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

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.