Advertisement

A multicenter prospective study to assess the effect of early cleavage on embryo quality, implantation, and live-birth rate

      Objective

      To investigate the impact of early cleavage (EC) on embryo quality, implantation, and live-birth rates.

      Design

      Prospective cross-sectional study.

      Setting

      Multicenter study.

      Patient(s)

      Seven hundred embryo transfers and 1,028 early-stage human embryos.

      Intervention(s)

      None.

      Main Outcome Measure(s)

      Implantation according to the presence of EC and embryo quality.

      Result(s)

      The presence of EC is associated with embryo quality, especially in cycles with autologous oocytes. However, the use of EC as an additional criterion for selecting an embryo for transfer does not appear to significantly improve likelihood of implantation. Furthermore, embryos that presented EC had live-birth rates per implanted embryo similar to those that did not show any sign of cleavage.

      Conclusion(s)

      At least for conventional embryo culture and morphologic evaluations, the additional evaluation of EC in embryos may not be valuable to improve embryo implantation.

      Key Words

      To read this article in full you will need to make a payment

      References

        • Ciray H.N.
        • Karagenc L.
        • Ulug U.
        • Bener F.
        • Bahceci M.
        Use of both early cleavage and day 2 mononucleation to predict embryos with high implantation potential in intracytoplasmic sperm injection cycles.
        Fertil Steril. 2005; 84: 1411-1416
        • Ciray H.N.
        • Karagenc L.
        • Ulug U.
        • Bener F.
        • Bahceci M.
        Early cleavage morphology affects the quality and implantation potential of day 3 embryos.
        Fertil Steril. 2006; 85: 358-365
        • Ciray N.
        Even early cleavage and day 2 embryo score [author reply].
        Reprod Biomed Online. 2007; 14: 666
        • Lundin K.
        • Bergh C.
        • Hardarson T.
        Early embryo cleavage is a strong indicator of embryo quality in human IVF.
        Hum Reprod. 2001; 16: 2652-2657
        • Neuber E.
        • Rinaudo P.
        • Trimarchi J.R.
        • Sakkas D.
        Sequential assessment of individually cultured human embryos as an indicator of subsequent good quality blastocyst development.
        Hum Reprod. 2003; 18: 1307-1312
        • Hardarson T.
        • Hanson C.
        • Sjogren A.
        • Lundin K.
        Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation.
        Hum Reprod. 2001; 16: 313-318
        • Salumets A.
        • Hyden-Granskog C.
        • Makinen S.
        • Suikkari A.M.
        • Tiitinen A.
        • Tuuri T.
        Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures.
        Hum Reprod. 2003; 18: 821-825
        • Shoukir Y.
        • Campana A.
        • Farley T.
        • Sakkas D.
        Early cleavage of in-vitro fertilized human embryos to the 2-cell stage: a novel indicator of embryo quality and viability.
        Hum Reprod. 1997; 12: 1531-1536
        • Shoukir Y.
        • Chardonnens D.
        • Campana A.
        • Bischof P.
        • Sakkas D.
        The rate of development and time of transfer play different roles in influencing the viability of human blastocysts.
        Hum Reprod. 1998; 13: 676-681
        • Rienzi L.
        • Ubaldi F.
        • Iacobelli M.
        • Romano S.
        • Minasi M.G.
        • Ferrero S.
        • et al.
        Significance of morphological attributes of the early embryo.
        Reprod Biomed Online. 2005; 10: 669-681
        • Van Montfoort A.P.
        • Dumoulin J.C.
        • Kester A.D.
        • Evers J.L.
        Early cleavage is a valuable addition to existing embryo selection parameters: a study using single embryo transfers.
        Hum Reprod. 2004; 19: 2103-2108
        • Meseguer M.
        • Herrero J.
        • Tejera A.
        • Hilligsoe K.M.
        • Ramsing N.B.
        • Remohi J.
        The use of morphokinetics as a predictor of embryo implantation.
        Hum Reprod. 2011; 26: 2658-2671
        • Wong C.C.
        • Loewke K.E.
        • Bossert N.L.
        • Behr B.
