Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development

Wirka, Kelly Athayde; Chen, Alice A.; Conaghan, J.; Ivani, K.; Gvakharia, M.; Behr, Barry; Suraj, Vaishali; Tan, Lei; Shen, S.

doi:10.1016/j.fertnstert.2014.02.050

Cited by 146 publications

(59 citation statements)

References 30 publications

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“…The incidence of DUC-1 in our study was 9.8% which was within the previously reported range (8.3%-26%) [10, 14–16]. In contrast, DUC-2 incidence of 9.1% was much lower than reported elsewhere (17–18%) [5, 14].…”

Section: Discussionsupporting

confidence: 76%

“…Previously published studies on human DUCs have been based on abnormally fertilized oocytes or small sample sizes where gamete source or other clinical factors were not reported [6, 14, 16]. Our results show no significant differences in the incidence of DUCs between the maternal or paternal age groups or oocyte source (Table 1).…”

Section: Discussioncontrasting

confidence: 43%

“…It has also been reported that unequal cleavages are common in tripronuclear human oocytes [11–13]. In 2PN human embryos, DUC-1 (at the 1 st cleavage) was reported with large variations in frequency ranging from 8.3% to 26% [10, 14–16]. DUCs were observed at the 2 nd cleavage stage with similar frequency 17–18% [5, 14].…”

Section: Introductionmentioning

confidence: 99%

“…In 2PN human embryos, DUC-1 (at the 1 st cleavage) was reported with large variations in frequency ranging from 8.3% to 26% [10, 14–16]. DUCs were observed at the 2 nd cleavage stage with similar frequency 17–18% [5, 14]. This abnormal mitosis suggests that the occurrence of tripolar mitosis can impair early embryo development in human two-pronuclear embryos [5, 10, 14, 17].…”

Section: Introductionmentioning

confidence: 99%

“…DUCs were observed at the 2 nd cleavage stage with similar frequency 17–18% [5, 14]. This abnormal mitosis suggests that the occurrence of tripolar mitosis can impair early embryo development in human two-pronuclear embryos [5, 10, 14, 17]. A correlation between the occurrence of DUCs, impaired embryo development, and implantation potential was observed in both animal and human embryos [5, 9, 10, 12–14, 17].…”

Section: Introductionmentioning

confidence: 99%

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Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome

et al. 2016

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ObjectiveTo investigate the prevalence, developmental potential, chromosomal constitution and clinical outcome of embryos with direct unequal cleavages (DUC).DesignA retrospective observational study.SettingAcademic Institution.Participant21,261 embryos from 3,155 cycles cultured in EmbryoScope®.ResultsThe total incidence of DUCs per embryo occupying the first three cleavages were 26.1%. Depending of the cell stage, DUC rate was 9.8% at first cleavage (DUC-1), 9.1% at second cleavage (DUC-2), and 3.7% at third cleavage (DUC-3) with 3.6% of embryos exhibiting multiple DUCs (DUC-Plus). The occurrence of DUCs was not correlated with female gamete age or source. The incidence of DUC-1 was significantly higher in embryos fertilized by epididymal and testicular sperm (13.6% and 11.4%, respectively) compared to ejaculated sperm (9.1%, all p<0.05). The total incidences of DUCs were strongly correlated with the onset of blastomere multinucleation (MNB) during the first three divisions. In MNB embryos, DUCs incidence are two to three times more likely to develop when compared to non-MNB embryos (OR = 3.11, 95% CI [2.64, 3.67] at 1-cell stage, OR = 2.64, 95% CI [2.39, 2.91] at 2-cell stage and OR = 2.51, 95% CI [1.84, 3.43] at 4-cell stage). The blastocyst formation rates gradually decreased from 61.0% in non-DUC to 40.2% in DUC-3, 18.8% in DUC-2, 8.2% in DUC-1 and 5.6% in multiple DUC embryos (DUC-Plus). The known implantation rates (FH) for day 3 (D3) transfers were 12.42% (n = 3172) in Non-DUC embryos, 6.3% (n = 127) in DUC-3, and 2.7% (n = 260) in DUC-2 embryos. No live births resulted from either DUC-1 (n = 225) or DUC-Plus (n = 100) embryo transfers. For blastocyst transfers, lower implantation rates (33.3%) but similar live birth (LB) rates (40%) were observed if DUC blastocysts were transferred. Comparatively rates in Non-DUC blastocyst were 45.2% and 34.8%, respectively. The euploid rate gradually increased from DUC-1, -2, -3 to Non-DUC (13.3%, 19.5%, 33.3%, 45.6%, p<0.001) for D3 biopsied embryos. Interestingly, the trend of decreased euploidy disappeared in DUC D5/6 biopsied embryos and similar rates were exemplified in DUC (D5 56.3%, D6 35.6%) vs. non-DUC (D5 51.4%, D6 33.8%) embryos.ConclusionBlastocyst formation, implantation potential and euploid rate were significantly reduced in DUC embryos. DUC embryos should be deselected for D3 transfers, but should be culture to blastocyst stage for possible ET.

