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Cited by 236Sperm and Testicular FunctionReproductive Health and TechnologiesMale Reproductive Health Studies

Total motile sperm count: a better indicator for the severity of male factor infertility than the WHO sperm classification system

Open access
Hamilton, J. A. M., Cissen, M., Brandes, M., Smeenk, J. M. J., de Bruin, J. P., Kremer, J. A. M., Nelen, W. L. D. M., Hamilton, C. J. C. M.·2015·Human Reproduction
DOI 10.1093/humrep/dev058
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Abstract

STUDY QUESTION: Does the prewash total motile sperm count (TMSC) have a better predictive value for spontaneous ongoing pregnancy (SOP) than the World Health Organization (WHO) classification system? SUMMARY ANSWER: The prewash TMSC shows a better correlation with the spontaneous ongoing pregnancy rate (SOPR) than the WHO 2010 classification system. WHAT IS KNOWN ALREADY: According to the WHO classification system, an abnormal semen analysis can be diagnosed as oligozoospermia, astenozoospermia, teratozoospermia or combinations of these and azoospermia. This classification is based on the fifth percentile cut-off values of a cohort of 1953 men with proven fertility. Although this classification suggests accuracy, the relevance for the prognosis of an infertile couple and the choice of treatment is questionable. The TMSC is obtained by multiplying the sample volume by the density and the percentage of A and B motility spermatozoa. STUDY DESIGN, SIZE, DURATION: We analyzed data from a longitudinal cohort study among unselected infertile couples who were referred to three Dutch hospitals between January 2002 and December 2006. Of the total cohort of 2476 infertile couples, only the couples with either male infertility as a single diagnosis or unexplained infertility were included (n = 1177) with a follow-up period of 3 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: In all couples a semen analysis was performed. Based on the best semen analysis if more tests were performed, couples were grouped according to the WHO classification system and the TMSC range, as described in the Dutch national guidelines for male infertility. The primary outcome measure was the SOPR, which occurred before, during or after treatments, including expectant management, intrauterine insemination, in vitro fertilization or intracytoplasmic sperm injection. After adjustment for the confounding factors (female and male age, duration and type of infertility and result of the postcoital test) the odd ratios (ORs) for risk of SOP for each WHO and TMSC group were calculated. The couples with unexplained infertility were used as reference. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 514 couples did and 663 couples did not achieve a SOP. All WHO groups have a lower SOPR compared with the unexplained group (ORs varying from 0.136 to 0.397). Comparing the couples within the abnormal WHO groups, there are no significant differences in SOPR, except when oligoasthenoteratozoospermia is compared with asthenozoospermia [OR 0.501 (95% CI 0.311-0.809)] and teratozoospermia [OR 0.499 (95% CI: 0.252-0.988)], and oligoasthenozoospermia is compared with asthenozoospermia [OR 0.572 (95% CI: 0.373-0.877)]. All TMSC groups have a significantly lower SOPR compared with the unexplained group (ORs varying from 0.171 to 0.461). Couples with a TMSC of <1 × 10(6) and 1-5 × 10(6) have significantly lower SOPR compared with couples with a TMSC of 5-10 × 10(6) [respectively, OR 0.371 (95% CI: 0.215-0.64) and OR 0.505 (95% CI: 0.307-0.832)]. LIMITATIONS, REASON FOR CAUTION: To include all SOPs during the follow-up period of 3 years, couples were not censured at the start of treatment. WIDER IMPLICATIONS OF THE FINDINGS: Roughly, three prognostic groups can be discerned: couples with a TMSC <5, couples with a TMSC between 5 and 20 and couples with a TMSC of more than 20 × 10(6) spermatozoa. We suggest using TMSC as the method of choice to express severity of male infertility. STUDY FUNDING/COMPETING INTERESTS: None.

AI snapshot

Written from the paper’s full text.

TL;DR

In a Dutch longitudinal cohort of 1177 infertile couples with male factor or unexplained infertility, prewash total motile sperm count (TMSC) correlated better with spontaneous ongoing pregnancy rate (SOPR) than the WHO 2010 semen classification. The authors conclude TMSC is more useful for expressing severity of male factor infertility and suggest three prognostic groups: TMSC <5×10^6, 5–20×10^6, and >20×10^6.

