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Kaimen Rigor review

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

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

DOI: 10.1136/bmj-2025-087045
Record issued: 2026-08-10
Engine: 7.29.0
Exported: 2026-09-21

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/7024dbe7-c476-4b01-a4df-592937749b61 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

3.5 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ReportingEthical approvals partially met−0.25★
ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.29.0Source: full text

Not verified in this report

No data or code availability links were detected to verify.

Findings by category

101ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 103AuthenticityData authenticity concerns 204DisclosureReporting gaps 05AvailabilityNone found · partly checked 06Copyedit7 minor suggestions

This Kaimen Rigor review uses Kaimen 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, adequately powered multicentre randomised trial comparing natural vs programmed endometrial preparation for frozen embryo transfer. Methods, blinding, power, and outcome reporting are strong, and the statistical verification found no arithmetic errors. The main weaknesses are reporting gaps: a truncated data-availability URL, supplemental-only code, a missing CONSORT checklist statement, threshold-only p-values, and an over-claim of equivalence without a non-inferiority margin.

Both reviewers rated six dimensions pass and two warn; we downgraded statistical analysis to warn because the rubric treats threshold-only p-values (P<0.001) as imprecise reporting despite the reviewers' pass ratings. No demonstrable arithmetic errors were found; statistics verification recomputed 10 tests, all consistent. Citation check found no retracted or unresolved references.

