Transcriptomic approach to study the effect of polypectomy on human endometrial receptivity

Abstract

Background: Endometrial polyps are common in women at reproductive ages, and found in more than 11% of infertile women. Hysteroscopic polypectomy is recommended to alleviating symptoms in patients with abnormal uterine bleeding. While the relationship between an endometrial polyp and subfertility is not clearly established, there is some evidence that hysteroscopic polypectomy may improve fertility outcome in IVF patients. Accumulating evidence suggested that elevated levels of activated mast cells as well as elevated matrix MMPs and cytokines levels in the patients who suffer from endometrial polyps. Moreover, significant increases in glycodelin levels were found in patients’ plasma and uterine. And there was a significant negative relationship between plasma glycodelin and progesterone levels in patients with endometrial polyps. To further understand whether hysteroscopic polypectomy affects endometrial microenvironment that is conductive to embryo implantation, we recruited 9 IVF patients and use microarray to compare their endometrial gene expressions before and after polypectomy. Methods: We investigated the change of endometrial gene expression patterns before and after polypectomy. Three out of 9 samples were subjected to microarray study. Quantitative-PCR (qPCR) was used to confirm the expression in all 9 samples, and compared with endometrial samples taken from patients underwent natural (LH+7 days, n = 8) and stimulated (hCG+7 days, n = 8) IVF cycles but without polyps. The outcome of subsequent IVF cycle was obtained to correlate the change of gene expression patterns. Results: Microarray analysis demonstrated that no genes are commonly differentially expressed in all 3 samples. One of the samples has shown very heterogeneous result. Sixteen genes (hERα, hERβ, OLFM1, OLFM2, IL15, CXCL14, GPX3, CCL4, UPKIB, PAEP, MMP26, SLC1A1, MUC15, MUC16, TM4SF4 and TFPI2) that are differentially expressed in any 2 of the samples and genes related to endometrial receptivity (OLFM1, IL15, CXCL14, GPX3, PAEP, MMP26, SLC1A1, MUC16) were selected for further analysis. We found that 3 samples have a gene expression pattern similar to natural cycle (LH+7 days) after polypectomy; while the other samples have a gene expression similar to the stimulated cycle (hCG+7 days). Clinical findings of the treated patients did not have strong correlation with pregnancy outcome. One out of two patients who had gene expression patterns similar to natural cycle got pregnant; while one out of seven patients who has gene expression patterns similar to stimulated cycle get pregnant after polypectomy. Conclusion: Polypectomy modulates endometrial gene expression patterns in some patients similar to those in natural cycles. However, our data did not support endometrial polypectomy significantly improved pregnancy outcome in the limited number of patient subjects (n=9) in this study.