GnRH agonist and letrozole in women with recurrent implantation failure.

GnRH analogues have also been shown to alter integrin expression in endometrium (23). Integrins are basement membrane proteins and transmembrane receptors for extracellular matrix (ECM). They are made up of two noncovalently associated subunits, α and β. Increased expression of integrin heterodimer αVβ3 and αVβ5 by letrozole in eutopic endometrium of endometriosis can help in repairing the ER (24). There are studies establishing correlation between integrin expression, endometrial thickness and the ER. The αVβ3 integrin expression is significantly low in disrupted ER. This suggests that under expression of αVβ3 integrin in human endometrium can be the cause of disrupted window of implantation. Letrozole is likely to benefit the disrupted window of implantation in endometriosis. To conclude, this research has avidly proved that aromatase inhibitors in women with endometriosis likely alter the intracellular harmony between estrogen and progesterone action in endometrium, and therefore restores the effect of progesterone in down-regulating estrogen receptors (a critical phenomenon during implantation) (25). As ανβ3 integrin is indirectly regulated by progesterone, this is the most likely cause. Further prospective studies are required to establish these results and to rationalize the use of GnRH agonist and letrozole combination in improving ER in the RIF. Acknowledgments The author acknowledges the management of ARC and Saveetha Institute of Technical and Medical Sciences for the support provided. Footnote Conflicts of Interest: The author has no conflicts of interest to declare. Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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