Key findings

  • Of 1177 couples, 514 achieved a spontaneous ongoing pregnancy (43.7%); of the 663 who did not, 335 conceived after treatment and 328 did not conceive.
  • All WHO groups had lower SOPR than unexplained infertility (adjusted ORs 0.136–0.397). Among abnormal WHO groups, no significant differences were found except OAT vs A [OR 0.501 (95% CI 0.311–0.809)], OAT vs T [OR 0.499 (95% CI 0.252–0.988)], and OA vs A [OR 0.572 (95% CI 0.373–0.877)].
  • All TMSC groups had significantly lower SOPR than unexplained infertility (ORs 0.171–0.461). TMSC <1×10^6 and 1–5×10^6 had lower SOPR than 5–10×10^6 [OR 0.371 (95% CI 0.215–0.640) and OR 0.505 (95% CI 0.307–0.832)]. Abnormal TMSC groups had SOPR 23–42% vs 60% for unexplained infertility; TOPR was 61–74%.
  • When classifications disagreed, WHO-normal/TMSC-abnormal had worse SOP and TOP (37.5% and 62.5%) than WHO-abnormal/TMSC-normal (46.3% and 75.0%).

Methods

  • Longitudinal cohort study using the Brandes cohort: unselected infertile couples referred to three Dutch hospitals between January 2002 and December 2006, with 3-year follow-up. From 2476 couples, those with female infertility factors, combined female/male factors, or azoospermia were excluded, leaving 1177 couples with male factor infertility as a single diagnosis or unexplained infertility.
  • The best prewash semen analysis was used. Couples were grouped by WHO 2010 criteria and by prewash TMSC ranges (<1, 1–5, 5–10, 10–20, >20×10^6, plus a normalized group). Primary outcome was SOPR (fetal heartbeat at 12 weeks); secondary outcome was total ongoing pregnancy rate including IUI, IVF, and ICSI.
  • Analysis used univariate selection followed by binary logistic regression with backward selection. Adjusted ORs controlled for female and male age, duration and type of infertility, and postcoital test result; unexplained infertility was the reference group.

Limitations

  • Stated: this was an observational study in which couples received expectant management and various treatments (IUI, IVF, ICSI); couples were not censored at treatment start, so spontaneous pregnancies during and after treatment were included. The authors note it is difficult to know how many couples would have conceived without treatment.
  • Stated: the finding that normalized semen after an initially abnormal analysis has a prognosis similar to persistently poor semen “should be evaluated further in a larger group.” The TMSC classification also lacked a validated classification, so groups were based on Dutch guideline ranges.
  • Evident from the text: treatment was not randomized and varied by prognosis/TMSC, so comparisons across groups may reflect treatment selection; the authors call for prospective RCTs to determine the best treatment by TMSC class.

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

Integrity signals

Registry

Crossref · 10.1093/humrep/dev058

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

7 of 27 cited sources checked · 4 supported · 1 flagged · accuracy not yet measured

  • Interpretationcitation

    The semen analysis is a poor predictor of pregnancy in the low TMSC range.

    “Once again it is shown that the semen analysis is a poor predictor of pregnancy in this low range (Van der Steeg et al., 2011).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Van der Steeg et al., 2011 source

      The paper’s conclusion (FIGURE 2; page not supplied) says reinterpreted semen parameters correlate strongly with natural conception and explicitly rejects dismissing semen analysis as a predictor. The Reinterpretation of the Semen Parameters section also reports associations at lower sperm counts. It does find that WHO normal-versus-abnormal categories discriminate poorly, but it does not establish poor prediction specifically in a low total motile sperm count (TMSC) range. (LLM, conf=0.84)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    In Van der Steeg et al. (2011), the different WHO categories did not show a clear pattern of success rate.

    “In their study the different WHO categories did not show a clear pattern of success rate.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Van der Steeg et al. (2011) source
  • Findingown data

    Quite a number of spontaneous pregnancies occur during and after treatment, even in couples that according to national guidelines must be offered ICSI directly.

    “We have shown that quite a number of spontaneous pregnancies occur during and after treatment, even in couples that according to the national guidelines must be offered ICSI directly.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Pregnancies occurring during or after treatment are spontaneous.
  • Findingown data

    Couples with a TMSC of less than 1 × 10 6 have a significantly lower spontaneous ongoing pregnancy rate compared with couples with a TMSC of 5-10 × 10 6 (OR 0.371, 95% CI 0.215-0.64).

