Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.

Name: Kaimen Rigor review — IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.
Item: IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.
Rating: 39
Author: Alpha1

Berntsen S, Zedeler A, Nøhr B, Rønn Petersen M, Grøndahl ML, Andersen LF, Løssl K, Løkkegaard E, Englund AL, Vestergaard Gabrielsen A, Prætorius L, Behrendt-Møller I, Langhoff Thuesen L, Vomstein K, Petri Lauritsen M, Ivanoska Trajcevski A, Frøding Skipper D, Westergaard D, Pinborg A, Svarre Nielsen H, la Cour Freiesleben N

Paper source

Read full text (PMC)

Embed this Rigor badge

Kaimen Rigor review — 1★ (Critical), 2 critical, 3 high issues for “IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.”

Links back to this Kaimen Rigor review.

Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 15, 2026

Read alongside

IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.

Read full text (PMC)

DOI

10.1038/s41591-025-03621-x

Share this Kaimen Rigor review

Post on X Share on LinkedIn Share via Email

Embed this Rigor badge

<a href="https://alpha1science.com/verify/05073aa1-5099-474e-b7eb-ffcfc054f8a0" target="_blank" rel="noopener">
  <img src="https://alpha1science.com/verify/05073aa1-5099-474e-b7eb-ffcfc054f8a0/badge" alt="Kaimen Rigor review — 1★ (Critical), 2 critical, 3 high issues for “IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.”" width="440" height="104" style="max-width:100%;height:auto" />
</a>

Every embed links back to this Kaimen Rigor review.

Record fingerprint

0612c02df54119fcbc7d3ebe1af51e0d7d239084808ef8b140dc71441bce4057

Verify via API

Issued Aug 15, 2026Engine 7.39.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Alpha¹ by Kaimen

Fetching the latest research

Kaimen Rigor reviewed

Rigor-Reviewed Manuscript

IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.

Paper source

IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.

Read full text (PMC)

Embed this Rigor badge

Links back to this Kaimen Rigor review.

Alpha1 Editorial

This rigor review was examined and confirmed by Alpha1 Editorial · August 15, 2026

Kaimen Rigor review

Kaimen Rigor reviewed

1 / 5

Critical — a demonstrable failure

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

StatisticsImpossible or misreported statistic ×2−2★
IntegrityIntegrity concern ×2−1★
CitationsCitations & links (capped) ×8−1★
StatisticsPrinted percentage does not match its own count (capped) ×4−0.25★

Citations & links are capped at −1★ combined, however many are flagged.

A demonstrable critical failure caps the rating at the minimum, regardless of the deductions above.

Model-reported confidence: moderateReviewer agreement: lowEngine: 7.39.0Source: full text

Biggest issues2 demonstrable

01Printed percentage does not match its own countdemonstrable
criticalArithmeticrecomputedFull detail
68.5% does not match the reported count 242/414
“242/414 (68.5%)”
Find in source
02Printed percentage does not match its own countdemonstrable
criticalArithmeticrecomputedFull detail
2.9% does not match the reported count 3/179
“3/179 (2.9%)”
Find in source
03Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
16.4% does not match the reported count 67/414
“67/414 (16.4%)”
Find in source
04Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
5.3% does not match the reported count 10/193
“10/193 (5.3%)”
Find in source
05Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
2.1% does not match the reported count 4/179
“4/179 (2.1%)”
Find in source
06Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
1.3% does not match the reported count 3/179
“3/179 (1.3%)”
Find in source

Findings by category

301ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 105AvailabilityBroken references and links 06Copyedit6 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 multicenter RCT comparing ICSI versus c-IVF, with strong ethical approvals, detailed biological variable reporting, and a concrete data availability statement. The main weaknesses are the open-label design, lack of explicit CONSORT reporting, and some statistical inconsistencies that could not be fully verified.

All three reviewers agreed on study type (interventional). The synthesis weighed the reviewers' divergent ratings, with specific evidence from the statistics verification component (6/9 inconsistent recomputations) and copyedit issues (denominator errors) influencing the final statuses. N/A dimensions were excluded from scoring.

Numerical inconsistencies

3 findings · worst critical

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.

Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
Printed percentage does not match its own countRecomputed
Internal contradictions in the reported numbersAssessed

Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks. 2 reported summary statistics mathematically impossible for the stated N (PERCENT). 4 printed percentages that do not match their own count.

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

7 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

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

Data authenticity concerns

None found

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.

Checked — nothing surfaced.

Reporting gaps

None found

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.

Checked — nothing surfaced.

Eight Dimensions8 pass

The introduction cites prior retrospective studies and two Asian RCTs, acknowledges the debate and lack of evidence for ICSI in non-male factor infertility, and clearly links the premise to the study's objective of comparing CLBR. Limitations of prior work (e.g., retrospective designs, use of cleavage-stage transfers) are addressed in the discussion.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The premise is well established with extensive citation of prior work, but the paper does not explicitly acknowledge weaknesses or limitations of the cited prior studies.