Numerical inconsistencies

1 finding · worst low

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

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

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .490 · recomputed p = .490Reviewer 1
Primary outcome healthy live birth: chi-square comparison of 910/2185 versus 890/2191
“In the intention-to-treat analysis, 910 (41.6%) of 2185 patients in the natural ovulation regimen group and 890 (40.6%) of 2191 in the programmed regimen group had a healthy live birth (difference between groups 1.0% (95% CI −1.9% to 3.9%); relative ratio 1.03 (95% CI 0.96 to 1.10); P=0.49).”
Find in source
Taken as given: 910 and 890 are the event counts in the two groups; 2185 and 2191 are the corresponding group totals; The test is a two-tailed Pearson chi-square test with 1 degree of freedom; No continuity correction is applied, matching SAS default for chi-square
Method: Two-tailed Pearson chi-square computed from the 2x2 cell counts.
How we recomputed it: pChi2x2(910, 2185-910, 890, 2191-890)
CONSISTENTreported p = .020 · recomputed p = .024Reviewer 1
Coprimary safety outcome pre-eclampsia among clinical pregnancies: 38/1302 versus 61/1326
“The risk of pre-eclampsia was lower in the natural ovulation regimen group among patients who achieved clinical pregnancy than in the programmed regimen group (2.9% (38 of 1302) v 4.6% (61 of 1326); 0.63 (0.43 to 0.94); P=0.02).”
Find in source
Taken as given: 38 and 61 are the pre-eclampsia event counts among clinical pregnancies; 1302 and 1326 are the clinical pregnancy denominators; The p-value corresponds to a two-tailed Pearson chi-square test with continuity correction not applied
Method: Two-tailed Pearson chi-square computed from the 2x2 cell counts.
How we recomputed it: pChi2x2(38, 1302-38, 61, 1326-61)
CONSISTENTreported p = .020 · recomputed p = .024Reviewer 1
Secondary outcome first trimester pregnancy loss: 158/1302 versus 201/1326
“the natural ovulation regimen group had lower risks of first trimester pregnancy loss compared with the programmed regimen group (12.1% (158 of 1302) v 15.2% (201 of 1326); relative ratio 0.80 (0.66 to 0.97); P=0.02)”
Find in source
Taken as given: 158 and 201 are first trimester pregnancy loss counts; 1302 and 1326 are the clinical pregnancy denominators; The p-value is two-tailed from Pearson chi-square without continuity correction
Method: Two-tailed Pearson chi-square computed from the 2x2 cell counts.
How we recomputed it: pChi2x2(158, 1302-158, 201, 1326-201)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Secondary outcome postpartum haemorrhage among all deliveries: 22/1117 versus 67/1100
“postpartum haemorrhage (2.0% (22 of 1117) v 6.1% (67 of 1100); 0.32 (0.20 to 0.52); P<0.001)”
Find in source
Taken as given: 22 and 67 are postpartum haemorrhage event counts among all deliveries; 1117 and 1100 are the delivery denominators; The reported p is a threshold (<0.001) and the recomputed two-tailed Pearson chi-square p is far below 0.001
Method: Two-tailed Pearson chi-square computed from the 2x2 cell counts.
How we recomputed it: pChi2x2(22, 1117-22, 67, 1100-67)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Cycle cancellation during first attempt at endometrial preparation: 354/2185 versus 251/2191
“The natural ovulation regimen group had a higher rate of cancellation during the first attempt of endometrial preparation than the programmed regimen group (16.2% (354 of 2185) v 11.5% (251 of 2191)), mainly because of no follicle development or arrested follicle development”
Find in source
Taken as given: 354 and 251 are cycle cancellation counts; 2185 and 2191 are the randomized group totals; The p-value for this comparison is reported elsewhere as P<0.001 in Table 2; The recomputed two-tailed Pearson chi-square p is far below 0.001