    “Couples with a TMSC of ,1 × 10 6 and 1-5 × 10 6 have significantly lower SOPR compared with couples with a TMSC of 5-10 × 10 6 [respectively, OR 0.371 (95% CI: 0.215-0.64)and OR 0.505 (95% CI: 0.307 -0.832)].”
    Quote in the paperSubstantial claim
  • Findingown data

    Oligoasthenozoospermia compared with asthenozoospermia is associated with a lower odds ratio of spontaneous ongoing pregnancy (OR 0.572, 95% CI 0.373-0.877).

    “Comparing the couples within the abnormal WHO groups, there are no significant differences in SOPR, except when oligoasthenoteratozoospermia is compared with asthenozoospermia [OR 0.501 (95% CI 0.311-0.809)]and teratozoospermia [OR 0.499 (95% CI: 0.252-0.988)],and oligoasthenozoospermia is compared with asthenozoospermia [OR 0.572 (95% CI: 0.373-0.877)].”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 20
  • May combine two claims. 25

  • Classified as probably not a substantial claim.

    Premisecitation

    Van der Steeg et al. (2011) concluded that the predictive value of the WHO classification of semen analysis was poor.

    “Van der Steeg et al. (2011) tried to validate the 1999-WHO criteria (WHO, 1999) for spontaneous pregnancy chance in a large longitudinal cohort of infertile couples and concluded that the predictive value of the WHO classification of semen analysis was poor.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Van der Steeg et al. (2011) source

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

    Study design and conductcitation

    According to the available literature, only variables commonly related to spontaneous pregnancy chance were included: male and female age, duration and type of infertility, female BMI, smoking habits, CAT and PCT results, and semen parameters.

    “According to the available literature, only variables which are commonly related to spontaneous pregnancy chance were included, i.e. male and female age, duration and type of infertility, female BMI, smoking habits, CAT and PCT results and semen parameters (Hunault et al., 2004;Van der Steeg et al., 2007;Brandes et al., 2011c).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Hunault et al., 2004

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

    • cites Van der Steeg et al., 2007 source

      The Reply (page not available in our copy) describes a spontaneous-pregnancy prediction model with and without the post-coital test (PCT), supporting that item in the list. It does not identify the other listed variables or say that only variables commonly related to spontaneous-pregnancy chance were included. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites Brandes et al., 2011c

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

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

    Premisecitation

    Badawy et al. (2009) showed that IUI is less successful when both the total number of inseminated motile spermatozoa is low and postwash morphology is poor.

    “Badawy et al. (2009) showed that IUI is less successful when both total number of inseminated motile spermatozoa is low and postwash morphology is poor.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Badawy et al. (2009) source

  • May combine two claims.

    Premisecitation

    Van der Steeg et al. (2011) concluded that the WHO cut-off values are not good predictors, as their spline curves show that actual values are more informative than purely dichotomizing the parameters.

    “They concluded that the cut-off values as defined by the WHO are not good predictors, as the spline curves of the different sperm parameters they produced clearly show that the actual values are more informative than purely dichotomizing the parameters, as the WHO does.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites van der Steeg et al. (2011) source

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

    Premisecitation

    Male factor infertility is the most common cause of involuntary childlessness.

    “Male factor infertility is the most common cause of involuntary childlessness (Hull et al, 1985;Brandes et al. 2011a).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Hull et al, 1985 source

      The Discussion (p. 1697) says defective sperm function was the most commonly defined cause of infertility, occurring in about a quarter of cases. The claim omits the qualification “defined” and presents a finding from couples in one English health district as a general statement about involuntary childlessness. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Brandes et al. 2011a

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

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

    Findingown data

    Of the study population of 1177 couples, 514 achieved a spontaneous ongoing pregnancy (43.7%).

    “Of the study population of 1177 couples, 514 achieved SOP (43.7%).”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Both mean female and male ages are lower in the spontaneous ongoing pregnancy group (both P < 0.0001).

    “Both mean female and male ages are lower in the SOP group (both P , 0.0001).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The total ongoing pregnancy rate of couples in the WHO male infertility groups varies between 63 and 82% and is not significantly different.

