Alternative patterns of partial embryo compaction: prevalence, morphokinetic history and possible implications

Published:December 01, 2019DOI:


      Research question

      The morula stage is a poorly understood developmental stage. In the morula, cell compaction can involve all or only some blastomeres, with largely unknown implications. Here, the prevalence, underlying morphokinetic mechanisms and possible consequences of partial compaction, were investigated.


      Preimplantation genetic testing for aneuploidies (PGT-A) cycles of women whose embryos were observed by time-lapse technology were studied. PGT-A data, generated by array comparative genomic hybridization analysis and assessed in three age groups (≤34, 35–39 and ≥40 years), were obtained from trophectoderm biopsies after development to blastocyst stage.


      Compaction occurred according to three modalities: (i) full compaction, with all blastomeres included (FCM); partial compaction (partially compacted morula [PCM]), with blastomeres (ii) excluded from the outset (excluded-PCM) or (iii) extruded after compaction (extruded-PCM). Partial compaction occurred more frequently than full compaction. Excluded-PCM displayed the slowest morphokinetics at most stages and were most often associated with abnormal cleavage. After compaction, embryo degeneration was more frequently associated with cell extrusion. In excluded-PCM, loss of ≥2 cells impacted blastocyst rate. In embryos of both younger and middle age groups, no statistical differences were observed in the rate of aneuploidy in relation to the three compaction groups, unlike what observed in ≥40 years women. Implantation rates after transfer of euploid blastocysts were not statistically different between the three groups.


      Alternative modalities of incomplete compaction were detected. Such patterns are characterized by different morphokinetic behaviours overarching the entire preimplantation development, and by different developmental abilities.


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        • Alikani M.
        Epithelial cadherin distribution in abnormal human pre-implantation embryos.
        Hum. Reprod. 2005; 20: 3369-3375
        • Alpha Scientists in Reproductive Medicine, ESHRE Special Interest Group of Embryology
        The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.
        Hum. Reprod. 2011; 26: 1270-1283
        • Barbash-Hazan S.
        • Frumkin T.
        • Malcov M.
        • Yaron Y.
        • Cohen T.
        • Azem F.
        • Amit A.
        • Ben-Yosef D.
        Preimplantation aneuploid embryos undergo self-correction in correlation with their developmental potential.
        Fertil. Steril. 2009; 92: 890-896
        • Bissiere S.
        • Gasnier M.
        • Alvarez Y.D.
        • Plachta N.
        Cell Fate Decisions During Preimplantation Mammalian Development.
        Current Topics in Developmental Biology. 2018: 37-58
        • Borini A.
        • Tarozzi N.
        • Bizzaro D.
        • Bonu M.A.
        • Fava L.
        • Flamigni C.
        • Coticchio G.
        Sperm DNA fragmentation: Paternal effect on early post-implantation embryo development in ART.
        Hum. Reprod. 2006; 21: 2876-2881
        • Coticchio G.
        • Lagalla C.
        • Sturmey R.
        • Pennetta F.
        • Borini A.
        The enigmatic morula: mechanisms of development, cell fate determination, self-correction and implications for ART.
        Hum. Reprod. Update. 2019; 25: 422-438
        • 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: 61-66
      1. ESHRE Atlas of Human Embryology[WWW Document], n.d.

