P-550: Implantation markers are decreased in endometrium of women with adenomyosis during the implantation window

Abstract

Leukemia inhibitory factor (LIF) and interleukin (IL)-11 are known as molecular markers of endometrial receptivity during implantation window. We have previously reported that implantation ratio is significantly lower in women with adenomyosis compared to women without adenomyosis. Our hypothesis is that adenomyosis may have a detrimental effect on the expression of molecular regulators of implantation (LIF, LIF-receptor-α (LIF-Rα), and IL-11), which may cause a decrease in endometrial receptivity in women with adenomyosis. Therefore, we studied the expression of molecular markers of implantation in adenomyosis. A comparative study of implantation markers in endometrium during the implantation window in women with adenomyosis in both eutopic and adenomyotic endometrium, and in women without adenomyosis or endometriosis. Endometrial tissues demonstrating adenomyotic and eutopic endometrium in tissue sections were collected from women with adenomyosis (n = 8). Normal endometrial biopsies were collected from women without endometriosis or adenomyosis (n = 8). All endometrial tissues were from implantation window (19th-24th day of the menstrual cycle) based on the women’s menstrual history and confirmed by histological examination. The expressions of LIF, LIF-Rα, and IL-11 were detected using immunohistochemistry and evaluated in a semi-quantitative manner using HSCORE. Statistical analysis of the data was performed using Student’s t-test and ANOVA test. In normal mid-secretory endometrium, the immunoreactivity of LIF and LIF-Rα proteins was detected throughout glandular and stromal cells, ranging from a moderate to strong intensity. The IL-11 immunoreactivity was exclusively detected in glandular cells only, and was distributed homogeneously or in a densely-stained vesicular fashion in the apical part of these cells. In comparisons, the immunoreactivity of LIF in the eutopic endometrium (141.3±36.7) of adenomyosis specimens was significantly lower than that of normal endometrium (198.5±50.9, p<0.05). Moreover, significant decreases (p<0.05) were detected for LIF immunoreactivity in both stroma (56.9±21.7) and glands (122.5±39.6) of adenomyotic endometrial cells compared to that of the stroma (98.8±28.1) and glands (168.8±39.8) of eutopic endometrial cells within the adenomyosis specimen. The intensity of LIF-Rα staining in glandular cells was also decreased in eutopic (120.0±36.0) and adenomyotic endometrium (91.6±48.6) when compared to normal endometrium (205.0±20.0; p<0.05). Highly variable IL-11 immunoreactivity was observed in different adenomyotic patients, but the expression of IL-11 (90.0±61.8) decreased significantly (P=0.01) in the endometrium of adenomyosis compared to that of normal patients (172.5±33.0). Our findings indicated that adenomyosis may cause suppression of the molecular markers of endometrial receptivity with significant decreases in the expression of LIF, LIFR, and IL-11. This may be one of the molecular mechanisms associated with the decreased implantation rate observed in women with adenomyosis.