Method: Two-tailed Pearson chi-square computed from the 2x2 cell counts.
How we recomputed it: pChi2x2(354, 2185-354, 251, 2191-251)
CONSISTENTreported p = .490 · recomputed p = .395Reviewer 2
Healthy live birth relative ratio CI implies p=0.49
“910 (41.6%) of 2185 patients in the natural ovulation regimen group and 890 (40.6%) of 2191 in the programmed regimen group had a healthy live birth (difference between groups 1.0% (95% CI −1.9% to 3.9%); relative ratio 1.03 (95% CI 0.96 to 1.10); P=0.49)”
Find in source
Taken as given: The 1.03 is the relative ratio estimate and 0.96-1.10 its 95% CI; The CI is two-sided at 95% and the p-value is two-sided; The RR is analysed on the log scale
Method: Recovered the two-sided p-value from the log-RR and its 95% CI via the normal approximation (pCI with log=1).
How we recomputed it: pCI(1.03, 0.96, 1.10, 1)
CONSISTENTreported p = .020 · recomputed p = .021Reviewer 2
Pre-eclampsia among clinical pregnancies RR CI implies p=0.02
“the natural ovulation regimen group had a lower risk of pre-eclampsia among those who achieved clinical pregnancy (2.9% (38 of 1302) v 4.6% (61 of 1326), P=0.02), with a difference between groups of −1.7% (95% CI −3.1% to −0.2%) and a relative ratio of 0.63 (95% CI 0.43 to 0.94)”
Find in source
Taken as given: The 0.63 is the relative ratio estimate and 0.43-0.94 its 95% CI; The CI is two-sided at 95% and the p-value is two-sided; The RR is analysed on the log scale
Method: Recovered the two-sided p-value from the log-RR and its 95% CI via the normal approximation (pCI with log=1).
How we recomputed it: pCI(0.63, 0.43, 0.94, 1)
CONSISTENTreported p = .020 · recomputed p = .024Reviewer 2
Pre-eclampsia cell-count chi-square (38/1302 vs 61/1326)
“Pre-eclampsia among clinical pregnancies | 38/1302 (2.9) | 61/1326 (4.6) | −1.7 (−3.1 to −0.2) | 0.63 (0.43 to 0.94) | 0.02”
Find in source
Taken as given: 38 and 61 are the event counts for the natural and programmed groups respectively; 1302 and 1326 are the group totals (clinical pregnancies) so non-events are 1264 and 1265; df = 1 because the table is 2x2; Pearson chi-square test was used
Method: Pearson chi-square on the 2x2 table of cell counts, two-tailed p on 1 df.
How we recomputed it: pChi2x2(38, 1264, 61, 1265)
CONSISTENTreported p = .001 · recomputed p = .001Reviewer 2
Caesarean delivery cell-count chi-square (776/1117 vs 831/1100)
“Caesarean delivery among all deliveries | 776/1117 (69.5) | 831/1100 (75.6) | −6.1 (−9.8 to −2.4) | 0.92 (0.87 to 0.97) | 0.001”
Find in source
Taken as given: 776 and 831 are the caesarean counts for the natural and programmed groups respectively; 1117 and 1100 are the group totals (all deliveries) so non-caesarean are 341 and 269; df = 1 because the table is 2x2; Pearson chi-square test was used
Method: Pearson chi-square on the 2x2 table of cell counts, two-tailed p on 1 df.
How we recomputed it: pChi2x2(776, 341, 831, 269)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Postpartum haemorrhage cell-count chi-square (22/1117 vs 67/1100)
“Postpartum haemorrhage among all deliveries | 22/1117 (2.0) | 67/1100 (6.1) | −4.1 (−5.8 to −2.5) | 0.32 (0.20 to 0.52) | <0.001”
Find in source
Taken as given: 22 and 67 are the postpartum haemorrhage counts for the natural and programmed groups respectively; 1117 and 1100 are the group totals (all deliveries) so non-events are 1095 and 1033; df = 1 because the table is 2x2; Pearson chi-square test was used
Method: Pearson chi-square on the 2x2 table of cell counts, two-tailed p on 1 df; reported as <0.001.
How we recomputed it: pChi2x2(22, 1095, 67, 1033)

