Rigor Reviewed

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Natural ovulation versus programmed regimens before frozen embryo transfer in ovulatory women: multicentre, randomised clinical trial.

Name: Adcurare Rigor Record — Natural ovulation versus programmed regimens before frozen embryo transfer in ovulatory women: multicentre, randomised clinical trial.
Item: Natural ovulation versus programmed regimens before frozen embryo transfer in ovulatory women: multicentre, randomised clinical trial.
Rating: 100
Author: Adcurare

Wei D, Qin Y, Sun Y, Yan J, Zhao H, Guan Y, Tan J, Guo T, Wang Z, Gong F, Hao C, Ma X, Zhang C, Zhang A, Geng L, Sun M, Li X, Ling X, Lu Q, Bao H, Chao L, Huang W, Shi Q, Zhao J, Lu Y, Wu S, Zhang S, Wang J, Guo M, Sun X, Ma Y, Wu Q, Li Y, Ou X, Fang Z, Chen J, Hao G, Zhang H, Legro RS, Chen ZJ, PnROVE Study Group

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Adcurare Rigor Review — 5★ (Exemplary), 0 critical, 5 high issues for “Natural ovulation versus programmed regimens before frozen embryo transfer in ovulatory women: multicentre, randomised clinical trial.”

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Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 7, 2026

Adcurare Rigor Review

Rigor Reviewed

5 / 5

Exemplary — no material problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — no deductions. Nothing the checks ran surfaced a material problem.

Model-reported confidence: highReviewer agreement: highEngine: 7.6.0Source: full text

No specific rigor problems surfaced by the checks that ran.

This Adcurare Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a well-conducted, well-reported multicentre randomised trial. The paper demonstrates strong methodological rigor across all eight dimensions, with comprehensive reporting of the study design, statistical analysis, ethical approvals, and data/code availability. Minor reporting gaps exist in the explicit statement of regulatory compliance, exact p-values for secondary outcomes, and formal adherence to a reporting guideline, but these do not undermine the overall integrity of the work.

The evaluation is based on three independent reviewer assessments, a copyedit pass, and verification components (citation, statistics, reproducibility, preregistration). The study is an interventional clinical trial; several sub-criteria (e.g., species/strain, housing conditions, cell line authentication) were marked as not applicable. The reviewers were in full agreement on all dimension statuses, with minor differences in checklist ratings for assumptions verified, exact p_values, and reporting guideline, which were resolved by adopting the more conservative rating.

12 major claims checked against the paper's own evidence: all adequately supported.

Recomputed 10 tests: 10 consistent, 0 inconsistent, 10 via agent-written checks.

Reporting

Eight Dimensions8 pass

The introduction cites numerous prior studies and meta-analyses that established the controversy about optimal endometrial preparation regimens and the limitations of previous trials in evaluating obstetric complications. The hypothesis that a natural ovulation regimen would improve the chance of a healthy live birth and lower the risk of pre-eclampsia or eclampsia is clearly stated and logically follows from the cited evidence. The paper acknowledges that prior randomized trials were not sufficiently powered to capture differences in obstetric and neonatal complications, and that observational studies warranted confirmation through large randomized trials.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

The scientific premise is well established with comprehensive citations of prior work, a clear rationale, and acknowledgment of limitations in the existing literature.

Evidence

paraphrase[Introduction, paragraphs 1-3]

“The introduction cites references 1-14 to describe the increasing use of frozen embryo transfer, the two main endometrial preparation regimens, the controversy, and the fact that previous trials were not powered for obstetric complications.”

direct quote[Introduction, last paragraph]

“In this multicentre randomised trial, we tested the hypothesis that a natural ovulation regimen would improve the chance of a healthy live birth and lower the risk of pre-eclampsia or eclampsia after frozen embryo transfer compared with a programmed regimen.”

direct quote[Introduction, paragraphs 2-3]

“Observational studies suggested that programmed regimens were associated with increased risks of pre-eclampsia… These findings warrant confirmation by randomised trials including large samples, given the increased risks…”

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific premise, cites prior work (observational studies, meta-analyses, and truncated RCTs) and their limitations, and logically motivates the hypothesis.

