Unexplained infertility can be incredibly frustrating because it suggests an underlying diagnosis has not been identified for your unsuccessful attempts at getting pregnant and having a baby. Whether you have been trying to conceive for a while without success, have experienced recurrent implantation failure during IVF, or have grieved multiple miscarriages, it can be devastating not to know the reason behind your inability to get – or stay – pregnant. Typically, the underlying problem involves either the embryo or the endometrium. Most IVF centers offer PGT-A testing to ensure the selection of a normal, or euploid, embryo. When failure continues even with normal embryos, it might be time to look at the endometrium.

Unexplained infertility: Could it be endometriosis?

Endometriosis is a condition where tissue similar, but not identical, to the lining of the uterus is found elsewhere in the body.  While many people associate endometriosis with painful periods, excessive bleeding, fatigue, and pain during sex, endometriosis can go unnoticed for years. It takes an average of 7 years to diagnose endometriosis, with doctors often discovering it long after you have had trouble conceiving or carrying a pregnancy to term. “Silent” endometriosis is one of the leading causes of infertility among women worldwide.  

Unexplained infertility is a term used by clinicians to describe women who have failed IVF multiple times despite good embryos and a full workup for other conditions. However, many of these women are unsuccessful due to undiagnosed endometriosis, often asymptomatic. Endometriosis can also be an underlying condition in women who experience recurrent pregnancy loss, defined as two or more miscarriages. 

What are some signs of silent endometriosis?

From a fertility perspective, the main sign of silent endometriosis is recurrent pregnancy loss and/or failed implantation with none of the “normal” symptoms of endometriosis. Endometriosis affects the uterine wall lining, impacting the ability of an embryo to implant itself and grow in the uterus. The condition can even develop outside of the uterus, affecting other organs like the ovaries. The absence of symptoms makes silent endometriosis harder to diagnose and it can be a common culprit when it comes to unexplained infertility. 

While silent endometriosis has no outward or “typical” symptoms, asymptomatic endometriosis can still cause endometrioma or blood-filled cysts located in the ovaries. The old blood causes the cysts to have a chocolatey (brown) color. Ovarian cysts affect the oocyte reserves and egg quality, often leading to fertility issues. A fertility specialist can find these cysts during a pelvic exam or through laparoscopic surgery. However, laparoscopies are not typically performed or offered if no symptoms are obvious.

Another sign of asymptomatic endometriosis is hormonal changes. A provider can conduct a blood test to check for abnormalities in your hormone levels, such as progesterone and estrogen. These hormones support pregnancy, so less than-optimal levels can make conceiving or sustaining a pregnancy difficult. 

woman comforting a friend in distress

Women with silent endometriosis also face a higher risk of developing other conditions. Diseases like lupus, thyroid issues, rheumatoid arthritis, multiple sclerosis, and fibromyalgia are all linked to endometriosis. If you have been diagnosed with any of these conditions, your doctor may want to actively look for endometriosis. These same conditions can also lead to chronic inflammation, which is never beneficial for optimal fertility. 

How can I find out if I have silent endometriosis?

Thankfully, your OBGYN or Reproductive Endocrinologist can check for signs of silent endometriosis either before you start fertility treatment or after several unsuccessful IVF attempts. Fertility specialists now use a test called ReceptivaDx to look for a protein marker called BCL6 that is highly associated with endometriosis and helps clinicians diagnose the underlying causes of infertility as well as predict IVF outcomes. 

For your healthcare provider, a negative BCL6 result provides reassurance that endometriosis is not the problem. But if the test is positive, then it is likely that endometriosis or some uterine inflammatory condition is the problem. According to Dr. Bruce Lessey, a Reproductive Endocrinologist, professor, and the leading expert and patent holder of the BCL6 test, the specificity (accuracy) of this test is greater than 95% (closer to 97%). 

woman getting a diagnostic test for endometriosis

Without treatment, you can get pregnant with a positive BCL6 result using IVF, but the chances are low, about 12%  according to studies. However, with treatment, either hormone suppression or surgical laparoscopy, chances improve substantially to over 62%. ReceptivaDx helps patients with silent endometriosis have an accurate diagnosis and start treatment early. In fact, when women with recurrent implantation failure in IVF test positive for ReceptivaDx and receive the appropriate treatment, they more often than not go on to have a successful transfer.

Because ReceptivaDx detects all stages of endometriosis, using this test after even a single failure makes sense. If your doctor uses the term ‘unexplained infertility”, or you have experienced recurrent IVF failure or multiple miscarriages, it’s worth asking your doctor about getting tested. It could just be the missing puzzle piece you need to help you achieve your ultimate goal of a healthy baby.

Kristyn Hodgdon is the Co-Founder and Chief Creative Officer at Rescripted.