The value of noninvasive preimplantation genetic testing for aneuploidy on human cell-free dna from blastocoele fluid with genome sequencing: a prospective cohort study.

Noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) on cell-free DNA in blastocoele fluid (BF) is a promising but controversial method for selecting euploid embryos in assisted reproductive technologies. Examine whether niPGT-A of BF can predict clinical outcomes and identify fetal ploidy for clinical use. In this prospective cohort study performed in a single IVF center, 182 blastocysts from patients undergoing their first in vitro fertilization and embryo transfer (IVF-ET) cycle in 2017 were analyzed (one blastocyst per patient). There were 33 withdrawals from the study. BF was collected prior to blastocyst vitrification. Clinical pregnancy outcomes were followed up till baby was born and karyotyping. Cell-free DNA from the BF was amplified (WGA) for next generation sequencing (NGS) -based comprehensive chromosome screening (CCS). The results were compared with clinical outcomes from newborn baby karyotyping, Chorionic Villus Sampling (CVS) results from miscarriages, or fetal Noninvasive Prenatal Test (NIPT) results from ongoing pregnancies. A total of 139 BF samples produced CCS results for analysis (76.37%). Balanced euploidy was observed in 34 samples (24.46%) and aneuploidy in 92 samples (75.54%). A total of 113 patients (76.87%) achieved clinical pregnancy. Of those, 14 (11.38%) miscarried in their first trimester. CVS analysis results revealed a weak correlation between miscarriage tissue DNA samples and BF DNA samples. All 97 live-born babies showed normal phenotype and almost matched their NIPT results from pregnancies, even though some of the results of BF tests indicated abnormal genotypes. When compared all the testing results of BF, NIPT and CVS, there were about 30% consistencies. When compared with PGS, niPGT-A is a lower risk method for the preimplantation screening of embryos, but currently can only identify weak correlations between clinical outcomes and BF ploidy analysis results. The future of niPGT-A is promising but the technology is not yet ready for clinical use.