How the ERA Test and Genetic Testing Can Help Those with Unexplained Infertility

presented by Igenomix

People have been having babies for thousands of years, yet for hopeful parents struggling to conceive, there are still so many unknowns. 

When dealing with infertility, the lack of control, of not knowing why or what to do can be frustrating, even devastating, the longer the journey drags on.

Lindsey Corey was a woman on a mission—to have a baby—so she kept searching for answers. She shared her fertility story in an Igenomix podcast, and for her, reproduction genetic testing was critical to achieving her dream of having a family.

Searching, Waiting, Testing for a Solution

Lindsey, an executive assistant in South Florida, was in her mid 30s and started TTC in 2016. But with her PCOS and her husband’s sperm morphology issues, they were on a tough fertility journey. They went through multiple IVF cycles, resulting in a lot of waiting—so much waiting—often followed by crushing disappointment. Over the course of her process, she had 65 eggs retrieved, which resulted in only three Day 5 embryos.

They went through multiple IVF cycles, resulting in a lot of waiting often followed by crushing disappointment. Over the course of her process, she had 65 eggs retrieved, which resulted in only three Day 5 embryos.

She worked with her fertility specialist to discuss options, do bloodwork, as well as try special diets. She made all the lifestyle changes she could. 

She says: “I read all these books, took supplements. I said at the time, ‘These embryos are going to come out with superhero capes on!’ I was so determined.”

But, still, her goal of a baby went unfulfilled. 

Then a woman in her online fertility support group mentioned the Endometrial Receptivity Analysis (ERA) test. ERA helps determine a woman’s receptivity for implantation—the right time to try implanting an embryo into a woman’s uterus so it will stick. 

Lindsey asked her doctor about it. It wasn’t being used in her Florida clinic at the time, but when she finally had a new round of embryos to transfer, her doctor had her do the ERA. 

She says he told her: “‘It’s all about optimization. You throw everything you have at it.'”

Lindsey says: “I came back ‘receptive,’ which was great. Then I went to transfer the first PGT-tested embryo. I had only a chemical pregnancy…so we decided to do another ERA [before trying again]. Whenever you have a trauma to the body or uterus, it’s sure to shift something. I had had the miscarriage, I had lost a lot of weight before that egg retrieval, and sure enough, my receptivity time shifted by 17 hours. 

“Then we transferred another [embryo, which became my son] and I felt him dig in. I knew right away. I remember where I was. I was sitting on my friend’s couch. And I said: ‘I’m afraid to move right now’. I knew it was happening.”

Genetic Testing Gets to the Root of the Problem

Tiffany Stankewicz, Endometrial Specialist and Senior Scientific Advisor at Igenomix, a reproduction genetics testing company, says that Lindsey’s success isn’t assured for everyone, but that the Igenomix ERA test has helped many women get pregnant.

She adds that “a randomized controlled trial showed a 71% live birth rate with frozen embryos and ERA testing and timing vs. a 55% live birth rate with frozen embryos at standard time without ERA testing.” 

Tiffany Stankewicz, Endometrial Specialist and Senior Scientific Advisor at Igenomix

A randomized controlled trial showed a 71% live birth rate with frozen embryos and ERA testing and timing vs. a 55% live birth rate with frozen embryos at standard time without ERA testing.

When people are struggling, it’s helpful to know the science, what’s going on under the hood (so to speak). 

She says, “With implantation, we have to have a competent embryo and receptive endometrium. A blastocyst has to implant in the uterine lining. Before, it was assumed that all women would be receptive on Day 5. But we now know that every woman has her own unique window of implantation. 

“Our ERA looks at the transcriptome, or gene expression; it assesses the expression of 248 genes. Certain genes are going to be turned on and off before, during, and after the receptive period. With ERA, we can tell which genes are turned on and off. In more than 90% of cases, we’re able to give a specific recommendation for transfer timing.”

Recommendations are for 12-to-48 hours before or after traditional receptivity. Most commonly, it is 12 hours before or 12-to-24 hours after.

For Lindsey, in 2019, the ERA-assisted embryo held and she gave birth to her son, Owen.

Lindsey says: “I remember being on the C-section table and I heard him cry for the first time and I felt fireworks go off in my body. There’s nothing like it. I cherish every day and never take for granted that I’m that little boy’s mommy. I worked really hard for him.”

This year, she also became pregnant with daughter, Molly, with the help of four additional ERA tests. That many ERA tests (or uterine biopsies) is very unusual, but she says it’s worth it.

Lindsey says: “I would not be willing to waste an embryo, by not doing an ERA. It has led me to where I am”—being the mother of two children.

Reproductive Genetic Testing Basics

Of course, genetic testing, to help parents get pregnant and have healthy babies, goes beyond the ERA test.

There are three types of testing—for use during preconception, preimplantation, and prenatal stages.