    “The SOPR of couples with male infertility according to the WHO classification varies between 18 and 44%, while the TOPR of couples in these groups varies between 63 and 82% and are not significantly different.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    If the semen is normal according to WHO criteria but abnormal according to the TMSC classification, both the SOP and TOP are worse (37.5% and 62.5%) than when the semen is abnormal by WHO criteria in combination with a normal TMSC (46.3% and 75.0%).

    “If the semen is normal according to the WHO criteria, but abnormal according to the TMSC classification, then both the SOP and TOP are worse (respectively, 37.5% and 62.5%), compared with results that are classified as abnormal by WHO criteria in combination with a normal TMSC (respectively, 46.3% and 75.0%).”
    Quote in the paperSubstantial claim

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

    Findingown data

    Of the 663 couples who did not achieve a spontaneous pregnancy, 335 became pregnant after treatment and 328 did not become pregnant at all.

    “Of the 663 couples who did not achieve a spontaneous pregnancy, 335 couples became pregnant after treatment and 328 couples did not become pregnant at all.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    In the group with a spontaneous ongoing pregnancy, a higher percentage of secondary infertility and non-smoking men is seen.

    “In the group with a SOP, also a higher percentage of secondary infertility and non-smoking men is seen.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the abnormal TMSC groups, the spontaneous ongoing pregnancy rate varies between 23 and 42%, compared with 60% for couples with unexplained infertility.

    “Looking at the abnormal TMSC groups, the SOPR varies between 23 and 42% compared with a SOPR of 60% for the couples with unexplained infertility.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Despite 90% of couples with a TMSC below 1 × 10^6 starting with ICSI, 25% conceived spontaneously over a period of 3 years.

    “Despite the fact that we started with 90% of couples with a TMSC of ,1withICSI, 25%conceived spontaneously over a period of 3 years.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Pregnancies occurring during or after treatment are spontaneous.

  • May combine two claims.

    Findingown data

    When TMSC was used to diagnose male infertility, 702 men (60%) had abnormal sperm at the time of first analysis and 475 (40%) had normospermia.

    “When on the other hand, TMSC was used to diagnose male infertility 702 men (60%) had abnormal sperm at the time of first analysis, and 475 (40%) had a normospermia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Type of infertility, smoking habits of the male, PCT, sperm concentration, motility, morphology, and TMSC showed a significant relationship to spontaneous ongoing pregnancy in the univariate model.

    “Also, type of infertility of the couple, smoking habits of the male, the PCT, sperm concentration, motility and morphology of the semen and the TMSC showed a significant relationship to SOP in the univariate model.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The total ongoing pregnancy rate of couples with normalized semen analysis is lower than the total ongoing pregnancy rate of couples with unexplained infertility (68% and 74% using WHO and TMSC classification vs 72% and 79%), but this is not significant.

    “The TOPR of the couples with normalized semen analysis is lower (68% and 74%, respectively, using the WHO and TMSC classification) than the TOPR of the couples with unexplained infertility (72 and 79%, respectively, using the WHO and TMSC classification), but this is not significant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    When the WHO criteria were used, 889 couples (76%) were diagnosed with male factor infertility as a single diagnosis at the time of first semen analysis and 288 couples (24%) had normospermia.

    “When the WHO criteria were used, 889 couples (76%) were diagnosed with male factor infertility as single diagnosis at the time of first semen analysis and 288 couples (24%) had a normospermia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    All WHO groups have a lower spontaneous ongoing pregnancy rate (SOPR) compared with the unexplained infertility group, with odds ratios varying from 0.136 to 0.397.

    “All WHO groups have a lower SOPR compared with the unexplained group (ORs varying from 0.136 to 0.397).”
    • Also stated in: § Results · plain
      “If couples are diagnosed with abnormal or normalized semen according to the WHO classification, their chance to achieve a SOP is significantly lower than in couples with unexplained infertility (Table III).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    For daily practice, three prognostic groups can be discerned: couples with a TMSC below 5 × 10^6, couples with a TMSC between 5 and 20 × 10^6, and couples with a TMSC above 20 × 10^6 spermatozoa (normospermia).

