Should pre-implantation genetic screening (PGS) be recommended for high risk and low risk patients?

Abstract

High-resolution next generation sequencing (HR-NGS) allows for more accurate detection of mosaicism, which has been shown to play a role in pregnancy loss and approximately 30% of embryos are mosaic at the blastocyst stage (2). Mosaic embryos may lead to a viable pregnancy, but the chance of implantation is greatly reduced (1). Increased detection of mosaicism with HR-NGS provides more information for viable embryo selection to expedite time to conception and to increase the likelihood of a healthy, term delivery; suggesting both high risk and low risk patients would benefit from HR-NGS. In an effort to further validate the necessity of PGS in high risk patients and broaden the range of patients it is considered for, chromosomal profiles of HR-NGS tested embryos from high risk and low risk groups were retrospectively reviewed. Patients undergoing IVF, trophectoderm biopsy, and HR-NGS between January 2016 and April 2017 at Coastal Fertility Medical Center were categorized into two groups. The high risk group included women diagnosed with one or more of the following: advanced maternal age (AMA), recurrent pregnancy loss (RPL), recurrent implantation failure (IF), and severe male factor (MF). The low risk group included patients 37 years of age or younger with ovulation disorders, endometriosis, tubal disorders, uterine factor, and/or family balancing. Chromosomal profiles from 565 HR-NGS tested embryos from low and high risk groups were analyzed. Patients underwent stimulation protocols to obtain oocytes. Intracytoplasmic sperm injection was performed. On day 3, embryos were hatched using a 250um pulse Zilos laser and trophectoderm biopsy on day 5 or 6 with a 450um pulse. Trophectoderm cells were prepared for HR-NGS analysis. Vitrification occurred within two hours of biopsy. Data was analyzed via Chi-Squared test and significance was set at p<0.05. A significant difference in euploidy exists between low risk and high risk patients (43.9% and 25.9%, respectively; p<0.000023). A significant difference in aneuploidy + mosaic exists between low risk and high risk patients (56.1% and 74.1%, respectively; p<0.000023). No significant difference in mosaicism exists between low risk and high risk patients (18.1% and 24.6%, respectively; p>0.17). High risk patients have a lower likelihood of creating euploid embryos and PGS should be utilized. Low risk patients may benefit from the use of HR-NGS, as 15-40% of untested embryos miscarry (3). Our study indicates mosaicism readily exists and is not significantly different between patient groups. HR-NGS increases implantation and live birth rate, and decreases miscarriage. This study suggests the efficacy of widespread use of HR-NGS across all patient groups.Table 1Comparison of ploidy profile between low risk and high risk patients (n=565).EuploidMosaicAneuploid + MosaicLow Risk75/171 (43.9%)31/171 (18.1%)96/171 (56.1%)High Risk102/394 (25.9%)97/394 (24.6%)292/394 (74.1%)p0.000023aby Chi-Square analysis0.17aby Chi-Square analysis0.000023aby Chi-Square analysisa by Chi-Square analysis Open table in a new tab