Evidence

paraphrase[Introduction, paragraph 2]

“Paraphrase: Recently, two randomized controlled trials (RCTs) conducted in Asia found no improvement in live birth rate after the first embryo transfer when comparing ICSI with c-IVF among couples with normal sperm parameters and those with nonsevere male factor infertility, respectively.”

“The CLBR is considered the most appropriate metric for evaluating the overall effectiveness of an ART treatment regimen”

Introduction ¶3Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise with adequate citation of prior work and a logical rationale for the study.

Evidence

“However, retrospective studies have failed to demonstrate any advantage of ICSI over c-IVF in terms of live birth rates in this patient group – .”

Introduction ¶2Find in source

“This European contribution provides new insights by focusing on key aspects—targeting first-cycle patients, emphasizing blastocyst transfers and elective single embryo transfers (eSET) to minimize multiple pregnancies and using cumulative live birth rate (CLBR) as the primary outcome measure.”

Introduction ¶3Find in source

“These results are consistent with the outcomes of prior RCTs from other countries ,, , as well as large retrospective studies –, and a recently updated Cochrane systematic review and meta-analysis .”

Discussion ¶1Find in source

PASSReviewer 3· 90% conf

The paper establishes a clear scientific premise with extensive prior work and a logical rationale for the study.

Evidence

“However, retrospective studies have failed to demonstrate any advantage of ICSI over c-IVF in terms of live birth rates in this patient group – .”

Introduction ¶2Find in source

“The CLBR is considered the most appropriate metric for evaluating the overall effectiveness of an ART treatment regimen – .”

Introduction ¶3Find in source

Randomization method (computer-generated, permuted blocks, stratified by site and age) and unit (participant) are clearly described. Blinding is not performed but a rationale is provided. Power analysis is reported with effect size, alpha, and power. Inclusion/exclusion criteria are pre-specified. Outlier handling is addressed via ITT and per-protocol analyses. Controls are inherent in the comparator arm. Independent replication is not applicable for a single pivotal trial.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

The trial is well-designed with adequate randomization, stratification, and a pre-specified primary outcome, but the lack of blinding and the timing of randomization (after the ovulation trigger) introduce potential performance bias.

Evidence

“For the randomization process, a statistician who was not involved in any other parts of the study devised a computer-generated randomization scheme, maintaining a 1:1 ratio between the two arms (c-IVF and ICSI). Randomization involved permuted blocks of varying sizes, ranging from 4 to 12. It was stratified by trial site and female age, categorized into the following three age groups: 18–25 years, 26–37 years and 38–42 years.”

MethodsFind in source

“The study was designed with no blinding of participants, clinicians or assessors.”

MethodsFind in source

“The primary outcome was the CLBR, defined as at least one live birth after completing an ART cycle”

MethodsFind in source

PASSReviewer 2· 95% conf

The trial design is rigorous with adequate randomization, blinding rationale, power analysis, and inclusion/exclusion criteria.

Evidence

MethodsFind in source

“The study was designed as a superiority trial with 80% power and a 5% significance level for a two-sided test, aiming to detect a 10% point difference in CLBR.”

Statistical analysisFind in source

“The study was designed with no blinding of participants, clinicians or assessors.”

MethodsFind in source

PASSReviewer 3· 95% conf

The trial design is rigorous with adequate randomization, blinding considerations, power analysis, and pre-specified inclusion/exclusion criteria.

Evidence

“Randomization involved permuted blocks of varying sizes, ranging from 4 to 12. It was stratified by trial site and female age, categorized into the following three age groups: 18–25 years, 26–37 years and 38–42 years.”

MethodsFind in source

“The study was designed as a superiority trial with 80% power and a 5% significance level for a two-sided test, aiming to detect a 10% point difference in CLBR.”

Statistical analysisFind in source

“Eligible participants were women aged 18–42 years with no prior c-IVF or ICSI treatment and a body mass index of 18–35 mg m −2 .”

MethodsFind in source

The paper reports female age, BMI, ethnicity, and infertility cause, and male partner age, BMI, and detailed semen parameters. The study population is female participants and their male partners or sperm donors, so sex is inherent. Missing data are reported for several variables.

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· 90% conf

Biological variables are adequately reported for the female participants and male partners, with the exception of a few missing data points.

Evidence

“Table 1 Baseline characteristics (ITT analysis)”

Table 1Find in source

“Sperm characteristics were assessed from the sample used on the day of oocyte retrieval.”

Table 1Find in source

PASSReviewer 2· 90% conf

Biological variables are well reported for a human trial, including sex, age, BMI, and demographics.

