BlueGnome, a Cambridge, UK-based firm that has traditionally sold arrays and software to the neonatal cytogenetics research market, has now begun offering arrays and services for specific use in in vitro fertilization studies, according to a company official.
The new platform, called 24Sure, uses a bacterial artificial chromosome array and software to screen for abnormal or aneuploid chromosomes.
CEO Nick Haan told BioArray News this week that the Nottingham, UK-based CARE Fertility Group used 24Sure to select two normal chromosome content eggs that resulted in a successful birth. CARE is one of several IVF centers in Europe and North America that are evaluating 24Sure for potential use in the IVF process.
Using an amplification protocol co-developed with Ann Arbor, Mich.-based Rubicon Genomics, customers can use BlueGnome's 24Sure service to screen haploid or diploid cells for aneuploidy. BlueGnome is also now offering catalog 24Sure arrays and will eventually sell a complete system, Haan said.
"We are working with a small number of customers, getting feedback, and getting good results," Haan said. "US labs won’t be able to send samples to us for routine service work, due to time constraints." he said. "In practice, we are trying to get a small number of partner labs up and running in the US so they can turn around samples fast enough for transfer within an IVF cycle."
Currently, the standard technology used in IVF centers for aneuploidy screening is fluorescent in situ hybridization. However, FISH is only capable of screening for a limited number of chromosomes at a time, a constraint that makes it difficult to effectively screen cells for aneuploidy in the typical 42-hour window of time available between egg retrieval and fertilization, Haan said. Embryos with consistent aneuploidy across multiple cells frequently result in miscarriage, he said.
According to Haan, CARE was one of several centers that approached BlueGnome last year seeking a more efficient way to screen cells for aneuploidy. "They are trying to select which embryos to implant in order to maximize pregnancy and live birth rates while reducing miscarriage rates," Haan said. CARE has been running a "mini study," he said, in which a number of patients have had polar bodies — a by-product of egg development — screened for aneuploidy.
"It's very exciting [that] we have now had our first birth with 24sure," he said of the recent success of the study. "The mother had previously had multiple failed cycles and was 41 years old, putting her in a challenging group," he added. "We are pleased to see our technology make a difference."
Simon Fishel, managing director of CARE Fertility, said in a statement that since chromosomal abnormality plays a major part in the failure to establish a pregnancy, full chromosome analysis may "double the chance of success in couples who have a poor chance of conceiving or a history of failed treatments and miscarriage and maximize the chance of pregnancy in all couples."
He added that "up to half of the eggs in younger women and up to 75 percent in women over 39 are chromosomally abnormal," making access to a technology like 24Sure an option for IVF centers.
"We needed a robust and rapid technology to provide unequivocal data on all 23 pairs of chromosomes [and] that could also be used on polar bodies, blastomeres, and trophectoderm cells; and to work with a team who had the capability and desire to develop and improve their own technology to suite that required by human eggs and pre-implantation embryos," Fishel told BioArray News in an e-mail this week.
He said that, going forward, CARE envisions using the technology in "all cases, not just those that have had a very poor prognosis." He cautioned, though, that adoption would "depend on the cost of the technology, which, at present, is limiting."
According to Haan, customers can currently access the 24Sure service to look at up to eight cells for £1,800 ($2,970).
Fishel added that 24Sure would not displace current technologies used in the IVF screening process. "This is purely an addition that we have been waiting for, for more than a decade," he said.
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BlueGnome competes with firms such as Illumina, Affymetrix, Oxford Gene Technology, and others that sell array-based technologies for cytogenetic research. At least 30 papers have been published to date describing the use of array platforms in the IVF process.
Since its inception in 2001, BlueGnome has sold a variety of products for use in cytogenetics research, but 24Sure is its first move into IVF. The company sells BAC and oligonucleotide versions of its CytoChip for characterization of chromosomal imbalances, with specific CytoChips available for constitutional and hematology studies. BlueGnome also sells BlueFISH probes and BlueFuse software for the analysis of comparative genomic hybridization and expression-profiling data.
"We have our traditional market in postnatal cytogenetics and we are looking at different options for our technology in hematology and possibly in oncology," Haan said. "24sure is quite separate; it is very focused on the IVF market," he said. "It is something we are very enthusiastic about and we feel there is a potentially large market for 24Sure, if further clinical studies prove that aneuploidy screening of polar bodies, blastomeres, or blastocyst biopsy significantly improves birth rates."
According to Haan, the current market for 24Sure is "quite limited." At the same time, "people in the field know that aneuploidy is highly correlated with IVF success rates and believe in the potential of single-cell screening." Haan said it is "not unreasonable" that if BlueGnome's technique is shown to offer advantages for IVF "at least 10 percent of those cycles could be relevant."
According to Haan, several centers in Europe and North America are currently evaluating 24Sure. Among them are members of the European Society of Human Reproduction and Embryology's task force on pre-implantation genetic screening. This month, the PGS task force and BlueGnome began a pilot study using 24Sure to study PGS in one of each pair of 23 chromosomes in polar bodies. If the pilot study shows that 24Sure is feasible, the researchers intend to carry out an international randomized trial, Haan said.
"Right now, the ESHRE trial is getting set up," Haan said. "The primary aim is technical; to validate the reproducibility of the 24sure platform and the correspondence between what you see in a biopsied polar body and the contents of the oocyte," or immature egg cell, he said.
24Sure will be evaluated by Markus Montag and Hans van der Ven at the University of Bonn's Kryobank in Germany, and Luca Gianaroli and Cristina Magli of the Italian Society for the Study of Reproductive Medicine in Bologna. Sjoerd Repping of the Academic Medical Center in Amsterdam, the Netherlands, will analyze the data from the pilot study. The ESHRE researchers hope to present the data at their annual conference in Rome next year, with the intention to conduct a randomized clinical trial with at least six centers in Europe later in 2010.
"Because this is a new technology, we need to carry out a pilot study in order to be sure that the analysis can be completed within a time period that allows for fresh transfer, as well as to ensure the reliable identification of the chromosomal status of an oocyte in at least 90 percent of polar body biopsy attempts," Gianaroli said in a June statement discussing the project.
All eggs used in studies where 24Sure is used are volunteers who have given their informed consent, Haan said.