Nonselection Pilot Study to Assess the Clinical Efficacy of Noninvasive Preimplantation Genetic Testing for Aneuploidy

Hypothesis:

Analysis of cell free DNA (cfDNA) released from developing embryos into spent culture media (SCM) can serve as a non-invasive method for performing preimplantation genetic testing for aneuploidy (PGT-A). A non-selection study that compares clinical outcomes to the NI-PGT-A results of the transferred embryos in a blinded fashion will characterize the diagnostic accuracy by determination of positive and negative predictive values

Justification:

During the in vitro fertilization (IVF) process, the selection of a healthy embryo is limited by the inability of the microscopic appearance to reveal the chromosomal complement. Thus, in order to reliably select chromosomally normal embryos, preimplantation genetic testing for aneuploidy (PGT-A) is performed. PGT-A requires biopsy of the embryo, amplification of the DNA, then next generation sequencing (NGS) to determine chromosome copy number.

While the clinical utility of PGT-A has been demonstrated, the process has limitations, the most significant of which is the requirement for embryo biopsy. Typically, 5-10 cells are removed from the TE after the zona pellucida has been breached. While the procedure can be safely and effectively performed by trained embryologists, the obvious concern for damage to the embryo is relevant. Even if implantation successfully occurs, concern has been raised that biopsy of the embryo at this stage can lead to complications such as miscarriage, or issues with placental function later in pregnancy. Furthermore, because the TE is destined to differentiate to placenta rather than the fetus itself, there is controversy regarding if the chromosomal analysis of these cells is always representative of the chromosomal complement of the fetus. For these reasons, and because TE biopsy is laborious and expensive, PGT-A has still not supplanted morphological evaluation as the clinical standard for embryo selection.