Evidence

“Age at inclusion, mean (s.d.) | 33.0 (4.6) | 33.5 (4.4)”

Table 1Find in source

paraphrase[Table 1]

“Ethnicity, n (%) | Europe, the Middle East or North Africa | 370/414 (89.4%) | 368/408 (90.2%)”

PASSReviewer 3· 90% conf

Biological variables are well reported for a human trial, including sex, age, BMI, and demographics.

Evidence

“No sex or gender analysis was carried out, as the study population enrolled only female participants assigned female sex at birth and male partners or sperm donors, with a focus on their biological contributions to the outcomes.”

MethodsFind in source

“Age at inclusion, mean (s.d.) | 33.0 (4.6) | 33.5 (4.4)”

Table 1Find in source

paraphrase[Table 1]

“Ethnicity, n (%) | Europe, the Middle East or North Africa | 370/414 (89.4%) | 368/408 (90.2%)”

The study was approved by the Scientific Ethical Committee of the Capital Region of Denmark (H-19022201) and the Danish Knowledge Centre on Data Protection Compliance, and was performed in accordance with the Helsinki Declaration. Written informed consent was obtained from all participants. The trial was registered at ClinicalTrials.gov (NCT04128904).

Sub-criteria

informed consentADEQUATE

iac الدايرهN/A

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethics approval and informed consent are clearly documented for this human RCT.

Evidence

“Approval for the study was obtained from the Scientific Ethical Committee of the Capital Region of Denmark (H-19022201) and the Danish Knowledge Centre on Data Protection Compliance.”

EthicsFind in source

“Couples/women who wished to participate in the study were asked to sign an informed consent form before enrollment.”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethical approvals and consent are adequately reported.

Evidence

“Approval for the study was obtained from the Scientific Ethical Committee of the Capital Region of Denmark (H-19022201) and the Danish Knowledge Centre on Data Protection Compliance.”

MethodsFind in source

“Couples/women who wished to participate in the study were asked to sign an informed consent form before enrollment.”

MethodsFind in source

“The study was performed according to Danish Law and ethical principles in the Helsinki Declaration.”

MethodsFind in source

PASSReviewer 3· 95% conf

Ethical approvals and consent are adequately reported.

Evidence

“Approval for the study was obtained from the Scientific Ethical Committee of the Capital Region of Denmark (H-19022201) and the Danish Knowledge Centre on Data Protection Compliance.”

MethodsFind in source

“Couples/women who wished to participate in the study were asked to sign an informed consent form before enrollment.”

MethodsFind in source

“The study was performed according to Danish Law and ethical principles in the Helsinki Declaration.”

MethodsFind in source

The trial compares two fertilization techniques; the procedures are described in detail. Statistical software (R v4.2.2) and packages are identified. No antibodies, cell lines, or other bench reagents are applicable.

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· 85% conf

The investigational product (ICSI) is adequately identified, and the statistical software is named; however, the specific culture media and other reagents are not fully specified.

Evidence

paraphrase[Methods, Oocyte insemination and embryo transfer]

“Oocyte insemination was performed by either ICSI or c-IVF, based on randomization, following standard procedures at the trial sites.”

paraphrase[Methods, Statistical analysis]

“All statistical analyses were performed using R (v4.2.2)”

PASSReviewer 2· 85% conf

The investigational product (ICSI vs c-IVF) is adequately described, and software is identified.

Evidence

“All statistical analysis was done using R (v4.2.2), using the packages sjPlot (v2.8.15) and marginal effects (v0.18.0).”

Statistical analysisFind in source

PASSReviewer 3· 90% conf

The investigational product (ICSI vs c-IVF) is adequately described, and software tools are identified.

Evidence

“Fertility treatment procedures adhered to established practices, encompassing ovarian stimulation, transvaginal ultrasound, ovulation triggering, insemination (ICSI or c-IVF), embryo culture, luteal phase support, embryo transfer and cryopreservation.”

MethodsFind in source

“All statistical analysis was done using R (v4.2.2), using the packages sjPlot (v2.8.15) and marginal effects (v0.18.0).”

Statistical analysisFind in source

Tests are named (Wald test, Mann-Whitney U). Assumptions are handled by design (GLM, non-parametric tests). Exact p-values are reported. Effect sizes with CIs are reported. Software is identified. Data presentation is adequate for a clinical trial (tables with n, percentages, CIs). Mathematical plausibility checks were not possible for most outcomes due to continuous data and large N, but no inconsistencies were found.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The statistical analysis is generally well-reported with named tests, exact p-values, and effect estimates with confidence intervals, but the mathematical plausibility of several reported statistics could not be independently verified from the printed numbers.

Evidence

paraphrase[Methods, Statistical analysis]

“The primary analysis was performed using an intention-to-treat approach. ... The P values for binary variables were calculated using a Wald test, with effect estimates (β) and s.e. derived from a generalized linear model.”

paraphrase[Table 2, Results]

“The CLBR was 43.2% (179/414) in the ICSI group and 47.3% (193/408) in the c-IVF group (risk ratio = 0.91, 95% CI = 0.79–1.06; Table 2).”

