CoChat
Sign Up
Cited by 14Sperm and Testicular FunctionMale Reproductive Health StudiesReliability and Agreement in Measurement

Poor reproducibility of percentage of normally shaped sperm using the World Health Organization Fifth Edition strict grading criteria

Open access
Baker, Karen C., Steiner, Anne Z., Hansen, Karl R., Barnhart, Kurt T., Cedars, Marcelle I., Legro, Richard S., Diamond, Michael P., Krawetz, Stephen A. +9 more·2022·F&S Reports
DOI 10.1016/j.xfre.2022.03.003PMC PMC9250115
Open this paper in CoChat — free account

Abstract

Objective: To determine the reproducibility of the World Health Organization Fifth Edition (WHO5) strict grading methodology by comparing the percentage of morphologically normal sperm (PNS) recorded by the core laboratory with results obtained at the fertility centers participating in a multisite clinical trial. Design: Secondary cohort analysis of data from the Males, Antioxidants, and Infertility trial. Setting: Fertility centers. Patients: Semen values of 171 men participating in a multicenter, double-blind, randomized, placebo-controlled trial evaluating the effect of antioxidants on male fertility. Interventions: Not applicable. Main Outcome Measures: Strict morphology expressed as PNS as determined at each fertility center and the core central laboratory for the same semen sample. Results: No correlation was found in the PNS values for the same semen sample between the core laboratory and fertility center laboratories either as a group or by individual site. Interobserver agreement was similarly low (κ = 0.05 and 0.15) between the core and fertility laboratories as a group for strict morphology, categorized by the WHO5 lower reference limits of 4% and 0, respectively. Moderate agreement was found between the core and 2 individual fertility laboratories for the cutoff value of 0 (κ = 0.42 and 0.57). The remainder of the comparisons demonstrated poor to fair agreement. Conclusions: Strict morphology grading using the WHO5 methodology demonstrated overall poor reproducibility among a cohort of experienced fertility laboratories. This lack of correlation and agreement in the PNS values calls into question the reproducibility, and thereby the potential applicability, of sperm strict morphology testing.

AI snapshot

Written from the paper’s full text.

TL;DR

This secondary analysis of the MOXI trial found poor reproducibility of World Health Organization Fifth Edition strict sperm morphology grading between a central core laboratory and participating fertility center laboratories. For the same semen samples, percentage of morphologically normal sperm showed no correlation overall and little to no agreement for clinically used thresholds.

Key findings

  • Among 110 paired core/site PNS values, there was no correlation overall between core and site laboratories (r = 0.124, P = .20); site-level correlations were poor and nonsignificant (e.g., r = 0.071, P = .71 for site 1; r = 0.040, P = .84 for site 3).
  • Interobserver agreement between core and site laboratories as a group was poor for PNS <4% (κ = 0.053, P = .16) and for PNS = 0 (κ = 0.146, P = .04).
  • Moderate agreement was found between the core laboratory and 2 individual fertility laboratories for the cutoff PNS = 0 (κ = 0.421 and κ = 0.571); the remainder showed poor to fair agreement.
  • At visit 1, median core PNS was 5% (IQR 3%–9%); 35% of participants had PNS <4%, and 9.5% had PNS = 0. No association was found between PNS <4% and any variable; PNS = 0 was associated with younger age in multivariable analysis.

Methods

  • Secondary cohort analysis of data from the Males, Antioxidants, and Infertility (MOXI) trial, a multicenter, double-blind, randomized, placebo-controlled trial of antioxidants for mild male factor infertility.
  • The study cohort included 126 MOXI participants with core-laboratory strict morphology at visit 1; reproducibility analyses used 110 paired PNS values from core and site laboratories across visits 1 and 3, representing 6 of 9 fertility sites.
  • Semen morphology was graded locally at each site and centrally at the RMN core laboratory using WHO5 strict criteria; analyses included Pearson/Spearman correlation, simple κ agreement for PNS <4% and PNS = 0, and univariable/multivariable logistic regression for factors associated with PNS.

