Noninvasive preimplantation genetic testing for aneuploidy exhibits high rates of deoxyribonucleic acid amplification failure and poor correlation with results obtained using trophectoderm biopsy

Objective: To validate a commercially available noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) assay by investigating the following: prevalence of deoxyribonucleic acid (DNA) amplification failure with niPGT-A; factors affecting amplification failure with niPGT-A; and frequency of discordant results between niPGT-A and traditional preimplantation genetic testing for aneuploidy. Design: Prospective cohort study. Setting: Academic-affiliated private practice. Patient(s): One hundred sixty-six blastocysts and their surrounding culture media from couples undergoing in vitro fertilization between July 2019 and May 2020 were analyzed. Intervention(s): Blastocyst-stage spent culture media samples underwent niPGT-A using a commercially available kit that used wholegenome amplification with a modified multiple annealing and looping-based amplification cycle protocol followed by next-generation sequencing. Preimplantation genetic testing for aneuploidy of trophectoderm (TE) biopsies was performed using targeted next generation sequencing. Main Outcome Measure(s): The primary outcome was failure to achieve an interpretable result with niPGT-A. Factors affecting DNA amplification were also assessed. Discrepancies between niPGT-A and TE biopsy results were analyzed, and clinical outcomes were evaluated. Result(s): Deoxyribonucleic acid amplification failures with niPGT-A were observed in 37.3% (62/166) of the samples. With TE biopsy, no embryos exhibited DNA amplification failure. Embryos with a shorter duration of exposure to the culture media and no evidence of whole-chromosome aneuploidy on the TE biopsy displayed high rates of DNA amplification failure with niPGT-A. Of 104 embryos with both niPGT-A and TE biopsy results available, whole-chromosome discordance was noted in 42 cases (40.4%). Three embryos classified as aneuploid based on the niPGT-A result progressed to successful delivery. Conclusion(s): The rates of DNA amplification failure were high among the niPGT-A samples, virtually precluding the clinical applicability of niPGT-A in its current form. (C)2021 by American Society for Reproductive Medicine.

Automated summary

The study validated a commercially available noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) assay, investigating DNA amplification failure rates, factors affecting amplification failure, and discordant results between niPGT-A and traditional preimplantation genetic testing for aneuploidy. The findings revealed high rates of DNA amplification failure with niPGT-A, limiting its clinical applicability in its current form. Whole-chromosome discordance was noted in 40.4% of cases between niPGT-A and TE biopsy results.