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-reported, with exact p-values and effect sizes with CIs.

Evidence

“The P values for binary variables were calculated using a Wald test, with effect estimates ( β ) and s.e. derived from a generalized linear model. The P values for continuous variables were calculated using a Mann–Whitney U test.”

Table 2Find in source

“The fertilization rate (two pronuclei (2PN)) per oocyte retrieved was substantially lower in the ICSI group than in the c-IVF group (53.5% (1,940/3,628) versus 58.1% (1,983/3,412); P ≤ 0.001; Table ).”

Results ¶2Find in source

“The CLBR was 43.2% (179/414) in the ICSI group and 47.3% (193/408) in the c-IVF group, yielding a risk ratio of 0.91 (95% confidence interval, 0.79–1.06).”

AbstractFind in source

PASSReviewer 3· 90% conf

Statistical analysis is rigorous with named tests, exact p-values, effect sizes with CIs, and appropriate data presentation.

Evidence

Table 2Find in source

“CLBR | 179/414 (43.2%) | 193/408 (47.3%) | −0.04 (−0.11 to 0.03) | 0.91 (0.79–1.06) | 0.24”

Table 2Find in source

paraphrase[Table 2]

“Risk ratio (95% CI) | 0.91 (0.79–1.06)”

The data availability statement provides a concrete route: controlled access via the Health Research Ethics Committees and GDPR compliance, with a review timeframe. Repository deposit and accession numbers are not applicable for identifiable patient data. Code sharing is not applicable as no custom code was developed.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data availability statement is present, but it describes only controlled access upon reasonable request, with no repository deposit or accession numbers.

Evidence

“Individual de-identified participant data will be available upon reasonable request.”

Data availabilityFind in source

absence[Data availability]

No data repository deposit or accession numbers are provided.

PASSReviewer 2· 90% conf

Data availability is adequately described with a concrete access route, and code availability is stated.

Evidence

“Individual de-identified participant data will be available upon reasonable request. Access will require approval from the Health Research Ethics Committees for the Capital Region of Denmark (H-19022201) and compliance with the General Data Protection Regulation. Requests can be directed to N.l.C.F. and will be reviewed within 4 weeks.”

Data availabilityFind in source

“No custom computational code or software was developed for this study.”

Data availabilityFind in source

PASSReviewer 3· 90% conf

Data availability is adequately described with a concrete access route, and code availability is stated.

Evidence

Data availabilityFind in source

“No custom computational code or software was developed for this study.”

Data availabilityFind in source

The trial is registered (NCT04128904). A reporting guideline is not explicitly mentioned but the paper follows CONSORT-like structure. All outcomes are reported, including negative results. Limitations are discussed. Conclusions are proportional. Funding and COI are disclosed.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The methods are detailed and reproducible, but the trial was not registered in a primary registry with a number, and no reporting guideline (CONSORT) is referenced.

Evidence

“ClinicalTrials.gov registration: NCT04128904 (https://clinicaltrials.gov/study/NCT04128904)”

DiscussionFind in source

paraphrase[Methods, ethics approval]

“The study was prospectively registered before the first participant was enrolled.”

paraphrase[Discussion]

“The study does have limitations. First, participants were randomized before oocyte retrieval, and there was no blinding, which introduces the possibility of performance bias.”

PASSReviewer 2· 95% conf

Reporting is transparent with trial registration, funding/COI statements, and proportional conclusions.

Evidence

“ClinicalTrials.gov registration: NCT04128904 (https://clinicaltrials.gov/study/NCT04128904) .”

AbstractFind in source

“However, the study does have limitations. First, participants underwent randomization before oocyte retrieval, and there was no blinding, introducing the possibility of performance bias.”

Discussion ¶4Find in source

“The preparation of the study was funded by Gedeon Richter (unrestricted grant to N.l.C.F.).”

AcknowledgementsFind in source

PASSReviewer 3· 95% conf

Reporting is transparent with trial registration, reporting guideline, complete outcome reporting, limitations, proportional conclusions, and funding/COI statements.

Evidence

“ClinicalTrials.gov registration: NCT04128904 (https://clinicaltrials.gov/study/NCT04128904) .”

AbstractFind in source

“Further information on research design is available in the linked to this article.”

AbstractFind in source

“However, the study does have limitations. First, participants underwent randomization before oocyte retrieval, and there was no blinding, introducing the possibility of performance bias.”

Discussion ¶4Find in source

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

1 finding · worst low

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.

References not resolvable to a published paperRecomputed

Checked 53 references by DOI: 44 verified — 8 DOI unresolved, 1 no DOI (shown, not verified).

2 data/code links checked; 2 live.

Copyediting

6 minor

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

No major wording or formatting errors. 6 minor suggestions below.

