Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst

Victor, Andrea; Griffin, Darren K.; Brake, Alan; Tyndall, Jack C.; Murphy, Alex; Lepkowsky, Laura; Lal, Archana; Zouves, Christo; Barnes, Frank L.; McCoy, Rajiv C.; Viotti, Manuel

doi:10.1093/humrep/dey327

Cited by 111 publications

(85 citation statements)

References 43 publications

(21 reference statements)

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“…Recently, after analysing disaggregated blastocysts using NGS, 31% were found to have a euploid ICM despite TE abnormalities, the majority of which were mosaic defects . Reassuringly, another recent paper that focused on blastocysts diagnosed as aneuploid on TE biopsy (euploid and mosaic embryos excluded) found high concordance rates in the ICM for whole chromosome aneuploidies (97%, 90 of 93) but not for segmental aneuploidies (43%, three of seven) …”

Section: Can Pgt‐a Definitively Assign Abnormality?mentioning

confidence: 99%

“…Collectively, therefore, based on multiple‐biopsy analyses, blastocyst mosaicism rates range from 14% to 50% with a mean of 36%, much higher than previously thought. However, if uniform whole chromosome aneuploidy is identified on TE biopsy, there is a high likelihood (>95%) that the ICM is also aneuploid . Despite this high likelihood, TE aneuploidy does not guarantee uniform embryonic aneuploidy as three of 93 embryos with aneuploid TEs had either mosaic or euploid ICMs …”

Section: Can Pgt‐a Definitively Assign Abnormality?mentioning

confidence: 99%

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Preimplantation genetic testing for aneuploidy (PGT‐A): The biology, the technology and the clinical outcomes

Homer

2019

Aust NZ J Obst Gynaeco

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Preimplantation genetic testing for aneuploidy (PGT-A) seeks to identify preimplantation embryos with a normal chromosome complement (euploid) during in vitro fertilisation (IVF). By sifting out embryos with abnormal chromosome numbers (aneuploid), PGT-A should theoretically improve pregnancy success.However, earlier versions of PGT-A were ineffective, and in some cases, detrimental, due to biopsy-induced trauma and because the technology at the time could analyse only a fraction of all chromosomes. More recently, the emergence of technologies enabling all chromosomes to be analysed and a switch to less traumatic blastocyst-stage biopsy have seen widespread uptake of PGT-A.Assessing the full impact of blastocyst biopsy PGT-A requires consideration of multiple factors, including embryonic mosaicism, sensitivity of the technological platform used, embryo loss during long-term in vitro culture, embryo cryopreservation and inter-clinic variability in expertise. Significantly, there hasn't yet been an appropriately designed randomised controlled trial (RCT) of blastocyst biopsy PGT-A analysed by intention-to-treat that accounts for all these parameters on a per-cycle basis. The three RCTs reporting benefits studied outcomes on a per-embryo transfer basis were small and underpowered and demonstrated benefits for a very select sub-group of good prognosis patients. The liberal use of this very expensive IVF add-on for other patient populationshas not yet been shown to be effective, or indeed, without harm. K E Y W O R D Saneuploidy, embryo, in vitro fertilisation, mosaicism, next generation sequencing, PGT-A THE TECHNOLOGY: NEW AND IMPROVED PGT-AEmbryonic aneuploidy, most often arising from meiotic errors in oocytes, is the major cause of early pregnancy wastage. 1,2 While the hypothesis that pregnancy success should increase by screening out aneuploid embryos is therefore entirely plausible, the previous iteration of preimplantation genetic testing for aneuploidy (PGT-A: so-called PGS 1.0) was unsuccessful. 3 Meta-analysis of 11 randomised controlled trials (RCTs) failed to demonstrate any benefit for PGS 1.0 and indeed, found that it was detrimental for older women. 4 PGS 1.0 had shortcomings, 3,5 for instance, it involved removal of 1-2 cells from 6-8-cell cleavage-stage embryos, leading to the loss of a large proportion of cell mass (Fig. 1). In one study, implantation rates of 53% for non-biopsied cleavagestage embryos decreased to 31% post-biopsy. 6 Furthermore,

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Section: Can Pgt‐a Definitively Assign Abnormality?mentioning

confidence: 99%

Section: Can Pgt‐a Definitively Assign Abnormality?mentioning

confidence: 99%

Preimplantation genetic testing for aneuploidy (PGT‐A): The biology, the technology and the clinical outcomes

Homer

2019

Aust NZ J Obst Gynaeco

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“…The results showed eight (16%, 8/51) blastocysts with some level of discordance among the ICM and the three TE pieces [9]. Victor et al employed a similar approach and found the concordance rate was 97% (93/96) in case of whole chromosome aneuploidy, but the rate decreased to 43% (3/7) in case of segmental aneuploidy [5]. A further study re-analyzed previously tested abnormal blastocysts and results showed the concordance was 50% (3/6) [6].…”

