Single nucleotide polymorphism microarray–based concurrent screening of 24-chromosome aneuploidy and unbalanced translocations in preimplantation human embryos

Treff, Nathan R.; Northrop, Lesley E.; Kasabwala, Khushabu; Su, Jing; Levy, Brynn; Scott, Richard T.

doi:10.1016/j.fertnstert.2010.11.004

Cited by 120 publications

(85 citation statements)

References 14 publications

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“…37,38 Array comparative genomic hybridisation and single nucleotide polymorphism microarray provide copy number information for every other chromosome in addition to those involved in the chromosome rearrangement. [39][40][41][42] However, these findings will reduce the number of embryos available for transfer by detecting abnormalities, which may not persist during embryo development, or may be clinically insignificant. The data we present here demonstrate that reciprocal translocation couples are likely to have relatively few normal/balanced embryos; rejecting embryos with apparent 30 Keymolen et al 31 Ko et al 24 Harper et al 6 Outcome measure per cycle Calculated % (95% CI) Calculated % (95% CI) Calculated % (95% CI) Calculated % (95% CI) Calculated % (95% CI)…”

Section: Discussionmentioning

confidence: 99%

Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

et al. 2013

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Preimplantation genetic diagnosis (PGD) using fluorescence in situ hybridisation probes was carried out for 59 couples carrying reciprocal translocations. Before treatment, 85% of pregnancies had resulted in spontaneous miscarriage and five couples had achieved a healthy live-birth delivery. Following treatment, 33% of pregnancies failed and 21of 59 couples had a healthy live-born child. The accuracy of diagnosis was 92% (8% false abnormal and 0% false normal results). The overall incidence of 2:2 alternate segregation products was 44%; however, products consistent with 2:2 adjacent segregation were Btwice as likely from male heterozygotes, and those with 3:1 disjunction were three times more likely from female heterozygotes. Our results indicate that up to three stimulation cycles per couple would give an B50% chance of a successful live birth, with the risk of miscarriage reduced to the level found in the general population. In our study, 87% of all normal/balanced embryos available were identified as being suitable for transfer. We conclude that PGD provides benefit for couples with high-risk translocations by reducing the risk of miscarriage and avoiding a pregnancy with an unbalanced form of the translocation; however, for fertile carriers of translocations with a low risk of conceiving a chromosomally unbalanced offspring, natural conception may be a more viable option.

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Section: Discussionmentioning

confidence: 99%

Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

et al. 2013

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“…The embryonic DNA is amplified by whole genome amplification and then tested by chromosome microarray analysis to distinguish balanced from unbalanced embryos. Successful application of these diagnostic technologies on a large number of patient embryos has resulted in increased implantation, pregnancy and live birth rates, and importantly, lower miscarriage rates [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Further, in those embryos that are diagnosed as balanced, there is the possibility of additional incidental aneuploidies, including whole or partial chromosomal gains and losses, mosaicism, and segmental imbalances in other chromosomes that are known to commonly arise by either non-disjunction errors [15] or breakage-fusion-bridge cycles [16]. So far, the technology developed for PGD of translocations has primarily focused on the detection of unbalanced chromosome derivatives and incidental whole or partial chromosomal aneuploidies using 24-chromosome testing either by chromosome microarray analysis [11,12] or next-generation sequencing (NGS) [13,[17][18][19][20]. We speculated that a higherresolution technology with the capacity to additionally detect more subtle chromosomal abnormalities might further benefit patients undertaking PGD cycles for translocations.…”

Section: Introductionmentioning

confidence: 99%

Clinical application of next-generation sequencing in preimplantation genetic diagnosis cycles for Robertsonian and reciprocal translocations