6 copyedit issues flagged: mostly consistency, typo, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is largely robust, but an informed reader should weigh the open-label design and the statistical inconsistencies flagged by the verification component. The copyedit issues (denominator errors, stray numbers) are minor but should be corrected in any erratum. The lack of explicit CONSORT reporting and the registration number not in Methods are reporting gaps that could be addressed in a correction.

1.
CRITICALstatistics
Correct or explain the statistically impossible value: PERCENT: 68.5% does not match the reported count 242/414
Demonstrable critical failure — blocks the verdict from passing.
2.
CRITICALstatistics
Correct or explain the statistically impossible value: PERCENT: 2.9% does not match the reported count 3/179
Demonstrable critical failure — blocks the verdict from passing.
3.
HIGHstatistics
In the statistical analysis section, clarify the discrepancies found in the recomputation of reported statistics (e.g., fertilization rates, percentages) by providing the exact denominators and raw data or correcting any typographical errors.
The statistics verification component found 6 of 9 recomputed tests inconsistent, which could indicate reporting errors that need correction.
4.
HIGHreporting
Add the ClinicalTrials.gov registration number (NCT04128904) to the Methods section, not just the abstract and discussion.
The registration number is a key transparency element that should be prominently reported in the Methods.
5.
HIGHreporting
Explicitly state adherence to the CONSORT reporting guideline in the Methods or Reporting Summary.
Referencing CONSORT strengthens reporting transparency and is expected for randomized trials.
6.
MEDIUMcopyedit
Correct the denominator error in Table 2 for the c-IVF group in the row 'Participants with no embryo transfer' (should be 67/408, not 67/414).
The copyedit pass flagged this as a consistency issue that could mislead readers.
7.
MEDIUMcopyedit
Fix the typo in Table 5 for 'Gestational hypertension' where the risk difference is written as '−6.31 −3 (−0.06 to 0.04)' — should be '−6.31 × 10⁻³'.
The unusual formatting is a typographical error that should be corrected for clarity.
8.
MEDIUMcopyedit
Remove stray numbers in the Abstract header ('31 6 1939 1939–1948').
The copyedit pass flagged stray numbers that appear to be a formatting error.
9.
MEDIUMreporting
Clarify the definition of the per-protocol population in the main text, not just in the figure legend.
Reviewer 2 suggested this to improve clarity for readers.
10.
MEDIUMdata code
Consider adding a data-sharing statement in the main text, even though the Data Availability section is adequate.
Reviewer 2 suggested this to make the data availability more prominent.
11.
MEDIUMstatistics
Report the exact p-value for the fertilization rate comparison instead of 'P ≤ 0.001'.
Reviewer 3 suggested this to improve precision.
12.
LOWreporting
Clarify the distinction between 'missing data' and 'unavailable data' in tables.
Reviewer 3 suggested this to avoid confusion.
13.
LOWreporting
Consider adding a statement about the availability of the statistical analysis plan (SAP) in a public repository.
Reviewer 3 suggested this to enhance transparency.
14.
LOWother
Clarify the internal contradiction regarding the number of spontaneous pregnancies in the c-IVF group (Table 3 footnote says one, text says two).
The integrity check flagged this as a low-severity internal contradiction that should be resolved.

Full text (71,998 chars)Analyzed: Aug 15, 2026

Start the discussion on JRNLClub

Community discussion on jrnlclub.com

Read alongside

IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.

Read full text (PMC)

DOI

10.1038/s41591-025-03621-x

Share this Kaimen Rigor review

Post on X Share on LinkedIn Share via Email

Embed this Rigor badge

<a href="https://alpha1science.com/verify/05073aa1-5099-474e-b7eb-ffcfc054f8a0" target="_blank" rel="noopener">
  <img src="https://alpha1science.com/verify/05073aa1-5099-474e-b7eb-ffcfc054f8a0/badge" alt="Kaimen Rigor review — 1★ (Critical), 2 critical, 3 high issues for “IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial.”" width="440" height="104" style="max-width:100%;height:auto" />
</a>

Every embed links back to this Kaimen Rigor review.

Record fingerprint

0612c02df54119fcbc7d3ebe1af51e0d7d239084808ef8b140dc71441bce4057

Verify via API

Issued Aug 15, 2026Engine 7.39.0

Alpha1 assesses methodological rigor, not the importance of the findings. See how we calibrate →

Kaimen Rigor review

Kaimen Rigor reviewed

1 / 5

Critical — a demonstrable failure

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

StatisticsImpossible or misreported statistic ×2−2★
IntegrityIntegrity concern ×2−1★
CitationsCitations & links (capped) ×8−1★
StatisticsPrinted percentage does not match its own count (capped) ×4−0.25★

Citations & links are capped at −1★ combined, however many are flagged.

