Objective Pelvic Support and Patient-Reported Outcomes After Non-Ablative Vaginal Er:YAG Laser Therapy in Women with Pelvic Floor Dysfunction: A Prospective Single-Arm Interventional Study in a Real-World Care Setting

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The manuscript is generally well structured and transparent about several methodological limitations. However, important issues require clarification and strengthening before the work can be considered for publication.
1-The single-arm design represents the main methodological limitation. The Discussion occasionally implies treatment-related effects in a manner that may overstate the strength of the evidence.

2-In addition, the lack of systematic recording of concomitant treatments during follow-up (even though participants were advised not to modify them) introduces potential confounding. This is particularly relevant in a real-world cohort where physiotherapy or behavioral modifications could influence POP-Q findings. So, some consideration in discussion and conclusion must be "more cautios"

3- only 37% of patients completed FUP. This is a major limitation. Given the progressive reduction in sample size across timepoints, there is a significant risk of attrition bias. A more detailed characterization of losses to follow-up and a structured discussion of their potential impact on anatomical staging results are necessary

4- Although statistically significant reductions in vaginal hiatus and improvements in anterior/posterior compartment staging are reported, the manuscript does not sufficiently address clinical relevance. It is unclear how many patients achieved clinically meaningful changes

5- The comparison with existing literature on prolapse treatment should be strengthened. In particular, the manuscript would benefit from a clearer contextualization of established surgical techniques for pelvic organ prolapse and their reported anatomical and functional outcomes (see PMID: 31452267; PMID: 38711094; PMID: 29289624; PMID: 35308533):

PMID: 31452267
Comparison of laparoscopic techniques for apical organ prolapse repair - a systematic review of the literature
https://pubmed.ncbi.nlm.nih.gov/31452267/

PMID: 38711094
Mid-term outcomes of laparoscopic vaginal stump–round (Kakinuma method) and stump–uterosacral (Shull method) ligament fixation for pelvic organ prolapse: A retrospective comparative study
https://pubmed.ncbi.nlm.nih.gov/38711094/

PMID: 29289624
Laparoscopic Approach for Shull Repair of Pelvic Floor Defects
https://pubmed.ncbi.nlm.nih.gov/29289624/

PMID: 35308533
Laparoscopic High Uterosacral Ligament Suspension vs. Laparoscopic Sacral Colpopexy for Pelvic Organ Prolapse: A Case-Control Study
https://pubmed.ncbi.nlm.nih.gov/35308533/

Author Response

Dear Reviewer 1,

We would like to thank you and the reviewers for the time and effort dedicated to the evaluation of our manuscript entitled:

“Objective pelvic support and patient-reported outcomes after non-ablative vaginal Er laser in women with pelvic floor dysfunction: A prospective cohort study in a real-world care setting” (Manuscript ID: healthcare-4189554).

Response to Reviewers

We sincerely thank the Editor and Reviewers for their careful evaluation of our manuscript and for their constructive and insightful comments. We have revised the manuscript accordingly to improve clarity, methodological transparency, and balance in the interpretation of findings. In particular, we have strengthened the discussion of study limitations, clarified methodological aspects, corrected inconsistencies, and adopted more cautious language throughout to reflect the observational design. Below, we provide a detailed point-by-point response to each comment. All corresponding changes have been incorporated into the revised manuscript.

 

REVIEWER 1

Comment 1:

The single-arm design represents the main methodological limitation and may lead to overinterpretation.

Response:

We agree and have revised the manuscript to remove causal language throughout. Terms such as “effect” and “supports” have been replaced with “association” and “is consistent with.” The Discussion and Conclusions have been updated to clearly reflect the observational nature of the study.

 

Comment 2:

Lack of systematic recording of concomitant treatments introduces potential confounding.

Response:

This has been addressed by clarifying in the Methods section that concomitant treatments were not systematically recorded. In addition, the Discussion has been expanded to explicitly acknowledge this as a potential source of confounding in a real-world setting.

 

Comment 3:

High attrition (37%) raises risk of bias.

Response:

We agree. Follow-up completion rates are now clearly reported, and a dedicated paragraph has been added to the Discussion addressing the potential for attrition bias. Later timepoints are now explicitly described as exploratory due to the reduced sample size.

 

Comment 4:

Clinical relevance of anatomical changes is unclear.

Response:

We have addressed this by clarifying in both the Results and Discussion that, although statistically significant, the magnitude of anatomical changes was modest and their clinical relevance cannot be determined in the absence of established thresholds for clinically meaningful improvement.

