Genomic Prediction Inc., North Brunswick Township, New Jersey; Division of Life Sciences, Department of Molecular Biology and Biochemistry, School of Arts and Sciences, Rutgers University-New Brunswick, Nelson Biological Laboratories, Piscataway, New Jersey.
Genomic Prediction Inc., North Brunswick Township, New Jersey.
F S Sci. 2023 May;4(2S):27-35. doi: 10.1016/j.xfss.2023.02.003. Epub 2023 Mar 1.
To validate the detection of abnormal ploidy in preimplantation embryos and evaluate its frequency in transferrable blastocysts.
A high-throughput genome-wide single nucleotide polymorphism microarray-based preimplantation genetic testing (PGT) platform was validated using multiple positive controls, including cell lines of known haploid and triploid karyotypes and rebiopsies of embryos with initial abnormal ploidy results. This platform was then tested on all trophectoderm biopsies in a single PGT laboratory to calculate the frequency of abnormal ploidy and the parental and cell division origins of error.
Preimplantation genetic testing laboratory.
PATIENT(S): The embryos from in vitro fertilization patients who elected for PGT were evaluated. Any patients who provided saliva samples were further analyzed for the parental and cell division origins of abnormal ploidy.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): Evaluable positive controls showed 100% concordance with original karyotypes. The overall frequency of abnormal ploidy within a single PGT laboratory cohort was 1.43%.
RESULT(S): All cell lines showed 100% concordance with the expected karyotype. Additionally, all evaluable rebiopsies showed 100% concordance with the original abnormal ploidy karyotype. The frequency of abnormal ploidy was 1.43%, with 29% of those being haploid or uniparental isodiploid, 2.5% uniparental heterodiploid, 68% triploid, and 0.4% tetraploid. Twelve haploid embryos contained maternal deoxyribonucleic acid, and 3 contained paternal deoxyribonucleic acid. Thirty-four triploid embryos were of maternal origin, and 2 were of paternal origin. Thirty-five triploid embryos had a meiotic origin of error, and 1 was of mitotic error. Of those 35 embryos, 5 originated from meiosis I, 22 originated from meiosis II, and 8 were deemed inconclusive. On the basis of specific abnormal ploidy karyotypes, 41.2% of embryos would be falsely classified as euploid, and 22.7% would be false-positive mosaics with the use of the conventional next-generation sequencing-based PGT methods.
CONCLUSION(S): This study demonstrates the validity of a high-throughput genome-wide single nucleotide polymorphism microarray-based PGT platform to accurately detect abnormal ploidy karyotypes and predict the parental and cell division origins of error of evaluable embryos. This unique method improves the sensitivity of detection for abnormal karyotypes, which can reduce the chances of adverse pregnancy outcomes.
验证胚胎植入前异常倍性的检测，并评估其在可转移囊胚中的频率。
使用多个阳性对照物（包括已知单倍体和三倍体核型的细胞系以及初始倍性异常胚胎的再活检）验证高通量全基因组单核苷酸多态性微阵列胚胎植入前遗传检测（PGT）平台。然后，该平台在单个 PGT 实验室的所有滋养外胚层活检中进行测试，以计算异常倍性的频率以及错误的亲本和细胞分裂来源。
胚胎植入前遗传检测实验室。
选择 PGT 的体外受精患者的胚胎进行评估。提供唾液样本的任何患者都将进一步分析异常倍性的亲本和细胞分裂来源。
无。
可评估的阳性对照物与原始核型完全一致。单个 PGT 实验室队列中异常倍性的总体频率为 1.43%。
所有细胞系均与预期核型完全一致。此外，所有可评估的再活检均与原始异常倍性核型完全一致。异常倍性的频率为 1.43%，其中 29%为单倍体或单亲同二倍体，2.5%为单亲异倍体，68%为三倍体，0.4%为四倍体。12 个单倍体胚胎含有母源脱氧核糖核酸，3 个含有父源脱氧核糖核酸。34 个三倍体胚胎为母源来源，2 个为父源来源。35 个三倍体胚胎的错误来源于减数分裂，1 个来源于有丝分裂错误。在这 35 个胚胎中，5 个来源于第一次减数分裂，22 个来源于第二次减数分裂，8 个结果不确定。根据特定的异常倍性核型，41.2%的胚胎将被错误地归类为整倍体，22.7%将被传统的基于下一代测序的 PGT 方法错误地归类为假镶嵌体。
本研究证明了高通量全基因组单核苷酸多态性微阵列 PGT 平台准确检测异常倍性核型并预测可评估胚胎错误的亲本和细胞分裂来源的有效性。这种独特的方法提高了异常核型的检测灵敏度，从而降低了不良妊娠结局的机会。