Section: Introductionmentioning

confidence: 99%

“…Compared to the original one-cell biopsy from day 3 embryos , TE biopsy (5-10 cells per time) has been shown to provide more accurate diagnosis and a lower allele drop-out rate [2,3]; and the biopsy itself appears to have little or no negative impact on subsequent embryo implantation [4]. TE biopsy combined with NGS for PGT-SR has now become the most widely used approach in clinics throughout the world [5][6][7]. Furthermore, the NGS approach offers the option of quantitative chromosome analysis and the ability to report mosaic embryos.…”

Section: Introductionmentioning

confidence: 99%

Re-analysis of whole blastocysts after trophectoderm biopsy indicated chromosome aneuploidy

Chen

Yin

et al. 2020

Hum Genomics

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Background: To compare the concordance between trophectoderm (TE) analysis and whole blastocyst analysis of embryos from chromosomal structural rearrangement (SR) carriers. Method: Sixty-three abnormal blastocysts identified by preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) were included. The whole blastocysts were processed through multiple displacement amplification cycle and sequenced for 24-chromosome aneuploidy screening by next-generation sequencing (NGS). The sequencing results were compared with those of TE biopsy from the same blastocysts and the primary chromosomal rearrangement of the couples.Results: Analysis of the 63 blastocysts showed 68% (43/63) complete concordance between TE sequencing analysis and whole blastocyst results. Approximately one third (20/63, 32%) of the sequencing results showed some level of discordance between the two samples. Of these, 14% (9/63) of the embryos were identified as euploid after whole blastocyst sequencing. Among them, seven blastocysts were classified as chromosome mosaicism (five whole chromosomes, two segmental) after TE analysis, while two displayed non-SR related segmental changes in the TE biopsy. Of the original analyses, 70% (44/63) of findings were associated with the primary parental chromosomal rearrangement, while 30% (19/63) had no association. Conclusions: TE biopsy with NGS for PGT-SR is an efficient strategy to identify embryos suitable for transfer. While there was a high concordance between TE and whole blastocyst chromosome results, some embryos classified as mosaic in the original analysis and therefore unsuitable for transfer were reclassified as chromosomally balanced. To maximize the number of embryos available for PGT-SR patients, we suggest that embryos with mosaic non-SR chromosomal rearrangement should be stored and considered for transfer after appropriate counseling.

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“…Currently, NGS is regarded as a PGT technique with superior accuracy for chromosomal mosaicism compared to aCGH, quantitative polymerase chain reaction (qPCR) and single nucleotide polymorphism (SNP) array. NGS has also been proven to be highly effective in identifying segmental losses/ gains, with improved precision than previous methods [5]. Furthermore, reports from IVF centers indicate increased implantation rate (71.6% vs. 64.6%) and live birth rate (62% and 54.4% %) after NGS-PGT compared to aCGH-PGT array [6].…”

Section: Introductionmentioning

confidence: 99%

Preimplantation genetic testing: method and two case studies of familial three-way complex translocations

Staykova

Staneva

Stamenov³

et al. 2019

Biotechnology & Biotechnological Equipment

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Preimplantation genetic testing (PGT) is presently the only option available for detecting genetic conditions in embryos created through in vitro fertilization (IVF) prior to implantation. Thus PGT eliminates the dilemma of pregnancy termination following unfavorable prenatal diagnosis test results. Complex chromosome rearrangements (CCRs), although very rarely reported in humans, represent a significant clinical problem for their carriers. CCRs include at least three breakpoints affecting two or more chromosomes. In three-breakpoint translocations, theoretically sixty-four different chromosomal sets are produced. Only two of them will be balanced and will lead to the birth of a phenotypically normal child. Therefore, CCR carriers are at increased risk of chromosomally unbalanced conceptions, resulting in spontaneous abortions or birth of offspring with intellectual disability and/or congenital anomalies. The reproductive options before such families are: natural conception followed by prenatal diagnosis; donor gametes; adoption or PGT. In this paper we discuss the current state of the PGT field and report on two PGT-cases for CCR in families with infertility and recurrent pregnancy losses. The families underwent IVF-PGT on day 3 and day 5 embryos and whole genome microarray analysis. ARTICLE HISTORY

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Assessment of aneuploidy concordance between clinical trophectoderm biopsy and blastocyst

Abstract: The version in the Kent Academic Repository may differ from the final published version. Users are advised to check http://kar.kent.ac.uk for the status of the paper. Users should always cite the published version of record.

Cited by 111 publications

References 43 publications

Preimplantation genetic testing for aneuploidy (PGT‐A): The biology, the technology and the clinical outcomes

Preimplantation genetic testing for aneuploidy (PGT‐A): The biology, the technology and the clinical outcomes

Re-analysis of whole blastocysts after trophectoderm biopsy indicated chromosome aneuploidy

Preimplantation genetic testing: method and two case studies of familial three-way complex translocations

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