Sequential comprehensive chromosome analysis on polar bodies, blastomeres and trophoblast: insights into female meiotic errors and chromosomal segregation in the preimplantation window of embryo development

Capalbo, Antonio; Bono, Sara; Spizzichino, Letizia; Biricik, Anıl; Baldi, Marina; Colamaria, Silvia; Ubaldi, Filippo Maria; Rienzi, Laura; Fiorentino, Francesco

doi:10.1093/humrep/des394

Cited by 179 publications

(135 citation statements)

References 15 publications

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“…When FISH was compared to CCS, it was found that mosaicism was three times more common in FISH [35]. When compared to polar body biopsy it was found that blastomere biopsy with CCS was very accurate (94.2 %) when compared to trophoectoderm biopsy with CCS [3]. These findings support analysis of cleavage-stage biopsy with CCS techniques such as SNP or CGH, so that PGS could still be utilized with fresh-embryo transfer.…”

Section: Introductionmentioning

confidence: 72%

Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages

Keltz

Vega

Sirota

et al. 2013

J Assist Reprod Genet

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Purpose To determine benefits of cleavage-stage preimplantation genetic screening (PGS) by array comparative genomic hybridization (CGH). Methods A retrospective case-control study was performed at a tertiary care university-affiliated medical center. Implantation rate was looked at as a primary outcome. Secondary outcomes included clinical and ongoing pregnancy rates, as well as multiple pregnancy and miscarriage rates. Thirty five patients underwent 39 fresh cycles with PGS by aCGH and 311 similar patients underwent 394 invitro fertilization cycles. Result(s) The implantation rate in the CGH group doubled when compared to the control group (52.63 % vs. 19.15 %, p=<0.001), clinical pregnancy rate was higher (69.23 % vs. 43.91 %, p=0.0002), ongoing pregnancy rate almost doubled (61.54 % vs. 32.49 %, p=<0.0001), multiple pregnancy rate decreased (8.33 % vs. 34.38 %, p=0.0082) and miscarriage rate trended lower (11.11 % vs. 26.01 %, p=0.13). Conclusion Cleavage stage PGS with CGH is a feasible and safe option for aneuploidy screening that shows excellent outcomes when used in fresh cycles. This is the first report of cleavage stage PGS by CGH showing improved ongoing pregnancy rates.

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Section: Introductionmentioning

confidence: 72%

Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages

Keltz

Vega

Sirota

et al. 2013

J Assist Reprod Genet

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“…All inconsistencies (five embryos) were attributable to chromosomal/ segmental copy number mosaicism in the ICM or TE. Embryonic mosaicism is derived from a variety of mechanisms including chromosome anaphase lagging (Coonen et al 2004, Capalbo et al 2013a, nondisjunction (Bean et al 2001) or endoreplication.…”

Section: Discussionmentioning

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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“…The initial diagnosis obtained by aCGH was performed by a commercial reference laboratory according to the manufacturer's protocol (BlueGnome) and as previously described. 20 The second …”

Section: Genetic Testing Methodsmentioning

confidence: 99%

Comparison of array comparative genomic hybridization and quantitative real-time PCR-based aneuploidy screening of blastocyst biopsies

et al. 2014

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Comprehensive chromosome screening (CCS) methods are being extensively used to select chromosomally normal embryos in human assisted reproduction. Some concerns related to the stage of analysis and which aneuploidy screening method to use still remain. In this study, the reliability of blastocyst-stage aneuploidy screening and the diagnostic performance of the two mostly used CCS methods (quantitative real-time PCR (qPCR) and array comparative genome hybridization (aCGH)) has been assessed. aCGH aneuploid blastocysts were rebiopsied, blinded, and evaluated by qPCR. Discordant cases were subsequently rebiopsied, blinded, and evaluated by single-nucleotide polymorphism (SNP) array-based CCS. Although 81.7% of embryos showed the same diagnosis when comparing aCGH and qPCR-based CCS, 18.3% (22/120) of embryos gave a discordant result for at least one chromosome. SNP array reanalysis showed that a discordance was reported in ten blastocysts for aCGH, mostly due to false positives, and in four cases for qPCR. The discordant aneuploidy call rate per chromosome was significantly higher for aCGH (5.7%) compared with qPCR (0.6%; Po0.01). To corroborate these findings, 39 embryos were simultaneously biopsied for aCGH and qPCR during blastocyst-stage aneuploidy screening cycles. 35 matched including all 21 euploid embryos. Blinded SNP analysis on rebiopsies of the four embryos matched qPCR. These findings demonstrate the high reliability of diagnosis performed at the blastocyst stage with the use of different CCS methods. However, the application of aCGH can be expected to result in a higher aneuploidy rate than other contemporary methods of CCS.

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Sequential comprehensive chromosome analysis on polar bodies, blastomeres and trophoblast: insights into female meiotic errors and chromosomal segregation in the preimplantation window of embryo development

Abstract: These findings provide critical insights into the mechanisms causing errors during female meiosis and the preimplantation embryo development period to improve the design and treatment outcome of PGS.

Cited by 179 publications

References 15 publications

Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages

Preimplantation Genetic Screening (PGS) with Comparative Genomic Hybridization (CGH) following day 3 single cell blastomere biopsy markedly improves IVF outcomes while lowering multiple pregnancies and miscarriages

Chromosomal analysis of blastocysts from balanced chromosomal rearrangement carriers

Comparison of array comparative genomic hybridization and quantitative real-time PCR-based aneuploidy screening of blastocyst biopsies

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