        • Fabozzi G.
        • Alteri A.
        • Rega E.
        • Starita M.F.
        • Piscitelli C.
        • Giannini P.
        • Colicchia A.
        Morphological assessment on day 4 and its prognostic power in selecting viable embryos for transfer.
        Zygote. 2015; 24: 477-484
        • Feil D.
        • Henshaw R.C.
        • Lane M.
        Day 4 embryo selection is equal to Day 5 using a new embryo scoring system validated in single embryo transfers.
        Hum. Reprod. 2008; 23: 1505-1510
        • Fragouli E.
        • Alfarawati S.
        • Spath K.
        • Wells D.
        Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos.
        Mol. Hum. Reprod. 2014; 20: 117-126
        • Gardner D.K.
        • Lane M.
        • Stevens J.
        • Schlenker T.
        • Schoolcraft W.B.
        Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer.
        Fertil. Steril. 2000; 73: 1155-1158
        • Ivec M.
        • Kovacic B.
        • Vlaisavljevic V.
        Prediction of human blastocyst development from morulas with delayed and/or incomplete compaction.
        Fertil. Steril. 2011; 96
        • Iwata K.
        • Yumoto K.
        • Sugishima M.
        • Mizoguchi C.
        • Kai Y.
        • Iba Y.
        • Mio Y.
        Analysis of compaction initiation in human embryos by using time-lapse cinematography.
        J. Assist. Reprod. Genet. 2014; 31: 421-426
        • Jedrusik A.
        Making the first decision: lessons from the mouse.
        Reprod. Med. Biol. 2015; 14: 135-150
        • Johnson M.H.
        • Ziomek C.A.
        The foundation of two distinct cell lineages within the mouse morula.
        Cell. 1981; 24: 71-80
        • Lagalla C.
        • Barberi M.
        • Orlando G.
        • Sciajno R.
        • Bonu M.A.
        • Borini A.
        A quantitative approach to blastocyst quality evaluation: morphometric analysis and related IVF outcomes.
        J. Assist. Reprod. Genet. 2015; 32: 705-712
        • Lagalla C.
        • Tarozzi N.
        • Sciajno R.
        • Wells D.
        • Di Santo M.
        • Nadalini M.
        • Distratis V.
        • Borini A.
        Embryos with morphokinetic abnormalities may develop into euploid blastocysts.
        Reprod. Biomed. Online. 2017; 34: 137-146
        • Leese H.J.
        Metabolism of the preimplantation embryo: 40 Years on.
        Reproduction. 2012; 143: 417-427
        • McCoy R.C.
        • Newnham L.J.
        • Ottolini C.S.
        • Hoffmann E.R.
        • Chatzimeletiou K.
        • Cornejo O.E.
        • Zhan Q.
        • Zaninovic N.
        • Rosenwaks Z.
        • Petrov D.A.
        • Demko Z.P.
        • Sigurjonsson S.
        • Handyside A.H.
        Tripolar chromosome segregation drives the association between maternal genotype at variants spanning PLK4 and aneuploidy in human preimplantation embryos.
        Human Molecular Genetics. 2018; 27: 2573-2585
        • Tao J.
        • Tamis R.
        • Fink K.
        • Williams B.
        • Nelson-White T.
        • Craig R.
        The neglected morula/compact stage embryo transfer.
        Hum. Reprod. 2002; 17: 1513-1518
        • Veeck L.L.
        • Zaninovic N.
        An atlas of human blastocysts.
        Parthenon Pub. Group, 2003
        • Watson A.J.
        The cell biology of blastocyst development.
        Mol. Reprod. Dev. 1992; 33: 492-504
        • White M.D.
        • Bissiere S.
        • Alvarez Y.D.
        • Plachta N.
        Mouse Embryo Compaction.
        Current Topics in Developmental Biology. 2016: 235-258
        • White M.D.
        • Zenker J.
        • Bissiere S.
        • Plachta N.
        • Lechler T.
        • Salas R.C.
        How cells change shape and position in the early mammalian embryo This review comes from a themed issue on Cell Architecture.
        Curr. Opin. Cell Biol. 2017; 44: 7-13
      2. World Heatlh Organization, 2010. Laboratory manual for the examination and processing of human semen. Geneva.

        • Zacà C.
        • Bazzocchi A.
        • Pennetta F.
        • Bonu M.A.
        • Coticchio G.
        • Borini A.
        Cumulative live birth rate in freeze-all cycles is comparable to that of a conventional embryo transfer policy at the cleavage stage but superior at the blastocyst stage.
        Fertil. Steril. 2018; 110: 703-709
        • Zakharova E.E.
        • Zaletova V.V.
        • Krivokharchenko A.S.
        Biopsy of Human Morula-Stage Embryos: Outcome of 215 IVF/ICSI Cycles with PGS.
        PLoS ONE. 2014; 9:e106433–6
        • Zhan Q.
        • Ye Z.
        • Clarke R.
        • Rosenwaks Z.
        • Zaninovic N.
        Direct unequal cleavages: Embryo developmental competence, genetic constitution and clinical outcome.
        PLoS One. 2016; 11


      Cristina Lagalla developed her career as clinical embryologist at Sant’Orsola Hospital, Bologna and subsequently at SISMER IVF, Bologna. She’s currently senior embryologist at Family and Fertility Center, Bologna. Her major interests are PGT and embryo morphokinetics. She published 25 papers and has been lecturer at several university courses.
      Key message
      Time-lapse and genomic technologies have been used to detect for the first time alternative modalities of embryo compaction. This provides novel information on a developmental stage largely neglected in human assisted reproduction, extending the range of applicability of time-lapse microscopy for studying developmental processes and assessing embryo quality.