Evaluation of targeted next-generation sequencing-based preimplantation genetic diagnosis of monogenic disease

Fertil Steril. 2013 Apr;99(5):1377-1384.e6. doi: 10.1016/j.fertnstert.2012.12.018. Epub 2013 Jan 9.


Objective: To investigate the applicability of next-generation sequencing (NGS) to preimplantation genetic diagnosis (PGD); to evaluate semiconductor-based NGS for genetic analysis of human embryos.

Design: Blinded.

Setting: Academic center for reproductive medicine.

Patient(s): Six couples at risk of transmitting single-gene disorders to their offspring.

Intervention(s): None.

Main outcome measure(s): Embryonic genotype consistency of NGS with two independent conventional methods of PGD.

Result(s): NGS provided 100% equivalent PGD diagnoses of compound point mutations and small deletions and insertions compared with both reference laboratory- and internally developed quantitative polymerase chain reaction (qPCR)-based analyses. Furthermore, NGS single-gene disorder screening could be performed in parallel with qPCR-based comprehensive chromosome screening.

Conclusion(s): NGS can provide blastocyst PGD results with a high level of consistency with established methodologies. This study and its design could serve as a model for further development of this important and emerging technology.

Publication types

  • Clinical Trial

MeSH terms

  • Aneuploidy
  • Blastocyst / physiology*
  • Female
  • Fertilization in Vitro
  • Gene Deletion
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / epidemiology
  • Genetic Diseases, Inborn / genetics*
  • Genetic Testing
  • Genotype
  • Humans
  • Lymphocytes / physiology
  • Male
  • Mutagenesis, Insertional / genetics
  • Point Mutation / genetics
  • Predictive Value of Tests
  • Pregnancy
  • Preimplantation Diagnosis / methods*
  • Risk Factors