A demonstrable critical failure caps the rating at the minimum, regardless of the deductions above.

Model-reported confidence: moderateReviewer agreement: lowEngine: 7.39.0Source: full text

Biggest issues2 demonstrable

01Printed percentage does not match its own countdemonstrable
criticalArithmeticrecomputedFull detail
68.5% does not match the reported count 242/414
“242/414 (68.5%)”
Find in source
02Printed percentage does not match its own countdemonstrable
criticalArithmeticrecomputedFull detail
2.9% does not match the reported count 3/179
“3/179 (2.9%)”
Find in source
03Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
16.4% does not match the reported count 67/414
“67/414 (16.4%)”
Find in source
04Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
5.3% does not match the reported count 10/193
“10/193 (5.3%)”
Find in source
05Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
2.1% does not match the reported count 4/179
“4/179 (2.1%)”
Find in source
06Printed percentage does not match its own count
mediumArithmeticrecomputedFull detail
1.3% does not match the reported count 3/179
“3/179 (1.3%)”
Find in source

Findings by category

301ArithmeticNumerical inconsistencies 102OverreachOverstated conclusions 03AuthenticityNone found 04DisclosureNone found 105AvailabilityBroken references and links 06Copyedit6 minor suggestions

Numerical inconsistencies

3 findings · worst critical

Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
Printed percentage does not match its own countRecomputed
Internal contradictions in the reported numbersAssessed

Overstated conclusions

1 finding · worst low

Conclusions only partially backed by the presented evidenceAssessed

7 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.

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

Data authenticity concerns

None found

Checked — nothing surfaced.

Reporting gaps

None found

Checked — nothing surfaced.

Eight Dimensions8 pass

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The premise is well established with extensive citation of prior work, but the paper does not explicitly acknowledge weaknesses or limitations of the cited prior studies.

Evidence

paraphrase[Introduction, paragraph 2]

“The CLBR is considered the most appropriate metric for evaluating the overall effectiveness of an ART treatment regimen”

Introduction ¶3Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise with adequate citation of prior work and a logical rationale for the study.

Evidence

“However, retrospective studies have failed to demonstrate any advantage of ICSI over c-IVF in terms of live birth rates in this patient group – .”

Introduction ¶2Find in source

Introduction ¶3Find in source

Discussion ¶1Find in source

PASSReviewer 3· 90% conf

The paper establishes a clear scientific premise with extensive prior work and a logical rationale for the study.

Evidence

“However, retrospective studies have failed to demonstrate any advantage of ICSI over c-IVF in terms of live birth rates in this patient group – .”

Introduction ¶2Find in source

“The CLBR is considered the most appropriate metric for evaluating the overall effectiveness of an ART treatment regimen – .”

Introduction ¶3Find in source

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

Evidence

MethodsFind in source

“The study was designed with no blinding of participants, clinicians or assessors.”

MethodsFind in source

“The primary outcome was the CLBR, defined as at least one live birth after completing an ART cycle”

MethodsFind in source

PASSReviewer 2· 95% conf

The trial design is rigorous with adequate randomization, blinding rationale, power analysis, and inclusion/exclusion criteria.

Evidence

MethodsFind in source

“The study was designed as a superiority trial with 80% power and a 5% significance level for a two-sided test, aiming to detect a 10% point difference in CLBR.”

Statistical analysisFind in source

“The study was designed with no blinding of participants, clinicians or assessors.”

MethodsFind in source

PASSReviewer 3· 95% conf

The trial design is rigorous with adequate randomization, blinding considerations, power analysis, and pre-specified inclusion/exclusion criteria.

Evidence

MethodsFind in source

“The study was designed as a superiority trial with 80% power and a 5% significance level for a two-sided test, aiming to detect a 10% point difference in CLBR.”

Statistical analysisFind in source

“Eligible participants were women aged 18–42 years with no prior c-IVF or ICSI treatment and a body mass index of 18–35 mg m −2 .”

MethodsFind in source

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· 90% conf

Biological variables are adequately reported for the female participants and male partners, with the exception of a few missing data points.

Evidence

“Table 1 Baseline characteristics (ITT analysis)”

Table 1Find in source

“Sperm characteristics were assessed from the sample used on the day of oocyte retrieval.”

Table 1Find in source

PASSReviewer 2· 90% conf

Biological variables are well reported for a human trial, including sex, age, BMI, and demographics.

Evidence

“Age at inclusion, mean (s.d.) | 33.0 (4.6) | 33.5 (4.4)”

Table 1Find in source

paraphrase[Table 1]

“Ethnicity, n (%) | Europe, the Middle East or North Africa | 370/414 (89.4%) | 368/408 (90.2%)”

PASSReviewer 3· 90% conf

Biological variables are well reported for a human trial, including sex, age, BMI, and demographics.

