A prenatal test can accurately detect an incorrect number of chromosomes more quickly and at about one-tenth the cost of current clinical genetic tests, new data suggest.
Aneuploid pregnancies are a major cause of pregnancy loss, developmental delays, and fetal structural abnormalities, so there is high interest in screening options.
Study leader Zev Williams, MD, PhD, professor of women’s health and chief of the division of reproductive endocrinology and infertility at Columbia University, New York, and colleagues, describe a test they have developed and validated in a letter to the editor published in the New England Journal of Medicine.
The new test is called STORK (Short-Read Transpore Rapid Karyotyping) and can be used in doctors’ offices. The test uses a palm-sized, nanopore-based DNA sequencer to examine tissue from miscarriages or from a biopsy of the placenta or in vitro fertilization (IVF) embryo to determine if it has a normal count of chromosomes.
Results can be delivered in 2 hours, the researchers said. Sequencing times and costs range from 10 minutes and $200 for a single sample to 2 hours and less than $50 per sample when 10 samples are tested simultaneously.
The currently available tests and results cost thousands of dollars and results take days to weeks.
”What’s so exciting is that STORK can be used to rapidly assess chromosomal health across all reproductive tissue types,” Dr. Williams said in a press release.
“For those patients who are trying to get pregnant through IVF, the test gives the ability to conceive sooner,“ he said.
IVF embryos are typically biopsied for chromosomal testing on day 5 or 6 and are frozen for weeks until they can be implanted in a woman’s uterus. Freezing may not be necessary with rapid tests, as embryos found normal could be transferred immediately.
Dr. Williams added: “For those who are already pregnant, it gives more time to make important family-planning decisions. For those who have had a miscarriage, it can show why the loss happened so that steps can be taken to prevent future pregnancy losses.”
Existing tests include two main approaches. One is a rapid and target approach, which tests only a limited number of chromosomes and the other is a whole-genome approach, which takes days or weeks to get results and requires sending samples to specialized laboratories.
”The affordability of this [STORK] test also means that individuals who have suffered a miscarriage do not have to wait until a second or third loss before insurance will cover expensive lab tests, leaving many women in the dark and often blaming themselves,” Dr. Williams said.
The researchers used STORK to perform blinded testing using 218 specimens from miscarriage tissue, placenta samples, amniotic fluid, and biopsy specimens from embryos undergoing preimplantation genetic tests for aneuploidy (PGT-A).
They compared the results from STORK with those obtained using standard clinical testing,
For miscarriage tissue samples and placenta and amniotic-fluid samples, STORK results calculated the number of chromosomes “with 100% accuracy (95% confidence intervals, 94.3%-100%, 93.2%-100%, and 92.9%-100%, respectively),” the authors wrote.
For PGT-A samples, STORK results were 98.1% matched (95% CI, 89.7%-100%) with the clinical diagnosis of the embryos, they report.
According to the Columbia University press release, the researchers are waiting for authorization from the New York State Department of Health before the test can be offered to Columbia patients.
Dr. Sara Wernimont
Sarah Wernimont, MD, PhD, a maternal-fetal physician with the University of Minnesota, Minneapolis, who was not part of the study, said in an interview she found the results “exciting.”
“For patients I care for who have abnormal screening results, there’s the potential to receive diagnostic testing in a much faster way that can help parents make serious decisions about pregnancy care in a more timely fashion,” she said.
She said the quickest test they use in her practice for detection of aneuploidy, the fluorescence in situ hybridization test, takes 3 days to get results and tests only a few chromosomes.
The STORK test, she noted, has the potential to test all the chromosomes.
She said the sample size is small and she would like to see more external validation in a larger population, but “their sensitivity and specificity compared to the current standard seems to be excellent.”
The study was supported by the National Institutes of Health, the Biomedical Engineering Technology Accelerator at Columbia University and the Wendy and John Havens Innovation fund. Dr. Williams and one study coauthor are inventors on patents filed related to this work. Dr. Wernimont declared no relevant financial relationships.