Unexplained infertility – shining new light into the darkness

The Fertility Hub are delighted to introduce you to our new supplier ReceptivaDX who have developed a test, which gives hope to patients with endometriosis and unexplained infertility. If there is one-word scientists love, it is unexplained. Whereas for most people it is synonymous with the word frustration, scientists instead hear the words interesting challenge.

In few areas of human life is the word unexplained more frustrating than in terms of infertility. Not only is it frustrating, but demoralising, depressing and engenders a feeling of helplessness.

Unexplained infertility is an actual diagnosis! It is given when semen analysis shows normal and assessment of the ovaries and fallopian tubes also show no concerns. There is no explanation why a couple are not conceiving naturally.

Globally, about 10% of infertile couples are diagnosed with unexplained fertility, equating to around 5 million people worldwide. Bu unexplained does not mean there is no cause. It just means the cause is not detected using current methods.

That situation is all set to change! Scientists have found a protein present in blood that helps predict what is currently called unexplained infertility in women. This protein, known as BCL6, is a new biomarker for the presence of endometriosis.

Endometriosis is a condition where the tissue that lines the inside of the uterus, grows outside of it and attaches to other organs such as the ovaries and fallopian tubes. It is a potential cause of infertility, but it can be treated surgically.

A depiction of BCL6. BCL6 is a new biomarker for endometriosis.

BCL6 can predict unexplained infertility

Scientists set out to study whether high levels of BCL6 could predict IVF outcomes in women who have unexplained infertility.

They recruited women who were still infertile after undergoing IVF for one year or more. The study was conducted over 8 years. Of these women, 75% had high levels of BCL6, while 25% had normal BCL6 levels.

Results from the study showed:

  • Women who had low levels of BCL6 had a significantly higher pregnancy rate, at 64.7%
  • Women who had high levels of BCL6 had a pregnancy rate of only 17.3%.

More importantly, the live birth rate was significantly higher in women with low BCL6, at 58.8%. This compared to women with high BCL6, at only 11.5%.

From this it is clear that high BCL6 levels are associated with poor pregnancy outcomes

The authors concluded, “High levels of BCL6 expression in this cohort suggests that undiagnosed endometriosis may be a common factor that needs to be considered in women before undergoing IVF.”

In other words, the researchers are suggesting that women should get tested for BCL6 levels BEFORE attempting IVF or after their first failure. This would allow women with endometriosis to get it treated before undergoing IVF.


In January of 2019 there was a follow-up study published.  Women who had tested positive for BCL6 were treated with hormone suppression or surgical laparoscopy. This increased their likelihood of live birth success from below 15% without treatment to over 60% with treatment.  This data has been replicated by the hundreds of centers now using the test on their patients.

How do you test for BCL6?

A new diagnostic test is available called ReceptivaDx, which can be used to test patients for BCL6 prior to their first IVF treatment or after the first failure. The test uses an endometrial biopsy that is analyzed by a pathologist. Results give physicians in IVF centres the ability to diagnose endometriosis in patients with results taking just 3-5 days after reaching the lab.

The case for ReceptivaDX

One of the lead researchers, Dr Bruce Lessey, a Reproductive Endocrinologist in Greenville, South Carolina, in the US, said, “One of the toughest conversations you can have with your patient is why their IVF transfer failed.”

And around 100,000 of those conversations are currently taking place each year.

With this statistic clearly in mind, Lessey continued, “This test provides an opportunity for couples to better understand the basis of their infertility and will provide more options and higher success rates.”

It seems something of a no-brainer that women considering IVF should have access to this highly predictive test. After all, they are spending tens of thousands of dollars in the hope of starting a family, and the emotional costs of IVF failure are also extremely high.

Knowing their BCL6 status gives these women the opportunity to increase their chances of success, and for those that have low BCL6 levels, peace of mind.

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