lowinternal contradiction
The Discussion states 'the approximate 40% reduction in risk of developing pre-eclampsia' while the pre-eclampsia relative ratio is 0.63 (a 37% reduction); this is a minor rounding overstatement, not a substantive inconsistency.
“the approximate 40% reduction in risk of developing pre-eclampsia would have even greater impact on public health”
ConclusionFind in source

Overstated conclusions

1 finding · worst low

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Conclusions only partially backed by the presented evidenceAssessed

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

partialReviewers 1, 2
A natural ovulation regimen was as effective as a programmed regimen for achieving a healthy live birth after frozen embryo transfer.
The data show no statistically significant difference, but the trial was designed for superiority and no non-inferiority margin was pre-specified, so 'as effective' is a stronger claim than the design supports.
Evidence: Primary outcome: 910 (41.6%) of 2185 versus 890 (40.6%) of 2191; difference 1.0% (95% CI −1.9% to 3.9%); relative ratio 1.03 (95% CI 0.96 to 1.10); P=0.49.
“In ovulatory women, a natural ovulation regimen for endometrial preparation was as effective as programmed regimen in terms of achieving a healthy live birth after frozen embryo transfer, but with a lower risk of maternal complications during pregnancy.”
ConclusionFind in source
partialReviewer 2
The authors recommend a natural ovulation regimen based on its safety profile, especially for patients at high risk of hypertensive disorders of pregnancy.
The safety findings support prioritising the natural regimen, but the recommendation extends beyond the primary evidence; several supporting secondary outcomes were not adjusted for multiplicity (acknowledged by the authors), so the recommendation is reasonable but somewhat beyond the confirmatory evidence.
Evidence: Lower risks of pre-eclampsia and other maternal complications in the natural regimen; authors note secondary outcomes 'should not be interpreted as conferring statistical significance'.
“Therefore, we recommend a natural ovulation regimen based on its safety profile, especially for patients at high risk of hypertensive disorders of pregnancy, such as patients aged 38 years or older and those with obesity.”
ConclusionFind in source
supportedReviewer 1
The natural ovulation regimen reduced the risk of pre-eclampsia among patients who achieved clinical pregnancy.
The comparison is directly reported, statistically significant at the prespecified 0.025 level for the coprimary outcome, and consistent with adjusted and per-protocol analyses.
Evidence: Pre-eclampsia among clinical pregnancies: 2.9% (38 of 1302) v 4.6% (61 of 1326); relative ratio 0.63 (95% CI 0.43 to 0.94); P=0.02.
“The risk of pre-eclampsia was lower in the natural ovulation regimen group among patients who achieved clinical pregnancy than in the programmed regimen group (2.9% (38 of 1302) v 4.6% (61 of 1326); 0.63 (0.43 to 0.94); P=0.02).”
AbstractFind in source
supportedReviewer 1
The natural ovulation regimen lowered risks of early pregnancy loss, placenta accreta spectrum, caesarean section, and postpartum haemorrhage.
Each comparison is reported with a confidence interval excluding 1; the authors appropriately caution that no multiplicity adjustment was made for secondary outcomes.
Evidence: Early pregnancy loss RR 0.80 (0.66–0.97); placenta accreta spectrum RR 0.51 (0.31–0.83); caesarean section RR 0.92 (0.87–0.97); postpartum haemorrhage RR 0.32 (0.20–0.52).
“The incidences of early pregnancy loss (12.1% (158 of 1302) v 15.2% (201 of 1326); 0.80 (0.66 to 0.97)), placental accreta spectrum (1.8% (24 of 1302) v 3.6% (48 of 1326); 0.51 (0.31 to 0.83)), caesarean section (69.5% (776 of 1117) v 75.6% (831 of 1100); 0.92 (0.87 to 0.97)), and postpartum haemorrhage (2.0% (22 of 1117) v 6.1% (67 of 1100); 0.32 (0.20 to 0.52)) were lower in the natural ovulation regimen group.”
AbstractFind in source
supportedReviewer 1
The rate of cycle cancellation was higher with the natural ovulation regimen.
The difference is large, directly reported, and highly significant.
Evidence: 16.2% (354 of 2185) v 11.5% (251 of 2191); P<0.001.
“The rate of cycle cancellation was higher in the natural ovulation regimen (16.2% (354 of 2185) v 11.5% (251 of 2191), P<0.001).”
AbstractFind in source
supportedReviewer 1
The study provides proof of concept that a preconception intervention can lower maternal morbidity later in pregnancy.
This is a reasonable interpretation of the observed reductions in pregnancy complications, framed as proof of concept rather than a mechanism demonstration.
Evidence: Significant reductions in hypertensive disorders of pregnancy, pre-eclampsia, placenta accreta spectrum, and postpartum haemorrhage in the natural ovulation group.
“Our study provides proof of concept that an intervention started before conception can lower maternal morbidity later in pregnancy.”
DiscussionFind in source
supportedReviewer 2
The natural ovulation regimen carried a lower risk of pre-eclampsia.
The coprimary safety outcome was significantly lower (RR 0.63 (0.43 to 0.94), P=0.02, below the 0.025 threshold), and eclampsia was not observed.
Evidence: Pre-eclampsia among clinical pregnancies: 2.9% (38/1302) vs 4.6% (61/1326); relative ratio 0.63 (0.43 to 0.94); P=0.02.
“the natural ovulation regimen group had a lower risk of pre-eclampsia among those who achieved clinical pregnancy (2.9% (38 of 1302) v 4.6% (61 of 1326), P=0.02)”
ResultsFind in source
supportedReviewer 2
Risks of early pregnancy loss, hypertensive disorders of pregnancy, placenta accreta spectrum, caesarean section, and postpartum haemorrhage were lower in the natural ovulation regimen group.
Each of these secondary outcomes showed a statistically significant reduction with the natural regimen, as reported in the results and tables.
Evidence: First-trimester pregnancy loss RR 0.80 (0.66-0.97); hypertensive disorders RR 0.69 (0.53-0.89); placenta accreta spectrum RR 0.51 (0.31-0.83); caesarean RR 0.92 (0.87-0.97); postpartum haemorrhage RR 0.32 (0.20-0.52).
“The natural ovulation regimen group also had a lower likelihood of caesarean delivery (69.5% (776 of 1117) v 75.6% (831 of 1100); 0.92 (0.87 to 0.97); P=0.001) and postpartum haemorrhage (2.0% (22 of 1117) v 6.1% (67 of 1100); 0.32 (0.20 to 0.52); P<0.001)”
ResultsFind in source
supportedReviewer 2
Birth weight and risks of neonatal complications did not differ between the two regimens.
The reported comparisons for birth weight, large/small-for-gestational-age, and neonatal complications showed no statistically significant differences.
Evidence: Singleton birth weight 3349 vs 3380 g (P=0.16); neonatal complications such as congenital anomalies (RR 0.86 (0.60-1.23), P=0.41) were non-significant.
“We also found no differences in birth weight or incidences of large-for-gestational-age infants, small-for-gestational-age infants, neonatal complications, or congenital anomalies”
Table 4Find in source

