Reviewer ’s report  
 
Title: AlphaVBeta3 Integrin Expression within Uterine Endometrium in Unexplained Infertili ty: 
A Prospective Cohort Study.  
 
Version: 0 Date: 20 Jan 2017  
 
Reviewer: Jian-Zhong Sheng  
 
Reviewer's report:  
 
This manuscript by Ahmed Elnaggar et al. investigated whether the endometrial expression of 
αvβ3 integrin differs between women with unexplained infertility and women with normal 
fertility or not. The study included two group s of women: the unexplained infertility group, 
including 35 women diagnosed with unexplained primary infertility, and the fertile group, 
including 35 fertile parous women presented to the family planning clinic seeking contraception. 
Six days after detecti on of the LH surge, 2D transvaginal ultrasound scan (TVS) was performed 
to measure endometrial thickness, and subendometrial blood flow color Doppler Resistance 
Index (RI). On the same day of transvaginal ultrasound, endometrial samples were taken using 
the Endocell® office suction sampler for Immunohistochemistry (IHC) study using monoclonal 
mouse IgG antibodies to detect endometrial αvβ3 integrin. They found that, compared to the 
women of fertile group, the women in unexplained infertility group had a sig nificantly lower 
αvβ3 integrin score, significantly thinner endometrial thickness, and significantly higher 
subendometrial flow RI. They concluded that significantly lower alpha v beta 3 integrin levels in 
endometrium of unexplained primary infertile women  may be an unrecognized cause of 
infertility in this population of women.  
 
Main comments:  
1. Many studies have investigated the expression of integrins in endomentrium of infertile 
women and other women who were failed in IVF treatment. This work does not show new 
information.  
2. Assessment of endometrial thickness is a conventional examination in women who undergo 
IVF in ART clinic. Thin endometrial thickness is thought as an important cause of IVF -ET 
failure. Authors found that the unexplained infertile women had lower αvβ3 integrin 
expression levels and thinner endometrial thickness. Why authors thought that lower αvβ3 
integrin expression level, not thinner endometrial thickness, is an important cause of 
infertile?  
3. Immunohistochemical staining is not a good method to identify expression of proteins, 
because it is easy to get false positive and negative results. It is better to use western blot to 
identify αvβ3 integrin.  
4. As we known, it is not easy to get human samples, especially to get normal human  
endometrium. Authors should examine other implantation factors, such as leukemia 
inhibitory factor, in the same human endometria.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
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 editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questi ons: 
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or s hares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have  no competing interests.  
 
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