What about Uterine “Receptivity”?

Much is being said and written about endometrial (uterine lining) receptivity in the in vitro fertilization (IVF) setting, and especially in the context of the failed IVF cycle. Endometrial receptivity is one of the critical aspects of the complex process of embryo attachment, invasion, and successful implantation. The endometrium is a hormonally-responsive, shag carpet-like tissue that undergoes dynamic growth and developmental changes all within a single menstrual cycle. These proliferation and differentiation phases lead to a 3-6 day long “window of implantation,” or time of optimal receptivity, within the second half of the cycle, during which embryos are most likely to implant. Although this window of implantation has been suggested and studied for nearly seventy years, only relatively recently have more sophisticated techniques been applied to evaluating the endometrium.

Abnormalities of the uterus (fibroid tumors, adenomyosis, polyps, inflammation of the endometrium) are frequently encountered and are thought to alter endometrial receptivity by interfering with endometrial molecular expressions that promote implantation. Ultrasound or magnetic resonance imaging studies, alone, may be inadequate to determine receptivity deficits in the context of anatomic abnormalities and molecular studies (e.g., Endometrial Receptivity Analysis, Endometrial Function Test) may be indicated. In known or suspected endometriosis, inflammatory marker testing (ReceptivaDX) may be a consideration. For the best success, anatomic abnormalities and endometriosis may need to be treated medically or surgically prior to IVF and care should be individualized and prospective with diagnostic and treatment options carefully discussed with patients. Such an approach is exceedingly important for the couple who has had multiple failed embryo transfers with high quality embryos.

With 72-144 hours of potential receptivity, timing is not everything. In fact, endometrial functionality is more important than exact timing of embryo transfer and implantation. That is, implantation success is a matter of properly developed endometrial glands expressing the appropriate pattern of peptides, complex carbohydrates, and growth factors during a widely-opened window.

There is much more to learn about endometrial receptivity, the signaling between endometrium and embryo, and implantation; however, strides have been made during the last decade in understanding this conundrum, the biggest question mark in IVF.