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

Abstract

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.

Preimplantation genetic testing for aneuploidy: A review of published blastocyst reanalysis concordance data

“…In addition, 147 embryos were from patients who had an abnormal karyotype were used for analysis of positive controls. 36 2018 May 24 NGS Whole blastocyst NGS Tsuiko 37 2018 June 14 NGS ICM NGS Popovic 38 2018 July 58 NGS TE/ICM NGS Chuang 39 2018 December 29 NGS TE/ICM NGS Victor 16 2019 January 100 NGS TE/ICM NGS Victor 40 2019 February 8 NGS TE/ICM NGS Popovic 41 2019 April 45 NGS Blastocyst outgrowth NGS Lawrenz 42 2019 June 84 NGS TE/ICM NGS Huang 43 2019 July 50 NGS Whole blastocyst NGS Treff 44 2019 August 14 NGS TE SNP array Munne 45 2020 January 57 NGS TE NGS Ou 46 2020 January 63 NGS Whole blastocyst NGS Sachdev 47 2020 February 32 NGS TE/ICM NGS Girardi 9 2020 March 88 NGS TE/ICM NGS Navratil 48 2020 April 75 NGS TE/Whole blastocyst NGS Rubio 49 2020 May 64 NGS ICM NGS Lin 50 2020 June 41 NGS ICM NGS Abbreviations: aCGH, array comparative hybridization; CGH, comparative genomic hybridization; ICM, inner cell mass; NGS, next-generation sequencing; qPCR, quantitative real-time PCR; PGT-A, preimplantation genetic testing for aneuploidy; SNP, single nucleotide polymorphism; TE, trophectoderm.…”

Diagnostic efficiency of blastocyst culture medium in noninvasive preimplantation genetic testing

“…Previous studies have been conducted to analyze the concordance between niPGT-A and TE-biopsy PGT-A, or to compare the diagnostic efficiency between niPGT-A and TE-biopsy in ehivh the rest of the embryo or the whole embryo was regarded as the standard reference (13,19,(26)(27)(28). However, increasing evidence has demonstrated that the genetic results from TE biopsy, as well as the rest of the embryo mixed with ICM with TE, may not truly reflect the genetic status of the blastocyst-stage embryo due to mosaicism (9,13,29,30). A recommended, more reasonable way to verify the diagnostic efficiency of niPGT-A would be to compare BCM and multiple biopsy sites of the embryo, particularly the ICM samples (31).…”

Cell-free DNA in spent culture medium effectively reflects the chromosomal status of embryos following culturing beyond implantation compared to trophectoderm biopsy

“…Various studies have reported PGT-A results obtained using TE biopsy, but the concordance rate between TE and ICM karyotypes is approximately 62.1-86.2% [24][25][26]. Additionally, Ou et al re-examined embryos considered abnormal using PGT-SR and reported a concordance rate of 68% between TE biopsies and total blastocysts [27]. Another study conducted at our institution also found that the TE biopsy and total blastocysts had a chromosomal concordance rate of 67.7%.…”