Identification of mosaic and segmental aneuploidies by next-generation sequencing in preimplantation genetic screening can improve clinical outcomes compared to array-comparative genomic hybridization

Abstract

BackgroundChromosomal mosaicism is observed as the presence of both euploid and aneuploid cells in a particular blastocyst. Recent studies have reported that the implantation rate of mosaic embryo transfer is remarkably lower than the euploid embryos. The superior capability of next-generation sequencing (NGS) to detect chromosomal mosaicism in preimplantation genetic screening (PGS) remains controversial, and several data displayed similar implantation and pregnancy rates using NGS or array comparative genomic hybridization (aCGH).ResultsIn this study, the main inconsistency of aneuploidy detection and clinical performance between the NGS and aCGH were assessed. The phase I consisted of a parallel comparison in 182 blastocysts from 45 selected PGS patients for both the NGS and aCGH platforms. The phase II retrospectively compared the clinical outcomes of 90 patients with NGS-screened euploid embryo transfer to that of 129 patients with aCGH-screened euploid embryo transfer. The parallel comparison showed that the inconsistency of embryo euploidy was 11.8% (p = 0.01). Chromosomal mosaicism (10.7% with NGS vs. 3.9% with aCGH) and segmental aneuploidy (10.7% with NGS vs. 6.7% with aCGH) contributed to the discrepancy mainly. The chromosomally mosaic embryos (20%–50% of aneuploidy) and several embryos with segmental aneuploidy (≥10 Mbp) were hard to distinguish using the aCGH platform, but could be clearly identified using the NGS platform. After the first euploid embryo cryotransfer, the β-HCG(+) rate and implantation rate significantly increased in the PGS/NGS patients (HCG[+] rate: 73.3% in PGS/NGS vs. 60.5% in PGS/aCGH, p = 0.048; implantation rate: 53.2% in PGS/NGS vs. 45.0% in PGS/aCGH, p = 0.043). The clinical and ongoing pregnancy rates appeared higher in the NGS group, but did not reached statistical significance.ConclusionsThe results demonstrated that the NGS platform can identify embryos with chromosomal mosaicism and segmental aneuploidy more precisely than the aCGH platform, and the following clinical performance of NGS was more favorable.

Chromosomal analysis in IVF: just how useful is it?

“…The authors suggested that NGS detects mosaicism and triploidy better than aCGH, and this improvement in detection might have a positive impact on the clinical outcomes by decreasing the incidence of miscarriage (Maxwell et al 2016). The superiority of NGS for the detection of mosaicism has been supported by another study where there were 6.7% in overall inconsistencies of mosaicism between two methods (Lai et al 2017), NGS detected those not identified by aCGH. On the other hand, settings with a customized analysis software with a high specificity of detection of mosaicism might nonetheless pose a potential risk of overdiagnosing euploid embryos as mosaic.…”

The haplolethality paradox of thewupAgene inDrosophila

“…6 in [1]). In humans, about 1% of all pregnancies include some form of deviation from normal diploidy [25], and chromosomal deletions of embryonic malformations data revealed that about 11% of the genome has never been recovered in the haploid condition or any other copy number variation [26][27][28][29]. Although small deletions in human genomes are recognized as largely underestimated [30], segmental aneuploidies have been identified in oocytes, 10.4%, raising to 24.3% by three days of embryogenesis, and declining to 15.6% in preimplantation blastocysts [31].…”

An Examination of Machine Learning Algorithms for Missing Values Imputation

“…At 5-15%, complex systems are required to handle the imputation and when >15%, the estimation will be strongly affected. Several explanations have been given for the occurrence of MVs and most of them involve the presence of artifacts, hybridization failures, and low-resolution on the microarray [8].…”