Is live birth rate decline from frozen cycles performed during Chinese new year holiday season: A single center retrospective cohort

Jiajia Zhai; Songping Yi; Junyan Zhang; Aimin Li; Shibin Zhao; Bozheng Zhang; Guimin Hao

doi:10.1371/journal.pone.0330122

Peer Review History

Original SubmissionFebruary 18, 2025
4 May 2025 Decision Letter - Ayman Swelum, Editor PONE-D-25-01579 Is Live Birth Rate Decline from Frozen Cycles Performed During Chinese New Year Holiday Season a single center retrospective cohort PLOS ONE Dear Dr. Hao, 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 Jun 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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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 ****** 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: No Reviewer #2: Yes ****** 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: The article addresses an interesting and relevant question: whether sociocultural events like the Chinese New Year (CNY) affect live birth rates following frozen embryo transfer (FET) cycles. The manuscript is generally well-organized, and the methodology is robust with appropriate use of statistical techniques (multivariate logistic regression and propensity score matching). However, there are areas that need improvement for clarity, scientific rigor, and completeness. However, arears for improvement include: Title: There is a grammar issue in the title: ‘ Is Live Birth Rate Decline from Frozen Cycles Performed During Chinese New Year Holiday Season’ needs rephrasing The abstract is clear but misses specific data (e.g., p-values) in some result summaries and the wording is repetitive, especially in the purpose and conclusion sections. Methods Inclusion Criteria Description Error: The manuscript mentions "patients who had their initial ART and experienced a live birth", which is contradictory — it should mention "patients undergoing FET aiming for live birth," not only those who achieved live births (selection bias risk). Exposure Window Too Broad: Defining the CNY period as "January and February" may not precisely capture the CNY holiday influence. Typically, CNY affects a shorter window (around two weeks). This could dilute the true holiday effect. Data Presentation Tables are Dense and Crowded: Some tables (especially Tables 1 and 2) present too much detail at once, making them hard to read. Consider consolidating or summarising key variables. No Adjustment for Multiple Testing: The authors performed numerous comparisons without adjusting for type I error inflation (e.g., Bonferroni or FDR correction). Results Interpretation Although they found no statistically significant difference, the OR for live birth during CNY was 1.11 (95% CI 0.86–1.42), not close to 1.0. Thus, while no statistically significant difference was observed, the authors should avoid strongly concluding that there is no effect — it is more appropriate to say the study was underpowered to detect modest effects. Discussion While suggesting that FET cycles are less affected by stress than fresh transfers is plausible, the authors did not measure psychological stress in this study. Therefore, these interpretations are hypothetical and should be clearly labeled as such. Seasonality Confounder: Although oocyte retrieval seasonality was adjusted for, the season of embryo transfer itself may independently influence outcomes. This was not deeply discussed. Language and Grammar: Minor grammatical errors appear throughout the manuscript (e.g., missing articles like "the", awkward phrasing). Reviewer #2: Dear Editor I is my pleasure to review this manuscript @ Sorry for being late due to unexpected circumstances PONE-D-25-01579 Is Live Birth Rate Decline from Frozen Cycles Performed During Chinese New Year Holiday Season is a single center retrospective cohort study interesting topic well written and discussed it may add some to literature Regards Dr/ Funda AKPINAR ****** 6. 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. 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Revision 1
20 Jun 2025 Author Response Dear Reviewer #1, We would like to express our sincere appreciation for your valuable feedback on our article. Your comments on Questions were thoughtful and insightful, and we are grateful that you found these sections to be satisfactory without any modifications. Title: There is a grammar issue in the title: ‘ Is Live Birth Rate Decline from Frozen Cycles Performed During Chinese New Year Holiday Season’ needs rephrasing Decline in Live Birth Rate from Frozen Embryo Transfer Cycles Conducted During the Chinese New Year Holiday Season: A Single-Center Retrospective Cohort Study Response to Reviewer Comment: Thank you for your valuable feedback. We have revised the title to address the grammatical concerns and improve clarity. The updated title now uses a declarative structure. The abstract is clear but misses specific data (e.g., p-values) in some result summaries and the wording is repetitive, especially in the purpose and conclusion sections. Response to Reviewer Comment: Thank you for your kindly reminder. We’ve added the p-value in the abstract in line 27, p = 0.421. Response to Reviewer Comment: Thank you for your constructive feedback. We have revised the Purpose and Conclusion sections of the abstract to eliminate redundancy and enhance clarity. The Purpose now explicitly contrasts FET with fresh cycles and reframes the research question, while the Conclusion emphasizes novel insights about FET’s procedural advantages and broader implications. These adjustments ensure conciseness while maintaining scientific rigor. Lines17-21 Purpose: This study examines whether the Chinese New Year (CNY) holiday season impacts live birth outcomes in frozen embryo transfer (FET) cycles, contrasting with previous findings on fresh embryo transfers. While prior research identified reduced success rates in fresh cycles during CNY, it remains unclear if FET, with its distinct procedural timeline, is similarly influenced by sociocultural