Dear Dr. Wang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Dec 18 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Su-Ren Chen

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

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2. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Additional Editor Comments:

I agree with the comments from two reviewers and please address their concerns point-by-point in your revised manuscription.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: The research is very important, but need some modification to be more relevant to the aim of the study.

Reviewer #2: The authors have written an important and timely meta-analysis addressing the diagnostic yield of exome sequencing (ES) in nonobstructive azoospermia (NOA) with rigorous methodology. However, there are several areas that require clarification and improvement:

1. GRADE Assessment Not Reported: While the methods mention that the certainty of evidence was assessed using GRADE criteria, the results of this assessment are not shared anywhere in the manuscript. Please include a summary of the GRADE findings, either in the main text or as a supplementary table.

2. Sensitivity Analysis Missing: Sensitivity analysis is described in the methodology section, but no results from such an analysis are presented in the results or supplementary material. Kindly clarify whether this was performed and, if so, summarize the findings.

3. Limited Exploration of Predictive Value for TESE: The study rightly mentions the limited predictive value of ES for testicular sperm extraction (TESE) outcomes, but this point is not explored in sufficient depth. A more nuanced discussion on how specific gene variants or histopathological phenotypes correlate with TESE success would enhance the clinical relevance of the findings.

4. Heterogeneity Not Addressed in Discussion: The meta-analysis demonstrates substantial heterogeneity (I² = 90%), yet this is not adequately addressed in the discussion section. Please elaborate on potential sources of heterogeneity (e.g., study design, population differences, sequencing methods, variant interpretation criteria) and their impact on the robustness of your conclusions.

Addressing these points will significantly improve the clarity, rigor, and impact of your manuscript.

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what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: reviewer notices.docx

Diagnostic Yield of Exome Sequencing in Nonobstructive azoospermia (NOA): A Systematic Review and Meta-analysis

PONE-D-25-31306R1

Dear Dr. Wang,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Su-Ren Chen

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The two reviewers have no further concerns and this revision is recommended for acceptance.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Thank you for efforts.

Reviewer #2: The authors have carefully and comprehensively addressed all major and minor comments raised during the previous round of review. The manuscript has undergone substantial improvement in clarity, structure, and scientific rigor.

Specifically:

The GRADE assessment has now been appropriately included as Supplementary File 2.

The sensitivity analysis, previously missing, has been performed and summarized clearly.

The discussion of TESE predictive value has been expanded with relevant clinical and mechanistic context.

The sources of heterogeneity are now thoroughly examined, with an appropriate acknowledgment of methodological limitations given the limited number of included studies.

The discussion has been reorganized for improved readability, and the expanded explanation of the biological relevance of key genes strengthens the interpretability of the findings.

All issues related to clarity, background focus, and unnecessary content (e.g., the AI model reference) have been resolved.

Overall, the manuscript now meets PLOS ONE’s standards for scientific soundness, clarity, transparency of reporting, and methodological rigor. I have no further concerns.

I recommend acceptance.

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what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #1: Yes:  Weam Aldiban

Reviewer #2: No

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