Evidence

MethodsFind in source

“Age at inclusion, mean (s.d.) | 33.0 (4.6) | 33.5 (4.4)”

Table 1Find in source

paraphrase[Table 1]

“Ethnicity, n (%) | Europe, the Middle East or North Africa | 370/414 (89.4%) | 368/408 (90.2%)”

Sub-criteria

informed consentADEQUATE

iac الدايرهN/A

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethics approval and informed consent are clearly documented for this human RCT.

Evidence

“Approval for the study was obtained from the Scientific Ethical Committee of the Capital Region of Denmark (H-19022201) and the Danish Knowledge Centre on Data Protection Compliance.”

EthicsFind in source

“Couples/women who wished to participate in the study were asked to sign an informed consent form before enrollment.”

EthicsFind in source

PASSReviewer 2· 95% conf

Ethical approvals and consent are adequately reported.

Evidence

“Approval for the study was obtained from the Scientific Ethical Committee of the Capital Region of Denmark (H-19022201) and the Danish Knowledge Centre on Data Protection Compliance.”

MethodsFind in source

“Couples/women who wished to participate in the study were asked to sign an informed consent form before enrollment.”

MethodsFind in source

“The study was performed according to Danish Law and ethical principles in the Helsinki Declaration.”

MethodsFind in source

PASSReviewer 3· 95% conf

Ethical approvals and consent are adequately reported.

Evidence

“Approval for the study was obtained from the Scientific Ethical Committee of the Capital Region of Denmark (H-19022201) and the Danish Knowledge Centre on Data Protection Compliance.”

MethodsFind in source

“Couples/women who wished to participate in the study were asked to sign an informed consent form before enrollment.”

MethodsFind in source

“The study was performed according to Danish Law and ethical principles in the Helsinki Declaration.”

MethodsFind in source

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· 85% conf

The investigational product (ICSI) is adequately identified, and the statistical software is named; however, the specific culture media and other reagents are not fully specified.

Evidence

paraphrase[Methods, Oocyte insemination and embryo transfer]

“Oocyte insemination was performed by either ICSI or c-IVF, based on randomization, following standard procedures at the trial sites.”

paraphrase[Methods, Statistical analysis]

“All statistical analyses were performed using R (v4.2.2)”

PASSReviewer 2· 85% conf

The investigational product (ICSI vs c-IVF) is adequately described, and software is identified.

Evidence

“All statistical analysis was done using R (v4.2.2), using the packages sjPlot (v2.8.15) and marginal effects (v0.18.0).”

Statistical analysisFind in source

PASSReviewer 3· 90% conf

The investigational product (ICSI vs c-IVF) is adequately described, and software tools are identified.

Evidence

MethodsFind in source

“All statistical analysis was done using R (v4.2.2), using the packages sjPlot (v2.8.15) and marginal effects (v0.18.0).”

Statistical analysisFind in source

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

Evidence

paraphrase[Methods, Statistical analysis]

paraphrase[Table 2, Results]

“The CLBR was 43.2% (179/414) in the ICSI group and 47.3% (193/408) in the c-IVF group (risk ratio = 0.91, 95% CI = 0.79–1.06; Table 2).”

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-reported, with exact p-values and effect sizes with CIs.

Evidence

Table 2Find in source

Results ¶2Find in source

“The CLBR was 43.2% (179/414) in the ICSI group and 47.3% (193/408) in the c-IVF group, yielding a risk ratio of 0.91 (95% confidence interval, 0.79–1.06).”

AbstractFind in source

PASSReviewer 3· 90% conf

Statistical analysis is rigorous with named tests, exact p-values, effect sizes with CIs, and appropriate data presentation.

Evidence

Table 2Find in source

“CLBR | 179/414 (43.2%) | 193/408 (47.3%) | −0.04 (−0.11 to 0.03) | 0.91 (0.79–1.06) | 0.24”

Table 2Find in source

paraphrase[Table 2]

“Risk ratio (95% CI) | 0.91 (0.79–1.06)”

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data availability statement is present, but it describes only controlled access upon reasonable request, with no repository deposit or accession numbers.

Evidence

“Individual de-identified participant data will be available upon reasonable request.”

Data availabilityFind in source

absence[Data availability]

No data repository deposit or accession numbers are provided.

PASSReviewer 2· 90% conf

Data availability is adequately described with a concrete access route, and code availability is stated.

Evidence

Data availabilityFind in source

“No custom computational code or software was developed for this study.”

Data availabilityFind in source

PASSReviewer 3· 90% conf

Data availability is adequately described with a concrete access route, and code availability is stated.

Evidence

Data availabilityFind in source

“No custom computational code or software was developed for this study.”

Data availabilityFind in source

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The methods are detailed and reproducible, but the trial was not registered in a primary registry with a number, and no reporting guideline (CONSORT) is referenced.

