title: Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization.
abstract: 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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  In vitro fertilization unit at a university hospital.
  
  
  METHODS
  Thirty-four women, comprising of 19 patients with repeated IVF failure and 15 controls with proven fertility.
  
  
  METHODS
  Endometrial expression levels of the enzymes responsible for the PG synthesis were compared between the two groups.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Hanna
authors.initials: H
authors.lastname: Achache
authors.affiliation: Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel.
authors.forename: Avi
authors.initials: A
authors.lastname: Tsafrir
authors.affiliation: Department of Pathology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Diana
authors.initials: D
authors.lastname: Prus
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.affiliation: Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, Israel. Electronic address: arielrevel2@gmail.com.
authors.forename: Ariel
authors.initials: A
authors.lastname: Revel
mesh_terms: D000026:Abortion, Habitual / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D010064:Embryo Implantation / Q000235:genetics / Q000502:physiology; D020964:Embryo Loss / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology; D005307:Fertilization in Vitro; D054513:Group IV Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D052439:Lipid Metabolism Disorders / Q000150:complications* / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D054497:Phospholipases A2, Secretory / Q000235:genetics / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D011453:Prostaglandins; D018078:Receptors, Prostaglandin E; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D054513:Group IV Phospholipases A2; C516389:PLA2G4A protein, human; D054497:Phospholipases A2, Secretory