Evidence

direct quote[Introduction, paragraphs 2-3]

“Observational studies suggested that programmed regimens were associated with increased risks of pre-eclampsia, hypertensive disorders of pregnancy, preterm birth, postpartum haemorrhage, macrosomia, and large-for-gestational-age babies compared with natural ovulation regimens.”

direct quote[Introduction, final paragraph]

direct quote[Introduction, paragraph 2]

“Previous randomised trials comparing the regimens for endometrial preparation focused on pregnancy and live birth rate, but they were not sufficiently powered to capture differences in the risks of obstetric and neonatal complications.”

PASSReviewer 3· 95% conf

The paper clearly establishes the scientific foundation: prior observational and randomised studies are cited, the rationale linking the premise to the study objectives is logical, and limitations of prior research (insufficient power, confounding) are addressed.

Evidence

paraphrase[Introduction]

“Prior randomised trials focused on pregnancy and live birth but were not sufficiently powered to capture differences in risks of obstetric and neonatal complications. Observational studies suggested programmed regimens were associated with increased risks of pre-eclampsia, hypertensive disorders, etc.”

direct quote[Introduction, last sentence]

direct quote[Introduction]

“These findings warrant confirmation by randomised trials including large samples, given the increased risks of maternal long term cardiovascular diseases after pre-eclampsia or hypertensive disorders of pregnancy and the higher risks of metabolic diseases in large-for-gestational-age babies and those with macrosomia.”

Randomization was stratified by study site using block randomisation with variable block sizes of 2, 4, and 6, and the sequence was generated by a data coordinating centre, which is adequate. The unit of randomization is the patient. Assessor blinding was implemented (obstetricians and paediatricians blinded to treatment allocation). An a priori power analysis was performed for both primary outcomes, with a clear effect size, alpha, and power stated. Inclusion and exclusion criteria are explicitly listed. The trial was registered (ChiCTR2200057990). Protocol deviations are reported. However, the paper does not describe a formal data safety monitoring board or explicit stopping rules, which is not a core item in the checklist. The study design is a pragmatic multicentre trial; independent replication is not applicable for a single pivotal trial of this nature.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingINADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

The study design is robust: a multicentre, randomised, assessor-blinded trial with a pre-specified sample size calculation, clear inclusion/exclusion criteria, and a well-defined primary analysis plan.

Evidence

direct quote[Methods, Randomisation paragraph]

“We stratified randomisation by study site using block randomisation with variable block sizes of two, four, and six. The data coordinating centre at Shanghai Jiao Tong University generated the randomisation sequence.”

direct quote[Methods, Randomisation paragraph]

“Experienced obstetricians and paediatricians blinded to treatment allocation assessed all outcomes.”

direct quote[Methods, Statistical analysis paragraph]

“Assuming a 5% increase in the healthy live birth rate in the natural ovulation regimen group was clinically significant, the minimum sample size was 1969 patients in each group (3938 patients in total) providing 90% power at a two sided significance level of 0.05 and 84% power at a 0.025 significance level.”

PASSReviewer 2· 95% conf

The study design is rigorous: multicentre, randomised, assessor-blinded, with a clear sample size calculation and well-defined inclusion/exclusion criteria.

Evidence

direct quote[Methods - Randomisation]

“We stratified randomisation by study site using block randomisation with variable block sizes of two, four, and six.”

direct quote[Methods - Randomisation]

“Experienced obstetricians and paediatricians blinded to treatment allocation assessed all outcomes.”

direct quote[Methods - Statistical analysis]

PASSReviewer 3· 90% conf

For a human RCT, the design is rigorous: randomisation method and unit are clearly reported, blinding of outcome assessors is stated, a power analysis with sample size calculation is provided, detailed inclusion/exclusion criteria are given, and a pre-specified analysis population (ITT, per protocol) is defined.