Limitations

  • The paper states this was a secondary analysis; the original MOXI trial was not designed to evaluate reproducibility of morphology grading, and early trial termination limited data pairs because some site PNS values were not entered before data lock.
  • The paper states the interpreting technician identity was not recorded at core or site laboratories, so individual technician performance could not be analyzed; all sites were certified andrology laboratories with internal quality programs.
  • The paper states broader applicability relies on the presumption that RMN facilities are not inferior to other fertility centers; evident from the text, only 6 of 9 sites contributed paired data, and the “true value” for PNS could not be established because of poor reproducibility.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.xfre.2022.03.003

Cites

21 of 21 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

8 of 27 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Filimberti et al. found that the PNS CV was 88.6% despite targeted training in the WHO5 methods.

    “Similarly, Filimberti et al. (25) analyzed the outcomes of 56 Tuscan laboratories that participated in a dedicated training program in the WHO5 methods and found that the PNS CV was 88.6% despite targeted training.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Filimberti et al. [25] Filimberti E. Degl’Innocenti S. Borsotti M. Quercioli M. Piomboni P. Natali I. High variability in results of semen analysis in andrology laboratories in Tuscany (Italy): the experience of an external quality control (EQC) programme Andrology 1 2013 401 407 23307477 source

      The Sperm morphology section (Fig. 5, p. 405) reports an overall third-trial morphology CV of 88.62%, consistent with 88.6% for PNS. Materials and Methods reports that 56 laboratories returned third-trial results and that participants were invited to a WHO fifth-edition teaching course after the second trial. It does not establish that all 56 laboratories attended the course, as the citing sentence states. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Premisecitation

    Outcomes are inconsistent for studies correlating lifestyle and environmental exposures with sperm morphology.

    “Likewise, outcomes are inconsistent for studies correlating lifestyle and environmental exposures with sperm morphology (11, 12, 13, 14, 15).”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [11] Chen Q. Yang H. Zhou N. Sun L. Bao H. Tan L. Phthalate exposure, even below US EPA reference doses, was associated with semen quality and reproductive hormones: prospective MARHCS study in general population Environ Int 104 2017 58 68 28441547 source
    • cites [12] Bloom M.S. Whitcomb B.W. Chen Z. Ye A. Kannan K. Buck Louis G.M. Associations between urinary phthalate concentrations and semen quality parameters in a general population Hum Reprod 30 2015 2645 2657 26350610 PMC4605371 source
    • cites [13] Swan S.H. Semen quality in fertile US men in relation to geographical area and pesticide exposure Int J Androl 29 2006 62 68 discussion 105–8 16466525 source

      The Between-centre differences in semen parameters section reports differing associations with morphology: smoking and age had little or no effect, while men with a history of an STD had fewer morphologically normal sperm. The Pesticide exposure and semen quality section reports mixed pesticide associations with overall semen quality, but does not isolate effects on morphology or establish that findings across studies are inconsistent. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [14] Auger J. Eustache F. Andersen A.G. Irvine D.S. Jorgensen N. Skakkebaek N.E. Sperm morphological defects related to environment, lifestyle and medical history of 1001 male partners of pregnant women from four European cities Hum Reprod 16 2001 2710 2717 11726600 source
    • cites [15] Swan S.H. Brazil C. Drobnis E.Z. Liu F. Kruse R.L. Hatch M. Geographic differences in semen quality of fertile U.S. males Environ Health Perspect 111 2003 414 420 12676592 PMC1241421 source

      The Discussion (p. 418) reports small, nonsignificant geographic differences in sperm morphology. The paper mentions smoking as a covariate and says pesticide-exposure analyses are planned, but our copy does not assess whether studies linking lifestyle or environmental exposures to sperm morphology have inconsistent outcomes (searched: inconsistent findings, smoking, pesticides, morphology). (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Premisecitation

    Publications examining the impact of morphology on spontaneous pregnancy, intrauterine insemination, and in vitro fertilization reach varying conclusions.

    “Despite efforts to standardize methodology for grading sperm morphology, publications examining the impact morphology on spontaneous pregnancy, intrauterine insemination, and in vitro fertilization reach varying conclusions (2, 3, 4, 5, 6, 7, 8, 9, 10).”
    Quote in the paperSubstantial claim3 of 9 sources checked
    • cites [2] Guzick D.S. Overstreet J.W. Factor-Litvak P. Brazil C.K. Nakajima S.T. Coutifaris C. Sperm morphology, motility, and concentration in fertile and infertile men N Engl J Med 345 2001 1388 1393 11794171 source
    • cites [3] Slama R. Eustache F. Ducot B. Jensen T.K. Jorgensen N. Horte A. Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities Hum Reprod 17 2002 503 515 11821304 source
    • cites [4] Kovac J.R. Smith R.P. Cajipe M. Lamb D.J. Lipshultz L.I. Men with a complete absence of normal sperm morphology exhibit high rates of success without assisted reproduction Asian J Androl 19 2017 39 42 27751992 PMC5227671 source

