The Genetics and IVF Institute, a Virginia and Maryland-based fertility practice, has joined a small group of early adopters now offering pre-implantation genetic screening using comparative genomic hybridization with BlueGnome’s 24sure arrays.
At GIVF, the service will be used to screen embryos prior to implantation in women undergoing in vitro fertilization. The CGH screening will allow the center to select the best embryos either by absence of a genetic disease like cystic fibrosis or Huntington’s, or by an embryo’s chromosomal constitution — a marker of general hardiness for embryos in women who are of advanced reproductive age or have had multiple miscarriages or failed IVF cycles, Harvey Stern, GIVF’s Director of Reproductive Genetics, told BioArray News.
"This is really achieving what we hoped [pre-implantation genetic diagnosis] would accomplish from the beginning," Stern said, both because it allows for reduced waiting time between testing and implantation, and because it eliminates the need to freeze embryos or to biopsy too early in development.
"Chromosome abnormalities in an embryo are the most common reason for failed IVF cycles and miscarriage after pregnancy," the center announced last week in a release. Transferring embryos with normal microarray results "decreases the risk for miscarriage while increasing the likelihood of successful implantation and of achieving a normal pregnancy," they wrote.
GIVF will perform the testing using arrays made by Cambridge, UK-based BlueGnome. BlueGnome launched its research-use-only product, which uses a bacterial artificial chromosome array and software to screen for abnormal or aneuploid chromosomes, two years ago (BAN 9/8/2009).
Stern said GIVF didn't consider any competing technologies, and was primarily interested in BlueGnome because the company's arrays are designed specifically for PGD.
Founded in 1984, GIVF comprises two clinics in Fairfax, Va., and Bethesda, Md. Stern said that the center used to routinely offer PGD using fluorescence in situ hybridization, which he said was a less accurate, though also less expensive, method.
The center also experimented with more generic arrays from Illumina and other manufacturers, but Stern said these arrays have longer analysis times than BlueGnome's more focused arrays and therefore require freezing embryos, which reduces their viability.
"With many of the more comprehensive arrays being used, embryos have to be frozen because the analysis just takes too long," he said. "With the BlueGnome, we can complete an analysis in 12 hours. Basically we are doing it overnight."
According to Stern, the speed of the BlueGnome system also allows the center to take a biopsy from an embryo on its fifth day rather than its third. "Data has suggested that removing cells on the fifth day has very little detrimental effect compared to the old procedure of biopsy on the third day," he said.
Additionally, BlueGnome's PGD-specific arrays reduce the likelihood of amplification-induced artifacts that can complicate analysis, he said.
"In embryos, the majority of abnormalities one sees are absences or additions of a whole chromosome," Stern said. "With a lower-density array, like the BlueGnome system… you have much less of an issue with results from smaller alterations that could indicate a variant of unknown significance or some other artifact in the system."
In previous work with more sensitive arrays, "the amplification process introduced artifacts, particularly in GC-rich regions, so we were picking up all kinds of artifacts and had to do a number of manipulations to make the data clean," he added.
"Going down to a lower-resolution array like the BlueGnome, these artifacts are really less of an issue," he said. "We used to joke that [using Illumina arrays] was like shooting a fly with a bazooka."
Pacific Reproductive Center, a Southern California fertility medical practice, beat GIVF to the in-house array CGH market, announcing in May that it had adopted BlueGnome 24Sure and claiming to be the first US IVF center to offer array-based CGH in its own lab (BAN 5/17/2011).
Livingston, NJ-based Reprogenetics also offers screening of embryos using BlueGnome arrays to a number of IVF centers, but not as an in-center service.
Stern predicted that array CGH won't spread much beyond the "handful" of US centers that have already been offering other types of PGD, but noted that it is a superior technique to what was previously available from these labs and institutes.
According to Stern, IVF patients are quite knowledgeable about the available technologies, and "have been asking for [the service]" since GIVF announced it had adopted the BlueGnome arrays.
"I think it's going to be well received, especially if we can improve the outcome of IVF cycles for patients in high-risk groups," he said.
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