VF Clinic Deploys Ion Torrent Sequencing in Embryo Screening
By Kevin Davies
February 22, 2013 | A reproductive clinic in New Jersey has successfully used next-generation sequencing (NGS) to screen embryos conceived in otherwise routine in vitro fertilization (IVF) cases prior to implantation. The news was reported in a talk yesterday evening at the Advances in Genome Biology and Technology (AGBT) conference by Dagan Wells, a geneticist at the University of Oxford.
“This could become a game changer in terms of IVF and a better reproductive option for couples,” Wells told Bio-IT World in an interview before his presentation.
IVF-webThe application of NGS in reproductive genetics is reaching new highs. Several companies have launched non-invasive prenatal screening tests for chromosomal abnormalities such as trisomy 21; two groups reported progress in determining the full sequence a fetal genome non-invasively; and Stephen Kingsmore and colleagues reported the rapid 50-hour genome analysis of newborns in the intensive care unit.
Now NGS is beginning to make its mark in IVF, says Wells, who first started working on preimplantation genetic diagnosis (PGD) as a Ph.D. student at University College London 21 years ago. He currently runs a lab at the National Institute of Health Research Oxford Biomedical Research Centre, and partners with Reprogenetics, a leading IVF clinic in New Jersey where he previously worked and helped set up PGD (in which DNA from a cell plucked from an undifferentiated 3-day embryo is analyzed for the presence of specific gene mutations and help instruct the selection of healthy embryos for implantation). IVF clinics such as Reprogenetics and Genesis Genetics in Michigan currently offer PGD for hundreds of different genetic disorders.
“We need to look for newer technologies for high accuracy tests, to lower costs, and confer benefits to a much larger group of patients,” says Wells. The logical next step is NGS, particularly given the possibility of multiplexing and barcoding to reduce costs.
For several reasons, Wells selected the Ion Torrent PGM platform from Life Technologies. “We wanted something user friendly, we could imagine it being moved into a diagnostics environment, and not too fiddly,” he says. “We also needed something that was fast… Because the Ion Torrent system was the quickest available for this kind of sequencing, we decided to go down that route.”
Even as the DNA test is being conducted at Day 3, the embryo continues to develop. “Once it reaches five days, it really needs to be transferred to the uterus in order to implant,” says Wells. “Outside that window, you risk the embryo having developed too far or the uterus no longer being receptive.” Speed as well as accuracy is of the essence.
Furthermore, many IVF clinics lack their own genetics expertise so they must send the cell to a specialist reference lab for testing, which takes a day. (The new trend of analyzing the embryo DNA later, at Day 5, also narrows the window.)
Wells and Ion Torrent have been working together for about one year. He says he tries to treat the embryo DNA just like any other genomic DNA sample. “Our experience with single cells, particularly embryos, is the simpler you keep the procedure, the better the chances of a robust result.”
Wells says the PGM has “a very nice user-friendly interface with iPhone-like apps. We use one of those that assigns each DNA fragment to its chromosome of origin, so we count how many fragments come from each chromosome. That’s pretty reproducible for a normal sample.”