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

ADEQUATESurrogate endpoint
The primary efficacy claim is based on hard clinical outcomes: healthy live birth (a composite of singleton live birth at ≥37 weeks, normal birth weight, no major congenital anomalies) and pre-eclampsia (a clinical diagnosis per ACOG criteria). These are not surrogate endpoints.
“Primary outcomes were a healthy live birth and pre-eclampsia or eclampsia after a frozen embryo transfer.”
Find in source
ADEQUATEEffect size
The primary effect size for pre-eclampsia is a relative ratio of 0.63 (95% CI 0.43 to 0.94) with an absolute risk reduction of 1.7% (from 4.6% to 2.9%). The authors explicitly anchor this as clinically relevant, comparing it to the 15% reduction from aspirin and noting the impact on long-term health.
“Given the impact of pre-eclampsia on the long term health of mothers and children and that women undergoing in vitro fertilisation are at increased risk of pre-eclampsia, even this modest reduction in risk has clinical relevance.”
Find in source

Data authenticity concerns

1 finding · worst low

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Other integrity concernAssessed

2 integrity concerns flagged (0 high).

lowother
The public data URL is truncated in the manuscript ('https://githu'), so the stated access route is incomplete; this is a reporting defect rather than a validity issue.
“The data underlying the findings in this paper are openly and publicly available at https://githu”
Data availabilityFind in source

Reporting gaps

2 findings · worst medium

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Data/code availability incompleteAssessed
Ethics/consent reporting incompleteAssessed

Eight Dimensions6 pass · 2 warn

Prior work is cited in the form of previous randomised trials and observational studies/meta-analyses; their main weakness (insufficient power for obstetric complications; residual confounding) is explicitly acknowledged. The rationale links the observational associations to a testable hypothesis about a natural ovulation regimen improving healthy live birth and reducing pre-eclampsia. The limitations of prior research are directly addressed by designing a large, adequately powered randomised trial.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The introduction clearly establishes the clinical controversy, cites prior randomised trials and observational studies, and uses their limitations to justify the trial hypothesis.

Evidence

“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.”

IntroductionFind in source

“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.”

IntroductionFind in source

“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.”

IntroductionFind in source

PASSReviewer 2· 90% conf

The scientific premise is well established: prior observational studies and underpowered trials are cited, and a clear hypothesis is presented.

Evidence

Introduction ¶2Find in source

“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.”

IntroductionFind in source

Introduction ¶2Find in source

Randomisation was stratified by study site with variable block sizes of two, four, and six, generated by a data coordinating centre and delivered through an online central platform. Patients and doctors were unmasked, but outcome assessors were blinded. The power calculation covers both primary outcomes and includes inflation for 10% dropout. Inclusion/exclusion criteria are detailed, and the analysis population is clearly defined (ITT with explicit handling of no-transfer and lost-to-follow-up patients, plus per-protocol analyses). Bench-science criteria (biological vs technical replicates, wet-lab controls, independent replication) are not applicable to a human RCT.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The trial is methodologically strong: central stratified block randomisation, assessor blinding, explicit power calculations, detailed inclusion/exclusion criteria, and prespecified ITT and per-protocol analyses.

Evidence

“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.”

MethodsFind in source

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

MethodsFind in source

“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.”

Statistical analysisFind in source

PASSReviewer 2· 90% conf

Core design elements—randomisation, blinding, sample-size calculation, pre-specified eligibility, and analysis-population handling—are all adequately described.

Evidence

MethodsFind in source

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

MethodsFind in source

“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.”

Statistical analysisFind in source

The study is confined to ovulatory women aged 20-40 (sex inherent to the study question; male participants are ineligible by design, so no single-sex justification is demanded). Table 1 reports age, BMI categories, blood pressure, parity, infertility duration, and other demographics extensively. Species/strain/housing and demographics sub-criteria: species/housing n/a; demographics adequately reported.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 70% conf

The study reports extensive female reproductive and baseline characteristics (age, BMI, parity, blood pressure, chronic hypertension), though race/ethnicity is not explicitly stated.