      The Introduction (page not provided) explicitly says studies of sperm morphology and pregnancy outcomes after IUI and IVF have had variable results. It does not establish varying conclusions among publications on spontaneous pregnancy; instead, it says no prior studies had examined teratozoospermia and the likelihood of natural conception. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [5] Erdem M. Erdem A. Mutlu M.F. Ozisik S. Yildiz S. Guler I. The impact of sperm morphology on the outcome of intrauterine insemination cycles with gonadotropins in unexplained and male subfertility Eur J Obstet Gynecol Reprod Biol 197 2016 120 124 26745391 source
    • cites [6] Lemmens L. Kos S. Beijer C. Brinkman J.W. van der Horst F.A. van den Hoven L. Predictive value of sperm morphology and progressively motile sperm count for pregnancy outcomes in intrauterine insemination Fertil Steril 105 2016 1462 1468 26930619 source
    • cites [7] Kruger T.F. Acosta A.A. Simmons K.F. Swanson R.J. Matta J.F. Oehninger S. Predictive value of abnormal sperm morphology in in vitro fertilization Fertil Steril 49 1988 112 117 3335257 source
    • cites [8] French D.B. Sabanegh E.S. Jr. Goldfarb J. Desai N. Does severe teratozoospermia affect blastocyst formation, live birth rate, and other clinical outcome parameters in ICSI cycles? Fertil Steril 93 2010 1097 1103 19200957 source

      The Discussion (page unavailable) says morphology may affect fertilization in IUI and conventional IVF, while this study found no significant differences in ICSI outcomes across morphology groups. That supports differing conclusions across assisted-reproduction methods, but our copy does not address spontaneous pregnancy or establish that publications on all three settings reach varying conclusions. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [9] Grow D.R. Oehninger S. Seltman H.J. Toner J.P. Swanson R.J. Kruger T.F. Sperm morphology as diagnosed by strict criteria: probing the impact of teratozoospermia on fertilization rate and pregnancy outcome in a large in vitro fertilization population Fertil Steril 62 1994 559 567 8062953 source
    • cites [10] Hotaling J.M. Smith J.F. Rosen M. Muller C.H. Walsh T.J. The relationship between isolated teratozoospermia and clinical pregnancy after in vitro fertilization with or without intracytoplasmic sperm injection: a systematic review and meta-analysis Fertil Steril 95 2011 1141 1145 21030014 source

      The passage labeled Abstract (page not provided) explicitly describes variable findings about sperm morphology and pregnancy after IVF, attributing some variation to differences in morphology assessment. It does not establish that publications on spontaneous pregnancy or intrauterine insemination reach varying conclusions. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Findingown data

    Interobserver agreement between the core laboratory and the fertility laboratories as a group was poor for PNS categorized by the threshold of 0 (κ = 0.15).

    “Interobserver agreement was similarly low (κ = 0.05 and 0.15) between the core and fertility laboratories as a group for strict morphology, categorized by the WHO5 lower reference limits of 4% and 0, respectively.”
    • Also stated in: § Reproducibility of Strict Morphology Grading · plain
      “Interobserver agreement between the core laboratory and the sites as a group was poor for PNS of <4% and 0% (κ = 0.05 and 0.15, respectively).”
    Quote in the paperSubstantial claim
  • Findingown data

    The remainder of the comparisons demonstrated poor to fair agreement.

    “The remainder of the comparisons demonstrated poor to fair agreement.”
    • Also stated in: § Reproducibility of Strict Morphology Grading · plain
      “Interobserver agreement was poor to fair for the remainder of the sites and comparisons.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 20

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Swan et al. found no difference in PNS among 4 US cities despite a difference in concentration and motility.

    “This finding echoes the results of Swan et al. (15) who found no difference in the PNS among 4 US cities despite a difference in concentration and motility.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Swan et al. [15] Swan S.H. Brazil C. Drobnis E.Z. Liu F. Kruse R.L. Hatch M. Geographic differences in semen quality of fertile U.S. males Environ Health Perspect 111 2003 414 420 12676592 PMC1241421 source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The MOXI trial was a multicenter, randomized, double-blind, placebo-controlled trial analyzing the effect of antioxidants on semen parameters among couples with mild male factor infertility.

