Endometriosis, Infertility and the Curious Role of Progesterone Resistance

on Thursday, 10 August 2017. Posted in Dr. Lessey's Blog, All Blogs

My first blog on ReceptivaDx comes just as our Nature paper on BCL6/SIRT1 and KRAS was released in Scientific Reports on PubMed. It reminds me how far we have come in understanding implantation and provides me an opportunity to pause and reflect on the origins of progesterone resistance and how it might cause infertility. The endometrium has been my muse and a source of great mystery during my scientific adolescence. In my adult “life” it has challenged me and withheld its secrets! The uterus, it turns out, is the only place embryos won’t attach in the body, except during a narrow “window” of receptivity. The endometrium is the “mucosal” layer of the uterus that is normally a barrier to pregnancy, but undergoes a short period of perfect kindness, allowing embryos to attach, invade and thrive for up to 9 months, despite being a foreign tissue that would normally be rejected by any competent immune system. This period of uterine acceptance is, unfortunately, not available to everyone. For many women, the experience is one of ultimate frustration; they are able to fertilize embryos but never achieve pregnancy; or worse, to implant a viable embryo only to lose the pregnancy in miscarriage. For these individuals, answers were few and options were limited.

The main culprit in this scenario is endometriosis, a sinister disease that often lurks in a woman’s body with few signs and symptoms. While some women are ravaged by the disease beginning with their first period, the actual diagnosis of endometriosis may only come years later. There are several reasons for this. Often the symptoms are similar to “normal” menstruation, with moderate to severe pain but within the threshold of what others feel. This pain then becomes generalized and accepted by both the woman and her physician. On the opposite spectrum are the women who experience no physical symptoms but end up with unexplained infertility. Ironically, the one definitive endometriosis diagnostic tool available, surgical laparoscopy, is performed less and less since it is costly and invasive. Thus, the average time to diagnosis in the US has been greater than 10 years!

Unexplained Infertility Is NOT A Final Diagnosis!

Written by ReceptivaDx on Monday, 24 July 2017. Posted in All Blogs, Women & Families



Unexplained infertility can be a frustrating diagnosis. Even the simple act of remaining hopeful can become difficult as a result. For those struggling with getting pregnant, the journey can be an emotional roller coaster of fear, hope, elation, frustration, and disappointment. But we are willing to take this journey in the hopes and joy of a new life. A life so fulfilling, it makes the emotional and financial struggle worth it.

For many stuck in the frustration and disappointment phase, we must stay strong, do research, and believe in the process. CiceroDx is here to help find answers for “unexplained infertility.” Let’s start with some relevant facts and the basics for women who (1) have tried unsuccessfully to get pregnant, (2) are considering IVF for the first time, and/or (3) have had failed IVF cycles. Just by reading these facts, you will quickly see you are not alone.

  • In the last 10 years, American birth rates have declined, but the number of babies born through IVF has increased to record levels.
  • Over 6 million women have infertility issues associated with getting pregnant.
  • The average cost of one IVF treatment and cycle is over $12,000.
  • The average number of cycles needed for a successful pregnancy and live birth is between 2 and 3 cycles.
  • Over 30% of women that had three fertility cycles will still not get pregnant.
  • Women who do not get pregnant after failing multiple cycles, fall back into category of “unexplained infertility”. Until recently, this group of women had very few options left to consider.

For patients seeking IVF treatment, it is likely that endometriosis is the cause of unexplained infertility. That fact is not disputed by anyone in the reproductive medical community. Over 50,000 women each year going through IVF are impacted by endometriosis. That might seem high at first glance, but it makes a lot of sense when you consider endometriosis affects over 175 million women worldwide.

Diagnosis of this silent epidemic is often missed. This may be due to a lack of “typical” symptoms and the unavailability of a definitive diagnosis without surgery. In the US, it takes an average of 8-12 years before the diagnosis is achieved. Can you believe that? Women suffering from unexplained infertility might not have any other symptoms of endometriosis other than their infertility. So, what is this disease that is causing all this trouble?


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