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Illumina Launches NGS-based Preimplantation Genetic Screening Test

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NEW YORK (GenomeWeb) – Illumina has launched its VeriSeq test for preimplantation genetic screening on the MiSeq platform, the company said this week. VeriSeq is a single-cell whole-genome sequencing test that screens embryos for chromosomal aneuploidies from women undergoing in vitro fertilization.

The technique is similar to the low-pass sequencing counting method used in NGS noninvasive prenatal tests for fetal aneuploidies, except that it is applied to single embryos instead of maternal plasma. Last month, researchers from Italy's Genoma Molecular Genetics Laboratory in Rome published a validation of VeriSeq in the journal Fertility and Sterility that retrospectively demonstrated 100 percent sensitivity and specificity in identifying aneuploid embryos.

According to Tristan Orpin, Illumina's general manager of reproductive and genetic health, the commercial version of the test has the same general concept as the Fertility and Sterility publication, except for some tweaking of algorithms.

The assay combines the whole-genome amplification technology used in Illumina's BlueGnome array with the company's TruSeq chemistry for single-end sequencing with 36-bp reads. And it integrates with BlueGnome's BlueFuse software for analysis and clinical reporting. Turnaround time from sample to result is 12 hours with 2.5 hours of hands-on time, Orpin said. The test will begin shipping for use on the MiSeq in June and will enable 24 samples to be assessed in one run. Later this year, Illumina will launch a version for the NextSeq 500 that will enable simultaneous testing of 96 samples.

Orpin told Clinical Sequencing News that the VeriSeq test fits into Illumina's strategy to provide clinical offerings within reproductive health from preconception carrier screening to in vitro fertilization, prenatal screening, and newborn screening and diagnosis.

The VeriSeq test is especially important, he added, because it addresses a major unmet need. Of the approximately 1.3 million IVF cycles that are performed every year around the world, there are only about 350,000 births — a success rate of only 27 percent. The "biggest contributing factor to that by far is that many embryos are aneuploidy," Orpin said. "By having this tool, you can identify normal embryos and only transfer those," he added.

Currently, Orpin said that PGS is performed in only about 3 percent of IVF cycles. Past clinical trials used fluorescent in situ hybridization, which was not very sensitive and did not evaluate all 24 chromosomes, he said. Now, microarray technology is the primary way PGS is performed, but the technique is expensive.

Simon Fishel, managing director of CARE Fertility in the UK, said that PGS adds £2,300 to £2,400 ($3,900 to $4,000) to the cost of an IVF cycle, around £5,000 ($8,400). CARE Fertility currently uses Illumina's 24sure BlueGnome array-based test, but Fishel was an early access tester of the VeriSeq test and he said he will be switching to that assay. Initially, he said VeriSeq will not offer any cost savings for patients, but over time, he expects costs to drop.

Illumina's Orpin said that VeriSeq cost will depend in part on volume, but that the reagent costs would be around $120 to $150 per embryo screened, and that VeriSeq would be less expensive than the company's 24sure array-based test.

In addition, while VeriSeq and array-based PGS tests currently test for the same indication — chromosomal aneuploidy — because VeriSeq is based on next-generation sequencing, there will be opportunities to expand the range of disorders for which it screens, Fishel said.

"Its opportunities going forward are very exciting," Fishel said. At CARE Fertility, he said that he sees patients that are interested in screening for chromosomal aneuploidy and also patients that want to screen for single-gene disorders. A single NGS-based test can screen for both types of abnormalities, he said.

Fishel added that currently about 7 percent of patients at CARE Fertility opt for PGS, a number he expects will increase with the implementation of VeriSeq. Currently in the UK, PGS is offered to women that have a poor prognosis with respect to IVF success, either because of previous miscarriages or a family history or advanced maternal age, Fishel said. But, "if we can demonstrate that we can have a greater [success] by choosing the normal embryo, then more patients, even younger ones," will receive testing. Even in younger patients, around 40 percent of embryos carry a chromosomal abnormality, Fishel said.

However, because there is no clinical data that shows that the use of such a test increases the success rate of IVF, patients often have a hard time justifying the extra expense. Fishel said that his center is currently involved in Illumina's prospective randomized clinical trial to demonstrate VeriSeq's ability to improve pregnancy success rates. Orpin said the company is still finalizing the details of the trial, including the number of women it will enroll and the timeline, but he said it will be multinational. Both CARE Fertility and Genoma will participate.

Orpin said that while VeriSeq is being launched to detect whole-chromosome aneuploidies, it already has the resolution to identify deletions or amplifications between 10 and 20 megabases in size. He added that an advantage of using NGS for PGS is that the "exact same protocol" can be applied to "increase resolution and look for smaller sized deletions and different sub-chromosomal changes." Orpin said that VeriSeq would evolve to include testing for sub-chromosomal changes, but declined to say when or what types of disorders it would be expanded to include.

Illumina will market the assay to large testing centers, including both generalized laboratories as well as those that focus specifically on PGS and PGD, Orpin said. He said the test would likely not be marketed directly to fertility clinics because they "generally don't have the lab infrastructure" to support such testing. "There are a lot of companies that are set up as call labs for doing reproductive biology testing, and they're who we're partnering with for these solutions," he said.

Illumina did not have to go through the US Food and Drug Administration clearance process to launch VeriSeq as a clinical test because neither the FDA nor the EU regulates the preconception space, Orpin said. However, Illumina would have to obtain clearance from the China FDA to launch it in that country, Orpin said, adding that the company is "working with the China FDA on many different programs," although he did not specify which ones or their status.

Illumina is not the only one looking to develop NGS-based tests for PGS. Reproductive Medicine Associates of New Jersey is enrolling patients in a clinical trial of an NGS-based test developed on Life Technologies' Ion Torrent PGM.

Dagan Wells from the University of Oxford's Nuffield department of obstetrics is also developing an NGS-based test on the PGM in collaboration with Reprogenetics, a New Jersey-based firm that specializes in preimplantation genetic diagnosis. And Harvard University's Sunney Xie is employing his MALBAC method for whole-genome amplification and NGS to infer chromosomal aneuploidy in embryos by screening polar bodies.

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