Peer Review History

Original SubmissionFebruary 27, 2022
Decision Letter - Antonio Simone Laganà, Editor

PONE-D-22-05900Clinical implications of first-trimester ultrasound dating in singleton pregnancies obtained through in vitro fertilizationPLOS ONE

Dear Dr. Dallagiovanna,

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.

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We look forward to receiving your revised manuscript.

Kind regards,

Antonio Simone Laganà, M.D., Ph.D.

Academic Editor

PLOS ONE

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“ES handled donations or grants of research from Ferring, Theramex and Merck-Serono, in addition he received personal fees from Theramex and Merck-Serono. EP handled donations or grants from Merck-Serono, Ferring, MSD, Finox and IBSA. All other authors do not have conflicts of interest to declare.

AMCR, CD, MR, MGP, VA, GF, NP, SB have nothing to disclose.”

We note that one or more of the authors are employed by a commercial company: name of commercial company.

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Additional Editor Comments (if provided):

The reviewers have expressed positive comments regarding your article, raising only few concerns. Considering this point, I invite authors to perform the required minor revisions.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

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 requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I read with interest this article related to pregnancy dating after ART. Specifically, authors compare gestational age detected through embryo transfer calculation and ultrasound assessment.

I have only few suggestion

- line 91: what GA was decided for the aprioristici first trimester ultrasound scan inclusion criteria (11-13+6), the GAivf o GAus?

- Line 270: "On these bases, we suggest to date IVF pregnancies using GAUS because it could realign IVF pregnancies to natural pregnancies." I think that this statement should be discuss more in the discussion section, since reading the discussion the "magnitude of the phenomenon" is modest.

- Please comment this question: What do you think, instead, of choosing the GAivf for its more replicable and quite standardized assessment in IVF center rather than GAus which is operator-dependent?

Reviewer #2: The manuscript entitled "Clinical implications of first-trimester ultrasound dating in singleton pregnancies obtained through in vitro fertilization" analyzes the first trimester dating in IVF pregnancy. The authors compared the dating of the embryos with the actual practice (taking into account the transfer date) and with the crown rump length.

Their results revealed that in IVF pregnancies these two methods are not overlapping and the use of the CRL method should be more appropriate.

The topic of the manuscript is interesting and falls within the scope of the journal “Plos One”. The Methodology is well written and the tables are detailed. The results are well represented, and the discussion is exhaustive.

I suggest the authors to discuss, at least briefly, the limitations of the study for example, the small population analyzed.

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Reviewer #1: No

Reviewer #2: No

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 1

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.

We thank the Editor for the correction. The manuscript has been modified according to PLOS ONE’s style requirements.

2. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files.

All the tables have been included in the manuscript and the individual files have been removed.

3. Thank you for stating the following in the Competing Interests/Financial Disclosure* (delete as necessary) section:

“ES handled donations or grants of research from Ferring, Theramex and Merck-Serono, in addition he received personal fees from Theramex and Merck-Serono. EP handled donations or grants from Merck-Serono, Ferring, MSD, Finox and IBSA. All other authors do not have conflicts of interest to declare.

AMCR, CD, MR, MGP, VA, GF, NP, SB have nothing to disclose.”

We note that one or more of the authors are employed by a commercial company: name of commercial company.

There has probably been a misunderstanding on this point. None of the authors is employed by any commercial company. One of them has received honoraria for presentations at meeting. We have modified the “Conflict of interest” section in order to make that point clearer.

4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available.

We apologize for the forgetfulness. We have now uploaded our minimal data set as Supporting information, as indicated.

Review Comments to the Author

Reviewer #1: I read with interest this article related to pregnancy dating after ART. Specifically, authors compare gestational age detected through embryo transfer calculation and ultrasound assessment.

I have only few suggestion

- line 91: what GA was decided for the aprioristici first trimester ultrasound scan inclusion criteria (11-13+6), the GAivf o GAus?

We thank the Reviewer for the acute observation. This aspect was indeed not properly specified.

