Abstract
Purpose
To investigate the occurrence of multinucleated blastomeres (MNB) in poor ovarian response (POR) women defined under the Bologna criteria.
Methods
This observational study was designed in a prospective controlled manner. Among 380 cases evaluated for eligibility, 102 women were found suitable and recruited; 51 with POR in accordance with the Bologna criteria defined as the study group and 51 with normal ovarian response defined as the control group.
Results
Among the 51 women in each group, 8 and 2 did not achieve embryos in the study and control group, respectively (P < 0.05). The percentage of women that had at least one embryo with one MNB was significantly higher in the study as compared to the control group, corresponding to 49 and 29 %, respectively. The total number of embryos evaluated was 416; 167 in the study and 249 in the control groups. Among these embryos, the MNB rate was significantly higher in the study as compared to the control group, corresponding to 19 and 8 %, respectively.
Conclusions
Blastomere multinuclearity is significantly more common in women and embryos of POR cases, defined under the Bologna criteria. Future studies are warranted to substantiate our observation that has the potential to be clinically implemented in this sub-group of women undergoing assisted reproductive technologies (ART) treatment.
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References
Pickering SJ, Taylor A, Johnson MH, Braude PR. An analysis of multinucleated blastomere formation in human embryos. Hum Reprod. 1995;10:1912–22.
Scott L. The biological basis of non-invasive strategies for selection of human oocytes and embryos. Hum Reprod Update. 2003;9:237–49.
Levy R, Benchaib M, Cordonier H, Souchier C, Guerin J. Laser scanning confocal imaging of abnormal or arrested human preimplantation embryos. J Assist Reprod Genet. 1998;15:485–95.
Hardarson T, Hanson C, Sjögren A, Lundin K. Human embryos with unevenly sized blastomeres have lower pregnancy and implantation rates: indications for aneuploidy and multinucleation. Hum Reprod. 2001;16:313–8.
Van Royen E, Mangelschots K, Vercruyssen M, De Neubourg D, Valkenburg M, Ryckaert G, et al. Multinucleation in cleavage stage embryos. Hum Reprod. 2003;18:1062–9.
Moriwaki T, Suganuma N, Hayakawa M, Hibi H, Katsumata Y, Oguchi H, et al. Embryo evaluation by analysing blastomere nuclei. Hum Reprod. 2004;19:152–6.
Yakin K, Balaban B, Urman B. Impact of the presence of one or more multinucleated blastomeres on the developmental potential of the embryo to the blastocyst stage. Fertil Steril. 2005;83:243–5.
Scott L, Finn A, O’Leary T, McLellan S, Hill J. Morphologic parameters of early cleavage-stage embryos that correlate with fetal development and delivery: prospective and applied data for increased pregnancy rates. Hum Reprod. 2007;22:230–40.
Gerris J, De Neubourg D, Mangelschots K, Van Royen E, Van de Meerssche M, Valkenburg M. Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial. Hum Reprod. 1999;14:2581–7.
Saldeen P, Sundström P. Nuclear status of four-cell preembryos predicts implantation potential in in vitro fertilization treatment cycles. Fertil Steril. 2005;84:584–9.
Sundström P, Saldeen P. Early embryo cleavage and day 2 mononucleation after intracytoplasmatic sperm injection for predicting embryo implantation potential in single embryo transfer cycles. Fertil Steril. 2008;89:475–7.
Pelinck MJ, Hoek A, Simons AH, Heineman MJ, van Echten-Arends J, Arts EG. Embryo quality and impact of specific embryo characteristics on ongoing implantation in unselected embryos derived from modified natural cycle in vitro fertilization. Fertil Steril. 2010;94:527–34.
Fauque P, Audureau E, Leandri R, Delaroche L, Assouline S, Epelboin S, et al. Is the nuclear status of an embryo an independent factor to predict its ability to develop to term? Fertil Steril. 2013;99:1299–304.
Van Royen E, Mangelschots K, De Neubourg D, Valkenburg M, Van de Meerssche M, Ryckaert G, et al. Characterization of a top quality embryo, a step towards single-embryo transfer. Hum Reprod. 1999;14:2345–9.
Holte J, Berglund L, Milton K, Garello C, Gennarelli G, Revelli A, et al. Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval. Hum Reprod. 2007;22:548–57.
