When sperm meets egg not every match is a winning one. That is particularly true in the petri dishes of the scientific dating game called IVF, or in vitro fertilization. For the first two or three days after the arranged coupling, scientists carefully scrutinize the budding relationship for any signs that it has veered off course. Embryos with a good shape and rapidly dividing cells receive high marks and may be selected for implantation in a woman’s womb or frozen for future use. Embryos with poor chemistry, however, are typically cast aside.
Those embryos dawdle or multiply into odd cell numbers—three and then maybe seven cells, as opposed to a healthy two to four to eight progression—and studies suggest those abnormalities may indicate embryos would not be as likely to eventually form a promising blastocyst, a rapidly dividing ball of over 100 cells. By day five that cluster of cells should form a well-defined inner cell mass that will become the baby. The outer circle of cells will become the placenta.
Specialists routinely check on a candidate embryo in those early days by removing it from its incubator, placing it on a slide and scrutinizing it under a microscope. Yet that inspection process, called morphological analysis, is highly subjective, resting on opinions of individual embryologists and when they happen to look.
Barry Behr says he has added another, better, test to the process, and the U.S. Food and Drug Administration approved it last year. Behr, director of the In Vitro Fertilization Laboratory at Stanford University, has created the Early Embryo Viability Assessment (EEVA) test. It is the only such FDA–approved technology designed to analyze embryos and help fertility specialists select the embryo or embryos most likely to proceed to the blastocyst stage.
One day, Behr hopes, the test could help reproductive specialists and patients choose just one egg to implant in women—the current imprecise evaluation is one reason many women implant several embryos, a process that can also lead to twins or triplets that are born at low, risky birthweights or preterm. But for all the EEVA buzz, there is still no clinical data answering the big question: Does using the EEVA lead to more successful pregnancies or live births? “I think those are questions that scientists have to ask,” says Andrew La Barbera, chief scientific officer for the American Society for Reproductive Medicine. “Intuitively you would think if the embryo is dividing at regular intervals it would be healthy and we should use it, but there have not yet been any randomized controlled trials that have demonstrated [this technology] is predictive” he says.
The EEVA has two parts: First, a time-lapse camera is affixed to an incubator so that it can take snapshots of the embryo every five minutes for the first 48 hours of cell division. That data is then automatically fed into a specialized algorithm that assigns each embryo in that incubator a “grade,” judging how good it looks compared with a benchmark normal embryo. The EEVA system is not meant to be used instead of traditional morphology evaluation but rather as a complement after embryo specialists have winnowed down their top candidates using the usual methods. Then, the EEVA’s software will analyze the images it took of the embryo and spit out its “high” or “low” grades assessing which embryos will likely do well progressing to the blastocyst stage.
Ideally, the embryo would be transferred into the uterus three days after the egg was inseminated to minimize the amount of time it spends outside of the body, although some clinics do wait until day five. “I’m impressed that [the EEVA] does such a good job,” says Arthur Wisot, a staff physician at the southern California–based fertility clinic, Reproductive Partners Medical Group. “The thing that differentiates it from other time-lapse systems is that it has unique time-lapse image analysis software that, automatically, without subjective human involvement, can tell us that this embryo has a high probability of reaching the blastocyst stage or not,” he says.
Armed with such technology some specialists say that they are better positioned to make more informed embryo choices with patients. Indeed, data has shown that under some circumstances the assessment can help specialists successfully identify embryos with better odds of making it to the blastocyst stage by day five. One study indicated that the EEVA boosted the odds of experts accurately predicting which embryo would develop into a blastocyst by 53 percent compared with when they only used traditional morphological grading alone. The recent study compared embryologists’ experiences across five clinics with 54 patients undergoing IVF. Embryologists at each center had predicted blastocyst formation using day-three morphology alone versus day-three morphology followed by EEVA test results.
But still, a blastocyst does not a baby make.
Even after selecting a top-notch embryo, with pregnancy there are still no guarantees. Problematic hormonal imbalances in the uterus at the time of implantation can still block the embryo from implanting there. The EEVA test is also not approved to help embryologists glean information about chromosomal abnormalities in the embryo that can also change the fate of the pregnancy.
The technology cleared its final FDA approval for its automated assessment system last November. No independent organization is tracking how many clinics are now using the EEVA. Ten fertility clinics around the country—including that of its creator at Stanford—are currently employing the test, according to Auxogyn, the company that markets it. Yet other clinics remain skeptical of the system.
To use the EEVA, at least some of the embryos would need to look pretty good, says Norbert Gleicher, medical director and chief scientist at the Center for Human Reproduction in New York City. The technology is designed to help assess which candidate is better than other embryos, especially when more than one is dividing in desired ways. But sometimes patients undergoing IVF will have no embryos that meet that bar, he says. That’s one reason not all fertility clinics—including his—are convinced the technology is a good fit for their clientele, he says. Gleicher’s private fertility clinic and research center decided not to buy the EEVA or any time-lapse imaging technology because they believe investing in the cost would not improve patient outcomes. “In order to get the benefit of selection and say it’s helping to find the best one there has to be a ‘best’ embryo—and if all of them are just average the system won’t create a benefit,” he says. Because insurance companies usually do not cover the technology—for which some clinics charge around $1,500—it can also make an IVF cycle even pricier for patients. In Gleicher’s practice, which has a large population of women over age 40 who have had unsuccessful IVF cycles elsewhere, most patients do not have good embryos; they are more often average to poor so there would be no benefit and it would raise costs, he says.
The EEVA “gives you a high or low potential for viability now, but it is not absolute,” Behr says. What it can do is help select which embryos to start off the pregnancy. For now, clinicians must decide if that is enough.