Large, Non-Cavity Distorting Intramural Leiomyomas Decrease Leukemia Inhibitory Factor in the Secretory Phase Endometrium.

Abstract

Despite mounting evidence that large intramural leiomyomas decrease fecundity during in vitro fertilization cycles, few studies have demonstrated a mechanism for this impact. We hypothesize that large intramural leiomyomas (IM) decrease the expression of endometrial implantation factors during the window of implantation. We prospectively recruited sub-fertile patients with IM 3cm or greater in size planning myomectomy and performed endometrial biopsies the day of planned myomectomy (n = 9). Preoperative screening demonstrated no intercavitary lesions. Control endometrial samples were obtained from young, normally menstruating women free of uterine leiomyomas (n= 8). Endometrial samples were obtained in the mid-secretory phase (average cycle day for control patients and intramural leiomyoma patients were 24.5 and 21.3, respectively). Expression of implantation markers HOXA10, leukemia inhibitory factor (LIF), ER-α, and PR was compared using quantitative immunohistochemistry. Standard descriptive statistics were used to compare H-scores between the cohorts. Patients with intramural leiomyomas were found to have decreased LIF compared to controls (p value < 0.001). Expressions of HOXA10 and PR were no different between cohorts; however, ER-α showed a trend toward increased expression in the fibroid cohort (p value 0.07). LIF is downregulated in the endometrium of patients with large IM. This study is among the first to show decreased LIF expression in patients with uterine leiomyomas. We hypothesize that this difference from previously published work is due to sampling the endometrium at the height of LIF expression. Further work is needed to show if LIF downregulation is corrected with leiomyoma resection.