 

Comment 5:

Comparison with surgical literature should be strengthened.

Response:

We appreciate the reviewer’s suggestion. However, we consider that direct comparison with surgical approaches may not be methodologically appropriate in this context. Surgical and non-ablative laser interventions differ substantially in mechanism of action, invasiveness, patient selection, and expected magnitude of effect. As such, direct comparison may be misleading. Instead, we have clarified this distinction in the Discussion and positioned our findings within the context of minimally invasive, non-surgical management strategies.

 

We hope that the revisions and clarifications provided have adequately addressed all reviewer comments. We believe that the manuscript has been substantially improved in terms of clarity, methodological transparency, and interpretative balance. We thank the Editor and Reviewers for their valuable feedback and consideration.

Sincerely, Inés Ramírez-García on behalf of all authors

Reviewer 2 Report

Comments and Suggestions for Authors

Abstract:
-  please clarify inconsistency in sample size across follow-ups (108 vs 136 at FU1 reported elsewhere)
- please avoid redundancy: “prospective cohort study” and “prospective single-arm cohort study” repeated
- please specify clinical relevance of anatomical changes (e.g., minimal clinically important difference)
- FSFI results are vague, please quantify key findings instead of “small domain-level variations”
- please consider shortening background and emphasizing key numerical results.

Introduction
- please reduce repetition regarding “lack of randomized trials” and “limited objective endpoints”
- please clearly state primary hypothesis (currently implied, not explicit)
- please strengthen novelty statement, what exactly differentiates this study from prior laser studies?
- please move attrition discussion to Methods/Limitations instead of Introduction
- please provide more balanced view (include negative/neutral evidence on vaginal laser therapies)

Materials and Methods
- please clarify discrepancy in FU1 sample size (136 vs 108 in Abstract/Results)
- please report whether a sample size calculation/power analysis was performed
- please specify handling of missing data (beyond “complete cases” vs “available pairs”)
- please standardize terminology: sometimes “prospective cohort”, sometimes “interventional”
- - please more detail needed on operator variability and training (potential measurement bias)

Results
- please resolve inconsistencies in participant numbers across sections and tables
- Some statistical reporting unclear (e.g., Δ CI formatting: “−0.5 to −0.75” reversed)
- please avoid overinterpretation of small effect sizes (e.g., FSFI domain changes).
- Tables contain formatting inconsistencies (commas vs dots in decimals, “None”, “NR”) - please revise
- please clarify clinical vs statistical significance throughout

Discussion
- please tone down causal language (e.g., “supports hypothesis”, “effect”) given single-arm design
- please expand discussion on high attrition (only 37%) and its impact on bias
- please better integrate contradictory evidence or regulatory concerns (e.g., FDA warnings)
-overreliance on supportive studies, please include more critical literature
- Mechanistic explanations (collagen remodeling) are speculative, please state this more cautiously

Conclusions
- conclusions slightly overstated given study design, please rephrase to be more cautious
- please avoid generalization to clinical practice without controlled trials
- please emphasize exploratory nature of findings more clearly
- please reduce repetition from Abstract/Discussion
- please add one sentence on future research directions (RCTs, long-term outcomes

Author Response

Dear Reviewer 2,

We would like to thank you and the reviewers for the time and effort dedicated to the evaluation of our manuscript entitled:

“Objective pelvic support and patient-reported outcomes after non-ablative vaginal Er laser in women with pelvic floor dysfunction: A prospective cohort study in a real-world care setting” (Manuscript ID: healthcare-4189554).

Response to Reviewers

We sincerely thank the Editor and Reviewers for their careful evaluation of our manuscript and for their constructive and insightful comments. We have revised the manuscript accordingly to improve clarity, methodological transparency, and balance in the interpretation of findings. In particular, we have strengthened the discussion of study limitations, clarified methodological aspects, corrected inconsistencies, and adopted more cautious language throughout to reflect the observational design. Below, we provide a detailed point-by-point response to each comment. All corresponding changes have been incorporated into the revised manuscript.

 

REVIEWER 2

Comment:

Abstract: Sample size inconsistency.

Response:

Corrected. The FU1 sample size has been standardized across the Abstract, Methods, and Results sections.

 

Comment:

Abstract: Redundant study design wording.

Response:

Revised to consistently describe the study as a “prospective single-arm interventional cohort study.”

 

Comment:

Abstract: Clinical relevance of anatomical changes unclear.

Response:

A statement has been added to clarify that the observed anatomical changes were modest and that their clinical relevance remains uncertain.

 

Comment:

Abstract: FSFI results vague.

