New Test Brings Hope and New Answers for Unexplained Infertility, Failed IVF and Miscarriage

Infertility has touched many people’s lives; sometimes there are no answers as to why it occurs. Research towards uncovering the cause of otherwise unexplained infertility has led to some large research initiatives recently and has discovered that undiagnosed endometriosis may be the culprit in many cases. Endometriosis is a condition in women that causes uterine tissue to grow outside of the uterus, creating scar tissue over time (called adhesions) that can cause severe pain, heavy periods, and infertility. While it is a common problem affecting 1 in 10 women of reproductive age, confirming its diagnosis used to rely on laparoscopic surgery to physically see the adhesions inside the woman’s abdomen.

Now, research has identified biomarkers specific to endometriosis and is working towards the development of less invasive tests to help identify women likely to have endometriosis, even if they don’t have any symptoms. These tests can also have meaningful impact on women struggling with unexplained infertility by giving them an answer to their infertility and providing treatment options to aid in getting pregnant. One of these tests is called ReceptivaDx offered through CiceroDx.

BioSpace spoke to Christopher Jackson, CEO and President of CiceroDx, to get more information.

Can you briefly summarize CiceroDx?

Christopher: “We are a company focused on women’s reproductive health with an emphasis on developing testing modalities to detect conditions such as endometriosis that are difficult to diagnose yet have a huge impact on the ability to start a family or to enjoy a normal healthy lifestyle.”

What is ReceptivaDx?

Christopher: “ReceptivaDx is a test that helps women who are struggling to get pregnant and have a baby either naturally or through in vitro fertilization (IVF). Even in the best IVF centers in the US, at least 40% of women still cannot get pregnant. While endometriosis has always been suspected as the primary cause in these unexplained failures, detecting endometriosis via laparoscopic surgery is an invasive and expensive procedure that has all but vanished. It’s now typically reserved for patients with heavy bleeding or major pelvic pain. ReceptivaDx is the first test to provide a non-invasive means for detecting inflammation of the uterine lining often without symptoms.

ReceptivaDx has been commercially available since February of 2017. Before the end of 2019, CiceroDx will have analyzed over 3,000 samples.”

What are the limitations of ReceptivaDx testing?

Christopher: “Infertility is a complex issue, so many potential areas of concern need to be addressed. Although we are a new and important piece of the puzzle, we are still just one piece. Our data suggests we can help 6 out of 10 women with unexplained infertility. While that is exciting, we still can’t provide answers for everyone. But we take that as a challenge.”

What does the process of getting ReceptivaDx testing look like?

Christopher: “A simple discussion with a woman’s healthcare provider to get the ball rolling is all that’s required. The endometrial biopsy is done during the ‘window of implantation’ 7-10 days after ovulation (days 20-24 of the menstrual cycle). Most women will use an ovulation kit to detect their luteinizing hormone (LH) surge, which occurs right before ovulation. If you detect your LH surge on a Monday for example, your biopsy window would start the following Monday for four days. Fertility doctors can also control cycles, referred to as “mock” cycles, with medications like progesterone. In these instances, a biopsy is taken during days 5-10 of progesterone administration.

An endometrial biopsy, which is not considered a surgical procedure, can be performed during a regular visit to either an Ob-Gyn or fertility center. While there is temporary pain and discomfort, the procedure is over in minutes and has fewer potential risks or side effects when compared to laparoscopy. Other than the office visit time, most women take less than a half day before returning to normal activities.

Once collected, the biopsy tissue sample is placed in a vial with preservative (formalin) and the vial is shipped via FedEx overnight to one of our two US lab locations for analysis. The endometrial tissue sample is processed by a pathology lab and slides are prepared for a pathologist to review. Pathologists look for a protein marker called BCL6 in the tissue, which is highly associated with endometriosis. In addition to applying a special stain that recognizes the presence of BCL6, each biopsy gets a full review by a pathologist to rule out everything from infection to even the presence of cancer or pre-cancerous cells. Results are available in about a week.”

Who is the ReceptivaDx test recommended for?

Christopher: “For women working with a fertility center, most referrals come from women who have failed IVF at least once or who have suffered multiple pregnancy losses either naturally or through IVF. Many women with limited or no fertility coverage from their health insurance will use the test upfront to see what their risks are before IVF. Statistically, less than 15% of families in the US have the financial ability or means to pursue a family through IVF. About 60% of women seeking assistance from fertility centers do not have fertility benefits coverage.

ReceptivaDx is an affordable option for families that have all but given up on their dream of having children. Women who test positive are five times less likely to conceive than women who test negative. If they test positive, treatment options can be applied to potentially allow them to conceive on their own without any further help.”

What does a positive test result mean? What about a negative result?

Christopher: “A positive result indicates the presence of inflammation in the uterine lining most commonly associated with endometriosis. The test measures the levels of a certain marker called BCL6 in endometrial tissue. We can’t decipher the extent or location of the disease based on the result, but we know the presence of inflammation due to the body’s immune response to endometriosis. Once identified, women testing positive can be treated with hormone suppression medications to tame the inflammation, allowing for a more receptive uterine lining. Laparoscopy to remove the adhesions caused by endometriosis is also a treatment choice. However, more women are opting for hormone suppression due to lower cost and avoiding invasive surgery, unless they have other major symptoms of endometriosis like extreme pain.

A negative test allows providers to rule out endometriosis as a concern and assures families that future IVF attempts have a higher likelihood of success. In a study conducted in an IVF center in South Carolina, women testing negative for the BCL6 marker had a 59% success rate on their next IVF transfer compared to 11% in women who were positive for BCL6.”

By Chelsea Weidman Burke, Biospace