For patients undergoing in vitro fertilization, there is a common test to help determine the best time to transfer the embryo for a successful pregnancy. But new research has patients and doctors questioning whether the test — one of a growing number of expensive “add-ons” for I.V.F. patients — is effective for first-time patients.
The test, called an endometrial receptivity analysis, takes a biopsy of the interior 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 birthrates for first-time I.V.F. patients who had the E.R.A. to those who did not, and researchers found no difference between the two groups. In other words, the test does not improve chances of achieving an ongoing pregnancy in first-time patients, according to the findings.
The research, which was sponsored by Igenomix and has not been peer-reviewed or published in full, also noted that more studies were needed to assess whether the test could be beneficial for patients who have had multiple failed transfers. The study was led by researchers from Shady Grove Fertility, which has more than 40 clinics across the United States.
“It doesn’t improve the live birthrates for all women,” said Dr. Nicole Doyle, the study’s lead researcher and a reproductive endocrinologist at Shady Grove. “We had hoped for better results, but from a cost benefit, it’s not worth it,” she said of the test, which can cost patients up to $1,000.
“This type of study should have been done earlier,” said Dr. Eric Forman, the medical and laboratory director at Columbia University’s Fertility Center. He said the test had 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 in 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-time patients opted to do it. “They feel so empowered by having the option,” she said.
The Shady Grove study offered 767 first-time I.V.F. patients a free E.R.A. before transfer. (Genetic tests ruled out any failures involving an abnormal embryo.)
The patients each had one embryo transferred; half used the test and the other half did not. The results found that just over 54 percent of the group that used the test had an ongoing pregnancy, compared with just over 63 percent of the control group.
Igenomix said in an emailed statement that despite funding the research, the company had not had access to the raw data and was waiting for it to be published in a peer-reviewed journal before commenting on the results.
The company, which was acquired by Vitrolife in July, said that 25 other studies — 16 internal and nine independent — supported use of the test. In reality, the existing body of data shows mixed results about the test’s effectiveness.
A 2018 independent study of patients with two or fewer previous failed transfers found that the test did not improve pregnancy outcomes, but the study used only a small sample of participants.
One Igenomix study from 2013 found that one in four women with repeated I.V.F. failure had a displaced window of implantation and concluded that those patients could benefit from using the test. A randomized clinical trial sponsored by the company from 2020 used a sample of mostly first-time patients, with some who had experienced up to a few failed attempts. The trial concluded that those who used the test had a “significant improvement” in live birthrates, but did not differentiate between first-time patients and those with previous failed transfers. Some scientists have also criticized the study’s 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.”
Dr. Doyle and her team’s findings underscore critics’ ongoing concerns about the need for greater regulation of the I.V.F. industry. “It’s both irresponsible and unethical for clinics to sell I.V.F. add-ons that are scientifically unproven,” said Pamela Mahoney Tsigdinos, a patient advocate and the author of “Silent Sorority.”
While 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 E.R.A. is considered a laboratory-developed test, according to Igenomix, a category that can bypass F.D.A. scrutiny. (This same loophole allowed Theranos, the blood testing start-up founded by Elizabeth Holmes, to evade the agency’s oversight. Ms. Holmes is on trial for fraud charges.)
I.V.F. is a costly endeavor with no guarantee of success. A single I.V.F. cycle can exceed $20,000, according to data from FertilityIQ, a company that provides reviews of fertility clinics. Most people need at least three to four I.V.F. cycles to be successful.
There were almost 330,000 assisted reproductive technology cycles (which includes I.V.F. and egg freezing) performed in the United States in 2019, according to preliminary data from the Centers for Disease Control and Prevention, with nearly 78,000 patients giving birth.
“I.V.F. has reached maturity as a technology and we’re approaching the limits of its efficacy,” said Dr. Andrea Vidali, a reproductive immunologist and repeat miscarriage specialist in New York.
He believes add-ons like the E.R.A. are a result of an industry focused on “troubleshooting I.V.F. failure.” He said that doctors adopted the test because “patients don’t want to be told they have unexplained infertility when they ask for a reason as to why their I.V.F. transfer failed, and they are looking for answers.”
Patients undergoing I.V.F. are presented with a list of add-ons “with no ability” to assess the value, according to David Sable, a venture capital fund manager and reproductive endocrinologist.
In light of the new research, some fertility doctors are reconsidering the test’s use on first-time patients, while other doctors are further dissuaded from using it at all.
“We have always discouraged the E.R.A. test,” said Dr. Peter Klatsky, a founder of Spring Fertility, which has clinics in California, New York and Vancouver. He has observed the test’s popularity grow in recent years. “This study makes it easier to explain why we do not 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 of whether their success was a result of the test.
Nathalie Carpenter, the 42-year-old founder of a wellness marketing agency and a community advocate for infertility in Connecticut, received the test ahead of two I.V.F. cycles, each years apart. The first resulted in a daughter; the second failed. She wonders now whether the E.R.A. 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 scale toward a successful pregnancy regardless of the ambiguous data.
When 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 laboratory director, that she wanted an E.R.A., even though he was skeptical.
Having experienced multiple miscarriages before, 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 did the test and would do it again. “If it didn’t work out, I would wonder, ‘What if the implantation window was off?’” she said. “You want control. And that’s what the E.R.A. does — it gives an element of control over these things.”