Response:

Revised to include quantitative domain-level findings, specifying the observed changes in orgasm and pain scores.

 

Comment:

Introduction: Repetition and missing hypothesis.

Response:

Repetitive statements have been removed, and a clear study hypothesis has been added at the end of the Introduction.

 

Comment:

Introduction: strengthen novelty statement, what exactly differentiates this study from prior laser studies?

Response:

We thank the reviewer for this important comment. We have strengthened the novelty statement in the revised manuscript to more clearly define the contribution of our study in relation to prior laser literature.

Specifically, our study differs from previous reports in several key aspects. First, it provides standardized, objective anatomical assessment using the POP-Q system, whereas much of the existing literature has focused predominantly on symptom-based outcomes or condition-specific endpoints (e.g., stress urinary incontinence or genitourinary syndrome of menopause). Second, it evaluates these anatomical changes within a real-world clinical cohort, which remains underrepresented in controlled or highly selected study populations. Third, our study integrates anatomical outcomes with functional measures and detailed energy-delivery parameters, allowing a more comprehensive exploration of treatmentassociated changes.

We have clarified these points in the Introduction/Discussion to better contextualize the originality and clinical contribution of our findings.

 

Comment:

Introduction: Attrition placement.

Response:

The discussion of attrition has been removed from the Introduction and incorporated into the Methods and Discussion sections.

 

Comment:

Introduction: Need balanced evidence.

Response:

We have added a more balanced perspective by including mention of regulatory concerns and mixed evidence regarding vaginal laser therapies.

 

Comment:

Methods: Sample size discrepancy in FU1 sample size (136 vs 108 in Abstract/Results)

Response:

All inconsistencies in participant numbers have been corrected across the manuscript.

 

Comment:

Methods: Missing power calculation.

Response:

We have clarified in the Methods that no formal sample size calculation was performed, as this was an exploratory real-world cohort study.

 

Comment:

Methods: Missing data handling.

Response:

A detailed description of missing data handling has been added to the Methods, specifying the use of complete-case and available-pair analyses without imputation.

 

Comment:

Methods: standardize terminology: sometimes “prospective cohort”, sometimes “interventional”

Response:

Revised to consistently describe the study as a “Revised to consistently describe the study as a “prospective single-arm interventional cohort study.”

 

Comment:

Methods: Operator variability.

Response:

Additional clarification has been included regarding examiner training and the potential for inter-operator variability.

 

Comment:

Results: Formatting and inconsistencies.

Response:

Numerical inconsistencies and formatting issues (including decimal notation and confidence interval presentation) have been corrected throughout.

 

Comment:

Results: Overinterpretation. Clarify clinical vs statistical significance throughout

Response:

Language has been revised throughout the Results and Discussion to avoid overinterpretation of small effect sizes.

 

Comment:

Discussion: Tone and expand discussion on high attrition and its impact on bias.

Response:

Causal language has been removed, and the Discussion has been expanded to better address attrition bias and potential confounding.

 

Comment:

Discussion: Better integrate contradictory evidence or regulatory concerns (e.g., FDA warnings). Include more critical literature

Response:

We thank the reviewer for this important observation. We have revised the Discussion to better integrate contradictory evidence and regulatory concerns regarding vaginal laser therapies. Specifically, we have incorporated references to FDA safety communications and statements from professional societies such as ACOG and EUGA, which highlight the investigational nature of these devices and the current limitations of the evidence base. We have also balanced the discussion by acknowledging that existing studies report heterogeneous and sometimes inconsistent findings, including limited benefit in controlled settings. In addition, we have reduced the emphasis on supportive studies and introduced a more critical appraisal of the literature to ensure a balanced and scientifically rigorous interpretation of our results.

 

Comment:

Discussion: Mechanisms speculative.

Response:

Mechanistic interpretations have been revised to explicitly state their speculative nature.

 

Comment:

Conclusions: Overstated and avoiding generalization to clinical practice without controlled trials. Emphasize exploratory nature of findings more clearly.

Response:

The Conclusions have been rewritten to emphasize the exploratory nature of the findings and the limitations of the study design.

 

Comment:

Conclusions: Future research.

Response:

A statement has been added highlighting the need for randomized controlled trials with longer follow-up and clinically meaningful outcome measures.

 

We hope that the revisions and clarifications provided have adequately addressed all reviewer comments. We believe that the manuscript has been substantially improved in terms of clarity, methodological transparency, and interpretative balance. We thank the Editor and Reviewers for their valuable feedback and consideration.

Sincerely, Inés Ramírez-García on behalf of all authors