Evidence

“The trial included women aged 20-40 years with regular menstrual cycles (defined as a menstrual cycle of 24-38 days) who were planning to have a frozen single blastocyst transfer.”

MethodsFind in source

paraphrase[Results; Table 1]

“Baseline patient characteristics were well balanced between the two groups.”

absence[Table 1; entire text]

Race/ethnicity is not explicitly reported

PASSReviewer 2· 85% conf

Sex, age, weight/health status, and human demographics are comprehensively reported; species/housing criteria are not applicable.

Evidence

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

AbstractFind in source

“Mean (SD) age at randomisation (years) | 32.68 (3.92) | 32.67 (3.89)”

Table 1Find in source

The ethics statement names the approving committee and gives an approval ID, and consent is described as written. However, the paper does not name a specific regulatory-compliance framework, which is a reporting gap rather than evidence of misconduct. The dimension is therefore downgraded to warn.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceNOT REPORTED

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A named ethics committee approval with protocol ID and written informed consent are reported, but no named regulatory framework (e.g., Declaration of Helsinki, ICH-GCP) is stated.

Evidence

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

EthicsFind in source

“All patients provided written informed consent.”

EthicsFind in source

absence[Ethics statements]

No named regulatory framework is stated

WARNReviewer 2· 70% conf

Ethics approval with a named committee and ID, and written informed consent, are reported; however, no explicit regulatory-compliance statement (e.g., Declaration of Helsinki) is given.

Evidence

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

EthicsFind in source

“All patients provided written informed consent.”

EthicsFind in source

absence[Ethics statements (entire section)]

No named regulatory compliance framework (e.g., Declaration of Helsinki) stated

The drugs used (dydrogesterone, vaginal progesterone, oral oestrogen, hCG) are named with trade names, manufacturers, doses, and routes, which satisfies the investigational-product identification requirement for a clinical trial. SAS version 9.4 is named. Benchtop resource criteria are not applicable because the trial does not involve wet-lab reagents or cell lines.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational medicinal products are identified with manufacturers and dosing details, and the statistical software is identified with version; no antibodies, cell lines, or organisms are used.

Evidence

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

MethodsFind in source

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

MethodsFind in source

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

Statistical analysisFind in source

PASSReviewer 2· 80% conf

The investigational drugs (oestrogen/progesterone products) are named with manufacturers and dosing, and the analysis software is identified with version.

Evidence

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

MethodsFind in source

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

Statistical analysisFind in source

The paper names chi-square/Fisher tests, Wald confidence intervals, t-tests, Wilcoxon rank-sum tests, and Cochran-Mantel-Haenszel adjustment; normality was assessed by histograms and the Kolmogorov-Smirnov test. Effect estimates are accompanied by 95% CIs throughout. Most p-values are exact, but a few very small ones are reported as P<0.001, which is a minor reporting imprecision. Quick checks of reported proportions in baseline and outcome tables were consistent with the stated denominators.

Sub-criteria

tests namedADEQUATE

exact p valuesINADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical tests are named, distribution checks are described, effect sizes are given with 95% CIs, software is identified, and no arithmetic impossibilities were found; the only minor issue is that some very small p-values are printed as thresholds.

Evidence

“Categorical variables were reported as frequency (percentage) and compared using χ 2 test or Fisher’s test as appropriate.”

Statistical analysisFind in source

“relative ratio 1.03 (95% CI 0.96 to 1.10); P=0.49”

ResultsFind in source

“postpartum haemorrhage (2.0% (22 of 1117) v 6.1% (67 of 1100); 0.32 (0.20 to 0.52); P<0.001)”

Table 4Find in source

PASSReviewer 2· 85% conf

Statistical tests are named, assumptions handling, exact p-values, effect sizes with CIs, software, and data presentation are all adequate; recomputation of key p-values agreed.