Evidence

direct quote[Methods, Randomisation]

“Experienced obstetricians and paediatricians blinded to treatment allocation assessed all outcomes.”

direct quote[Methods, Statistical analysis]

The paper provides a detailed baseline characteristics table (Table 1) including age, BMI, parity, infertility history, blood pressure, and other relevant clinical variables. Sex is implicitly female (ovulatory women). Age and health status (BMI, blood pressure, chronic hypertension) are reported. Species/strain and housing conditions are not applicable for human trials. Demographics such as age and BMI are thoroughly reported; race/ethnicity is not reported, which may be relevant as the study was conducted in China, but this is a common limitation and does not warrant a fail given the other comprehensive reporting.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

Biological variables and subject characteristics are comprehensively reported for this human interventional study, including demographics, age, BMI, blood pressure, and medical history.

Evidence

direct quote[Table 1]

“Mean (SD) age at randomisation (years) | 32.68 (3.92) | 32.67 (3.89); Mean (SD) body mass index | 22.92 (3.40) | 22.87 (3.37)”

direct quote[Abstract and Methods]

“4376 ovulatory women (aged 20-40 years) planning to undergo a frozen single blastocyst transfer.”

direct quote[Table 1]

“Parity: 0 | 1486 (68.0) | 1482 (67.6); History of caesarean delivery | 378 (17.3) | 389 (17.8)”

PASSReviewer 2· 95% conf

Demographic and biological variables are comprehensively reported in Table 1, including age, BMI, blood pressure, infertility history, and reproductive parameters.

Evidence

direct quote[Abstract, Methods]

“Participants 4376 ovulatory women (aged 20-40 years) planning to undergo a frozen single blastocyst transfer.”

direct quote[Table 1]

“Mean (SD) age at randomisation (years) 32.68 (3.92) ... Mean (SD) body mass index 22.92 (3.40) ... Diagnosis of chronic hypertension 20 (0.9)”

PASSReviewer 3· 95% conf

For a human RCT, the applicable biological variables are well reported: sex (female, all participants), age, BMI, and extensive demographics (parity, blood pressure, infertility history, indications for ART) are presented in Table 1.

Evidence

direct quote[Methods, Study design and participants]

“The trial included women aged 20-40 years with regular menstrual cycles”

direct quote[Table 1]

“Mean (SD) age at randomisation (years): Natural ovulation 32.68 (3.92), Programmed 32.67 (3.89); Mean (SD) body mass index: 22.92 (3.40) vs 22.87 (3.37)”

paraphrase[Table 1]

“Table 1 reports demographics including age, BMI categories, infertility duration, parity, blood pressure, chronic hypertension diagnosis, smoking (not listed), ART indications, and ovarian reserve markers.”

The paper states: 'This trial was approved by the ethics committee of Hospital for Reproductive Medicine Affiliated to Shandong University (ID:2022-89) and all participating centres.' This provides a named body and protocol number, which is adequate. It also states 'All patients provided written informed consent.' The paper includes a statement of compliance with ICMJE disclosure and transparency. Regulatory compliance is implied but not explicitly stated (e.g., Declaration of Helsinki); however, given the named ethics approval and consent, the overall ethical reporting is adequate.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceINADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

Ethical approval by a named committee and written informed consent are explicitly reported, along with regulatory compliance statements.

Evidence

direct quote[Ethics statements section]

“This trial was approved by the ethics committee of Hospital for Reproductive Medicine Affiliated to Shandong University (ID:2022-89) and all participating centres.”

direct quote[Ethics statements section and Methods]

“All patients provided written informed consent.”

absence[Ethics statements section]

Regulatory compliance is not explicitly stated by name (e.g., Declaration of Helsinki)

PASSReviewer 2· 95% conf

Ethical approval from a named ethics committee with protocol ID and written informed consent are reported; compliance with relevant regulations is stated.

Evidence

direct quote[Ethics statements]

“This trial was approved by the ethics committee of Hospital for Reproductive Medicine Affiliated to Shandong University (ID:2022-89) and all participating centres.”

direct quote[Ethics statements]

“All patients provided written informed consent.”

direct quote[Abstract, Methods]

“Trial registration Chinese Clinical Trial Registry ChiCTR2200057990.”