stressors. Our aim is to determine whether FET outcomes exhibit seasonal resilience compared to fresh cycles. Lines 31-36 Conclusion: Our results demonstrate that FET cycles conducted during the CNY holiday season yield comparable live birth rates to non-holiday periods, diverging from the adverse effects observed in fresh transfers. This resilience may stem from FET’s abbreviated preparation phase, which minimizes exposure to psychological and logistical disruptions. These findings highlight FET’s potential stability amid cultural events and underscore the need for multicenter investigations to assess broader sociocultural impacts on assisted reproductive technologies. Methods Inclusion Criteria Description Error: The manuscript mentions "patients who had their initial ART and experienced a live birth", which is contradictory — it should mention "patients undergoing FET aiming for live birth," not only those who achieved live births (selection bias risk). Revised Text: Line69. Inclusion Criteria involve patients who had their initial Assisted reproductive technology (ART), including in vitro fertilization and intracytoplasmic sperm injection (ICSI), underwent a first frozen embryo transfer (FET) cycle from January 2012 to December 2022, aiming for live birth from the cycle. Response to Reviewer Comment: Thank you for highlighting this critical oversight. We acknowledge the error in the original description and have revised the inclusion criteria to address the selection bias concern. The corrected criteria now encompass all patients who underwent their first FET cycle during the study period, irrespective of live birth outcomes. This adjustment ensures that the analysis reflects the entire cohort of FET cycles performed during and outside the CNY holiday season, eliminating bias from excluding unsuccessful cases. Additional Clarification: To confirm, our dataset included both successful and unsuccessful FET cycles (e.g., biochemical pregnancies, miscarriages, or no implantation). Statistical analyses compared live birth rates between the CNY and non-CNY groups within this unbiased cohort. We appreciate your vigilance in ensuring methodological rigor, and this revision strengthens the validity of our findings. Exposure Window Too Broad: Defining the CNY period as "January and February" may not precisely capture the CNY holiday influence. Typically, CNY affects a shorter window (around two weeks). This could dilute the true holiday effect. Response to Reviewer Comment: Thank you for raising this important methodological consideration. We appreciate your insight into the potential dilution of the CNY holiday effect due to our broad exposure window. Below, we address your concern and provide additional analyses to validate our approach: 1.Rationale for the Original Definition of CNY Period In China, the sociocultural impact of CNY extends beyond the official 7-day national holiday. Preparations (e.g., travel, family gatherings) often begin weeks in advance, and post-holiday activities (e.g., regional festivals, delayed hospital workflows) frequently persist until the Lantern Festival (15th day of the lunar calendar), particularly in rural areas. Thus, defining CNY as January and February aligns with the prolonged societal disruption, including altered clinic workflows, staff availability, and patient stress levels, which may influence FET outcomes. 2.Sensitivity Analysis with a Narrower Exposure Window Lines277-284 To address your concern, we reanalyzed the data using a stricter CNY window: 7 days before and 15 days after the lunar New Year’s Eve (adjusted annually to Gregorian dates). This 22-day window reflects the core holiday period. Key findings remained consistent: oOriginal definition (Jan–Feb): OR = 1.11 (95% CI: 0.86–1.42, p = 0.421). oNarrower window (22-day): OR = 1.09 (95% CI: 0.82–1.45, p = 0.548). The lack of significant difference in both analyses suggests that FET outcomes are resilient to CNY-related stressors, regardless of exposure window breadth. 3.Discussion of Potential Dilution Lines315-317 This hypothesis is consistent with While the broader window may incorporate non-holiday days, the consistency across definitions implies that the sociocultural and logistical impacts of CNY extend beyond the official holiday. For instance, clinic workloads often decrease for weeks due to staff rotations and patient deferrals, indirectly affecting care continuity. 4.Revised Manuscript Updates We have added the sensitivity analysis to the Methods and Results sections and expanded the Discussion to acknowledge the window-definition limitation. We emphasize that our primary aim was to capture the holiday season’s extended societal influence, not solely the legal holiday period. Data Presentation Tables are Dense and Crowded: Some tables (especially Tables 1 and 2) present too much detail at once, making them hard to read. Consider consolidating or summarising key variables. Thank you for your suggestion. Table 1 and Table 2 have been streamlined. The redundant content is in the appendix table. No Adjustment for Multiple Testing: The authors performed numerous comparisons without adjusting for type I error inflation (e.g., Bonferroni or FDR correction). Thank you for your comments. As you mentioned, we did multivariate logistic regression in this study which include several variables in the model. As prior studies suggested, multivariate regression models already made control on the multiplicity comparisons, no alpha adjustment was needed [16, 17]. For the sensitivity analysis, propensity score matching (PSM) and logistic regression are employed to test the same research hypothesis and therefore belong to a unified analytical framework, unlike multiple testing correction, which is applied when independently testing multiple hypotheses, such as evaluating multiple endpoints or variables [18]. We understand your concern, which may also be shared by our readers, so we have added the following clarification in the Statistical Analysis section: Line153-154 As supported by statistical literature, alpha adjustment is not required in multivariate logistic regression models or in sensitivity analyses conducted under the same research hypothesis [16-18]. 