Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization

Abstract

To define the role of prostaglandins (PG) in the endometrium of patients with repeated failure of embryo implantation. Prostaglandins are produced after the sequential oxidation of arachidonic acid by cyclooxygenases (COX-1 and COX-2) and terminal PG synthases. Case-control study. In vitro fertilization unit at a university hospital. Thirty-four women, comprising of 19 patients with repeated IVF failure and 15 controls with proven fertility. Endometrial expression levels of the enzymes responsible for the PG synthesis were compared between the two groups. Cytosolic phospholipase A2 (cPLA2alpha) expression and activity were assessed by Western blot. Expression of cyclooxygenase-2, secretory phospholipase A2 group IIA, V, and IB (sPLA2-IIA, sPLA2-V, sPLA2-IB), glypican-1, PG E synthase, PG E receptors, and lysophosphatidic acid receptor 3 (LPA3) was measured by real-time polymerase chain reaction (PCR). Localization of COX-2, sPLA2-IIA, and LPA3 within the secretory endometrium was detected by immunohistochemistry. Patients displaying recurrent implantation failure expressed reduced levels of cPLA2alpha and COX-2 compared with controls. In response to this deficiency, sPLA2-IIA was found to be overexpressed. Interestingly, LPA3, which is known to converge on the cPLA2-arachidonic acid-COX-PG signaling pathway, was also decreased in these patients. Prostaglandin synthesis appears to be disrupted in patients with repeated IVF failure compared with fertile controls. We therefore suggest that reduced PG synthesis in the human endometrium may lead to poor endometrial receptivity.