Use of array comparative genomic hybridization (array-CGH) for embryo assessment: clinical results

Rubio, Carmen; Rodrigo, Lorena; Mir, Pere; Mateu, Emilia; Peinado, Vanessa; Milán, Miguel; Al‐Asmar, Nasser; Campos‐Galindo, Inmaculada; García, Sandra; Simón, Carlos

doi:10.1016/j.fertnstert.2013.01.094

Cited by 84 publications

(49 citation statements)

References 55 publications

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“…Fragouli et al, 2010;Yang et al, 2012;Rubio et al, 2013;Scott et al, 2013). The current investigation made use of one of these techniques to provide a sensitive evaluation of the impact of aneuploidy on embryo morphology at the cleavage (Day 3) and blastocyst (Day 5) stages.…”

Section: Introductionmentioning

confidence: 99%

Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos

Fragouli

Alfarawati²,

Spath

et al. 2013

Molecular Human Reproduction

168

107

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Morphological assessments are the main way in which fertility clinics select in vitro generated embryo(s) for transfer to the uterus.However, it is widely acknowledged that the microscopic appearance of an embryo is only weakly correlated with its viability. Furthermore, the extent to which morphology is affected by aneuploidy, a genetic defect common in human preimplantation embryos, remains unclear. Aneuploidy is of great relevance to embryo selection as it represents one of the most important causes of implantation failure and miscarriage. The current study aimed to examine whether morphological appearance can assist in identifying embryos at risk of aneuploidy. Additionally, the data produced sheds light on how chromosomal anomalies impact development from the cleavage to the blastocyst stage. A total of 1213 embryos were examined. Comprehensive chromosome analysis was combined with well-established criteria for the assessment of embryo morphology. At the cleavage stage, chromosome abnormalities were common even amongst embryos assigned the best morphological scores, indicating that aneuploidy has little effect on microscopic appearance at fixed time points up until Day 3 of development. However, at the blastocyst stage aneuploidies were found to be significantly less common among embryos of optimal morphological quality, while such abnormalities were overrepresented amongst embryos considered to be of poor morphology. Despite the link between aneuploidy and blastocyst appearance, many chromosomally abnormal embryos were able to achieve the highest morphological scores. In particular, blastocysts affected by forms of aneuploidy with the greatest capacity to produce clinical pregnancies (e.g. trisomy 21) were indistinguishable from euploid embryos. The sex ratio was seen to be equal throughout preimplantation development. Interestingly, however, females were overrepresented amongst the fastest growing cleavage-stage embryos, whereas a sex-related skew in the opposite direction was noted for the most rapidly developing blastocysts. In summary, this study confirms that, at the cleavage stage, chromosome abnormalities have little if any effect on morphological scores assigned using traditional criteria. At the blastocyst stage some forms of aneuploidy begin to affect microscopic appearance, but in most instances the impact is subtle. In the case of the most clinically relevant aneuploidies (those capable of forming a pregnancy) there was no detectable effect on morphology at any preimplantation stage.

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Section: Introductionmentioning

confidence: 99%

Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos

Fragouli

Alfarawati²,

Spath

et al. 2013

Molecular Human Reproduction

168

107

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show abstract

“…Previous PGD techniques include FISH to detect chromosome abnormalities (3) and Sanger sequencing after PCR to detect specific point mutations (4), but the two types of abnormality could not be detected at the same time. Genome-wide aneuploidy screening, such as comparative genomic hybridization (CGH) array (5,6), SNP array (7), multiplex quantitative PCR (8), and next-generation sequencing (NGS), have been used to select embryos free of aneuploidy and are increasingly applied in the PGS field (5,9).…”

mentioning

confidence: 99%

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses

Yan

Huang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

114

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In vitro fertilization (IVF), preimplantation genetic diagnosis (PGD), and preimplantation genetic screening (PGS) help patients to select embryos free of monogenic diseases and aneuploidy (chromosome abnormality). Next-generation sequencing (NGS) methods, while experiencing a rapid cost reduction, have improved the precision of PGD/PGS. However, the precision of PGD has been limited by the false-positive and false-negative single-nucleotide variations (SNVs), which are not acceptable in IVF and can be circumvented by linkage analyses, such as short tandem repeats or karyomapping. It is noteworthy that existing methods of detecting SNV/copy number variation (CNV) and linkage analysis often require separate procedures for the same embryo. Here we report an NGS-based PGD/PGS procedure that can simultaneously detect a single-gene disorder and aneuploidy and is capable of linkage analysis in a cost-effective way. This method, called “mutated allele revealed by sequencing with aneuploidy and linkage analyses” (MARSALA), involves multiple annealing and looping-based amplification cycles (MALBAC) for single-cell whole-genome amplification. Aneuploidy is determined by CNVs, whereas SNVs associated with the monogenic diseases are detected by PCR amplification of the MALBAC product. The false-positive and -negative SNVs are avoided by an NGS-based linkage analysis. Two healthy babies, free of the monogenic diseases of their parents, were born after such embryo selection. The monogenic diseases originated from a single base mutation on the autosome and the X-chromosome of the disease-carrying father and mother, respectively.

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“…1 The aCGH technique enables us to screen all 24 chromosomes within 24 hours and makes fresh transfer possible after blastomere biopsy or trophectoderm biopsy. 15 A randomised study has shown that PGS by aCGH plus selection by morphology of blastocysts can significantly improve the ongoing pregnancy rate in patients with good prognosis when compared with selection of blastocysts by morphology alone. 16 Another randomised study also showed an improvement in the implantation rate after PGS by aCGH in addition to morphological assessment of embryos.…”

Section: Discussionmentioning

confidence: 99%

Preimplantation genetic diagnosis and screening by array comparative genomic hybridisation: experience of more than 100 cases in a single centre

et al. 2017

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Use of array comparative genomic hybridization (array-CGH) for embryo assessment: clinical results

Cited by 84 publications

References 55 publications

Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos

Morphological and cytogenetic assessment of cleavage and blastocyst stage embryos

Live births after simultaneous avoidance of monogenic diseases and chromosome abnormality by next-generation sequencing with linkage analyses

Preimplantation genetic diagnosis and screening by array comparative genomic hybridisation: experience of more than 100 cases in a single centre

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