For patients undergoing in vitro fertilization, there is a general test to help determine the best time to transfer the embryo for a successful pregnancy. But new research has left patients and doctors questioning whether the test — one of a growing number of expensive “add-ons” for IVF patients — is effective for new patients.
The test, called an endometrial receptivity analysis, takes a biopsy of the inner lining of the uterus. Then, a lab analyzes the tissue for more than 200 genes to predict the best time to place the embryo in the uterus, according to the test’s manufacturer, Igenomix.
The study, whose findings were published in September, compared live birth rates for first-time IVF patients who had the ERA with those who had not, and researchers found no difference between the two groups. In other words, the test does not improve the chances of achieving an ongoing pregnancy in new patients, according to the findings.
The study, which was sponsored by Igenomix and has not been fully peer-reviewed or published, also noted that more studies were needed to assess whether the test could benefit patients who have had multiple transfer failures. The study was led by researchers at Shady Grove Fertility, which has more than 40 clinics in the United States.
“It doesn’t improve the live birth rate for all women,” says Dr. Nicole Doyle, principal investigator of the study and reproductive endocrinologist at Shady Grove. “We were hoping for better results, but given the cost benefit, it’s not worth it,” she said of the test, which could cost patients up to $1,000.
“This kind of research should have been done sooner,” says Dr. Eric Forman, the medical and laboratory director of Columbia University’s Fertility Center. He said the test has been used tens of thousands of times in the United States since it became available in 2011.
Some clinics offer the test for all patients, while others recommend it for those with failed cycles. Many patients request the test after reading about it on online forums. dr. Aimee Eyvazzadeh, a reproductive endocrinologist in San Ramon, Calif., said she offered the test to all patients, and about half of her first patients chose to do it. “They feel so empowered to have the option,” she said.
The Shady Grove trial offered 767 new IVF patients a free pre-transfer ERA. (Genetic testing ruled out any errors involving an abnormal embryo.)
One embryo was transferred to each of the patients; half used the test and the other half did not. The results showed that just over 54 percent of the group using the test had an ongoing pregnancy, compared to just over 63 percent of the control group.
Igenomix said in an emailed statement that despite funding the study, the company had no access to the raw data and was waiting for publication in a peer-reviewed journal before commenting on the results.
The company, which was acquired by Vitrolife in July, said 25 other studies – 16 internal and nine independent – supported the use of the test. In reality, the existing amount of data shows mixed results about the effectiveness of the test.
A 2018 independent study of patients with two or fewer prior transmission failures found that the test did not improve pregnancy outcomes, but the study only used a small sample of participants.
A 2013 Igenomix study found that one in four women with repeated IVF failure had a relocated implant window and concluded that those patients could benefit from using the test. A 2020 randomized clinical trial sponsored by the company used a sample of mostly new patients, with some having experienced up to a few failed attempts. The study concluded that those who used the test had a “significant improvement” in live birth rates, but did not distinguish between first-time patients and those with previous failed transmissions. Some scientists have also criticized the research methodology as flawed.
The Igenomix statement said that given the latest Shady Grove study, more research was needed to determine whether the test “could be clinically useful in all patients at the first appointment.”
The findings of Dr. Doyle and her team underline critics’ continued concerns about the need for greater regulation of the IVF industry. “It’s both irresponsible and unethical for clinics to sell IVF add-ons that aren’t scientifically proven,” said Pamela Mahoney Tsigdinos, a patient advocate and the author of “Silent Sorority.”
Although the test is certified and regulated by the Centers for Medicare and Medicaid Services, it is not approved by the Food and Drug Administration. The ERA is considered a lab-developed test, a category that can bypass FDA control, according to Igenomix. (This same loophole allowed Theranos, the blood-testing startup founded by Elizabeth Holmes, to evade agency oversight. Ms. Holmes is on trial for fraud charges.)
IVF is a costly undertaking with no guarantee of success. A single IVF cycle can exceed $20,000, according to data from FertilityIQ, a company that provides ratings of fertility clinics. Most people need a minimum of three to four IVF cycles to be successful.
According to preliminary data from the Centers for Disease Control and Prevention, nearly 330,000 cycles of assisted reproductive technology (including IVF and egg freezing) were performed in the United States in 2019, with nearly 78,000 patients giving birth.
“IVF has matured as a technology and we are approaching the limits of its efficacy,” said Dr. Andrea Vidali, a reproductive immunologist and recurrent miscarriage specialist in New York.
He believes add-ons like the ERA are the result of an industry focused on “fixing IVF errors.” He said doctors have adopted the test because “patients don’t want to be told they have unexplained infertility when they ask for a reason why their IVF transfer failed, and they’re looking for answers.”
According to David Sable, a venture capital fund manager and reproductive endocrinologist, patients undergoing IVF are given a list of add-ons “without ability” to assess value.
In light of the new research, some fertility doctors are reconsidering using the test in new patients, while others are further advising against using it altogether.
“We’ve always discouraged the ERA test,” says Dr. Peter Klatsky, founder of Spring Fertility, which has clinics in California, New York and Vancouver. He has seen the test’s popularity grow in recent years. “This study makes it easier to explain why we don’t recommend this test when patients have read positive testimonials online,” he said.
Some patients who had ongoing pregnancies after using the test are now unsure whether their success was the result of the test.
Nathalie Carpenter, the 42-year-old founder of a wellness marketing agency and a social advocate for infertility in Connecticut, received the test prior to two IVF cycles, each year apart. The first resulted in a daughter; the second fails. She now wonders if the ERA was effective. But at the time she said, “I trusted my doctor; I didn’t question it.”
Some patients remain hopeful that the test could tip the scales toward a successful pregnancy, regardless of the ambiguous data.
As Rhian Thomas, a 39-year-old television producer in New York, was preparing for her first embryo transfer at the Columbia University Fertility Center, she told Dr. Forman, the center’s medical and lab director, said she wanted an ERA, even though he was skeptical.
After experiencing multiple miscarriages, Ms. Thomas said she wanted to “go through every test on the planet” for the best chance of pregnancy. The transfer after the test resulted in a son, who is now seven months old.
Despite the new study, Ms. Thomas said she was glad she took the test and would do it again. “If it didn’t work, I’d be like, ‘What if the implant window was out?'” she said. “You want control. And that’s what the ERA does — it gives an element of control over these things.”