Evidence

“ClinicalTrials.gov registration: NCT04128904 (https://clinicaltrials.gov/study/NCT04128904)”

DiscussionFind in source

paraphrase[Methods, ethics approval]

“The study was prospectively registered before the first participant was enrolled.”

paraphrase[Discussion]

“The study does have limitations. First, participants were randomized before oocyte retrieval, and there was no blinding, which introduces the possibility of performance bias.”

PASSReviewer 2· 95% conf

Reporting is transparent with trial registration, funding/COI statements, and proportional conclusions.

Evidence

“ClinicalTrials.gov registration: NCT04128904 (https://clinicaltrials.gov/study/NCT04128904) .”

AbstractFind in source

“However, the study does have limitations. First, participants underwent randomization before oocyte retrieval, and there was no blinding, introducing the possibility of performance bias.”

Discussion ¶4Find in source

“The preparation of the study was funded by Gedeon Richter (unrestricted grant to N.l.C.F.).”

AcknowledgementsFind in source

PASSReviewer 3· 95% conf

Reporting is transparent with trial registration, reporting guideline, complete outcome reporting, limitations, proportional conclusions, and funding/COI statements.

Evidence

“ClinicalTrials.gov registration: NCT04128904 (https://clinicaltrials.gov/study/NCT04128904) .”

AbstractFind in source

“Further information on research design is available in the linked to this article.”

AbstractFind in source

“However, the study does have limitations. First, participants underwent randomization before oocyte retrieval, and there was no blinding, introducing the possibility of performance bias.”

Discussion ¶4Find in source

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Broken references and links

1 finding · worst low

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.

References not resolvable to a published paperRecomputed

Checked 53 references by DOI: 44 verified — 8 DOI unresolved, 1 no DOI (shown, not verified).

2 data/code links checked; 2 live.

Copyediting

6 minor

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

No major wording or formatting errors. 6 minor suggestions below.

6 copyedit issues flagged: mostly consistency, typo, clarity.

Kaimen Rigor Action ItemsFinal pass before journal submission

1.
CRITICALstatistics
Correct or explain the statistically impossible value: PERCENT: 68.5% does not match the reported count 242/414
Demonstrable critical failure — blocks the verdict from passing.
2.
CRITICALstatistics
Correct or explain the statistically impossible value: PERCENT: 2.9% does not match the reported count 3/179
Demonstrable critical failure — blocks the verdict from passing.
3.
HIGHstatistics
In the statistical analysis section, clarify the discrepancies found in the recomputation of reported statistics (e.g., fertilization rates, percentages) by providing the exact denominators and raw data or correcting any typographical errors.
The statistics verification component found 6 of 9 recomputed tests inconsistent, which could indicate reporting errors that need correction.
4.
HIGHreporting
Add the ClinicalTrials.gov registration number (NCT04128904) to the Methods section, not just the abstract and discussion.
The registration number is a key transparency element that should be prominently reported in the Methods.
5.
HIGHreporting
Explicitly state adherence to the CONSORT reporting guideline in the Methods or Reporting Summary.
Referencing CONSORT strengthens reporting transparency and is expected for randomized trials.
6.
MEDIUMcopyedit
Correct the denominator error in Table 2 for the c-IVF group in the row 'Participants with no embryo transfer' (should be 67/408, not 67/414).
The copyedit pass flagged this as a consistency issue that could mislead readers.
7.
MEDIUMcopyedit
Fix the typo in Table 5 for 'Gestational hypertension' where the risk difference is written as '−6.31 −3 (−0.06 to 0.04)' — should be '−6.31 × 10⁻³'.
The unusual formatting is a typographical error that should be corrected for clarity.
8.
MEDIUMcopyedit
Remove stray numbers in the Abstract header ('31 6 1939 1939–1948').
The copyedit pass flagged stray numbers that appear to be a formatting error.
9.
MEDIUMreporting
Clarify the definition of the per-protocol population in the main text, not just in the figure legend.
Reviewer 2 suggested this to improve clarity for readers.
10.
MEDIUMdata code
Consider adding a data-sharing statement in the main text, even though the Data Availability section is adequate.
Reviewer 2 suggested this to make the data availability more prominent.
11.
MEDIUMstatistics
Report the exact p-value for the fertilization rate comparison instead of 'P ≤ 0.001'.
Reviewer 3 suggested this to improve precision.
12.
LOWreporting
Clarify the distinction between 'missing data' and 'unavailable data' in tables.
Reviewer 3 suggested this to avoid confusion.
13.
LOWreporting
Consider adding a statement about the availability of the statistical analysis plan (SAP) in a public repository.
Reviewer 3 suggested this to enhance transparency.
14.
LOWother
Clarify the internal contradiction regarding the number of spontaneous pregnancies in the c-IVF group (Table 3 footnote says one, text says two).
The integrity check flagged this as a low-severity internal contradiction that should be resolved.

Full text (71,998 chars)Analyzed: Aug 15, 2026