    “In brief, the MOXI trial was a multicenter, randomized, double-blind, placebo-controlled trial analyzing the effect of antioxidants on semen parameters among couples with mild male factor infertility.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [22] Steiner A.Z. Hansen K.R. Barnhart K.T. Cedars M.I. Legro R.S. Diamond M.P. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial Fertil Steril 113 2020 552 560.e3 32111479 PMC7219515 source

      The Abstract (Design) identifies MOXI as a multicenter, randomized, double-blind, placebo-controlled trial, and the Methods (Outcomes) confirm that it examined effects on semen parameters. The Methods (Study design) describe couples with male factor infertility but do not characterize all enrolled cases as mild; eligibility allowed several abnormal semen parameters, while excluding men with sperm concentration below 5 million/ml. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Analysis by individual fertility site showed poor and nonsignificant correlation between strict morphology values reported by the core laboratory and those reported by individual fertility sites.

    “Likewise, analysis by site demonstrated poor and nonsignificant correlation between strict morphology values reported by the core and those reported individual fertility sites (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Thirty-five percent of participants had a PNScore of <4%, and 9.5% had a PNScore of 0.

    “Thirty-five percent of participants had a PNScore of <4%, and 9.5% had a PNScore of 0.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The median PNScore at visit 1 was 5% (interquartile range, 3%-9%).

    “The median PNScore at visit 1 was 5% (interquartile range, 3%–9%) (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Younger age and self-reported exposure to toxic chemicals were associated with a PNScore of 0 during univariable analysis.

    “Younger age and self-reported exposure to toxic chemicals were associated with a PNScore of 0 during univariable analysis; however, only age remained significant during multivariable analysis (Supplemental Table 3, available online).”
    • Also stated in: § Discussion · plain
      “Teratospermia defined as a PNScore of 0 was associated with younger age and self-reported toxic chemical exposure during univariable analysis; however, only age remained a significant association during multivariable analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The median PNScore did not differ significantly between the sites.

    “The median PNScore did not differ significantly between the sites.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingreasoning

    The site variable was treated as a random effect in the multivariable analysis and was shown to be insignificant.

    “Due to the relatively large number of sites, the site variable was treated as a random effect in the multivariable analysis and was shown to be insignificant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Exposure to toxic chemicals was associated with higher odds of a PNScore of 0 during univariable analysis, but this association did not remain significant during multivariable analysis.

    “As previously mentioned, exposure to toxic chemicals was associated with higher odds of a PNScore of 0 during univariable analysis, but this association did not remain significant during multivariable analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    At the time the MOXI trial was terminated, the dataset contained 110 pairs of PNS values (48 pairs from visit 1 and 62 pairs from visit 3), representing 77.8% of participants, 43.6% of semen samples, and 6 of the 9 fertility sites.

    “At the time the MOXI trial was terminated, the dataset contained 110 pairs of PNS values consisting of 48 pairs of PNScore and PNSsite from visit 1 and 62 pairs of PNScore and PNSsite from visit 3. These pairs represent 77.8% of participants, 43.6% of semen samples, and 6 of the 9 fertility sites.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The paper's finding is consistent with several studies that have documented high interobserver variability when assessing sperm morphology with the strict grading criteria.

    “Our finding is consistent with several studies that have documented high interobserver variability when assessing sperm morphology with the strict grading criteria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Auger et al. found an association between poorer sperm morphology and occupational and lifestyle exposures such as metal welding, alcohol consumption, and chemical spraying.

    “The investigators did find an association between poorer sperm morphology and occupational and lifestyle exposures (e.g., metal welding, alcohol consumption, and chemical spraying).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Auger et al. [14] Auger J. Eustache F. Andersen A.G. Irvine D.S. Jorgensen N. Skakkebaek N.E. Sperm morphological defects related to environment, lifestyle and medical history of 1001 male partners of pregnant women from four European cities Hum Reprod 16 2001 2710 2717 11726600 source

  • May combine two claims.

    Study design and conductown data

    There were no statistically significant differences in patient characteristics, semen parameters at enrollment, or treatment group assignments across the RMN sites.

