The Role of Aneuploidy Screening in Human Preimplantation Embryos

Thornhill, Alan R.; Handyside, Alan H.

doi:10.1007/978-1-60327-392-3_19

Cited by 2 publications

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References 75 publications

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“…Though embryos and blastomeres showed high rates of aneuploidy, most chromosomes (83.9%) were disomic (Table VI ). Monosomies were more common than trisomies (χ 2 , P < 0.0001), concordant with larger studies using FISH ( Munné et al ., 2004 ; Thornhill and Handyside, 2009 ). All chromosomes showed at least one monosomy or trisomy in at least one blastomere, demonstrating that no chromosome escapes copy number errors in human cleavage-stage embryos.…”

Section: Resultsmentioning

confidence: 99%

Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol

Johnson¹,

Gemelos²,

et al. 2010

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BACKGROUNDPreimplantation genetic screening (PGS) has been used in an attempt to determine embryonic aneuploidy. Techniques that use new molecular methods to determine the karyotype of an embryo are expanding the scope of PGS.METHODSWe introduce a new method for PGS, termed ‘parental support’, which leverages microarray measurements from parental DNA to ‘clean’ single-cell microarray measurements on embryonic cells and explicitly computes confidence in each copy number call. The method distinguishes mitotic and meiotic copy errors and determines parental source of aneuploidy.RESULTSValidation with 459 single cells of known karyotype indicated that per-cell false-positive and false-negative rates are roughly equivalent to the ‘gold standard’ metaphase karyotype. The majority of the cells were run in parallel with a clinical commercial PGS service. Computed confidences were conservative and roughly concordant with accuracy. To examine ploidy in human embryos, the method was then applied to 26 disaggregated, cryopreserved, cleavage-stage embryos for a total of 134 single blastomeres. Only 23.1% of the embryos were euploid, though 46.2% of embryos were mosaic euploid. Mosaicism affected 57.7% of the embryos. Counts of mitotic and meiotic errors were roughly equivalent. Maternal meiotic trisomy predominated over paternal trisomy, and maternal meiotic trisomies were negatively predictive of mosaic euploid embryos.CONCLUSIONSWe have performed a major preclinical validation of a new method for PGS and found that the technology performs approximately as well as a metaphase karyotype. We also directly measured the mechanism of aneuploidy in cleavage-stage human embryos and found high rates and distinct patterns of mitotic and meiotic aneuploidy.

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Section: Resultsmentioning

confidence: 99%

Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol

Johnson¹,

Gemelos²,

et al. 2010

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“…The use of PGD aneuploidy screening (PGD-AS) for the purposes of improving IVF success rates has met with widespread controversy (Mastenbroek et al, 2007;Summers and Foland, 2009;Thornhill and Handyside, 2009). One criticism, that PGD-AS using FISH screens only a small proportion of the total chromosome complement (Summers and Foland, 2009;Thornhill and Handyside, 2009) can also be addressed through aCGH, and clinical validation of this a Each embryo had one blastomere biopsied and a combination of mini-sequencing plus analysis of linked markers made the initial diagnosis of SLO status. Array comparative genomic hybridization on both polar bodies was used to carry out maternal aneuploidy analysis.…”

Section: Discussionmentioning

confidence: 99%

Live birth after PGD with confirmation by a comprehensive approach (karyomapping) for simultaneous detection of monogenic and chromosomal disorders

Natesan

Handyside

Thornhill

et al. 2014

Reproductive BioMedicine Online

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Preimplantation genetic diagnosis (PGD) for monogenic disorders has the drawback of time and cost associated with tailoring a specific test for each couple, disorder, or both. The inability of any single assay to detect the monogenic disorder in question and simultaneously the chromosomal complement of the embryo also limits its application as separate tests may need to be carried out on the amplified material. The first clinical use of a novel approach ('karyomapping') was designed to circumvent this problem. In this example, karyomapping was used to confirm the results of an existing PGD case detecting both chromosomal abnormalities and a monogenic disorder (Smith-Lemli-Opitz [SLO] syndrome) simultaneously. The family underwent IVF, ICSI and PGD, and both polar body and cleavage stage biopsy were carried out. Following whole genome amplification, array comparative genomic hybridisation of the polar bodies and minisequencing and STR analysis of single blastomeres were used to diagnose maternal aneuploidies and SLO status, respectively. This was confirmed, by karyomapping. Unlike standard PGD, karyomapping required no a-priori test development. A singleton pregnancy and live birth, unaffected with SLO syndrome and with no chromosome abnormality, ensued. Karyomapping is potentially capable of detecting a wide spectrum of monogenic and chromosome disorders and, in this context, can be considered a comprehensive approach to PGD.

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The Role of Aneuploidy Screening in Human Preimplantation Embryos

Cited by 2 publications

References 75 publications

Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol

Preclinical validation of a microarray method for full molecular karyotyping of blastomeres in a 24-h protocol

Live birth after PGD with confirmation by a comprehensive approach (karyomapping) for simultaneous detection of monogenic and chromosomal disorders

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