Reviewer ’s report  
 
Title: AlphaVBeta3 Integrin Expression within Uterine Endometriu m in Unexplained Infertility: 
A Prospective Cohort Study.  
 
Version: 0 Date: 23 Dec 2016  
 
Reviewer: Eva Dimitriadis  
 
Reviewer's report:  
 
This study compares endometrial changes in women with unexplained infertility compared to 
normal fertile women during the receptive phase of the menstrual cycle. The authors specifically 
measure endo metrial thickness, sub -endometrial resistance index (RI), and the receptor avb3 
integrin production by immunohistochemistry.  They then analyse the data using ROC curve 
analysis. The authors compare their data with other studies that have investigated avb3  
production during receptivity.  
The authors report that avb3 is reduced in endometrium during the receptive phase day, day 
LH+6 in women with unexplained infertility.  Statistically significant changes were also seen 
with endometrial thickness and sub -endometrial RI between the groups of women.  The infertile 
women had thinner endometrium and higher sub -endometrial RI compared to normal fertile 
women.  
The authors should define that the immunohistochemistry scores were specifically in the 
glandular epithel ium. The authors should also show a photo of the negative isotype control for 
the control group in particular. It is curios whey the authors did not determine the levels of avb3 
in the endometrial luminal epithelium - which luminal epithelium may not be pr esent in all 
tissues, it surely must be present in some tissues.  
I would like to authors to discuss how the immunohistochemistry was done - for instance, how 
many runs, were quality control tissues included to determine assay precision?  
In terms of the function of avb3 in receptivity, how do the authors propose that glandular 
production may alter endometrial adhesive capacity and implantation, given that avb3 is an 
adhesion molecule.  Please discuss this. Are there any functional studies investigating 
endometrial glandular avb3 in receptivity and embryo implantation? Please comment and discuss 
this and the relevance to your study. I would like the authors to provide an explanation for how 
glandular avb3 may be involved in implantation and why the authors did not examine the 
luminal epithelium, the first point of contact of embryos during implantation.  
Also, do the authors think that the decreased levels of avb3 may be due to the thinner 
endometrium? How was the immunohistochemistry scorin g done precisely?  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does th e work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable t o assess  
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the edi tors. 
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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