16. Gelman A, Hill J, Yajima M. Why we (usually) don't have to worry about multiple comparisons. Journal of research on educational effectiveness. 2012;5(2):189-211. 17. Rubin M. When to adjust alpha during multiple testing: A consideration of disjunction, conjunction, and individual testing. Synthese. 2021;199(3):10969-1000. 18. Lyles RH, Lin J. Sensitivity analysis for misclassification in logistic regression via likelihood methods and predictive value weighting. Stat Med. 2010;29(22):2297-309. doi: 10.1002/sim.3971. PubMed PMID: 20552681; PubMed Central PMCID: PMCPMC3109653. Results Interpretation Although they found no statistically significant difference, the OR for live birth during CNY was 1.11 (95% CI 0.86–1.42), not close to 1.0. Thus, while no statistically significant difference was observed, the authors should avoid strongly concluding that there is no effect — it is more appropriate to say the study was underpowered to detect modest effects. Response to Reviewer Comment: Thank you for your astute observation. We have revised the interpretation of the results to avoid overstating the conclusions and explicitly acknowledge the limitations in statistical power. The updated text now emphasizes the uncertainty inherent in the confidence interval, clarifies the potential for undetected modest effects, and underscores the need for further research. This adjustment ensures a balanced presentation of the findings while maintaining scientific rigor. Lines 250-256, While our analysis revealed no statistically significant difference in live birth rates between the CNY and non-CNY groups , the point estimate of the odds ratio (1.11) suggests a potential marginal association favoring FET cycles conducted during the CNY period. However, the confidence interval spans both null and modest positive effects, indicating uncertainty in the magnitude of this association. Given the width of the confidence interval and the study’s sample size, these findings should be interpreted cautiously, as the analysis may have been underpowered to detect clinically meaningful but modest effects. Lines287-295. Our results indicate that FET outcomes during the CNY holiday season are statistically comparable to those in non-holiday periods. However, the observed odds ratio (1.11) and its confidence interval (0.86–1.42) do not preclude the possibility of a small beneficial or neutral effect. The lack of statistical significance may reflect limitations in statistical power due to the relatively small number of FET cycles performed during the CNY window (n = 305). A post-hoc power analysis revealed that, with the current sample size, the study had 64% power to detect a 10% absolute difference in live birth rates (assuming a baseline rate of 40%), which falls below the conventional 80% threshold. Thus, while our findings suggest resilience of FET cycles to CNY-related disruptions, they do not definitively rule out modest effects. Larger, multicenter studies are warranted to confirm these observations and explore subtle associations that smaller cohorts may fail to capture. Discussion While suggesting that FET cycles are less affected by stress than fresh transfers is plausible, the authors did not measure psychological stress in this study. Therefore, these interpretations are hypothetical and should be clearly labeled as such. Response to Reviewer Comment: Thank you for emphasizing the need for caution in interpreting stress-related mechanisms. We fully agree that our discussion of psychological stress as a potential factor is hypothetical, given the absence of direct stress measurements. We have revised the text to: Lines 302-309 Lines 368-371 Lines 373-378 Seasonality Confounder: Although oocyte retrieval seasonality was adjusted for, the season of embryo transfer itself may independently influence outcomes. This was not deeply discussed. Language and Grammar: Minor grammatical errors appear throughout the manuscript (e.g., missing articles like "the", awkward phrasing). Revised Text in Discussion Section: Lines 337-344 Lines 379-382 Response to Reviewer Comment: Thank you for highlighting this critical point. We have expanded the discussion to address the potential confounding role of embryo transfer seasonality. A post-hoc sensitivity analysis was added to explicitly test for seasonal effects during the transfer window, and we now acknowledge the limitations of relying solely on calendar-based season definitions. Response to Reviewer Comment: Thank you for your meticulous review. We have thoroughly revised the manuscript to address grammatical errors and improve clarity. A professional proofreading service was additionally consulted to ensure linguistic precision. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0330122.r002
27 Jul 2025 Decision Letter - Ayman Swelum, Editor Decline in Live Birth Rate from Frozen Embryo Transfer Cycles Conducted During the Chinese New Year Holiday Season: A Single-Center Retrospective Cohort Study PONE-D-25-01579R1 Dear Dr. Hao, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support. 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, Ayman A Swelum Academic Editor PLOS ONE Additional Editor Comments (optional): 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: The revisions have effectively and thoroughly addressed my concerns. The methodology, interpretation, and presentation of results are now sound and clearly communicated. ****** 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: JACKLINE AKELLO ******** https://doi.org/10.1371/journal.pone.0330122.r003
Formally Accepted
Acceptance Letter - Ayman Swelum, Editor PONE-D-25-01579R1 PLOS ONE Dear Dr. Hao, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@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 Professor Ayman A Swelum Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0330122.r004

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