Evidence

“910 (41.6%) of 2185 patients in the natural ovulation regimen group and 890 (40.6%) of 2191 in the programmed regimen group had a healthy live birth (difference between groups 1.0% (95% CI −1.9% to 3.9%); relative ratio 1.03 (95% CI 0.96 to 1.10); P=0.49)”

ResultsFind in source

“which was tested by visual inspection of histograms and using the Kolmogorov-Smirnov test”

Statistical analysisFind in source

“Categorical variables were reported as frequency (percentage) and compared using χ 2 test or Fisher’s test as appropriate.”

Statistical analysisFind in source

A data availability statement is present and names a concrete open route ('The data underlying the findings in this paper are openly and publicly available at https://githu...'), but the URL is incomplete in the text. Code is 'found in the supplemental files' (reported_but_inadequate for code_sharing, since no versioned public repo with a permanent identifier is given). repository_deposit is rated adequate on the basis of the stated public availability; accession_numbers n/a for this patient-level trial. Since not all applicable criteria are adequate, the dimension is a warn.

Sub-criteria

code sharingINADEQUATE

accession numbersN/A

repository depositINADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 60% conf

A data availability statement exists and states public availability, but the repository URL is truncated in the text and no persistent identifier/accession is given; code is only mentioned as supplemental files.

Evidence

“The code used to analyse the data in the paper can be found in the supplemental files. The data underlying the findings in this paper are openly and publicly available at https://githu”

Data availabilityFind in source

absence[Data availability statement]

No persistent identifier or accession number is provided

WARNReviewer 2· 70% conf

A data availability statement exists and states data are openly available, but the URL is truncated and the code is only in supplemental files rather than a versioned public repository.

Evidence

“The data underlying the findings in this paper are openly and publicly available at https://githu”

Data availabilityFind in source

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

Data availabilityFind in source

The manuscript includes a CONSORT flow chart, trial registration, detailed methods, funding and COI statements, and transparent reporting of non-significant as well as significant outcomes. Limitations are explicitly discussed. No explicit reference to CONSORT or another reporting checklist is present in the text. The conclusion that the natural regimen 'was as effective' goes slightly beyond the superiority design because no non-inferiority margin was pre-specified.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Methods are detailed, the trial is registered, funding and competing interests are disclosed, outcomes are comprehensively reported, and limitations are discussed; the main gaps are the absence of an explicit CONSORT checklist statement and wording that implies equivalence without a non-inferiority margin.

Evidence

“Trial registration Chinese Clinical Trial Registry ChiCTR2200057990.”

AbstractFind in source

“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).”

FundingFind in source

absence[Entire text]

No explicit reporting checklist is referenced

PASSReviewer 2· 80% conf

Trial registration, CONSORT flow, transparent outcome reporting, limitations, proportional conclusions, and funding/COI are all present; only an explicit reporting-checklist reference is missing.

Evidence

“Trial registration Chinese Clinical Trial Registry ChiCTR2200057990.”

AbstractFind in source

paraphrase[Results, opening paragraph]

“Between July 2022 and November 2023, a total of 6302 patients were screened for eligibility, 4376 of whom were randomised (). Fig 1 CONSORT flow chart”

“This trial was funded by grants from the National Natural Science Foundation of China (32588201, 82421004, and 82495194)”

FundingFind in source

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

ClinicalTrials.gov

NCT04551807

ClinicalTrials.gov

NCT03642665

ClinicalTrials.gov

NCT04310683

Chinese Clinical Trial Registry

ChiCTR2200057990

Chinese Clinical Trial Registry

ChiCTR1900024192

Chinese Clinical Trial Registry

ChiCTR2000031793

Chinese Clinical Trial Registry

ChiCTR2100048138

Reporting guidelines: CONSORT

Broken references and links

None found · partly checked

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.

Checked 35 references by DOI: 34 verified — 1 lookup failed.

NOT CHECKED10.1136/bmj-2022-071653
Hypertensive disorders of pregnancy
[crossref] rate_limited 429 https://api.crossref.org/works/10.1136%2Fbmj-2022-071653?mailto=editorial%40alpha1science.com: HTTP 429

Copyediting

7 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 7 minor suggestions below.

7 copyedit issues flagged: mostly grammar, punctuation, typo.