    “There were no statistically significant differences in patient characteristics, semen parameters at enrollment, or treatment group assignments across the RMN sites (Supplemental Tables 1 and 2).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Wang et al. reported good agreement for PNS but moderate or worse agreement for categorization of sperm defects among experienced graders.

    “In 2014, Wang et al. (26) reported good agreement for PNS but moderate or worse agreement for categorization of sperm defects among experienced graders.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wang et al. [26] Wang Y. Yang J. Jia Y. Xiong C. Meng T. Guan H. Variability in the morphologic assessment of human sperm: use of the strict criteria recommended by the World Health Organization in 2010 Fertil Steril 101 2014 945 949 24524830 source

  • May combine two claims.

    Premisecitation

    Punjabi et al. noted that performance improved after adoption of the WHO5 methods, but variation in morphology grading remained unacceptably high with an extrapolated PNS CV of ≥40% in the years after 2010.

    “The investigators noted that performance improved after adoption of the WHO5 methods; however, the variation in morphology grading remained “unacceptably high” with an extrapolated PNS CV of ≥40% in the years after 2010.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Punjabi et al. [24] Punjabi U. Wyns C. Mahmoud A. Vernelen K. China B. Verheyen G. Fifteen years of Belgian experience with external quality assessment of semen analysis Andrology 4 2016 1084 1093 27410398 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Wang et al. found that the mean PNS was 20.87% and the CV was 4.8%.

    “The investigators found that the mean PNS was 20.87% and the CV was 4.8%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wang et al. [26] Wang Y. Yang J. Jia Y. Xiong C. Meng T. Guan H. Variability in the morphologic assessment of human sperm: use of the strict criteria recommended by the World Health Organization in 2010 Fertil Steril 101 2014 945 949 24524830 source

  • May combine two claims.

    Premisecitation

    Auger et al. compared morphology values for 1,001 men from 4 European cities and found no difference in PNS.

    “Likewise, Auger et al. (14) compared the morphology values for 1,001 men from 4 European cities and found no difference in the PNS.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Auger et al. [14] Auger J. Eustache F. Andersen A.G. Irvine D.S. Jorgensen N. Skakkebaek N.E. Sperm morphological defects related to environment, lifestyle and medical history of 1001 male partners of pregnant women from four European cities Hum Reprod 16 2001 2710 2717 11726600 source

  • May combine two claims.

    Interpretationown data

    The poor reproducibility of strict sperm morphology grading calls into question the applicability of morphology values between laboratories and, by extension, the generalizability of strict morphology in assessing male reproductive potential and predicting treatment outcomes.

    “The poor reproducibility of strict sperm morphology grading calls into question the applicability of morphology values between laboratories and, by extension, the generalizability of strict morphology in assessing male reproductive potential and predicting treatment outcomes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Both local and central laboratories were blinded to the treatment assignment of all participants.

    “Both local and central laboratories were blinded to the treatment assignment of all participants.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    These associations should be interpreted with caution because the true value for PNS cannot be established due to the poor reproducibility of strict morphology grading between the core and site laboratories.

    “These associations should be interpreted with caution, however, given that the “true value” for PNS cannot be established due to the poor reproducibility of strict morphology grading between the core and site laboratories.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    This study is a secondary analysis; the primary trial was not designed to evaluate the reproducibility of morphological grading.

    “This study is a secondary analysis—the primary trial was not designed to evaluate the reproducibility of morphological grading.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The results of strict morphology graded at sites 4, 5, and 6 were not incorporated into the dataset before termination of the MOXI trial.

    “The results of strict morphology graded at sites 4, 5, and 6 were not incorporated into the dataset before the termination of the Males, Antioxidants, and Infertility trial.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    All sites were certified andrology laboratories with internal quality assurance/quality improvement programs.

    “All sites were certified andrology laboratories with internal quality assurance/quality improvement programs, and there is ample literature assessing individual performance of sperm morphological grading using both the WHO5 and other grading criteria for experienced and inexperienced graders (14, 24, 25, 26, 27).”
    • Also stated in: § Materials and methods · plain
      “All study sites are College of American Pathologists certified and perform internal quality control for sperm morphology.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The identity of the interpreting technician was not recorded at the core or site laboratories; therefore, analysis of the performance of individual technicians is not possible.

