DENVER – Preimplantation genetic diagnosis using a novel 24-chromosome screen for aneuploidy on day 5 of embryonic development resulted in significantly increased rates of implantation and clinical pregnancy in a randomized controlled trial.
Dr. Richard T. Scott, Jr.
The implantation rate was 76% in fresh embryos transferred after day-5 trophectoderm biopsy showed them to be euploid, compared with 52% in embryos that didn’t undergo aneuploidy screening. That’s an absolute 24% difference in the primary study end point, Dr. Richard T. Scott Jr., noted at the annual meeting of the American Society for Reproductive Medicine.
"We believe this is a highly clinically important difference," added Dr. Scott of Reproductive Medicine Associates of New Jersey, Morristown, and the Robert Wood Johnson Medical School, New Brunswick.
He reported on 80 women randomized to 24-chromosome aneuploidy screening utilizing quantitative polymerase chain reaction (PCR) and copy number analysis followed by fresh embryo transfer or to day-5 blastocyst transfer without aneuploidy screening. The group of patients had a relatively good prognosis, with a mean age of 33 years (none over age 42 years), and not more than one prior failed cycle of in vitro fertilization. The mean number of embryos transferred per patient was 1.8 in the aneuploidy screening group, significantly less than the 2.0 in controls.
Sustained implantation occurred in 54 of 71 (76%) transferred embryos in the aneuploidy screening group, compared with 42 of 81 (52%) in the control arm.
The results were especially impressive in the group of 28 women aged 35 or older: a 74% implantation rate with aneuploidy screening, nearly double the 40% rate in controls, Dr. Scott continued.
Clinical pregnancy occurred in 37 of 39 women in the aneuploidy screening group, for a 95% success rate, compared with 78% in 41 controls. The ongoing or delivered pregnancy rate was 87% in the aneuploidy screening group, significantly better than the 68% rate in unscreened women.
The 24-chromosome aneuploidy screening technique Dr. Scott and coworkers have developed over the last 4-plus years provides reliable results within 4 hours, permitting same-day or next-morning embryo transfer without embryo freezing.
The rationale for developing this aneuploidy screening technique lies in the steep age-related rise in the prevalence of aneuploidy. For women aged 36-41 years, the prevalence of aneuploidy, including monosomies as well as trisomies, is 70%-80% among embryos deemed suitable for transfer based on conventional morphologic analysis.
A day-5 screening test had to be developed, because it’s impossible to tell aneuploid from euploid embryos on day 3. Besides, biopsy on day 3 is more stressful for the embryo, which is only eight cells in size at that point.
"We believe day-3 biopsy lowers implantation rates by as much as 15%-20%," Dr. Scott explained.
Just how reliable is the genetic screening test? In various studies to date, the investigators have transferred more than 970 embryos identified as euploid, with more than 650 resultant implantations. Three embryos identified as euploid on the screening test resulted in abnormal gestations: one tetraploidy, one Turner’s syndrome, and one trisomy 13. But the Turner’s syndrome and trisomy turned out to be mosaics on genetic analysis of the products of conception.
"The only clear diagnostic error was the tetraploid embryo. I should point out that our technology does not accurately evaluate for tetraploidy. Therefore the error rate attributable to the test itself is probably about 1 per 1,000," according to the fertility specialist.
The study presented at the ASRM meeting provides level I evidence that 24-chromosome aneuploidy screening enhances embryo selection and improves clinical outcomes, the final step in validation of the test. In the next few weeks, the test will be introduced at a select handful of fertility clinics around the country. Eventually it will become much more widely available. Although more than 100 clinics have inquired about offering the test, at present most don’t have the capability of doing day-5 biopsy, which is a prerequisite, Dr. Scott said in an interview.
"It’s a fairly complex methodology to do this. It’s extremely labor intensive, and you need a lot of expensive toys. The cost of the test is about $2,500 – that’s what we charge, the true cost with no markup," he added.
In an interview, session co-chair Dr. Eric Levens called Dr. Scott’s study one of the clear highlights of the meeting, an assessment later confirmed by the announcement that Dr. Scott tied for first place in the ASRM Scientific Program Prize Paper Awards.
This new ability to do a day-5 embryo biopsy and get the results back so fast that there’s no need to undertake a frozen embryo transfer is a significant advance, Dr. Levens said.