Evolution of aneuploidy up to Day 4 of human preimplantation development

Mertzanidou, Afroditi; Spits, Claudia; Nguyen, Ha Thi Thu; Velde, H. Van de; Sermon, Karen

doi:10.1093/humrep/det079

Cited by 53 publications

(40 citation statements)

References 43 publications

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“…Array CGH was also an important tool to start to understand the origin of post-zygotic chromosomal abnormalities in embryos. By arraying every cell of cleavage stage embryos, it was found that the majority of cleavage stage embryos were chromosomally abnormal [9,10,[44][45][46]. Mertzanidou et al found that 3/27 (11%) of cleavage stage embryos carried a meiotic abnormality, a figure that is in line with other researchers, for instance Chavez et al [45] who found 9/45 four-cell embryos to carry a meiotic abnormality.…”

Section: Array Comparative Genomic Hybridisation (Acgh)supporting

confidence: 52%

“…Moreover, day 3 of development seemed particularly affected by chromosomal abnormalities, often in mosaic form. Cleavage stage embryos can be mosaic for euploid and aneuploid lineages, and therefore the biopsy of one cell is not representative for the status and implantation potential of an embryo [9,10]. The development of comprehensive chromosome screening (CCS) based first on single nucleotide polymorphism (SNP) arrays or array comparative genomic hybridisation (CGH) and later on next generation sequencing (NGS), and the shift towards biopsy at a later stage of embryonic development, the blastocyst, heralded a renaissance in PGS.…”

Section: Introductionmentioning

confidence: 99%

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Preimplantation Genetic Screening

Sermon¹

2017

obm genet

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The main aim of PGS has always been to improve IVF outcome, especially in patient groups assumed to have higher rates of chromosomally abnormal embryos, such as patients of advanced maternal age. In that sense, PGS is quite different from other types of screening as discussed in other papers in this issue. Today it bears no doubt that blastocysts found to be uniformly aneuploid in a biopsy will fail to implant, or worse, will implant and lead to a pregnancy and birth carrying a major chromosomal abnormality, such as trisomy 21. However, it has been argued that a cohort of embryos cannot be improved, and that PGS is only a selection method for which efficiency has not been proven. PGS would never increase the live birth rate for that given cohort, even with a 100% efficiency rate of embryo cryopreservation. The current debate on whether PGS should be applied and to which patients it should be offered has shifted from the effect on live birth rates towards other outcomes such as the reduction of transfers and of miscarriages. Taking the undeniable higher cost of IVF into account when PGS is included, what is the benefit to the patient? The views on this question differ on whether PGS is an additional source of income for the IVF clinic and may or may not balance the extra cost for cryopreservation and embryo transfer for the patients, or whether society pays for IVF treatments and may decide not to want to invest in a medical act that does not improve the primary goal of IVF, i.e. having a healthy child. PGS is also often presented as diminishing patient anxiety and stress through decreasing unnecessary embryos transfers and miscarriages, although no data on this

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Section: Array Comparative Genomic Hybridisation (Acgh)supporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Preimplantation Genetic Screening

Sermon¹

2017

obm genet

View full text Add to dashboard Cite

show abstract

“…This embryo was transferred and the patient delivered a healthy baby carrying a chromosomal balanced translocation (tested by amniocentesis). There may be two reasons of this embryo, one is mosaicism [6][7][8][9][10], the other is self-correction during embryo development. Several reasons have been proposed for aneuploidy selfcorrection during later developmental stages, including primary misdiagnosis, aneuploidy allocation in the trophectoderm, cell growth advantage of diploid cells in mosaic embryos, lagging of aneuploid cell division, extrusion or duplication of an aneuploid chromosome, and abundance of DNA repair gene products [16].…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported a mosaicism rate at the cleavage stage ranging between 30 and 85 % [6][7][8]. Day 4 embryos have also been studied, with extensive abnormalities observed [9]. When embryos develop to the blastocyst stage they still show chromosomal abnormalities and mosaicism, although the proportion decreases [10].…”

Section: Introductionmentioning

confidence: 99%

Chromosomal characteristics at cleavage and blastocyst stages from the same embryos

Huang

Zhao

Wang

et al. 2015

J Assist Reprod Genet

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Purpose To investigate chromosomal characteristics in the same embryos at cleavage and blastocyst stage. Methods Six PGD/PGS cycles were retrospective studied, including five chromosomal translocation PGD cycles and one recurrent abortion PGS cycle. The cleavage embryos were biopsied one blastomere at day 3, followed by blastocyst culture. Trophectoderm cell biopsy was performed when embryos developed into the blastocyst stage. Whole genome amplification and 24-chromosomal analysis by CGH/SNP microarray was performed on each blastomere and trophectoderm cells. Results After PGD/PGS, only one couple had no euploid embryos to transfer. Five couples delivered a healthy, balancedkaryotype baby. A total of 18 embryos had both blastomere and trophectoderm cell reliable results available. Of the 18 embryos, eleven embryos contained identical chromosomes from cleavage stage to blastocyst stage and six embryos contained almost identical chromosomes . Only one embryo presented opposite chromosomal results for the cleavage and blastocyst stage, with abnormal chromosomes in the blastomere but normal chromosomes in trophectoderm cells. Conclusions Most embryos maintain chromosomal stability during embryonic development. Compared to cleavage stage, blastocyst stage may provide more reliable aneuploidy results.

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“…hESC colonies were dissociated into single cells using nonenzymatic cell dissociation solution (Sigma-Aldrich). Individual hESCs were manually washed by serial transfer in drops of phosphate-buffered saline (Cell Signaling Technologies) with 0.1% polyvinylpyrrollidone and collected into sterile PCR tubes as previously described 32,33 . The cell's DNA was amplified using the SurePlex DNA Amplification System (BlueGnome, Cambridge, UK), a ligation-mediated PCR-based technique, according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations

et al. 2014

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Current knowledge on chromosomal mosaicism in human cell cultures is mostly based on cytogenetic banding methods. The recent development of high-resolution full-genome analysis methods applicable to single cells is providing new insights into genetic and cellular diversity. Here we study the genetic content of 92 individual human cells, including fibroblasts, amniocytes and embryonic stem cells (hESCs), using single-cell array-based comparative genomic hybridization (aCGH). We find that human somatic and embryonic stem cell cultures show significant fractions of cells carrying unique megabase-scale chromosomal abnormalities, forming genetic mosaics that could not have been detected by conventional cytogenetic methods. These findings are confirmed by studying seven clonal hESC sub-lines by aCGH. Furthermore, fluorescent in situ hybridisation reveals an increased instability of the subtelomeric regions in hESC as compared to somatic cells. This genetic heterogeneity may have an impact on experimental results and, in the case of hESC, on their potential clinical use.

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Evolution of aneuploidy up to Day 4 of human preimplantation development

Abstract: Our data show extensive abnormalities in Day-4 embryos. We found no evidence of self-correction at this stage of development, suggesting that this process may start at a later stage of development.

Cited by 53 publications

References 43 publications

Preimplantation Genetic Screening

Preimplantation Genetic Screening

Chromosomal characteristics at cleavage and blastocyst stages from the same embryos

Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations

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