Effects of Hydrosalpinx on Endometrial Receptivity and Uterine Microbiome: An Interesting Case of Double Uterus with Unilateral Hydrosalpinx

Round 1

Reviewer 1 Report

This is an interesting manuscript where the authors have presented a case-study in a well organized manner. However, there are some minor comments that the authors can work upon and give a better explanations to make it clear to the audience. 

1. The authors have used both endometriosis and endometritis (eg; expansion for ALICE) throughout the text. I would suggest to maintain consistency. If there is a need for using different terms it is suggested to highlight the importance for their usage. 

2. Did the authors happen to look/or come across any other studies on immunological changes other than CD138 staining like macrophages natural killer cells and T cells? Since hydrosalpinx is well associated with inflammation, it is curious to know more about the inflammatory markers/immune cells in the uterine sample from the present study. 

Author Response

First, we would like to thank for your helpful comments.

Our responses to each of the comments are provided below.

Comment1: The authors have used both endometriosis and endometritis (eg; expansion for ALICE) throughout the text. I would suggest to maintain consistency. If there is a need for using different terms it is suggested to highlight the importance for their usage. 

Response to Comment 1: We mistyped ”endometriosis" when we should have stated “endometritis”. We apologize for your confusion. (Revised part: L148.)

Comment2: Did the authors happen to look/or come across any other studies on immunological changes other than CD138 staining like macrophages natural killer cells and T cells? Since hydrosalpinx is well associated with inflammation, it is curious to know more about the inflammatory markers/immune cells in the uterine sample from the present study. 

Response to Comment 2: We have investigated nothing but CD138 immunostaining in this study. It has been reported that inflammation in the hydrosalpinx spills over into the uterus and the inflammatory markers or immune cells are detected in the endometrium (Copperman, A.B. et al, 2006, Chukwuemeka, L. et al, 2002). We would like to investigate the immunological changes other than CD138 staining that you pointed out in our next study. Thank you very much for your useful suggestions.

Reviewer 2 Report

Comments for author File: Comments.docx

Author Response

First, we would like to thank for your helpful comments.

Our responses to each of the comments are provided below.

Comment1: The abstract does not accurately represent the course of events, in my opinion.

Response to Comment1: The name of the antibiotics and its duration of administration in the abstract were incorrect. Thank you for pointing this out. We have corrected the name of antibiotics and the duration of their use administered before the pregnancy was established. (Revised part: L25-26.)

Comment2: Hydrosalpinx reduces but does not eliminate the chance for pregnancy. Despite the comprehensive review of multiple facets of the case, this reviewer fails to see the reportable nature of the case.

Response to Comment2: As your comments, the presence of hydrosalpinx reduces the ART outcomes; the pregnancy rate with ART decreases up to 50%), various mechanisms for the poorer ART outcomes with hydrosalpinx, but so far no clear answer has been obtained. We believe that this study is significant because there has been only one report on the effect of hydrosalpinx on ERA, which investigates the implantation environment, and EMMA/ALICE, which examines the intrauterine microbiome.

Reviewer 3 Report

Manuscript ID: endocrines-1946534

Title: Effects of hydrosalpinx on endometrial receptivity and uterine microbiome: an interesting case of double uterus with unilateral hydrosalpinx

Authors: Junichiro Mitsui, Kiyotaka Kawai, Makiko Tajima, Kenichiro Hiraoka, Viviane Casaroli, Yoshimi Sato, Yoshiaki Furusawa, Tomonori Ishikawa, and Naoyuki Miyasaka

In this case report, the authors investigated and discussed the case of a 34-year-old infertile woman with uterus didelphys and unilateral hydrosalpinx who successfully achieved clinical pregnancy after antibiotic treatment with doxycycline within the context of a modified ART protocol. This case report is well-organized and informative. However, the authors missed the opportunity to fully disclose all the patient’s pertinent information particularly her ERA and EMMA data. Moreover, further edits are required for this case report to be fully informative.       

Main concerns:

- The authors discussed numerous endometrial receptivity markers and argued against Carranza et al (2018- reference #6); however, the actual data of their patient’s ERA analysis is missing. Moreover, the EMMA data are also lacking. Please provide and briefly elaborate on the patient’s ERA analysis and EMMA data in the results section- new figure(s) or table(s) may be necessary.

- Lines 115- 117 and Figure 3 (a and b): please clearly label the endometrial polyps as well as the ostium of the fallopian tubes in Figure 3.

Author Response

First, we would like to thank for your helpful comments.

Our responses to each of the comments are provided below.

Comment1: The authors discussed numerous endometrial receptivity markers and argued against Carranza et al (2018- reference #6); however, the actual data of their patient’s ERA analysis is missing. Moreover, the EMMA data are also lacking. Please provide and briefly elaborate on the patient’s ERA analysis and EMMA data in the results section- new figure(s) or table(s) may be necessary

Response to Comment 1: We added the actual data for ERA and EMMA in both uterine cavities to the Table 1. Please check the table. (Revised part: L162 and Table1.)

Comment2: Lines 115- 117 and Figure 3 (a and b): please clearly label the endometrial polyps as well as the ostium of the fallopian tubes in Figure 3.

Response to Comment 2: We added blue arrows and white circle to the Figure 3 to indicate the endometrial polyps and the ostium of the fallopian tubes, respectively. We also added explanations for the blue arrows and white circles to the figure legend. Please check them. (Revised part: L120, 121 and Figure 3.)

Round 2

Reviewer 2 Report

The report states endometritis was treated with augmentin. The discussion says doxicycline.  

Author Response

Thank you for your comment.

We have revised the discussion as follows.

“doxycycline” (L280) was mistyped for  amoxicillin/ clavulanic acid (L280).　

Antibiotics recommended for CE include not only doxycycline, but also ciprofloxacin, amoxicillin/ clavulanic acid, and others [27: Kitaya, et al, Endometritis: new time, new concepts. Fertil Steril 2018.].  We have added the reason for the choice of amoxicillin/ clavulanic acid in this case (L282-286).

We appreciate your review.

Reviewer 3 Report

Thank you for your revisions. 

Author Response

We appreciate your review.