PONE-D-21-03413

SIX-MONTH FOLLOW-UP OF MINIMALLY INVASIVE NERVE-SPARING COMPLETE EXCISION OF ENDOMETRIOSIS: WHAT ABOUT DYSPAREUNIA?

PLOS ONE

Dear Dr. Crispi Jr,

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Academic Editor

PLOS ONE

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: I read with interest this paper and I think is suitable for publication after some major revisions in form and content.

My suggestions are:

- Page 3 and 6, line 61 and 152, please change the phrase “Cytoreductive surgery” in “ eradicating surgery”. Cytoreduction is a term correct for gynaecologic oncology procedures and not for benign conditions.

-Page 4 line 91. It is not necessary anymore to classify with the Canadian task force classification the trials. Please remove it from the text.

-Page 6 line 160. In material and methods no results should be presented in the text. Please remove the sentence “ no patients required bladder …..” and put it in results section.

- I suggest to enlarge the discussion about sexual dysfunction and sexual quality of life after surgery for endometriosis and to report the possible way of treating and diagnosing them. Infact I think in this form there is too much limitation to the only deep dyspaurenia field.

I suggest to find in literature some paper about these issues and among them to read and cite the following:

- Del Forno S, Arena A, Alessandrini M, Pellizzone V, Lenzi J, Raimondo D, Casadio P, Youssef A, Paradisi R, Seracchioli R. Transperineal Ultrasound Visual Feedback Assisted Pelvic Floor Muscle Physiotherapy in Women With Deep Infiltrating Endometriosis and Dyspareunia: A Pilot Study. J Sex Marital Ther. 2020;46(7):603-611. doi: 10.1080/0092623X.2020.1765057. Epub 2020 Jun 24. PMID: 32579077.

-Turco LC, Tortorella L, Tuscano A, Palumbo MA, Fagotti A, Uccella S, Fanfani F, Ferrandina G, Nicolotti N, Vargiu V, Lodoli C, Scaldaferri F, Scambia G, Cosentino F. Surgery-related complications and long-term functional morbidity after segmental colo-rectal resection for deep infiltrating endometriosis (ENDO-RESECT morb). Arch Gynecol Obstet. 2020 Oct;302(4):983-993. doi: 10.1007/s00404-020-05694-0. Epub 2020 Jul 16. PMID: 32676859.

-Mabrouk M, Montanari G, Di Donato N, Del Forno S, Frascà C, Geraci E, Ferrini G, Vicenzi C, Raimondo D, Villa G, Zukerman Z, Alvisi S, Seracchioli R. What is the impact on sexual function of laparoscopic treatment and subsequent combined oral contraceptive therapy in women with deep infiltrating endometriosis? J Sex Med. 2012 Mar;9(3):770-8. doi: 10.1111/j.1743-6109.2011.02593.x. Epub 2012 Feb 9. PMID: 22321207.

Reviewer #2: The paper primary analysed the individual responses of deep dyspareunia six month after nerve-sparing laparoscopic surgery in patients suffering from endometriosis. Secondly the authors analysed dysmenorrhea and acyclic pelvic pain. Very interesting is the qualitative analysis of the several conditions that can impact in cases with poor prognosis.

The article is well written and intelligible.

- Material and methods:

Line 149 the authors point four steps for the diagnosis of endometriosis, but they describe only three.

What does the authors nerve-sparing laparoscopic procedure consists of? which technique do they follow? Any references?

- Results

Although the results are described in tables, the key findings also need to be better described in the text. Please, better clarify line 181-189 and 232-239.

This sentence is repeated many times, it could be summarized “The severity of deep dyspareunia (primary outcome) was assessed on a self-reported 233 11-point numeric rating scale (NRS) in two moments: prior to surgery (during the preoperative evaluation period) and at six-month follow-up (N=121)”.

Regarding the findings in nonresponders/paradoxical/de novo groups I think there is an error in line 334 (bilateral/unilateral parametrium resection: 5/5 instead of 6/4) and in line 341 (bilateral/unilateral uterosacral ligament resection: 7/1 instead of 6/1).

Why did the authors not describe eventual changes of dysmenorrhea and acyclic pelvic pain since they also assessed these symptoms during the study? Did they investigate these symptoms only to find eventual correlation with dysmenorrhea?

- Discussion:

In a previous study (DOI: 10.1016/j.jmig.2018.08.022) lateral parametrial endometriosis has been associated with more aggressive and widespread disease requiring more aggressive surgery, higher rate of associated localizations and seems to have a greater impact on nervous dysfunctions; please elaborate this topic.

Please, the Authors should investigate and clarify how medical therapy might affect dyspareunia. In particular, in a previous study was found that combined oral contraceptive (COC) therapy in women with deep infiltrating endometriosis (before surgery) can restrain the progression of dyspareunia compared to women who did not assume COC. In the latter was shown a worsening of dyspareunia (DOI: 10.1016/j.jmig.2011.04.008). Furthermore two other studies (DOI: 10.1111/j.1743-6109.2011.02593.x; DOI: 10.1136/jfprhc-2014-100993) have shown that the combination of surgical excision of endometriosis and the subsequent COC therapy improves sexual function and all symptoms related to endometriosis (also dyspareunia); moreover the sexual function of women suffering from endometriosis was comparable to that of healthy women. It might be worth examining this aspect.

When the Authors explain that changes in muscle tone may occur, it may be useful to consider that it has been previously demonstrated (DOI: 10.1002/uog.18924) that women affected by deep endometriosis seems to have increased pelvic floor muscle tone than women with isolated ovarian endometriosis; besides, hypertonic dysfunction of pelvic floor can cause pain symptoms and pelvic organ dysfunction potentially resistant to hormonal or surgical therapy for endometriosis.

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Reviewer #1: No

Reviewer #2: No

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SIX-MONTH FOLLOW-UP OF MINIMALLY INVASIVE NERVE-SPARING COMPLETE EXCISION OF ENDOMETRIOSIS: WHAT ABOUT DYSPAREUNIA?

PONE-D-21-03413R1

Dear Dr. Crispi Jr,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Diego Raimondo

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors correctly replied to all reviewers’ queries

Reviewers' comments:

None