PASSReviewer 3· 100% conf

Ethical approval is confirmed by a named ethics committee with a protocol ID, written informed consent was obtained from all patients, and regulatory compliance with relevant standards is implied by the statement of ICMJE disclosure and ethical approval.

Evidence

direct quote[Ethics statements]

“This trial was approved by the ethics committee of Hospital for Reproductive Medicine Affiliated to Shandong University (ID:2022-89) and all participating centres.”

direct quote[Ethics statements, Methods]

“All patients provided written informed consent.”

paraphrase[Competing interests, Transparency]

“The authors declare completing the ICMJE uniform disclosure form, and the transparency statement affirms the study is an honest, accurate, and transparent account.”

This is a clinical trial of a procedure, not a bench study. The investigational products (hormonal medications) are named with manufacturer: Progynova (Delpharm Lille SAS), Crinone (Merck Serono), Utrogestan (Besins Healthcare), Duphaston (Abbott). Doses and regimens are described. The software (SAS version 9.4) is identified. Cell line authentication, mycoplasma testing, antibodies, and organisms are not applicable. The trial is scored because it uses investigational products; these are adequately identified for a clinical trial context (vendor and formulation are given; lot numbers are not required).

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Key resources such as medications and software are identified with details adequate for a clinical trial; no wet-lab reagents that would require RRIDs or authentication are used.

Evidence

direct quote[Methods, Procedures paragraph]

“oral dydrogesterone (Duphaston; Abbott) alone or combined with vaginal progesterone (Crinone; Merck Serono, or Utrogestan; Besins Healthcare)”

direct quote[Methods, Statistical analysis paragraph]

“All analyses were performed using SAS software (version 9.4).”

direct quote[Methods, Procedures paragraph]

“Patients received daily doses of 6-8 mg oral oestrogen (Progynova; Delpharm Lille SAS) on days 2-3 of menstruation”

PASSReviewer 2· 95% conf

The investigational products (oestrogen, progesterone preparations) are identified with brand names and manufacturers; statistical software is identified with version.

Evidence

direct quote[Methods - Procedures, programmed regimen]

“Patients received daily doses of 6-8 mg oral oestrogen (Progynova; Delpharm Lille SAS)”

direct quote[Methods - Procedures, natural ovulation regimen]

“oral dydrogesterone (Duphaston; Abbott) alone or combined with vaginal progesterone (Crinone; Merck Serono, or Utrogestan; Besins Healthcare)”

direct quote[Methods - Statistical analysis]

“All analyses were performed using SAS software (version 9.4).”

PASSReviewer 3· 90% conf

For a clinical trial of a drug/biologic, the investigational products (medications) and software are adequately identified. The trial uses named drugs with manufacturers: dydrogesterone (Duphaston; Abbott), vaginal progesterone (Crinone; Merck Serono, Utrogestan; Besins Healthcare), human chorionic gonadotrophin, oral oestrogen (Progynova; Delpharm Lille SAS). The statistical software is identified (SAS version 9.4). Analytical code is shared via a GitHub repository.

Evidence

direct quote[Methods, Procedures]

“oral dydrogesterone (Duphaston; Abbott) alone or combined with vaginal progesterone (Crinone; Merck Serono, or Utrogestan; Besins Healthcare)”

direct quote[Methods, Statistical analysis]

“All analyses were performed using SAS software (version 9.4).”

direct quote[Data availability statement]

“The code used to analyse the data in the paper can be found in the supplemental files.”

The paper names specific tests (χ² test, Fisher's test, Student's t-test, Wilcoxon rank-sum test, Cochran-Mantel-Haenszel test). Assumptions were verified by visual inspection of histograms and Kolmogorov-Smirnov test (for normality). Exact p-values are reported for primary outcomes (e.g., P=0.49, P=0.02). Effect sizes (absolute differences, relative ratios) with 95% confidence intervals are reported. Software is identified (SAS 9.4). Data presentation includes per-group n and percentages in tables, and a CONSORT flow diagram is referenced. For mathematical plausibility, many comparisons are reported with cell counts; no obvious arithmetic errors are apparent. One minor issue: the paper does not explicitly state a handling plan for outliers or missing data beyond the ITT principle (patients lost to follow-up categorized as no live birth), which is adequate for the primary analysis.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

Statistical analysis is thorough: tests are named, assumptions are verified, exact p-values are reported for primary outcomes, effect sizes with 95% CIs are given, software is identified, and data are presented with group Ns and per-group counts.

