Dr. Lessey's Corner

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!

Dr Lessey and Family with Newborn
Progesterone
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