Advertisement
Article| Volume 43, ISSUE 4, P627-636, October 2021

Download started.

Ok

Early embryo development anomalies identified by time-lapse system: prevalence and impacting factors

      Abstract

      Research question

      What is the prevalence of embryo abnormal early cleavage (ACL) identified by time lapse and factors related to patients and treatment that explain ACL occurrence?

      Design

      A single-centre, retrospective cohort study. Data were collected on all IVF cycles for which embryos were observed in the EmbryoScope® between December 2015 and August 2017. Only diploid zygotes cleaved on day 2 were included. The study included 318 cycles (250 couples and 1343 embryos). Embryo videos were retrospectively analysed for ACL. The prevalence of each type of ACL was recorded. The influence of clinical factors (whether they were intrinsic to patients or specific to IVF treatment) on ACL occurrence was analysed in multivariate multilevel mixed-effect logistic regression analysis.

      Results

      A high prevalence of ACL was observed: 37.6% (505/1343) of embryos presented at least one ACL, 22.8% (306/1343) a trichotomous mitosis, 25.8% (347/1343) a rapid cleavage, 6.7% (90/1343) a cell fusion and two or more ACL (16.1%). Part of the variation (12–25%) in ACL occurrence could be explained by embryo origin. Trichotomous mitosis and two or more ACL phenotypes were less likely to occur in women with endometriosis or tubal pathology and tubal pathology alone, respectively. No factor related to IVF cycles was found to be statistically associated with ACL occurrence.

      Conclusions

      Our findings emphasize the importance of considering embryo origin when interpreting studies focusing on embryo characteristics and factors that could affect their quality. The present study is limited by a small sample size of known embryo implantations and monocentric criterion.

