recordings of IVF/ICSI-fertilized oocytes. Reprod Biomed Online 17:385–391CrossRefPubMed

16.

Ciray HN, Campbell A, Agerholm IE, Aguilar J, Chamayou S, Esbert M et al (2014) Time-Lapse User Group. Proposed guidelines on the nomenclature and annotation of dynamic human embryo monitoring by a time-lapse user group. Hum Reprod 29:2650–2660CrossRefPubMed

17.

Rubio I, Kuhlmann R, Agerholm I, Kirk J, Herrero J, Escribá MJ et al (2012) Limited implantation success of direct-cleaved human zygotes: a time-lapse study. Fertil Steril 98:1458–1463CrossRefPubMed

18.

Almagor M, Or Y, Fieldust S, Shoham Z (2015) Irregular cleavage of early preimplantation human embryos: characteristics of patients and pregnancy outcomes. J Assist Reprod Genet 32:1811–1815CrossRefPubMedPubMedCentral

19.

Liu Y, Chapple V, Roberts P, Matson P (2014) Prevalence, consequence, and significance of reverse cleavage by human embryos viewed with the use of the embryoscope time-lapse video system. Fertil Steril 102(1295–1300):e2

20.

Cruz M, Garrido N, Herrero J, Pérez-Cano I, Muñoz M, Meseguer M (2012) Timing of cell division in human cleavage-stage embryos is linked with blastocyst formation and quality. Reprod Biomed Online 25:371–381CrossRefPubMed

21.

Ebner T, Maurer M, Shebl O, Moser M, Mayer RB, Duba HC et al (2011) Planar embryos have poor prognosis in terms of blastocyst formation and implantation. Reprod Biomed Online 25:267–272CrossRef

22.

Paternot G, Debrock S, De Neubourg D, D’Hooghe TM, Spiessens C (2014) The spatial arrangement of blastomeres at the 4-cell stage and IVF outcome. Reprod Biomed Online 28:198–203CrossRefPubMed

23.

Liu Y, Chapple V, Roberts P, Matson P (2015) Clinical significance of intercellular contact at the four-cell stage of human embryos, and the use of abnormal cleavage patterns to identify embryos with low implantation potential: a time-lapse study. Fertil Steril 103(1485–1491):e1

24.

Ebner T, Oppelt P, Radler E, Allerstorfer C, Habelsberger A, Mayer RB et al (2016) Morphokinetics of vitrified and warmed blastocysts predicts implantation potential. J Assist Reprod Genet 34:239–244CrossRefPubMed

25.

Gardner RL (2002) Experimental analysis of second cleavage in the mouse. Hum Reprod 12:3178–3189CrossRef

26.

Cauffman G, Verheyen G, Tournaye H, Van de Velde H (2014) Developmental capacity and pregnancy rate of tetrahedral-versus non-tetrahedral-shaped 4-cell stage human embryos. J Assist Reprod Genet 31:427–434CrossRefPubMedPubMedCentral

27.

Piotrowska-Nitsche K, Zernicka-Goetz M (2005) Spatial arrangement of individual 4-cell stage blastomeres and the order in which they are generated correlate with blastocyst pattern in the mouse embryo. Mech Dev 122:487–500CrossRefPubMed

28.

Piotrowska-Nitsche K, Perea-Gomez A, Haraguchi S, Zernicka-Goetz M (2005) Four-cell stage mouse blastomeres have different developmental properties. Development 132:479–490CrossRefPubMed

29.

Antczak M, Van Blerkom J (1997) Oocyte influences on early development: the regulatory proteins leptin and STAT3 are polarized in mouse and human oocytes and differentially distributed within the cells of the preimplantation stage embryo. Mol Hum Reprod 3:1067–1086CrossRefPubMed

30.

Edwards RG, Beard HK (1997) Oocyte polarity and cell determination in early mammalian embryos. Mol Hum Reprod 3:863–905CrossRefPubMed

31.

Hiiragi T, Solter D (2004) First cleavage plane of the mouse egg is not predetermined but defined by the topology of the two apposing pronuclei. Nature 430(6997):360–364CrossRefPubMed

32.

Motosugi N, Bauer T, Polanski Z, Solter D, Hiiragi T (2005) Polarity of the mouse embryo is established at blastocyst and is not prepatterned. Genes Dev 19:1081–1092CrossRefPubMedPubMedCentral

33.

