Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization.
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.
Achache
Hanna
H
Department of Pharmacology, Faculty of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel.
Tsafrir
Avi
A
Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel.
Prus
Diana
D
Department of Pathology, Hadassah University Hospital, Jerusalem, Israel.
Reich
Reuven
R
Department of Pharmacology, Faculty of Pharmacy, Hebrew University of Jerusalem, Jerusalem, Israel.
Revel
Ariel
A
Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, Israel. Electronic address: arielrevel2@gmail.com.
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
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