New perspectives with the use of noninvasive chromosome screening (NICS) in ART

Abstract

After more than 20 years of use of preimplantation genetic tests for aneuploidies (PGS/PGT-A) there are still many problems related to the efficiency of this technique, most of them still without an adequate solution (Gleicher et al., 2018; Homer, 2019). From the clinical point of view, the benefits attributed to invasive PGT-A in the selection of euploid embryos remain controversial, especially due to the lack of scientific proof of its effectiveness in increasing live birth rates in various clinical situations, such as patients with advanced age, repeated implantation failures or recurrent miscarriages. In addition, evidence-based medicine also severely criticizes the rare randomized trials analyzing the clinical use of invasive PGT-A (Orvieto, 2016). If these criticisms were not enough, and undoubtedly one of the most important, it would be difficult to accurately assess the presence of embryonic mosaicism creating significant levels of false positive results, and worse, causing a real possibility of discarding healthy embryos. This makes the clinical application of PGT-A as a risky approach (Munné et al., 2017; Spinella et al., 2018). Another problem, not less important, would be the obligation to perform PGT-A by experienced embryologists, since otherwise the embryonic loss due to biopsy would be a frequent fact, something usually estimated below 10% but in some laboratories it may reach up to 30% of biopsied embryos (Munné, 2018). On the other hand, there are doubts about the future risks of invasive action of the usually 5-10 cell removed during biopsy for genetic diagnosis. Would there be repercussions for the health of these children? In animals, there are data suggesting that embryonic biopsies could be linked to changes in fetal neural tube or adrenal development (Wu et al., 2014; Zeng et al., 2013). Recently, Xu et al. (2016) described noninvasive chromosomal screening (NICS) by obtaining and sequencing free DNA dripped by embryos in the culture medium (without the need of embryo biopsy) creating a new non-aggressive and elegant perspective to preimplantation genetic diagnosis.

Keywords: NICS; noninvasive chromosome screening; PGS; PGTA; cell free DNA; blastocyst.