TY - JOUR
T1 - Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization
AU - Achache, Hanna
AU - Tsafrir, Avi
AU - Prus, Diana
AU - Reich, Reuven
AU - Revel, Ariel
PY - 2010/9
Y1 - 2010/9
N2 - Objective: 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. Design: Case-control study. Setting: In vitro fertilization unit at a university hospital. Patient(s): Thirty-four women, comprising of 19 patients with repeated IVF failure and 15 controls with proven fertility. Intervention(s): Endometrial expression levels of the enzymes responsible for the PG synthesis were compared between the two groups. Main Outcome Measure(s): Cytosolic phospholipase A2 (cPLA 2α) 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. Result(s): Patients displaying recurrent implantation failure expressed reduced levels of cPLA2α 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. Conclusion(s): 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.
AB - Objective: 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. Design: Case-control study. Setting: In vitro fertilization unit at a university hospital. Patient(s): Thirty-four women, comprising of 19 patients with repeated IVF failure and 15 controls with proven fertility. Intervention(s): Endometrial expression levels of the enzymes responsible for the PG synthesis were compared between the two groups. Main Outcome Measure(s): Cytosolic phospholipase A2 (cPLA 2α) 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. Result(s): Patients displaying recurrent implantation failure expressed reduced levels of cPLA2α 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. Conclusion(s): 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.
KW - endometrial receptivity
KW - Endometrium
KW - in vitro fertilization
KW - prostaglandins
KW - repeated implantation failure
KW - window of implantation
UR - http://www.scopus.com/inward/record.url?scp=77956190790&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2009.07.1668
DO - 10.1016/j.fertnstert.2009.07.1668
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C2 - 19815191
AN - SCOPUS:77956190790
SN - 0015-0282
VL - 94
SP - 1271
EP - 1278
JO - Fertility and Sterility
JF - Fertility and Sterility
IS - 4
ER -