Preconception genetic tests, or carrier screenings, help detect genetic abnormalities in the egg or sperm before conception. Pre-implantation genetic tests help reduce the risk for implantation failure or miscarriage and improve the chances for a healthy pregnancy. Prenatal genetic tests help discover whether a pregnancy is at increased risk for a genetic syndrome.

Tiffany says genetic testing to assist conception and pregnancy took off in the 1990s. First, it was focused on testing the embryos, then testing the carrier, and more recently, testing the carrier endometrium has become possible.

In the 2010s, there was a huge increase in genetic testing. The ERA test that helped Lindsey was introduced about 10 years ago. 

 Also, at this time use of PGT-A (Preimplantation Genetic Testing for Aneuploidy), or chromosome testing in embryos, increased.

In 2017, the American College of Obstetricians and Gynecologists (ACOG) doctors began recommending carrier screenings for all women. This has led to an increase in PGT-M (monogenetic disease testing in embryos) due to more data on carrier status.

Then Igenomix created the Analysis of Infectious Chronic Endometritis (ALICE) test. ALICE looks for chronic endometritis, or inflammation of the uterine lining. 

Tiffany says that clinical studies have shown a prevalence of endometritis in 30% of women with infertility, and 60% of women with recurrent implantation failure and pregnancy loss. The test looks for the DNA presence of nine bacterial pathogens. (ALICE was introduced to the United States in 2021.)

In 2018, Igenomix launched the Endometrial Microbiome Metagenomic Analysis (EMMA) test to help further understand what’s happening with implantation failure and pregnancy loss.

Tiffany says it offers a comprehensive view of the uterine microbiome. 

The microbiome is the bacterial environment—we have a gut microbiome, a skin microbiome, and a uterine microbiome. Positive bacteria in the microbiome help the body thrive. Negative bacteria or pathogens in the uterus can cause many problems, including infertility.

EMMA looks for bacterial pathogens of the reproductive tract not related to endometritis, such as Gardnerella, that might be in the endometrial lining. On the positive side, EMMA also tests for four species of Lactobacillus (the good bacteria). In a pilot study that retrospectively looked at patients who had receptive endometria, these women also showed high levels of Lactobacillus.

ERA is specifically for IVF patients. EMMA and ALICE tests can be used in an OB/GYN office to help any woman achieve an optimal microbiome for pregnancy.

Is It Worth It?

What is the price of knowledge? That is for each person to decide. 

In terms of actual cost, an ERA test is around $800. The Alice test is $300 and the more comprehensive EMMA test is $500. All three analyses can be done with a single biopsy for $1,000.

The tests are rarely covered by health insurance, but that’s something to discuss with health care practitioners and insurance providers based on individual circumstances.

What Does the ERA Test Feel Like?

Tiffany, of Igenomix, says that there may be some discomfort from the very brief endometrial biopsy procedure and some cramping or light bleeding afterward. The tiny sample is taken from the patient when it’s expected that she would be receptive.

Lindsey had a more challenging experience, but for her, the ERA test made all the difference.

She says: “Before I had my son, [the ERA test] was not a pleasant procedure. But it was well worth it. You do what you have to do. I don’t think anything is really pleasant in this [TTC] process. After I had my son, the four ERA tests that I had [to conceive my daughter] were not painful. I think something changes, especially with your uterus once you give birth. Then it didn’t hurt at all.”

Specifically, “You do this mock cycle, as if you are preparing for a frozen embryo transfer. On the day that you would transfer, you go in for the biopsy.” 

Testing Helps You Choose a Path

Of course, genetic test results are not outcome guarantees. Genetic testing may provide answers you love (you have healthy embryos, your body is receptive to pregnancy) or loathe (your system has a bacterial imbalance, you may pass along a genetic disease). 

But testing helps you make choices. 

Genetic testing may provide answers you love (you have healthy embryos, your body is receptive to pregnancy) or loathe (your system has a bacterial imbalance, you may pass along a genetic disease).  But testing helps you make choices.

Lindsey Corey and her family
Photo credit: Addison James Photography

Lindsey now shares her experience with many hopeful parents, urging the importance of talking with others and asking questions.

She says: “Some people, like the people with undiagnosed infertility, might not even know that they need the ERA test or [other tests]. One thing I learned is that my body was unpredictable in this process. If I have a tool that I can put my head down at night knowing that I did everything, why not do it?”

Tiffany, of Igenomix, is committed to sharing what’s possible in pregnancy with the help of science. Even outside the office, when women find out what she does she can talk about genetic testing for hours, and has—even when she was on her honeymoon in the Maui rainforest!

She says, “I love to share this knowledge because it’s a big thing to get pregnant, to have children.”

While reproduction genetic testing is not foolproof or for everyone, the results can help you break through information or emotion overload. 

There’s comfort, even a sense of power in having clarity, making testing worth exploring. 

Find out more about Igenomix here 

Hear Lindsey’s full story, via the Igenomix podcast below:


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