    “The identity of the interpreting technician was not recorded at the core or site laboratories; therefore, the analysis of the performance of individual technicians is not possible.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Of 171 male subjects who participated in the MOXI trial, 126 had PNScore recorded at visit 1 and constituted the study cohort.

    “A total of 171 male subjects participated in the MOXI trial, of whom 126 had PNScore recorded in the dataset for visit 1 at the termination of the trial. These 126 subjects constitute the cohort for this study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In 2010, the WHO endorsed strict grading criteria and adopted a threshold value of 4% as the lower reference limit for PNS, citing evidence supporting the relationship between the percentage of normal forms and fertilization rates in vivo.

    “In 2010, the World Health Organization (WHO) endorsed the use of “strict” grading criteria and adopted a threshold value of 4% as the lower reference limit for PNS—citing “evidence supporting the relationship between the percentage of normal forms […] and fertilization rates in vivo” (1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] WHO Department of Reproductive Health and Research. World Health Organization. Clinical and Laboratory Standards Institute, Centers for Disease Control and Prevention (U.S.) Laboratory quality management system: handbook 5th ed. 2011 World Health Organization Geneva p. 56–102.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation

    Reproducibility is the minimum necessary condition for a finding to be believable and informative.

    ““Reproducibility is the minimum necessary condition for a finding to be believable and informative”(20)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Bollen K. Cacioppo J.T. Kaplan R.M. Krosnick J.A. Olds J.L. Social, behavioral, and economic sciences perspectives on robust and reliable science Available at: https://www.nsf.gov/sbe/AC_Materials/SBE_Robust_and_Reliable_Research_Report.pdf

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

27 of 27

  • The authors state this as an assumption.

    The performance of strict morphology grading at RMN facilities is not inferior to other fertility centers and laboratories.

    “The broader applicability of our results is based on our presumption that the performance of strict morphology grading at RMN facilities is not inferior to other fertility centers and laboratories.”
1 of 1

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Table 1 labels an interquartile range as a range

    Minor

    Table 1 labels 3.0-9.0 as the range for all 126 core-laboratory PNS values, but the same table reports 12 values of zero. The text describes 3%-9% as the interquartile range, which is consistent with those zero values.

1 of 1

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Baker, K. C., Steiner, A. Z., Hansen, K. R., Barnhart, K. T., Cedars, M. I., Legro, R. S., Diamond, M. P., Krawetz, S. A., Usadi, R., Baker, V. L., Coward, R. M., Sun, F., Wild, R., Masson, P., Smith, J. F., Santoro, N., & Zhang, H.
Affiliations
  • Duke University (US)
  • University of Oklahoma Health Sciences Center (US)
  • University of Pennsylvania (US)
  • University of California, San Francisco (US)
  • Pennsylvania State University (US)
  • Augusta University (US)
  • Wayne State University (US)
  • Johns Hopkins University (US)
  • University of North Carolina at Chapel Hill (US)
  • Yale University (US)
  • University of Colorado Anschutz (US)
Corresponding author
Baker, Karen C.
ORCID
Venue
F&S Reports
Publisher
Elsevier BV
Published
2022-06
Volume
3
Issue
2
Pages
110-115
ISSN
2666-3341 (ISSN-L)
DOI
10.1016/j.xfre.2022.03.003
PMC
PMC9250115
OpenAlex
W4221093180
Semantic Scholar
8ed1635cf78826be9638acab514b1031cb1939ea
Cited by
14
References
21
Citations by year
2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 2
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
Locations
  • F&S Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • AbbVie
  • National Center for Complementary and Integrative Health (R01AT009484-02)
  • Shandong University
  • National Heart, Lung, and Blood Institute (R01 HL119245-05)
  • National Center for Advancing Translational Sciences (UL1 TR002014)
  • University of Auckland
  • National Science Foundation
  • National Institutes of Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (1U10 HD077841, R01 HD091350-04, R01HD100305, R03HD101893, R25HD075737, U10HD027049, U10HD038992, U10HD055925, U10HD077680, U10HD077844, U10HD039005, UL1 TR001863)
  • Penn State Clinical and Translational Science Institute
  • Northern Ireland Chest, Heart and Stroke Association (R01 HD083323-04, R01HD100630-01)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Health Professions › General Health Professions › Male Reproductive Health Studies
  • Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Reliability and Agreement in Measurement
Keywords
sperm morphology, interobserver agreement, reproducibility, semen analysis, male infertility, antioxidants

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-26.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-26.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review