Considerable amount of evidence has implicated prostaglandins (PG) to play a vital role in implantation and decidualization. A recent case-control study has linked defective endometrial prostaglandin (PG) synthesis in IVF patients with repeated embryo implantation failure, suggesting that the reduced synthesis of PG could result in poor endometrial receptivity. The findings of the study are published in the recent issue of the journal Fertility and Sterility.
Hanna Achache from the Hebrew University of Jerusalem, Israel, and co-workers evaluated 19 women with repeated IVF failure and 15 fertile controls, to identify the role of prostaglandin in repeated implantation failure. Prostaglandins, members of the eicosanoids family, are formed from membrane phospholipids with the activity of two enzymes: cyclooxygenase (COX) and cytosolic phospholipase A2 (cPLA2). The study assessed various outcome measures to evaluate the expression levels of the endometrial enzymes involved in the synthesis of PG, by utilizing different molecular biological techniques.
• Expression and activity of cPLA2 by Western blot
• Expression of secretory phospholipase A2 group IB, IIA and V (sPLA2-IB, sPLA2-IIA, sPLA2-V), COX-2, PG E receptors, PG E synthase, lysophosphatidic acid receptor 3 (LPA3), and glypican-1, using real-time polymerase chain reaction (RT-PCR)
• Localization of LPA3, COX-2, and sPLA2-IIA within the secretory endometrium, using immunohistochemistry
The researchers noted that, compared to controls, patients with recurrent implantation failure expressed lower levels of cPLA2 and COX-2; which in turn resulted in over expression of sPLA2-IIA. Expression of LPA3, an enzyme that takes part in cPLA2-arachidonic acid-COX-PG signaling pathway, was also reduced in these patients. The results suggested a role of reduced endometrial PG synthesis in causing poor endometrial receptivity and repeated implantation failure.
An earlier review study by Achache H et al (Human Reproduction Update, 2006) reported that PGs, as vasoactive factors, play a significant role in ovulation, fertilization and embryo implantation, and labor onset during late pregnancy. The study also showed that female mice models lacking cPLA2 or COX-2 enzyme suffered from several implantation defects, and that the exogenous administration of PG restored embryo implantation.
Poor endometrial receptivity has been attributed to be one of the causes of repeated implantation failure in IVF; however, factors influencing the receptivity of the endometrium for implantation remain elusive. Further understanding of the role of prostaglandins, and other diverse molecular and biochemical events that directly correlate with endometrial receptivity, could aid in optimizing assisted reproduction strategies to overcome repeated implantation failure.
References
1. Achache H, Tsafrir A, Prus D, Reich R, Revel A. Defective endometrial prostaglandin synthesis identified in patients with repeated implantation failure undergoing in vitro fertilization. Fertil Steril. 2009 Oct 6. [Epub ahead of print]
2. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006 Nov-Dec;12(6):731-46.