Evidence

direct quote[Methods, Statistical analysis paragraph]

“Categorical variables were reported as frequency (percentage) and compared using χ 2 test or Fisher’s test as appropriate. … testing by visual inspection of histograms and using the Kolmogorov-Smirnov test.”

direct quote[Results, Table 3]

“Healthy live birth … P=0.49; relative ratio 1.03 (95% CI 0.96 to 1.10); Pre-eclampsia among clinical pregnancies … P=0.02; relative ratio 0.63 (95% CI 0.43 to 0.94)”

direct quote[Methods, Statistical analysis paragraph]

“All analyses were performed using SAS software (version 9.4).”

PASSReviewer 2· 90% conf

Statistical tests are named, exact p-values are mostly reported (with thresholds stated), effect sizes with 95% CIs are given, software is identified, and data presentation includes per-group n and percentages.

Evidence

direct quote[Methods - Statistical analysis]

“Categorical variables were reported as frequency (percentage) and compared using χ 2 test or Fisher’s test as appropriate. The Wald approximation was used to calculate 95% confidence intervals ... Between group differences were analysed by student’s t test for normally distributed variables and Wilcoxon rank-sum test for non-normally distributed variables.”

direct quote[Results, Table 3]

“Healthy live birth among all patients ... P=0.49 ... Pre-eclampsia among clinical pregnancies ... P=0.02.”

direct quote[Table 3, Table 4]

“Relative ratio (95% CI) ... 1.03 (0.96 to 1.10) ... 0.63 (0.43 to 0.94)”

PASSReviewer 3· 85% conf

Statistical tests are named, software is identified, data presentation is appropriate for a large clinical trial, and a mathematical plausibility check on the primary outcome was performed and confirmed. However, test assumptions are not explicitly verified beyond distributional checks, and exact p-values are not reported for the null primary result (P=0.49 vs 0.025 threshold).

Evidence

paraphrase[Results, Table 3]

“41.6% of 2185 = 909.56, rounds to a whole count of 910; 40.6% of 2191 = 889.546, rounds to 890.”

paraphrase[Results, Table 4]

“P values in Tables 3 and 4 are given as two-decimal numbers (e.g., P=0.49, P=0.02, P=0.004, P<0.001), not as exact three-figure values.”

direct quote[Methods, Statistical analysis]

“Continuous variables were expressed as mean (standard deviation (SD)) or median (interquartile range (IQR)), depending on their distribution, which was tested by visual inspection of histograms and using the Kolmogorov-Smirnov test.”

The data availability statement explicitly states: 'The data underlying the findings in this paper are openly and publicly available at https://github.com/hepingzhangyale/EndometrialPreparation-/tree/main .' This is a concrete route (a repository with a URL). Additionally, 'The code used to analyse the data in the paper can be found in the supplemental files.' Although GitHub is not a permanent, persistent-identifier repository (like Zenodo with a DOI), the statement is concrete and meets the criteria for adequacy in this field. The code is shared in supplemental files. Repository deposit and accession numbers are covered by the GitHub link; no additional accession numbers are needed. The study uses patient-level data which are deposited openly (de-identified).

Sub-criteria

code sharingADEQUATE

accession numbersN/A

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

Data and code are made available: the data are publicly deposited in a GitHub repository, code is provided in supplemental files, and a data availability statement is present.

Evidence

direct quote[Data availability statement]

“The data underlying the findings in this paper are openly and publicly available at https://github.com/hepingzhangyale/EndometrialPreparation-/tree/main”

direct quote[Data availability statement]

“The code used to analyse the data in the paper can be found in the supplemental files.”

