Non-invasive prenatal testing has altered positive predictive value following transfer of a euploid blastocyst

Abstract

The positive predictive value (PPV) of non-invasive prenatal testing (NIPT) has been reported to range from 91.3-97.2% in the general population (1,2). However, PPV is dependent upon the prevalence of the disease in the population being tested. Patients who undergo in vitro fertilization (IVF) with preimplantation genetic testing for aneuploidy (PGT-A) and transfer a euploid embryo are presumably a lower risk population when compared to the general population. The objective of this study is to explore the PPV for NIPT following transfer of a euploid blastocyst. Retrospective cohort study. All patients at a single IVF center between 2014 and 2018 who pursued pre-implantation genetic testing for aneuploidy (PGT-A) and underwent transfer of a euploid blastocyst between 2014 and 2018 were contacted to request completion of a medical record release form authorizing release of antenatal records. Records were reviewed, and patients who had documentation of an abnormal NIPT were included in this study. Results of any subsequent prenatal or postnatal diagnostic testing were used to classify each positive NIPT as a “true positive” or a “false positive”. The PPV of NIPT was calculated. A total of 1,202 patients eligible for inclusion were contacted for completion of the medical record release form. Five patients with abnormal NIPT following transfer of a euploid blastocyst were identified. Four of these patients (80%) had subsequent definitive prenatal diagnostic testing which revealed a euploid karyotype concordant with their PGT-A results. One patient, who had a PGT-A result indicating 46,XX but a NIPT positive for Turner syndrome, underwent amniocentesis which confirmed Turner mosaicism (45,X karyotype in 80% of cells). Therefore, the PPV of NIPT in this patient cohort was 20%. The PPV of NIPT for patients undergoing transfer of a euploid blastocyst is lower than that for the general population. PGT-A may be more likely to yield inaccurate results in the presence of embryonic mosaicism, as illustrated by the true positive NIPT case in this study cohort. PGT-A is an imperfect screening tool and follow-up antenatal screening is advisable; however, clinicians and patients should recognize that patients undergoing transfer of a euploid blastocyst are at a relatively lower risk for fetal aneuploidy when compared to the general population and, as a result, the PPV of NIPT is altered in this setting.