Abstract
Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to select embryos having normal ploidy for transfer, but they require an invasive embryo biopsy procedure that may cause harm to the embryos and offspring. Therefore, a non-invasive approach to select embryos with normal ploidy for implantation is highly demanded. Non-invasive chromosome screening (NICS) methods have been proposed and applied in clinical practices, but a large-scale validation versus invasive preimplantation genetic testing (PGT) and the whole embryo ploidy has not yet been reported. In this study, by using the whole embryo as a gold standard, we validated NICS assay in a total of 265 donated human embryos and compared its performance with conventional trophectoderm (TE) biopsy PGT. The NICS assay showed promising performance, which is comparable to PGT-TE [sensitivity: 87.36 versus 89.66%; specificity: 80.28 versus 82.39%; negative predictive value (NPV): 91.2 versus 92.86%; positive predictive value (PPV): 73.08 versus 75.73%]. Additionally, NICS provides a scoring system for prioritizing embryo: embryos can be categorized into three groups with euploid prediction probabilities of 90.0, 27.8, and 72.2% for group euploid (A), aneuploid (B), and multiple abnormal chromosomes (MAC) (C), respectively. When an addition of TE assay is provided as a secondary validation, the accuracy significantly increases from 72.2 to 84.3% for group B and from 27.8 to 83.3% for group C. Our results suggest that NICS is a good rule in assay for identifying chromosomal normal embryos for transfer and might serve as a non-invasive approach for prioritizing embryos instead of preventing transfer of aneuploid and MAC embryos. It will help to ensure the safety of offspring and efficient utilization of embryos.
Highlights
How to prioritize embryo for transfer is the key issue in in vitro fertilization (IVF) treatments
We reported a non-invasive chromosome screening (NICS) assay that incorporates a multiple annealing and loopingbased amplification cycle (MALBAC)-next-generation sequencing (NGS) strategy conducted on the spent medium of IVF embryos, and we validated the assay versus the whole embryo in 42 embryos (Xu et al, 2016)
The copy number variation (CNV) patterns obtained from TE-preimplantation genetic testing (PGT), Non-invasive chromosome screening (NICS), and whole blastocyst embryos were graphed and compared (Figure 3 and Supplementary Table 1)
Summary
How to prioritize embryo for transfer is the key issue in in vitro fertilization (IVF) treatments. With the development of gene sequencing technology, preimplantation genetic testing (PGT) has been widely applied in IVF practices to select embryos. The long-term bio-safety issue of embryo biopsy has not been investigated in humans (Desmyttere et al, 2012), whereas negative influences from maternal placenta to offspring neural and adrenal developments have been observed in mice (Zeng et al, 2013; Wu et al, 2014; Yao et al, 2016). What is more, Zhang et al (2019) have recently shown that TE biopsy is associated with a threefold increase in the risk of preeclampsia Is it possible that the biopsy could reduce the developmental potential and the implantation of the embryo while not affecting the potentiality of the embryo in terms of increasing obstetric or neonatal risks? A noninvasive and convenient approach would facilitate the widespread application of PGT, thereby improving success rates
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