What is Endometriosis? 

Endometriosis is a complex and often painful condition that affects millions of women worldwide.  It occurs when tissue similar to the lining of the uterus grows outside the uterus, commonly in the pelvic region. This abnormal tissue growth can lead to a variety of symptoms, including pelvic pain, heavy menstrual bleeding, and infertility. Endometriosis is an estrogen-dependent inflammatory disorder of the uterine endometrium. About 5–10% of women of reproductive age are affected and up to 50% of these women are infertile. Endometriosis is associated with infertility owing to numerous factors such as distorted anatomy, local inflammatory effects on oocyte quality and an inhospitable endometrial environment for embryo implantation.

What is BCL6 and the link to endometriosis?

BCL6 is the primary biomarker in the ReceptivaDx test for detection of endometriosis. This protein is an “oncogene” associated with lymphoma and involved with inflammation. We found in our research that BCL6 pairs with another protein called Sirtuin 1 (SIRT1), and together these proteins appear to block the action of progesterone in the endometrium.  The actions of progesterone are critical to successful pregnancy and “progesterone resistance”, as it is called, and appears to be a primary mechanism involved in endometriosis and its pathophysiology leading to infertility.

With that said, let’s look at new clinical data: Women with unexplained infertility have a very high prevalence of elevated BCL6. We see the same finding of elevated BCL6 in most women with unexplained IVF failure.  Both these groups (Unexplained Infertility and Failed IVF) had endometriosis as a common finding at laparoscopy. Unfortunately, laparoscopy is being performed less often in most IVF centers. This has led to a vast under-reporting of perpetuating a false conclusion among many Reproductive Endocrinologists that endometriosis is not a major cause of IVF failure and frozen embryo transfer (FET) cycles.

How Does BCL6 Contribute to Endometriosis?

The exact mechanisms by which BCL6 contributes to endometriosis are still not fully understood. However, we believe that BCL6 may promote the survival and growth of endometrial tissue outside the uterus. This could potentially lead to the formation of endometriotic lesions, which are a hallmark of the condition.

Additionally, BCL6 may also contribute to the inflammation and immune dysfunction seen in endometriosis. Studies have found that BCL6 can modulate the activity of immune cells involved in the inflammatory response, which may contribute to the chronic inflammation seen in endometriosis.

Implications for Endometriosis Treatment

The discovery of the role of BCL6 in endometriosis opens new avenues for treatment. For women who have failed IVF, have recurrent pregnancy loss, or have low embryo reserves, knowing your BCL6 status can help you make informed treatment decisions. The gold standard for diagnosis is surgical laparoscopy which allows the doctor to see the lesions and excise them as necessary. The likelihood of a successful pregnancy after surgery rises 5-fold. Another treatment method is hormone suppression for 60 days which reduces the inflammatory effects of endometriosis enough for an embryo to attach and successfully grow to full term. or its downstream pathways could potentially help control the growth of endometrial tissue and reduce inflammation in patients with endometriosis. New research is now underway to further understand the role of BCL6 in endometriosis and to develop targeted therapies that may reduce the effect of progesterone resistance. 

Endometriosis is a complex condition that can have a significant impact on a woman’s quality of life. The discovery and proven role of BCL6 in detection of endometriosis opens new possibilities for understanding the underlying mechanisms of the condition and providing effective treatments for fertility patients. It also provides a clear marker for women just interested in knowing if they have endometriosis.

Patients with endometriosis should stay informed about the latest research and treatment options available to them. Working closely with healthcare providers can help ensure that patients receive the best possible care and management of their symptoms. By continuing to study BCL6 and its role in endometriosis, researchers hope to uncover new insights into the condition and continue to improve outcomes for patients.

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