Investigators at the Columbia University Fertility Center and Columbia University Irving Medical Center, New York City, have led the development of a same-day, point-of-care test to identify abnormal fetal chromosomes.
In the New England Journal of Medicine on Thursday, the investigators described a rapid nanopore sequencing-based screen for aneuploidy in reproductive care, saying they have developed and validated a new short-read-based approach for library preparation, sequencing, and data analysis.
The approach "enables accurate, inexpensive, and same-day genomewide aneuploidy detection with the use of a palm-sized, nanopore-based DNA sequencer," the researchers said.
The Short-read Transpore Rapid Karyotyping (STORK) test can detect extra or missing chromosomes, including aneuploidy, using samples collected from prenatal tests. Such samples include amniocentesis and chorionic villus sampling, as well as tissue obtained from miscarriages and biopsies from preimplantation embryos produced using in vitro fertilization (IVF).
The National Institutes of Health (NIH) funded the study with support from the National Cancer Institute and the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) through the Human Placenta Project.
According to the NIH, more work is needed to further validate STORK, but if results continue to show promise, the test could improve the quality of reproductive healthcare.
The study authors said the test may be particularly useful in identifying genetic causes of miscarriage.
Currently, professional societies only recommend genetic testing if a person has had multiple miscarriages, but an easy, cost-effective test such as STORK could be offered after the first miscarriage, NIH said.
The test, which can be completed at the point of care, eliminating the need to ship a sample to a clinical laboratory, can also be used to streamline IVF.
Currently, embryos must be frozen while genetic tests are run and analyzed before implantation. STORK's ability to provide results within hours can presumably eliminate this freezing step, saving time and cost, NIH said.
The study team compared STORK to standard methods by testing 218 samples that included tissue from miscarriages, chorionic villi, amniotic fluid, and trophectoderm biopsies, which are used to evaluate embryos before IVF implantation. In this set of samples, the test demonstrated an accuracy of 98% to 100%.
In a separate set of 60 samples, STORK demonstrated 100% accuracy in accordance with a standard setting when performed by technicians in a CLIA-certified lab, NIH said, adding that overall, the study showed that STORK is comparable to standard clinical tests and has many advantages.
For example, the new test is faster than standard clinical practice, NIH said, providing results within hours versus several days. Furthermore, the study team estimated STORK would cost less than $50 per sample if 10 samples are run at the same time, or up to $200 if a sample is run on its own.
There are some limitations to the assay, the researchers wrote, including "the inability to detect balanced translocations and some copy-number variants and types of polyploidy."