NIPT RESULTS IN PREGNANCIES RESULTING FROM EUPLOID EMBRYO TRANSFERS

Abstract

Preimplantation Genetic Testing for Aneuploidy (PGT-A) helps to optimize IVF outcomes by identifying euploid embryos for transfer. The typical approach involves trophoectoderm biopsy at the blastocyst stage, and chromosome copy number analysis with next generation sequencing (NGS). Depending on the technique, error rates of PGT-A are estimated to be 1-4 %; therefore, patients are typically counselled to also undergo routine prenatal screening. Non-invasive prenatal testing (NIPT), which uses maternal and placental circulating cell-free DNA (ccfDNA) to identify chromosomally abnormal pregnancies, can be performed as early as 9 weeks gestation and has shown to have greater diagnostic accuracy than precedent non-invasive prenatal screening. While the benefit of NIPT seems evident as first line aneuploidy screening, it is unknown if NIPT provides additional or discrepant diagnostic information for patients with PGT-A screen embryos. Our aim was to examine NIPT results for patients who conceived following euploid embryo transfer after PGT-A to determine the frequency of discrepant findings. Retrospective chart review. A chart review was completed at an independent fertility centre between April 2015 - January 2020 for patients who underwent single, euploid, frozen embryo transfer as determined by NGS- PGT-A, then chose to have NIPT. A total of 1723 euploid transfers were performed during these dates. 369 patients elected to have NIPT through the clinic following assisted reproduction (in vitro fertilization (IVF), in vitro fertilization – intracytoplasmic sperm injection (IVF-ICSI), and frozen embryo transfer), 52 of whom had undergone PGT-A prior to transfer. Patients’ ages ranged from 25 to 44 (mean 36.8 years). NIPT results were normal for 48 patients (92.3%), 1 patient (1.9%) had inconclusive results for the sex chromosomes (euploid for numerical chromosomes). 6 patients required an additional test (11.5%) and 3 patients (5.8%) had non-diagnostic results following 2 failed attempts secondary to low fetal ccfDNA fraction. In patients who had NIPT (without PGT-A), 15 patients required a second NIPT test (4.7%), all of which received results following a second sample. Of the 48 patients with normal NIPT findings, 37 delivered healthy neonates, 1 had a spontaneous loss at 24 weeks secondary to severe pre-eclampsia, and 10 currently have ongoing pregnancies. One patient elected to terminate after fetal anomalies were detected on anatomic ultrasound, although fetal karyotype was found to be normal. Almost all patients who underwent PGT-A with transfer of a euploid embryo, and subsequently obtained diagnostic NIPT results had normal findings (98.0%). The remaining inconclusive or non-diagnostic results may represent limitations of current NIPT technology. While sample size is limited, these results suggest that subsequent to euploid embryo transfer following PGT-A, NIPT may be of questionable additional value. However, given the possibility of malformations without a chromosomal etiology, anatomical ultrasound screening is still indicated.