Zhang

Liu

Wang

et al. 2016

J Assist Reprod Genet

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Purpose The purpose of this study was to apply nextgeneration sequencing (NGS) technology to identify chromosomally normal embryos for transfer in preimplantation genetic diagnosis (PGD) cycles for translocations. Methods A total of 21 translocation couples with a history of infertility and repeated miscarriage presented at our PGD clinic for 24-chromosome embryo testing using copy number variation sequencing (CNV-Seq).Results Testing of 98 embryo samples identified 68 aneuploid (69.4 %) and 30 (30.6 %) euploid embryos. Among the aneuploid embryos, the most common abnormalities were segmental translocation imbalances, followed by whole autosomal trisomies and monosomies, segmental imbalances of nontranslocation chromosomes, and mosaicism. In all unbalanced embryos resulting from reciprocal translocations, CNV-Seq precisely identified both segmental imbalances, extending from the predicted breakpoints to the chromosome termini. From the 21 PGD cycles, eight patients had all abnormal embryos and 13 patients had at least one normal/balanced and euploid embryo available for transfer. In nine intrauterine transfer cycles, seven healthy babies have been born. In four of the seven children tested at 18 weeks gestation, the karyotypes matched with the original PGD results. Conclusion In clinical PGD translocation cycles, CNV-Seq displayed the hallmarks of a comprehensive diagnostic technology for high-resolution 24-chromosome testing of embryos, capable of identifying true euploid embryos for transfer.

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“…Preimplantation genetic diagnosis (PGD) based on fluorescence in situ hybridization (FISH) (Conn et al 1998, Van Assche et al 1999, Coonen et al 2000, Alves et al 2002, Otani et al 2006, Bernicot et al 2010, Bernicot et al 2012, Ko et al 2013 and microarray-based profiling , Fiorentino et al 2011, Treff et al 2011, van Uum et al 2012, Huang et al 2013, Tan et al 2013 are widely used to select normal/balanced embryos for CR carriers to transfer.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, PGD based on cleavage-stage FISH for CR carriers may not accurately detect the imbalance of CR-associated chromosomes and effectively reflect the chromosomal composition in the corresponding blastocysts. Moreover, aneuploidy is common in embryos from CR carriers (Pujol et al 2003), even those that are normal/balanced for CR-associated chromosomes (Pujol et al 2006, Treff et al 2011, and CR-associated chromosomes can exert inter-chromosomal effects during meiosis and mitosis (Lejeune 1963, Pellestor et al 1989, Conn et al 1998, Munne et al 2005a, leading to an increased risk of chromosomal abnormality. As such, aneuploidy screening is recommended in parallel with the detection of CR-associated imbalances.…”

Section: Introductionmentioning

confidence: 99%

Chromosomal analysis of blastocysts from balanced chromosomal rearrangement carriers

Gui

Yao

et al. 2016

Reproduction

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Balanced chromosomal rearrangements (CRs) are among the most common genetic abnormalities in humans. In the present study, we have investigated the degree of consistency between the chromosomal composition of the blastocyst inner cell mass (ICM) and trophectoderm (TE) in carriers with balanced CR, which has not been previously addressed. As a secondary aim, we have also evaluated the validity of cleavage-stage preimplantation genetic diagnosis (PGD) based on fluorescence in situ hybridization (FISH) of blastocysts from CR carriers. Blastocyst ICM and TE were screened for chromosomal aneuploidy and imbalance of CR-associated chromosomes based on whole-genome copy number variation analysis by low-coverage next-generation sequencing (NGS) following single-cell wholegenome amplification by multiple annealing and looping-based amplification cycling. The NGS results were analyzed without knowledge of cleavage-stage FISH results. NGS results for blastocyst ICM and TE from CR carriers were 86.49% (32/37) consistent. Of the 1702 (37!46) chromosomes examined, 99.47% (1693/1702) showed consistency. However, only 40.0% (18/45) of all embryos had consistent results for chromosomes involved in CR, as determined by blastocyst NGS and cleavage-stage FISH. Of the 85 CR-affected chromosomes analyzed by FISH, 37.65% (32/85) were incongruous with NGS results, with 87.5% (28/32) showing imbalanced composition by FISH but balanced composition by NGS. These results indicate that chromosomal composition of blastocyst ICM and TE in balanced CR carriers is highly consistent, and that PGD based on cleavage-stage FISH is inaccurate; therefore, using blastocyst TE biopsies for NGS-based PGD is recommended for identifying chromosomal imbalance in embryos from balanced CR carriers.

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Single nucleotide polymorphism microarray–based concurrent screening of 24-chromosome aneuploidy and unbalanced translocations in preimplantation human embryos

Cited by 120 publications

References 14 publications

Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

Benefits and drawbacks of preimplantation genetic diagnosis (PGD) for reciprocal translocations: lessons from a prospective cohort study

Clinical application of next-generation sequencing in preimplantation genetic diagnosis cycles for Robertsonian and reciprocal translocations

Chromosomal analysis of blastocysts from balanced chromosomal rearrangement carriers

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