In Vitro Fertilization May Be More More Succesful If Scientists Test How 'Squishy' The Embryo Is
When bioengineers and physicians from Stanford University heard that the way an embryo feels — imagine holding the tiniest ball and giving it a gentle squeeze — could determine its viability, they decided to test the theory for themselves. Their findings, they argue in the journal Nature Communications, could yield a minimally invasive technique that has immediate applications in the in vitro fertilization (IVF) clinic.
Prior research has linked the stiffness of embryos and oocytes (the cells in an ovary that can become eggs) to pregnancy in humans and to maternal age in mice, according to the study. This suggests there may be a link between mechanics and viability, so the study authors developed a test to measure the mechanical properties of zygotes from 282 mice and 89 humans. They applied a small amount of pressure to the fertilized eggs an hour after fertilization to record how much each egg deformed.
The results showed that what the study authors called "squishiness" could predict with 90 percent accuracy whether a fertilized egg would grow into a well-formed blastocyst in both mice and humans. It’s the blastocyst that "hatches" and invades the uterine lining to ultimately release the the pregnancy hormone, called human chorionic gonadotropin, into the mother’s blood during embryo implantation.
Study authors found that, once transferred to mothers, the squishier mouse embryos were 50 percent more likely to result in a live birth than those classified as viable using conventional techniques. The authors are currently figuring out a similar viability test to apply to humans.
"Although cancer and other diseases involve stiff tumors or tissues, our colleagues have been surprised that we can gain so much information from this simple little mechanical test," said David Camarillo, an assistant professor of bioengineering at Stanford, in a press release. "It is still surprising to think that simply squeezing an embryo the day it was fertilized can tell you if it will survive and ultimately become a baby."
Traditionally, testing for viability in humans is invasive and puts stress on the embryo, which certainly factors into the estimated 70 percent failure rate associated with IVF. Because of the high failure rate, doctors often implant multiple embryos and hope at least one will take, which is why women undergoing IVF frequently give birth to twins.
The thing is, study authors wrote, this method "can increase the risk for neonatal mortality and cause complications for babies and the mothers." But with the mechanical test, doctors would be able to implant a single embryo they were certain was viable and improve patient outcomes.
"The ability to predict embryo viability at such an early stage strongly suggests that much of human embryo developmental potential is determined before fertilization by the contents of the oocyte," the authors wrote. "Although DNA fragmentation or damage in the sperm can lower a healthy oocyte’s developmental potential, it is the oocyte that contributes the vast majority of the cytoplasmic contents, which are also vital for successful development."
Study authors are still "ramping up to test viability in patients," but as is, these findings open the door to better assessments of oocyte quality and maturation. The potential impact on IVF success rates could be huge.
"From a clinical perspective, once confirmed, the benefit is immense in that it could give us a proxy of viability of the embryo in the blink of an eye, and from that information we can manipulate the patient's cycle in order to improve success," said study co-author Barry Behr, director of Stanford's IVF laboratory and professor of obstetrics and gynecology at the Stanford University Medical Center. "It's very exciting work, and I'm happy to be a part of it."
Source: Yanez LZ, Han J, Behr BB, Reijo Pera RA, Camarillo DB. Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization. Nature Communications. 2016.