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Section: Discussionsupporting

confidence: 76%

Section: Discussioncontrasting

confidence: 43%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome

et al. 2016

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Abnormalities in centrosome number in human embryos and embryonic stem cells

Ouyang

Dai

et al. 2016

Molecular Reproduction Devel

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Chromosomal abnormalities are common in human embryos. Previous studies have suggested links between centrosome number and chromosome abnormalities, but information regarding abnormalities in centrosome number in human embryos is limited. We analyzed abnormalities in centrosome number in human embryos and embryonic stem cells (hESCs). Following normal fertilization, supernumerary centrosomes were present at rates of 7.3% in two-pronucleus (2PN)-stage zygotes and 6.5% in first-cleavage zygotes. Supernumerary centrosomes were also detected in 24.4% of blastomeres from 60% of embryos derived from 2PN zygotes. Conversely, in mono- (1PN) and tri-pronucleus (3PN) zygotes, the frequency of abnormal centrosome number increased substantially at first cleavage. Rates in blastomeres of Day-3 embryos, however, were about the same between embryos derived from 1PN and 2PN zygotes, whereas abnormalities in centrosome number were higher in those from 3PN zygotes. By comparison, the rate of abnormal centrosome numbers in hESCs was 1.5-11.2%. Thus, abnormalities in centrosome number existed in human zygotes and cleaved embryos-especially those resulting from aberrant fertilization-but the frequency of such abnormalities was lower in hESCs derived from these embryos. These findings identify a source of the chromosomal instability in human embryos and hESCs, and highlight new safety issues for human assisted reproductive technology. Mol. Reprod. Dev. 83: 392-404, 2016. © 2016 Wiley Periodicals, Inc.

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Altered morphokinetics in equine embryos from oocytes exposed to DEHP during IVM

Marzano

Mastrorocco

Zianni

et al. 2019

Molecular Reproduction Devel

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Di‐(2‐ethylhexyl) phthalate (DEHP) is a commonly used plasticizer with endocrine‐disrupting properties. In this study, we used an equine model to investigate DEHP concentrations in ovarian follicular fluid (FF), and to determine the effects of exposure of oocytes to potentially toxic concentrations of DEHP during in vitro maturation (IVM) on embryo development and quality. Embryo development was evaluated using time‐lapse monitoring (TLM), a photomicroscopic tool that reveals abnormalities in cleavage kinetics unobservable by conventional morphology assessment. Blastocyst bioenergetic/oxidative status was assessed by confocal analysis. The possibility that verbascoside (VB), a bioactive polyphenol with antioxidant activity, could counteract DEHP‐induced oocyte oxidative damage, was investigated. DEHP was detected in FF and in IVM media at concentrations up to 60 nM. Culture of oocytes in the presence of 500 nM DEHP delayed second polar body extrusion, reduced duration of the second cell cycle, and increased the percentage of embryos showing abrupt multiple cleavage, compared with controls. Mitochondrial activity and intracellular levels of reactive oxygen species were reduced in blastocysts from DEHP‐exposed oocytes. VB addition during IVM limited DEHP‐induced blastocyst damage. In conclusion, DEHP is detectable in equine FF and culture medium, and oocyte exposure to increased concentrations of DEHP during IVM affects preimplantation embryo development. Moreover, TLM, reported for the first time in the horse in this study, is an efficient tool for identifying altered morphokinetic parameters and cleavage abnormalities associated with exposure to toxic compounds.

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Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development

Cited by 146 publications

References 30 publications

Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome

Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome

Abnormalities in centrosome number in human embryos and embryonic stem cells

Altered morphokinetics in equine embryos from oocytes exposed to DEHP during IVM

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