Van de Velde H, Cauffman G, Tournaye H, Devroey P, Liebaers I (2008) The four blastomeres of a 4-cell stage human embryo are able to develop individually into blastocysts with inner cell mass and trophectoderm. Hum Reprod 23:1742–1747CrossRefPubMed

34.

De Paepe C, Krivega M, Cauffman G, Geens M, Van de Velde H (2014) Totipotency and lineage segregation in the human embryo. Mol Hum Reprod 20:599–618CrossRefPubMed

35.

Ebner T, Oppelt P, Mayer RB, Shebl O (2014) Developmental capacity and pregnancy rate of tetrahedral-versus non-tetrahedral-shaped 4-cell stage human embryos. J Assist Reprod Genet 31:621CrossRefPubMedPubMedCentral

36.

Goodman LR, Goldberg J, Falcone T, Austin C, Desai N (2016) Does the addition of time-lapse morphokinetics in the selection of embryos for transfer improve pregnancy rates? A randomized controlled trial. Fertil Steril 105:275–285CrossRefPubMed

37.

Ergin EG, Calişkan E, Yalçinkaya E, Oztel Z, Cökelez K, Ozay A et al (2014) Frequency of embryo multinucleation detected by time-lapse system and its impact on pregnancy outcome. Fertil Steril 102(1029–1033):e1

38.

Balakier H, Sojecki A, Motamedi G, Librach C (2016) Impact of multinucleated blastomeres on embryo developmental competence, morphokinetics, and aneuploidy. Fertil Steril 106(608–614):e2

39.

Joergensen MW, Agerholm I, Hindkjaer J, Bolund L, Sunde L, Ingerslev HJ et al (2014) Altered cleavage patterns in human tripronuclear embryos and their association to fertilization method: a time-lapse study. J Assist Reprod Genet 31:435–442CrossRefPubMedPubMedCentral

40.

Yang Z, Zhang J, Salem SA, Liu X, Kuang Y, Salem RD et al (2014) 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 Genom 7:38CrossRef

41.

Chawla M, Fakih M, Shunnar A, Bayram A, Hellani A, Perumal V et al (2015) Morphokinetic analysis of cleavage stage embryos and its relationship to aneuploidy in a retrospective time-lapse imaging study. J Assist Reprod Genet 32:69–75CrossRefPubMed

42.

Kramer YG, Kofinas JD, Melzer K, Noyes N, McCaffrey C, Buldo-Licciardi J et al (2014) Assessing morphokinetic parameters via time lapse microscopy (TLM) to predict euploidy: are aneuploidy risk classification models universal? J Assist Reprod Genet 31:1231–1242CrossRefPubMedPubMedCentral

43.

Rienzi L, Capalbo A, Stoppa M, Romano S, Maggiulli R, Albricci L et al (2015) No evidence of association between blastocyst aneuploidy and morphokinetic assessment in a selected population of poor-prognosis patients: a longitudinal cohort study. Reprod Biomed Online 30:57–66CrossRefPubMed

44.

Campbell A, Fishel S, Bowman N, Duffy S, Sedler M, Hickman CF (2013) Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics. Reprod Biomed Online 26:477–485CrossRefPubMed

45.

Stecher A, Vanderzwalmen P, Zintz M, Wirleitner B, Schuff M, Spitzer D et al (2014) Transfer of blastocysts with deviant morphological and morphokinetic parameters at early stages of in vitro development: a case series. Reprod Biomed Online 28:424–435CrossRefPubMed

46.

Fan YL, Han SB, Wu LH, Wang YP, Huang GN (2016) Abnormally cleaving embryos are able to produce live births: a time-lapse study. J Assist Reprod Genet 33:379–385CrossRefPubMedPubMedCentral

Title: Time-lapse imaging provides further evidence that planar arrangement of blastomeres is highly abnormal
Authors: Thomas Ebner
Alexandra Höggerl
Peter Oppelt
Elisabeth Radler
Simon-Hermann Enzelsberger
Richard B. Mayer
Erwin Petek
Omar Shebl
Publication date: 01-12-2017
Publisher: Springer Berlin Heidelberg
Published in: Archives of Gynecology and Obstetrics / Issue 6/2017
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI: https://doi.org/10.1007/s00404-017-4531-5

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Time-lapse imaging provides further evidence that planar arrangement of blastomeres is highly abnormal

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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