      KEYWORDS

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

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Reproductive BioMedicine Online
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Almagor M.
        • Or Y.
        • Fieldust S.
        • Shoham Z.
        Irregular cleavage of early preimplantation human embryos: charapid cleavage teristics of patients and pregnancy outcomes.
        J. Assist. Reprod. Genet. 2015; 32: 1811-1815https://doi.org/10.1007/s10815-015-0591-2
        • Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group Embryology
        Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.
        Hum. Reprod. 2011; 22: 632-646https://doi.org/10.1093/humrep/der037
        • Auger J.
        • Eustache F.
        • Andersen A.G.
        • Irvine D.S.
        • Jørgensen N.
        • Skakkebæk N.E.
        • Suominen J.
        • Toppari J.
        • Vierula M.
        • Jouannet P.
        Sperm morphological defects related to environment, lifestyle and medical history of 1001 male partners of pregnant women from four European cities.
        Hum. Reprod. 2001; 16: 2710-2717https://doi.org/10.1093/humrep/16.12.2710
        • Basile N.
        • Morbeck D.
        • García-Velasco J.
        • Bronet F.
        • Meseguer M.
        Type of culture media does not affect embryo kinetics: a time-lapse analysis of sibling oocytes.
        Hum. Reprod. 2013; 28: 634-641https://doi.org/10.1093/humrep/des462
        • Basile N.
        • Vime P.
        • Florensa M.
        • Aparicio Ruiz B.
        • Garcian Velasco J.A.
        • Remohi J.
        • Meseguer M.
        The use of morphokinetics as a predictor of implantation: a multicentric study to define and validate an algorithm for embryo selection.
        Hum. Reprod. 2015; 30: 276-283https://doi.org/10.1093/humrep/deu331
        • Boynukalin F.K.
        • Serdarogullari M.
        • Gultomruk M.
        • Coban O.
        • Findikli N.
        • Bahceci M.
        The impact of endometriosis on early embryo morphokinetics: a case-control study.
        Syst. Biol. Reprod. Med. 2019; 65: 250-257https://doi.org/10.1080/19396368.2019.1573275
        • Chamayou S.
        • Patrizio P.
        • Storapid cleavage i G.
        • Tomaselli V.
        • Alecci C.
        • Ragolia C.
        • Crescendo C.
        • Guglielmino A.
        The use of morphokinetic parameters to select all embryos with full capacity to implant.
        J. Assist. Reprod. Genet. 2013; 30: 703-710https://doi.org/10.1007/s10815-013-9992-2
        • Ciray HN
        • Aksoy T
        • Goktas C
        • Ozturk B
        • Bahceci M
        • Ciray HN
        • et al.
        Time-lapse evaluation of human embryo development in single versus sequential culture media–a sibling oocyte study.
        J. Assist. Reprod. Genet. 2012; 29: 891-900https://doi.org/10.1007/s10815-012-9818-7
        • Ciray H.N.
        • Campbell A.
        • Agerholm I.E.
        • Aguilar J.
        • Chamayou S.
        • Esbert M.
        • Sayed S.
        Proposed guidelines on the nomenclature and annotation of dynamic human embryo monitoring by a time-lapse user group.
        Hum. Reprod. 2014; 29: 2650-2660https://doi.org/10.1093/humrep/deu278
        • Desai N.
        • Goldberg J.M.
        • Austin C.
        • Falcone T.
        Are cleavage anomalies, multinucleation, or specific cell cycle kinetics observed with time-lapse imaging predictive of embryo developmental capacity or ploidy?.
        Fertil. Steril. 2018; 109: 665-674https://doi.org/10.1016/j.fertnstert.2017.12.025
        • Fan Y.L.
        • Han S.B.
        • Wu L.H.
        • Wang Y.P.
        • Huang G.N.
        Abnormally cleaving embryos are able to produce live births: a time-lapse study.
        J. Assist. Reprod. Genet. 2016; 33: 379-385https://doi.org/10.1007/s10815-015-0632-x
        • Fréour T.
        • Le Fleuter N.
        • Lammers J.
        • Splingart C.
        • Reignier A.
        • Barriere P.
        External validation of a time-lapse prediction model.
        Fertil. Steril. 2015; 103: 917-922https://doi.org/10.1016/j.fertnstert.2014.12.111
        • Hox J.J.
        Applied Multilevel Analysis.
        TT-Publikaties, Amsterdam1995: 119
        • Kirkegaard K.
        • Sundvall L.
        • Erlandsen M.
        • Hindkjær J.J.
        • Knudsen U.B.
        • Ingerslev H.J.
        Timing of human preimplantation embryonic development is confounded by embryo origin.
        Hum. Reprod. 2016; 31: 324-331https://doi.org/10.1093/humrep/dev296
        • Kong X.
        • Yang S.
        • Gong F.
        • Lu C.
        • Zhang S.
        • Lu G.
        • Lin G.
        The relationship between cell number, division behavior and developmental potential of cleavage stage human embryos: a time-lapse study.
        PLoS One. 2016; 11e0153697https://doi.org/10.1371/journal.pone.0153697
        • 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: 385-391https://doi.org/10.1016/s1472-6483(10)60222-2
        • Liu Y.
        • Chapple V.
        • Roberts P.
        • Matson P.
        Prevalence, consequence, and significance of reverse cleavage by human embryos viewed with the use of the Embryoscope time-lapse video system.
        Fertil. Steril. 2014; 102: 1295-1300https://doi.org/10.1016/j.fertnstert.2014.07.1235
        • 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.
        Hum. Mol. Genet. 2018; 27 (https://doi.org): 2573-2585https://doi.org/10.1093/hmg/ddy147
        • Meseguer M.
        • Herrero J.
        • Tejera A.
        • Hilligsøe K.M.
        • Ramsing N.B.
        • Remohí J.
        The use of morphokinetics as a predictor of embryo implantation.
        Hum. Reprod. 2011; 26: 2658-2671https://doi.org/10.1093/humrep/der256