Agerholm IE, Hnida C, Crüger DG, Berg C, Bruun-Petersen G, Kølvraa S, et al. Nuclei size in relation to nuclear status and aneuploidy rate for 13 chromosomes in donated four cells embryos. J Assist Reprod Genet. 2008;25:95–102.
Yilmaz A, Zhang L, Zhang XY, Son WY, Holzer H, Ao A. Chromosomal complement and clinical relevance of multinucleated embryos in PGD and PGS cycles. Reprod Biomed Online. 2014;28:380–7.
Gardner DK, Schoolcraft WB, Wagley L, Schlenker T, Stevens J, Hesla J. A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization. Hum Reprod. 1998;13:3434–40.
Donoso P, Staessen C, Fauser BC, Devroey P. Current value of preimplantation genetic aneuploidy screening in IVF. Hum Reprod Update. 2007;13:15–25.
Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L, et al. ESHRE consensus on the definition of ’poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011;26:1616–24.
Younis JS, Ben-Ami M, Ben-Shlomo I. The Bologna criteria for poor ovarian response: a contemporary critical appraisal. J Ovarian Res. 2015;8:76.
Younis JS, Radin O, Mirsky N, Izhaki I, Majara T, Bar-ami S, et al. First polar body and nucleolar precursor body morphology is related to the ovarian reserve of infertile women. Reprod Biomed Online. 2008;16:851–8.
Younis JS. The Bologna criteria for poor ovarian response; has the job been accomplished? Hum Reprod. 2012;27:1874–5.
Younis JS, Jadaon J, Izhaki I, Haddad S, Radin O, Bar-Ami S, et al. A simple multivariate score could predict ovarian reserve, as well as pregnancy rate, in infertile women. Fertil Steril. 2010;94:655–61.
Balakier H, Cadesky K. The frequency and developmental capability of human embryos containing multinucleated blastomeres. Hum Reprod. 1997;12:800–4.
Jackson KV, Ginsburg ES, Hornstein MD, Rein MS, Clarke RN. Multinucleation in normally fertilized embryos is associated with an accelerated ovulation induction response and lower implantation and pregnancy rates in in vitro fertilization-embryo transfer cycles. Fertil Steril. 1998;70:60–6.
Baart EB, Martini E, Eijkemans MJ, Van Opstal D, Beckers NG, Verhoeff A, et al. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007;22:980–8.
Munné S, Cohen J. Unsuitability of multinucleated human blastomeres for preimplantation genetic diagnosis. Hum Reprod. 1993;8:1120–5.
Kligman I, Benadiva C, Alikani M, Munné S. The presence of multinucleated blastomeres in human embryos is correlated with chromosomal abnormalities. Hum Reprod. 1996;11:1492–8.
Laverge H, De Sutter P, Verschraegen-Spae MR, De Paepe A, Dhont M. Triple colour fluorescent in-situ hybridization for chromosomes X, Y and 1 on spare human embryos. Hum Reprod. 1997;12:809–14.
Ambroggio J, Gindoff PR, Dayal MB, Khaldi R, Peak D, Frankfurter D, et al. Multinucleation of a sibling blastomere on day 2 suggests unsuitability for embryo transfer in IVF-preimplantation genetic screening cycles. Fertil Steril. 2011;96:856–9.
Desai N, Ploskonka S, Goodman LR, Austin C, Goldberg J, Falcone T. Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles. Reprod Biol Endocrinol. 2014;12:54.
Goodman LR, Goldberg J, Falcone T, Austin C, Desai N. Does the addition of time-lapse morphokinetics in the selection of embryos for transfer improve pregnancy rates? A randomized controlled trial. Fertil Steril. 2016;105:275–85.
Gil M, D’Ommar G, Póo ME, Sosa A, Piras M, Piras R, et al. Insights on blastomere nuclearity. J Assist Reprod Genet. 2007;24:17–22.
Staessen C, Van Steirteghem A. The genetic constitution of multinuclear blastomeres and their derivative daughter blastomeres. Hum Reprod. 1998;13:1625–31.
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Blastomere multinuclearity is significantly more common in women and embryos of POR cases, defined under the Bologna criteria.
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Younis, J.S., Yazdi, V., Izhaki, I. et al. The association between multinucleated blastomeres and poor ovarian response under the Bologna criteria. J Assist Reprod Genet 33, 885–892 (2016). https://doi.org/10.1007/s10815-016-0731-3
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DOI: https://doi.org/10.1007/s10815-016-0731-3