When you're trying to conceive, you want to do everything in your power to increase your odds of success. But you also want to know that the tests, procedures, and medications offered to you are necessary and work, especially because you want as natural a treatment plan as possible.

One test you may have heard about is an endometrial biopsy – should you get one? Let’s talk about it.

What is an endometrial biopsy?

Simply put, an endometrial biopsy, of which there are several different kinds (we'll get into that soon), is when a doctor takes a small tissue sample of a woman’s uterine lining, also known as her endometrium, for testing. The endometrium is the tissue that sheds each month during a woman’s menstrual cycle and builds back up in anticipation of pregnancy.

Usually, the procedure is very quick (less than a minute) but may cause brief cramping. Your doctor may recommend over-the-counter painkillers before the biopsy to help with this cramping.

Once the biopsy is taken, it is analyzed in a lab for various biochemical markers, and results are usually available within two weeks. The results can help doctors diagnose a problem and decide the next steps in treatment.

Are endometrial biopsies always used for fertility purposes?

There are many reasons doctors may want to perform an endometrial biopsy, even outside of infertility.

For example,  an endometrial biopsy can also be taken if a non-pregnant woman has heavy or abnormal vaginal bleeding to rule out cancer or other serious conditions.

What fertility conditions can an endometrial biopsy diagnose?

Endometrial biopsies can be helpful in several ways, but whether they 'diagnose' certain conditions is up for debate. Some have been proven to work, while others have a spottier record. While some doctors will take an endometrial biopsy to see whether a patient has a bacterial infection preventing implantation, the two most common endometrial biopsies for infertility patients are an ERA and a ReceptivaDx.

What is an ERA?

ERA is short for Endometrial Receptivity Analysis, which is an endometrial biopsy taken to see whether your endometrium is receptive (or open) to receiving an embryo at a certain point in your cycle. It has been done for women with unexplained infertility, miscarriage, and Recurrent Implantation Failure (RIF). However, some of these indications for the ERA are coming into question.

Let’s back up a bit.

For pregnancy to occur, the embryo has to implant into the woman's uterus during her 'window of receptivity' or 'window of implantation.'

Essentially, this means the uterus has a short time frame each month (about 24 hours or less) during which it is ready and willing to accept an embryo. If the embryo is not near a uterine wall during that window, if it is not mature enough, or if it is chromosomally, abnormal implantation will not occur.

Plus, for the window to become active, the endometrium must be expressing the correct genes, a process primarily influenced by the hormone progesterone.

Does the ERA work?

The ERA test claims to predict whether, at the time the test is taken, a woman's uterus is in the window of receptivity, about to enter the window of receptivity, or past the window entirely. In theory, this information would help doctors determine whether they should time a woman’s embryo transfer differently, such as doing her transfer earlier or later in hopes of meeting the window and achieving pregnancy.

While the ERA is a fairly common test, many clinics have lessened their use of the test – or discontinued use entirely – following a clinical study earlier this year that showed the test did not improve outcomes except in a small subset of patients. In other words, this reliable scientific study (before which there was very little solid scientific data on the efficacy of the test) showed the test didn’t work for the general IVF population.

At Pearl, where we believe in scientific validation, we have limited our use of the ERA test to only those patients who have a clear need. However, we have seen promising results with one test we do offer: the ReceptivaDx test, another common fertility test offered via endometrial biopsy.

What is the ReceptivaDx?

The ReceptivaDx test uses an endometrial biopsy to diagnose inflammation caused by endometriosis or chronic endometritis.

Endometriosis is when endometrial tissue that usually grows inside the uterus grows outside. Endometritis is when your endometrium is inflamed or irritated, sometimes due to an infection.

Both conditions can lead to infertility. In the case of endometriosis, tissue can grow on your ovaries, your fallopian tubes, and inside your pelvic cavity, leading to painful inflammation and scar tissue that can cause infertility by blocking the meeting of sperm and egg, or preventing normal implantation.

With chronic endometritis, infertility is also caused by uterine wall inflammation that prevents proper implantation from occurring.

Historically, endometriosis, a far more common diagnosis than endometritis, took an average of 7-10 years to diagnose. ReceptivaDx offers a faster, more affordable, and less painful way to learn about a patient's chances of having either endometriosis or chronic endometritis.

Pearl provides this biopsy to women with unexplained infertility that have failed one or more IVF cycles or have experienced recurrent pregnancy loss or implantation failure.

For endometriosis, the biopsy works by identifying a gene repressor biomarker called BCL6, which is present when there is inflammation and likely causes progesterone resistance, which in turn causes implantation issues. In the case of endometritis, the test looks for CD138, a marker of this condition.

Women who get a negative result on either test can move onto other treatment options with their doctors, while women who test positive can talk about treatment plans that aim to combat the diagnosis – in the case of endometriosis, either medication or surgery.

How much does ReceptivaDx test cost?

The test is relatively affordable at $815 for the BCL6 and CD138 markers, and $125 for any additional markers your doctor may want to check.

Does ReceptivaDx work?

It appears to work, yes. While there is still not a ton of data on the test, early data is promising. According to the group behind the test, a 2017 cohort study linked the presence of BCL6 in patients with the likelihood of achieving a live birth on that patient’s next IVF transfer.

Another paper showed that BCL6 positive women who had surgery or took medications like Lupron had a 50% chance of a live birth compared to a 10% chance for BCL6 positive women who sought no treatment.

Do I need an endometrial biopsy to help me get pregnant?

It depends. Since ERA’s have been proven not to be effective, the best route for a patient who suspects she may have implantation window issues is to talk to your fertility doctor.

Based on your blood work and previous cycle results, and with a bit of protocol tweaking, your doctor should be able to figure out your ideal implantation timing. In terms of endometriosis, the ReceptivaDx appears to be a fast, affordable and innovative way to test for the potential presence of endometriosis. This diagnosis is essential for altering treatment plans for patients to go on to become pregnant and have a live birth. In all instances, talk to your doctor – she is your best advocate, your most knowledgeable resource and knows you and your particular situation the best.