At our institute, patients schedule the first trimester combined screening test between 11+0 and 13+6 weeks, based on the gestational age determined by the treating physician at the first ultrasound examination performed during pregnancy. When first trimester combined screening test is performed, the gestational age is reassessed on the basis of the CRL, and if it does not meet the Fetal Medicine Foundation criteria, the examination is rescheduled at a proper gestational age.

We have now better clarified this part in the manuscript.

- Line 270: "On these bases, we suggest to date IVF pregnancies using GAUS because it could realign IVF pregnancies to natural pregnancies." I think that this statement should be discuss more in the discussion section, since reading the discussion the "magnitude of the phenomenon" is modest.

We thank the Reviewer for the suggestion. What we meant to say is that the size of the phenomenon is overall modest, however, it cannot be overlooked that 1 in 8 patients have a discrepancy of more than 4 days. Such a difference may cover clinical relevance, especially in centers with high turnout. We have now better explain our point of view in the discussion session.

- Please comment this question: What do you think, instead, of choosing the GAivf for its more replicable and quite standardized assessment in IVF center rather than GAus which is operator-dependent?

We thank the Reviewer for the intriguing question. What we think is that we do not know for sure what actually happens once the cleavage-stage embryo or the blastocyst are transferred into the uterus: we have no way of knowing whether implantation takes place immediately or whether there is some latency, during which embryonic development may progress or be on hold. The only thing we can assume with plausible certainty is that the oocyte retrieval process, and consequently the fertilization of the oocyte, takes place earlier than the natural ovulation (this being the prerequisite for a successful oocyte retrieval).

On the other hand, GAUS is not as operator dependent as it seems: if the Fetal Medicine Foundation criteria are met, differences in the measurement of the CRL are only a few millimeters and do not affect the final determination of the correct gestational age.

From this point of view, the calculation of gestational age on the basis of the CRL measurement could be considered more in line with natural conceptions.

We have added a sentence in the manuscript to better explain our opinion on this issue.

Reviewer #2: The manuscript entitled "Clinical implications of first-trimester ultrasound dating in singleton pregnancies obtained through in vitro fertilization" analyzes the first trimester dating in IVF pregnancy. The authors compared the dating of the embryos with the actual practice (taking into account the transfer date) and with the crown rump length.

Their results revealed that in IVF pregnancies these two methods are not overlapping and the use of the CRL method should be more appropriate.

The topic of the manuscript is interesting and falls within the scope of the journal “Plos One”. The Methodology is well written and the tables are detailed. The results are well represented, and the discussion is exhaustive.

I suggest the authors to discuss, at least briefly, the limitations of the study for example, the small population analyzed.

We thank the Reviewer for the appreciation. We do agree that limitations of our study were not highlighted, however they deserved to be mentioned. We have thus included a dedicated paragraph at the end of the discussion section.

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Antonio Simone Laganà, Editor

Clinical implications of first-trimester ultrasound dating in singleton pregnancies obtained through in vitro fertilization

PONE-D-22-05900R1

Dear Dr. Dallagiovanna,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Antonio Simone Laganà, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Authors performed the required corrections, which were positively evaluated by the reviewers. I am pleased to accept this paper for publication.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

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?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

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 requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dear Authors,

I appreciate the efforts spent in increasing the overall quality of this article, which, in my opinion, deserves publication.

Reviewer #2: Authors improved the manuscript as requested

I suggest the acceptance of the manuscript in the present form

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7. PLOS authors have the option to publish the peer review history of their article (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: Giovanni Buzzaccarini

Reviewer #2: No

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Formally Accepted
Acceptance Letter - Antonio Simone Laganà, Editor

PONE-D-22-05900R1

Clinical implications of first-trimester ultrasound dating in singleton pregnancies obtained through in vitro fertilization First trimester ultrasound dating of in vitro pregnancies

Dear Dr. Dallagiovanna:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Antonio Simone Laganà

Academic Editor

PLOS ONE

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