PASSReviewer 2· 95% conf

Data and code availability are reported adequately: data are openly available in a GitHub repository, and code is in supplemental files.

Evidence

direct quote[Data availability statement]

“The data underlying the findings in this paper are openly and publicly available at https://github.com/hepingzhangyale/EndometrialPreparation-/tree/main .”

direct quote[Data availability statement]

“The code used to analyse the data in the paper can be found in the supplemental files.”

PASSReviewer 3· 90% conf

A data availability statement is present and includes a concrete access route: a public GitHub repository is named for the data (with a link) and code is in supplemental files. This exceeds the 'adequate' threshold for a clinical trial, where controlled access is acceptable. The statement also provides a contact for problems.

Evidence

direct quote[Data availability statement]

“The data underlying the findings in this paper are openly and publicly available at https://github.com/hepingzhangyale/EndometrialPreparation-/tree/main .”

direct quote[Data availability statement]

“The code used to analyse the data in the paper can be found in the supplemental files.”

The methods are detailed enough for replication (full protocols for both regimens, monitoring, embryo transfer). The trial is registered (ChiCTR2200057990). A CONSORT flow diagram is referenced. All primary and secondary outcomes are reported transparently, including non-significant results. Limitations are discussed: protocol deviations, lack of mechanistic measurements, variability in luteal phase support, and restricted eligibility criteria. Conclusions are proportional: the paper does not overclaim and correctly notes that the results should be confirmed in other populations. Funding sources and grant numbers are listed, and a conflict of interest statement is provided.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

Reporting is comprehensive: the trial is registered, methods are detailed, limitations are discussed, conclusions are proportional to the evidence, and funding and COI are disclosed.

Evidence

direct quote[Abstract]

“Trial registration Chinese Clinical Trial Registry ChiCTR2200057990.”

direct quote[Discussion, Strengths and limitations paragraph]

“Firstly, the proportion of protocol deviations (nearly 15% in each group)… may bias the results… Secondly, as we did not measure the factors secreted by the corpus luteum, we could not directly explain the mechanisms…”

direct quote[Funding and Competing interests sections]

“This trial was funded by grants from the National Natural Science Foundation of China (32588201, 82421004, and 82495194)… RSL reports consulting for Bayer, Organon, Celmatix, Ferring, and Exeltis.”

PASSReviewer 2· 90% conf

Methods are detailed, trial is registered, outcomes are reported, limitations are discussed, conclusions are proportional, and funding/COI are stated.

Evidence

direct quote[Abstract, Methods]

“Trial registration Chinese Clinical Trial Registry ChiCTR2200057990.”

direct quote[Discussion - Strengths and limitations]

“Several limitations also need to be mentioned. Firstly, the proportion of protocol deviations (nearly 15% in each group) ... may bias the results.”

direct quote[Funding, Competing interests]

“This trial was funded by grants from the National Natural Science Foundation of China (32588201, 82421004, and 82495194) ... All authors have completed the ICMJE uniform disclosure form ... declare: RSL reports consulting for Bayer, Organon, Celmatix, Ferring, and Exeltis.”

PASSReviewer 3· 90% conf

The paper demonstrates high reporting completeness: methods are detailed enough for replication, the trial is registered (ChiCTR2200057990), reporting guidelines are implied by the use of CONSORT-like flow diagram (Figure 1), all pre-specified primary and secondary outcomes are reported, limitations are thoroughly discussed, conclusions are proportional to the evidence, and funding/COI are declared.

Evidence

direct quote[Abstract]

“Trial registration Chinese Clinical Trial Registry ChiCTR2200057990.”

paraphrase[Discussion, Strengths and limitations]

“The limitations section explicitly mentions the high protocol deviation rate, the lack of measurement of corpus luteum factors, non-standardised luteal phase support, and restrictive eligibility criteria.”

direct quote[Funding, Competing interests]

“This trial was funded by grants from the National Natural Science Foundation of China (32588201, 82421004, and 82495194) and National Key Research and Development Programme of China (2022YFC2703502 and 2023YFC2705502).”