        • 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: 1481-1489https://doi.org/10.1016/j.fertnstert.2012.08.016
        • Petersen B.M.
        • Boeln M.
        • Montag M.
        • Gardner D.K.
        Development of a generally applicable morphokinetic algorithm capable of predicting the implantation potential of embryos transferred on day 3.
        Hum. Reprod. 2016; 31: 2231-2244https://doi.org/10.1093/humrep/dew188
        • Alviggi C.
        • Andersen C.Y.
        • Buehler K.
        • Conforti A.
        • De Placido G.
        • Esteves S.C.
        • Fischer R.
        • Galliano D.
        • Polyzos N.P.
        • Sunkara S.K.
        • M Ubaldi F.
        • Humaidan P.
        • Poseidon Group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number)
        A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept.
        Fertil. Steril. 2016; 105: 1452-1453https://doi.org/10.1016/j.fertnstert.2016.02.005
        • Radzinsky V.Y.
        • Orazov M.R.
        • Ivanov I.I.
        • Khamoshina M.B.
        • Kostin .IN.
        • Kavteladze E.V.
        • Shustova V.B.
        Implantation failures in women with infertility associated endometriosis.
        Gynecol. Endocrinol. 2019; 35: 27-30https://doi.org/10.1080/09513590.2019.1632089
        • Ramos L.
        • de Boer P.
        The Role of the Oocyte in Remodeling of Male Chromatin and DNA Repair: Are Events During the Zygotic Cell Cycle of Relevance to ART?.
        in: Rapid cleavage owsky C. Schlegel P. Fauser B. Carrell D. Biennial Review of Infertility. Springer, Boston, MA2011https://doi.org/10.1007/978-1-4419-8456-2_16
        • Reignier A.
        • Girard J.M.
        • Lammers J.
        • Chtourou S.
        • Lefebvre T.
        • Barriere P.
        • Fréour T.
        Performance of Day 5 KIDScore™ morphokinetic prediction models of implantation and live birth after single blastocyst transfer.
        J. Assist. Reprod. Genet. 2019; 36: 2279-2285https://doi.org/10.1007/s10815-019-01567-x
        • Rubio I.
        • Kuhlmann R.
        • Agerholm I.
        • Kirk J.
        • Herrero J.
        • Escriba M.J.
        • Bellver J.
        • Meseguer M.
        Limited implantation success of direct-cleaved human zygotes: a time-lapse study.
        Fertil. Steril. 2012; 98: 1458-1463https://doi.org/10.1016/j.fertnstert.2012.07.1135
        • Rubio I.
        • Galan A.
        • Larreategui Z.
        • Ayerdi F.
        • Bellver J.
        • Herrero J.
        • Meseguer M.
        Clinical validation of embryo culture and selection by morphokinetic analysis: a randomized, controlled trial of the EmbryoScope.
        Fertil. Steril. 2014; 102: 1287-1294https://doi.org/10.1016/j.fertnstert.2014.07.738
        • Sanchez A.M.
        • Vanni V.S.
        • Bartiromo L.
        • Papaleo E.
        • Zilberberg E.
        • Candiani M.
        • Orvieto R.
        • Viganò P.
        Is the oocyte quality affected by endometriosis? A review of the literature.
        J. Ovarian Res. 2017; 10: 43https://doi.org/10.1186/s13048-017-0341-4
        • Schenk M.
        • Kröpfl J.M.
        • Hörmann-Kröpfl M.
        • Weiss G.
        Endometriosis accelerates synchronization of early embryo cell divisions but does not change morphokinetic dynamics in endometriosis patients.
        PLoS One. 2019; 14e0220529https://doi.org/10.1371/journal.pone.0220529
        • Singer J.D.
        Using SAS Proc Mixed Proc to fit multilevel models, hierarchical models, and individual growth models.
        J. of Educ. Behav. 1998; 24: 323-355
        • Singh A.K.
        • Dutta M.
        • Chattopadhyay R.
        • Chakravarty B.
        • Chaudhury K.
        Intrafollicular interleukin-8, interleukin-12, and adrenomedullin are the promising prognostic markers of oocyte and embryo quality in women with endometriosis.
        J. Assist. Reprod. Genet. 2016; 33: 1363-1372https://doi.org/10.1007/s10815-016-0782-5
        • Wang J.
        • Xie H.
        • Fisher J.F.
        Multilevel Models: Applications using SAS®.
        Higher Education Press and Walter de Gruyter, Berlin, Germany2011: 275
        • Wirka K.A.
        • Chen A.A.
        • Conaghan J.
        • Ivani K.
        • Gvakharia M.
        • Behr B.
        • Suraj V.
        • Tan L.
        Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development.
        Fertil. Steril. 2014; 101: 1637-1648https://doi.org/10.1016/j.fertnstert.2014.02.050
        • Yang S.T.
        • Shi J.X.
        • Gong F.
        • Zhang S.P.
        • Lu C.F.
        • Tan K.
        • Leng L.Z.
        • Hao M.
        • He H.
        • Gu Y.F.
        • Lu G.X.
        • Lin G.
        Cleavage pattern predicts developmental potential of day 3 human embryos produced by IVF.
        Reprod. Biomed. Online. 2015; 30: 625-634https://doi.org/10.1016/j.rbmo.2015.02.008
        • Zhan Q.
        • Ye Z.
        • Clarke R.
        • Rosenwaks Z.
        • Zaninovic N.
        Direct unequal cleavages: embryo developmental competence, genetic constitution and clinical outcome.
        PLoS One. 2016; 11e0166398https://doi.org/10.1371/journal.pone.0166398

      Biography

      Xavier Ferraretto, MD, PhD, is a medical doctor and senior embryologist at the Reproduction Biology Department of Bichat Hospital in Paris (Assistance Publique – Hôpitaux de Paris). His research interests are embryo morphokinetics, fertility preservation and assisted reproductive technology in a viral context (hepatitis B, hepatitis C and human immunodeficiency virus).
      Key message
      Abnormal early cleavages can be partially explained by embryo origin, with only a few patient-related factors exerting an influence. It is important when analysing embryonic parameters, therefore, not to consider the embryos individually but to take into account whether or not they are from the same couple.