Are different markers of endometrial receptivity telling us different things about endometrial function?

Abstract

Problem: To what extent do endocrine, immunological, gene expression and histological markers of endometrial receptivity correlate? Method of study: Between November 2017 and September 2019, 121 women referred to a University Hospitals Fertility Clinic consented to inclusion in this cohort study. The women underwent timed endometrial biopsy followed by blood samples in a hormone-substituted cycle. Of these, 37 women had just started IVF treatment, and the remaining 84 had experienced recurrent implantation failure following IVF/ ICSI. The hormone-substituted cycle consisted of initiation with oral oestradiol followed by addition of vaginal progesterone treatment for five full days. Endometrial biopsies were subject to histological examination, immune cell markers by immunohistochemistry (CD56 + , CD16 + , CD163 + , FoxP3) and gene expression microarray analyses with the endometrial receptivity array (ERA ®) test (Igenomix). Plasma progesterone and oestradiol were measured on the day of biopsy. Results: CD56 + uterine natural killer (uNK) cell counts correlate with transcriptional markers of endometrial receptivity assessed by the ERA test. Endometrial maturation, receptivity and immunological markers were not correlated with mid-luteal blood plasma progesterone level. Mid-luteal serum oestradiol level correlated with markers of endometrial maturation and receptivity. The tests were carried out during a standard hormone substitution cycle, and the findings may not apply in the natural cycle. Conclusion: CD56 + uNK cell counts and endometrial receptivity assessed by the ERA test appear to be linked. Mid-luteal progesterone levels were not correlated to the tested markers of endometrial receptivity. In contrast, mid-luteal oestradiol level was inversely related to markers of endometrial receptivity and maturation.

Effectiveness comparison between endometrial receptivity array, immune profiling and the combination in treating patients with multiple implantation failure

“…15 It was reported that only 4.7% of RIF were without displaced or pathological WOI, 15 although the number varied between different research groups. 13,28,29 Regarding immune profiling, only 17.2% of RIF and 19.5% of RM patients showed no endometrial dysregulation. 16 In line with this evidence, our results showed that nearly 80% of multiple implantation failure patients had a displaced WOI and endometrial immune dysregulation independently or simultaneously.…”

“…Recently, another group found that the ERA results were correlated with the CD56 + NK cell counts, but not CD16 + NK cells, CD163 + Macrophage, and FOXP3 + Treg. 28 The variance in CD56 + NK cells may be due to different study populations' inconsistency and quantification methods. A correlation was found when CD56 was analyzed as a categorical variable or only existed in two extremes (pre-receptive and post-receptive) in their study when CD56 was analyzed as continuous variables.…”

“…A correlation was found when CD56 was analyzed as a categorical variable or only existed in two extremes (pre-receptive and post-receptive) in their study when CD56 was analyzed as continuous variables. 28 Interestingly, Malene et al…”

“…found that the percentage of CD56 + NK cells was higher in the receptive ERA phase compared with the pre-receptive, but the difference was diminished in RIF patients, 28 In this study, we only included patients who transferred the blastocysts. Performing embryo transferring at blastocyst stage is physiologically appropriate, given that the time is more closely to the natural implantation.…”

Glucocorticoid therapy in assisted reproduction

“…Glucocorticoids seem to increase the activity of regulatory T cells and decrease the cytotoxicity of NK cells simultaneously. However, recent studies on immune regulation have suggested that these regulatory activities could be individualized for each respective cell rather than being regulated in the manner of general suppression by glucocorticoids [ 65 , 66 ].…”