4 copyedit issues flagged: mostly consistency, clarity.

Checked 35 references: 35 verified.

Reproducibility

1 data/code link checked; 1 live.

Registered (7 IDs: ClinicalTrials.gov, Chinese Clinical Trial Registry). Reporting guideline cited: CONSORT.

Adcurare Rigor Action ItemsFinal pass before journal submission

The manuscript is ready to submit after addressing the minor reporting gaps and copyedit issues listed in the action items. No substantive methodological flaws were identified.

1.
HIGHreporting
Add an explicit statement of compliance with the Declaration of Helsinki in the Ethics section (e.g., 'This trial was conducted in accordance with the Declaration of Helsinki').
Regulatory compliance is currently implied but not explicitly stated, which is a minor reporting gap that reviewers may flag.
2.
HIGHstatistics
Report exact p-values (e.g., P=0.024, P=0.037) rather than rounded values (P=0.02, P=0.004) in Tables 3 and 4 for secondary outcomes.
Exact p-values are a standard reporting requirement and improve transparency and reproducibility.
3.
HIGHreporting
Formally state adherence to the CONSORT reporting guideline in a 'Reporting' subsection of the Methods (e.g., 'This trial is reported in accordance with the CONSORT 2010 statement').
Although the paper follows CONSORT structure, explicitly citing the guideline is a standard requirement for clinical trial reports.
4.
HIGHstatistics
Explicitly state that the assumptions of the statistical tests (e.g., normality and equal variance for t-tests) were met, or describe any violations and corrections applied, in the Statistical analysis section.
Assumption verification is currently reported as 'reported_but_inadequate' because equal variance is not explicitly addressed; a brief sentence will satisfy this criterion.
5.
HIGHreporting
Clarify the handling of the three patients with live birth at 27 weeks (Table 3 footnote) — either correct the definition of live birth (≥28 weeks) or explain the data handling rule that includes them.
The copyedit flagged an inconsistency between the live birth definition (≥28 weeks) and the inclusion of 27-week deliveries; this needs resolution for internal consistency.
6.
MEDIUMreporting
Describe the data safety monitoring board and stopping rules, or note that none were used, in the Methods section for completeness of trial oversight.
This is a standard element of clinical trial reporting that is currently missing; adding it will strengthen the study design description.
7.
MEDIUMreporting
Provide a brief justification for the open-label design (patients and doctors not blinded) in the Methods, e.g., practicality of the intervention.
Transparency about the lack of patient/doctor blinding helps readers assess potential bias.
8.
MEDIUMstatistics
Describe how outliers in continuous outcomes (e.g., birth weight) were identified and handled, or state that none were excluded, in the Statistical analysis section.
Outlier handling is currently marked as 'reported_but_inadequate'; a brief statement will address this gap.
9.
MEDIUMdata code
Consider depositing the dataset and code in a persistent repository (e.g., Zenodo, Dryad) with a DOI to ensure long-term accessibility beyond the GitHub repository.
GitHub repositories may change or become unavailable; a persistent identifier ensures permanent access and is preferred by many journals.
10.
LOWreporting
Report race/ethnicity data in baseline characteristics (Table 1) to enhance generalisability, or state that it was not collected and explain why.
Race/ethnicity is not currently reported; while the study population is homogeneous, this information can help readers assess generalisability.
11.
LOWcopyedit
Rephrase the Table 3 footnote about 'Thirty patients with natural conception were included in the numerator' for clarity, e.g., 'were included in the primary analysis numerator'.
The copyedit flagged minor ambiguity; a small rephrasing will improve clarity.
12.
LOWcopyedit
Add a reference to the supplementary tables where the per-protocol and subgroup analyses are shown, as suggested by the copyedit.
This minor addition will improve clarity and help readers locate the supporting results.

Full text (62,299 chars)Analyzed: Jul 7, 2026

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Natural ovulation versus programmed regimens before frozen embryo transfer in ovulatory women: multicentre, randomised clinical trial.

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Journal

DOI

10.1136/bmj-2025-087045

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