        • De Jonge C.J.
        • Baer T.M.
        • et al.
        Noninvasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage.
        Nat Biotechnol. 2010; 28: 1115-1121
      1. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.
        Hum Reprod. 2011; 26: 1270-1283
        • Hale C.A.
        • Fleiss J.L.
        Interval estimation under two study designs for kappa with binary classifications.
        Biometrics. 1993; 49: 523-534
        • Ardoy M.
        • Calderón G.
        • Arroyo G.
        • Cuadros J.
        • Figueroa M.
        • Herrer R
        • et al.
        ASEBIR criteria for the morphological evaluation of human oocytes, early embryos and blastocysts.
        ASEBIR clinical embryology papers. 2008; (Legal deposit M 6826-210. Available at:) (Last accessed January 28, 2014)
        • Giorgetti C.
        • Hans E.
        • Terriou P.
        • Salzmann J.
        • Barry B.
        • Chabert-Orsini V.
        • et al.
        Early cleavage: an additional predictor of high implantation rate following elective single embryo transfer.
        Reprod Biomed Online. 2007; 14: 85-91
        • Fenwick J.
        • Platteau P.
        • Murdoch A.P.
        • Herbert M.
        Time from insemination to first cleavage predicts developmental competence of human preimplantation embryos in vitro.
        Hum Reprod. 2002; 17: 407-412
        • Sakkas D.
        • Shoukir Y.
        • Chardonnens D.
        • Bianchi P.G.
        • Campana A.
        Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability.
        Hum Reprod. 1998; 13: 182-187
        • Hashimoto S.
        • Murata Y.
        • Kikkawa M.
        • Sonoda M.
        • Oku H.
        • Murata T.
        • et al.
        Successful delivery after the transfer of twice-vitrified embryos derived from in vitro matured oocytes: a case report.
        Hum Reprod. 2007; 22: 221-223
        • Emiliani S.
        • Fasano G.
        • Vandamme B.
        • Vannin A.S.
        • Verdoodt M.
        • Biramane J.
        • et al.
        Impact of the assessment of early cleavage in a single embryo transfer policy.
        Reprod Biomed Online. 2006; 13: 255-260
        • Rubio I.
        • Kuhlmann R.
        • Agerholm I.
        • Kirk J.
        • Herrero J.
        • Escriba M.J.
        • et al.
        Limited implantation success of direct-cleaved human zygotes: a time-lapse study.
        Fertil Steril. 2012; 98: 1458-1463
        • Lemmen J.G.
        • Agerholm I.
        • Ziebe S.
        Kinetic markers of human embryo quality using time-lapse recordings of IVF/ICSI–fertilized oocytes.
        Reprod Biomed Online. 2008; 17: 385-391
        • Artley J.K.
        • Braude P.R.
        • Johnson M.H.
        Gene activity and cleavage arrest in human pre-embryos.
        Hum Reprod. 1992; 7: 1014-1021
        • Braude P.
        • Bolton V.
        • Moore S.
        Human gene expression first occurs between the four- and eight-cell stages of preimplantation development.
        Nature. 1988; 332: 459-461
        • Cruz M.
        • Garrido N.
        • Herrero J.
        • Perez-Cano I.
        • Munoz M.
        • Meseguer M.
        Timing of cell division in human cleavage-stage embryos is linked with blastocyst formation and quality.
        Reprod Biomed Online. 2012; 25: 371-381
        • 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: 332-337

      Linked Article

      • Should early cleavage be assessed in routine practice?
        Fertility and SterilityVol. 101Issue 5
        • Preview
          In a recent study (1), an important question has been presented, namely: “Should we assess early cleavage between 25 and 27 hours after insemination, with the aim of yielding any benefit in the clinical outcomes?” The message I have been delivered by the results has been: “There was not any benefit of early cleavage assessment, unless all transfer embryos were of suboptimal quality.” Because they are promoted by the Asociación Española para el Estudio de la Biología Reproductiva with a clear aim to conclude with a scientifically based recommendation to embryologists, I think the results need to be evaluated under scrutiny.
        • Full-Text
        • PDF