When infertility doctors are about to help a couple conceive a baby through in vitro fertilization, they have to make some momentous bets. The possible consequences of those bets include a high-risk pregnancy with multiple infants, on one extreme, and no pregnancy at all on the other.
In their quest for a healthy birth, doctors must decide how many of the embryos created in the lab should be transferred to the mother’s womb, and which embryos are most likely to result in a pregnancy. To make the selection, clinicians now eyeball the candidate embryos through a microscope.
The Menlo Park, CA, startup Auxogyn is trying to help doctors make better bets by giving them a more sophisticated way to pick out the best embryos. Auxogyn’s CEO Lissa Goldenstein says the company’s computerized video analysis system–the Eeva test, for short—could help guide treatment plans for the expensive in vitro fertilization (IVF) procedure.
“Even at clinics that have high success rates, high success rates really aren’t all that high,’’ Goldenstein says.
Less than a third of IVF treatment cycles result in live births for US women between 35 and 37, according to 2010 data from the Centers for Disease Control and Prevention. Auxogyn’s first product, the Early Embryo Viability Assessment, or Eeva test, is designed to improve those odds; word from the FDA on whether it can be used in the United States could come as soon as next spring.
The test may help solve a dilemma for infertility doctors and their patients, Goldenstein says. They must decide whether to transfer multiple embryos into the womb, in the hope that at least one will yield a pregnancy. But this heightens the chance of twins, triplets, or even higher-order multiple births. That can result in greater risks for the mother and in premature births, with possible health consequences for the infants.
However, if fewer embryos are transferred, the odds of a pregnancy drop. Goldenstein says US parents can feel financial pressure to use more than one embryo. The average cost of an IVF cycle in the United States is $12,400, according to the American Society for Reproductive Medicine. The costs mount up if couples pay for several cycles before conceiving.
The key to success comes in choosing which embryos to transfer, and when. In natural conception, a fertilized one-celled embryo divides until it becomes a blastocyst of about 150 cells after five or six days. The blastocyst has a distinct outer wall that attaches to the wall of the womb, beginning a pregnancy. When embryos are created in a lab dish, they are often transferred to the mother in about three days, when they consist of about four cells. To choose the embryos, doctors try to predict which of those embryos will go on to form a blastocyst by counting the numbers of cells and assessing the form, or morphology, of the embryo.
As an alternative procedure, clinicians can delay the embryo transfer until the fifth day after fertilization, when some of the embryos may have progressed to form blastocysts. But Goldenstein says the development of the embryos can stall if they remain in a culture dish, leaving the patients with no viable embryos to use.
If doctors could feel confident of their selection early on, however, they could transfer the embryos—even perhaps a single embryo—on the third day. That possibility inspired Stanford University professor Renee Reijo Pera to look for factors that would predict blastocyst formation. Pera and her colleagues discovered that the timing of early cell division gave a forecast of the embryos’ fates. They co-founded Auxogyn in 2008 to commercialize their findings.
The resulting Eeva test system tracks the first growth spurt of the embryos sparked when eggs taken from a woman are fertilized in a lab dish with sperm taken from a man. Video images of the embryos, captured through microscopes, are analyzed by a computer program that looks for optimal patterns of cell division as the one-celled embryo grows to four cells. The best embryos for IVF are not the fastest to grow, Goldenstein says. Growth patterns at either extreme—either fast or slow—mean an embryo is less likely to form a blastocyst.
This monitoring of embryos over a period of days gives clinicians a layer of quantitative information beyond what can be observed by clinicians at a single time through the microscope, Goldenstein says. The private Menlo Park startup says it has demonstrated in several studies that fertility clinic embryologists make better predictions about the embryos destined to become blastocysts after they take the results of the Eeva test into account, along with their standard examinations of embryos through the microscope. Auxogyn presented some of the studies this week at the American Society for Reproductive Medicine’s annual meeting in San Diego.
The Eeva test is now under review by the FDA, with a possible decision on its safety and efficacy coming by the end of the first quarter of 2013, Goldenstein says. The US market for infertility services is more than $4 billion, the research firm Marketdata Enterprises reported in 2009.
In July, Auxogyn gained approval to market the Eeva test in the European Union, and installed its first system at a fertility center in Liverpool, UK in September. The European market is about 3.7 times larger than the US market, according to 2009 data compiled by the European Society of Human Reproduction and Embryology. Fertility clinics performed 537,287 IVF cycles in 33 European countries, compared with 142,435 cycles during the same year in the United States.
Auxogyn, which started operations in 2010 after receiving its first funding, recently formed an alliance with a leading producer of fertility drugs, Merck Serono of Geneva, Switzerland. The two companies announced Oct. 18 that Merck Serono would help Auxogyn to carry out multi-site clinical trials of the Eeva test, and to further develop the capabilities of the system. Financial terms of the deal were not made public.
The company is asking the FDA to approve the use of the Eeva test as an adjunct to the standard methods of embryo evaluation. But Goldenstein says the Eeva test may eventually be used as a standalone assessment. In the future, it may incorporate some of the standard tasks done by embryologists, such as counting the number of cells in each embryo.
In addition to improving the predictions of embryologists, Auxogyn plans to try to show that the Eeva test will boost key measures of success, such as the rate of pregnancies or live births for each IVF cycle. Such clinical trials would reveal clear results only if a single embryo were used in each mother, Goldenstein says. The trials would be easier to conduct in Europe, where single embryo transfers are considered the standard of care in some countries, she says.
In the United States, the average number of embryos transferred is two or more for women in most age groups, according to the CDC.
“The US has one of the highest success rates in the world, but we also have the highest rates of multiples,’’ Goldenstein says.
The global infertility industry has been growing by 5 to 10 percent a year, and an estimated five million babies have been born with the help of IVF since the technique was first used in humans in 1978. About one in six couples worldwide experience some form of difficulty with fertility, according to the European Society of Human Reproduction and Embryology.
Auxogyn has raised $38 million in two funding rounds from backers including Kleiner Perkins Caufield & Byers, SR One, TPG Biotech, and Merck Serono Ventures, the venture arm of Merck Serono, a unit of the German pharmaceutical company Merck
Goldenstein did not disclose revenue projections for the Eeva test, but she said Auxogyn’s pricing structure would make it easy for fertility clinics to adopt the technology. The clinics will pay low initial capital costs to have their existing incubators retrofitted for video monitoring of embryo growth. The fertility practices will then pay a fee for each use of the test. That cost will probably be passed along to patients as an optional add-on service to their basic IVF package, Goldenstein says.
US clinics where the systems have been tested are interested, Goldenstein says.
“We have a hard time taking them out after the studies,’’ she says.
Four California fertility practices participated in studies of the Eeva test, including the Pacific Fertility Center in San Francisco. Its medical director, Dr. Philip Chenette, said Auxogyn’s test “provides a new tool to investigate an old problem.”
“This technology provides new insights that help improve embryo selection and potentially improve IVF outcomes and pregnancy rates,” Chenette said in a press release Auxogyn issued at the San Diego conference.