MINORtypoResults, cycle cancellation sentence
“P<0.001for between group comparison”
→ P<0.001 for between group comparison
Missing space after the p-value.
MINORgrammarTransparency
“The corresponding author affirm that the manuscript is an honest, accurate, and transparent account”
→ The corresponding author affirms that the manuscript is an honest, accurate, and transparent account
Subject-verb agreement error.
MINORotherData availability statement
“openly and publicly available at https://githu”
→ Provide the complete URL or a DOI/repository identifier
The URL is truncated and cannot be resolved as printed.
MINORpunctuationAuthor list
“Geng Ling chief nurse, Sun Mei doctor Li Xiufang doctor”
→ Separate names and roles consistently with commas or semicolons
Roles and names run together without separators.
MINORgrammarTransparency section
“The corresponding author affirm that the manuscript is an honest”
→ The corresponding author affirms that the manuscript is an honest
Subject-verb agreement: 'author' is singular, so 'affirms' is required.
MINORpunctuationTable 2 footnote
“P<0.001for between group comparison”
→ P<0.001 for between group comparison
Missing space after the p-value.
MINORclarityData availability statement
“openly and publicly available at https://githu”
→ Provide the complete URL (e.g., https://github.com/...)
The URL is truncated mid-string, making the access route unusable as printed.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published trial is methodologically robust and its headline conclusions are supported by the data; an informed reader should weigh the minor reporting gaps (truncated data URL, supplemental-only code, missing CONSORT checklist statement, threshold p-values, and the equivalence wording) as documentation issues rather than validity threats. No erratum appears warranted for the core results, but the authors should correct the truncated URL and temper the 'as effective' wording.

1.
HIGHdata code
Complete the data availability statement by providing the full, resolvable repository URL (e.g., https://github.com/...) and add a persistent identifier (DOI/accession) for the dataset.
The truncated URL ('https://githu') makes the stated access route unusable as printed.
2.
HIGHdata code
Deposit the analysis code in a version-controlled public repository with a permanent identifier (e.g., Zenodo/GitHub DOI) instead of only supplemental files.
Supplemental-only code lacks a stable, citable identifier for reproducibility.
3.
HIGHreporting
Explicitly state adherence to CONSORT and include the completed CONSORT checklist (or a statement of where it can be found).
Only a flow diagram is present; the checklist is the reporting-guideline element reviewers expect.
4.
HIGHreporting
Temper the conclusion that the natural regimen 'was as effective' to 'no statistically significant difference was found', or pre-specify and report a non-inferiority margin.
The superiority design cannot support an equivalence claim without a pre-specified non-inferiority margin.
5.
HIGHethics
Add an explicit statement of compliance with a regulatory framework (e.g., Declaration of Helsinki or ICH-GCP) in the Ethics statements section.
Ethics approval and consent are reported, but no named compliance framework is given.
6.
HIGHstatistics
Replace threshold-only p-values (P<0.001) with exact values (or state that exact values are in supplementary tables) for the outcomes reported as thresholds.
Threshold-only p-values are treated as imprecise reporting and prevent a clean statistical pass.
7.
MEDIUMreporting
Add an explicit statement on race/ethnicity in Table 1 (or state that all participants were of a single racial/ethnic group).
Demographics are extensive but race/ethnicity is not explicitly reported.
8.
MEDIUMcopyedit
Fix the missing space in 'P<0.001for' (Results and Table 2 footnote) and correct 'The corresponding author affirm' to 'affirms'.
Copyedit issues are minor but should be corrected in any revision.
9.
MEDIUMcopyedit
Separate names and roles in the author list with consistent punctuation (e.g., 'Geng Ling, chief nurse; Sun Mei, doctor; Li Xiufang, doctor').
Author roles and names run together without separators.
10.
LOWother
Correct the Discussion's 'approximate 40% reduction' to the actual 37% (RR 0.63) for pre-eclampsia.
The integrity lens flagged a minor rounding overstatement.

Full text (52,431 chars)Analyzed: Aug 10, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

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

DOI

10.1136/bmj-2025-087045

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-21