Endometrial receptivity is a pivotal “check point” in human reproduction. Even a competent, genetically normal embryo must encounter in proper time a functioning “window” to be implanted
Embryo implantation is a complex multistep event that involves both the embryo and the endometrium, the internal lining of the uterus. It occurs within a strict time interval at the mid-luteal phase of a woman’s cycle, the so-called “window of implantation”.
The status and the ability of the endometrium to allow and promote implantation is termed endometrial receptivity
The status and the ability of the endometrium to allow and promote implantation is termed endometrial receptivity. A normally developing embryo must encounter a receptive endometrium to attach and invade. In fact, the endometrium actually blocks embryos from implanting except during the period of the “window of implantation”. It is a barrier to pregnancy, but has an “opening” that a timely developed embryo must find and go through. It is possible that this “opening”, the “window of implantation”, may never occur or might be of very short duration, or occur very early or very late during the luteal phase or as a combination of these situations. There is also the possibility that endometrial receptivity may be present but the embryo has not yet been appropriately developed, showing slow or fast development or carry some genetic abnormality affecting implantation. All above abnormalities may lead to implantation failure.
Endometrial maturation and attainment of the endometrial receptivity depends on the existence of a growing follicle in a natural cycle or on the ovarian stimulation process in IVF, culminating with a luteinization event. They are driven mainly by the sequential actions of estrogen and progesterone. A series of interdependent molecular and cellular properly timed changes occur leading to the development of endometrial receptivity. These events and factors that affect receptivity are not yet well understood.
IVF research has focused on ovarian stimulation, fertilization, embryo culture and embryo genetic analysis, aiming at optimization of embryo development and selection. In contrast, little research has been directed to the understanding of endometrial receptivity, and even less so on the diagnosis and treatment of its abnormalities. An implantation “bottleneck” has been observed regarding improvement of IVF outcomes. When interpreting a failed IVF cycle with the couple we are unable to clarify if the implantation failure is based on embryonic factors, endometrial receptivity or both.
When interpreting a failed IVF cycle with the couple we are unable to clarify if the implantation failure is based on embryonic factors, endometrial receptivity or both.
As yet, there are no practical clinically useful markers, or tests to identify endometrial receptivity abnormalities. Furthermore, there is no evidence – based intervention to correct them and to yield more pregnancies. In most cases, only empirical observations may drive to some empirical interventions. Within this context, for several years in our IVF practice we have identified a group of women that systematically showing failed IVF cycles in different IVF clinics, having transferred embryos graded as good and very good. For these cases, a hypothesis was made that abnormal endometrial receptivity could be the cause of failure. There is evidence that in some women the ovarian stimulation in IVF, specifically high responders, may be associated with endometrial receptivity defects, while endometrial receptivity is better in natural cycles or artificial cycles with exogenous estrogens and progesterone. We therefore hypothesize that if we split the IVF cycle by freezing all embryos and then transferring thawed embryos in a subsequent natural or artificial cycle we might increase implantation and pregnancy rates possibly having improved endometrial receptivity. This strategy has showed satisfactory results since implantation rates were restored to that of women of similar age.
if we split the IVF cycle by freezing all embryos and then transferring thawed embryos in a subsequent natural or artificial cycle we might increase implantation and pregnancy rates possibly having improved endometrial receptivity
Recently, studies have tested this freeze all strategy to unselected IVF cases and has showed no differences in pregnancy rates. It must be pointed out that endometrial receptivity abnormalities are expected to be the cause of IVF failure only in few, selected cases. In these women, specifically with embryos graded as good and very good, the freeze all embryo with transfer in natural or artificial cycle strategy might offer substantial help. The above strategy could offer these women the only chance for successful implantation. Splitting the IVF cycle in certain subgroups of patients might be a useful tool to overcome abnormalities in endometrial receptivity.
Endometrial receptivity is a pivotal “check point” in human reproduction. Even a competent, genetically normal embryo must encounter in proper time a functioning “window” to be implanted. Practical and clinically useful markers and tests are necessary to be developed for early identification of abnormalities in endometrial receptivity, understanding its importance for successful implantation. Treatments must be also promptly introduced to further improve pregnancy rates.