    “For daily practice, three prognostic groups can be discerned: couples with a TMSC ,5 × 10 6 , couples with a TMSC between 5 and 20 × 10 6 and couples with a TMSC of more than 20 × 10 6 spermatozoa (normospermia).”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    Sperm results above the reference limits do not guarantee the occurrence of a pregnancy, as other factors might influence the outcome.

    “On the other hand, sperm results above the reference limits do not guarantee the occurrence of a pregnancy, as other factors might influence the outcome.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The new WHO cut-off values were assessed in a population of 1953 men who had recently fathered a child or whose wives conceived, retrieved from different countries worldwide and with the condition that the time-to-pregnancy was less than 1 year.

    “The new cut-off values were assessed in a population of 1953 men who had recently fathered a child or whose wives conceived.The study population was retrieved from different countries worldwide and with the condition that the time-topregnancy was ,1 year (WHO, 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites WHO, 2010

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

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Other female infertility diagnoses were excluded.

    “We did exclude other female infertility diagnoses.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    The NICE fertility guidelines recommended performing more tests but did not validate their statement with pregnancy rates.

    “The NICE fertility guidelines recommended performing more tests, but did not validate their statement with pregnancy rates.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The relevance of the WHO classification for the prognosis of an infertile couple and the choice of treatment is questionable or poor.

    “Although this classification suggests accuracy, the relevance for the prognosis of an infertile couple and the choice of treatment is questionable.”
    • Also stated in: § Introduction · plain
      “In other words, although the WHO classification suggests accuracy, the relevance for the prognosis of the couple and the choice of treatment is poor (Esteves et al., 2012).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Esteves et al., 2012 source

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

    Premisecitation

    The WHO modified its criteria in 2010.

    “Forced by the increasing doubt about the composition of the reference populations used in earlier WHO manuals, the WHO modified its criteria in 2010 (Cooper et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cooper et al., 2010 source

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

    Interpretationcitation

    The finding that morphology was not discriminative is in agreement with Deveneau et al. (2014) in an IUI program.

    “This is in agreement with the recent study of Deveneau et al. (2014) in an IUI program.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Deveneau et al. (2014) source

  • May combine two claims.

    Premisecitation

    Most spontaneous pregnancies occur in the first year, yet the cumulative spontaneous pregnancy curve continues to rise even after IUI, IVF and ICSI are discontinued.

    “Most spontaneous pregnancies occur in the first year (Brandes et al., 2011a) yet the cumulative spontaneous pregnancy curve continues to rise, even after IUI, IVF and ICSI are discontinued.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Brandes et al., 2011a

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

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

    Study design and conductnone given

    To guarantee a standardized and complete dataset, information was collected at the first visit using predefined questionnaires.

    “To guarantee a standardized and a complete dataset, this information was collected at the first visit using predefined questionnaires.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The reason for the lack of discriminating potential might be that the WHO criteria make use of cut-off points, while the pregnancy rate increases continuously with increasing values for individual parameters.

    “The reason for the lack of discriminating potential might be that the WHO criteria make use of cut-off points, while the pregnancy rate increases continuously with increasing values for individual parameters.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The Dutch national network guideline and NICE fertility guidelines advise repeating the test if the first semen analysis is abnormal.

    “This is in contrast to the Dutch national network guideline and National Institute for Health and Care Excellence (NICE) fertility guidelines (National Institute for Health and Care Excellence, 2013) that advise repeating the test if the first one is abnormal.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites National Institute for Health and Care Excellence, 2013

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

  • May combine two claims.

    Study design and conductown data

    A strength of this study is that the spontaneous pregnancy rate was measured and corrected for confounding factors.

    “A strength of our study is that the spontaneous pregnancy rate was measured and that this rate was corrected for confounding factors.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    To include all spontaneous ongoing pregnancies during the follow-up period of 3 years, couples were not censored at the start of treatment.

    “To include all SOPs during the follow-up period of 3 years, couples were not censured at the start of treatment.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The confounding factors adjusted for were female and male age, duration and type of infertility, results of the postcoital test, and WHO classification.

    “Confounding factors were female and male age, duration and type of infertility, the results of the PCT and WHO classification.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    No correlation was found between the confounding factors female and male age, duration and type of infertility, results of the postcoital test, and WHO classification.

    “No correlation was found between those confounding factors.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    In view of the correlation between the WHO and TMSC classification, the odds ratios of the TMSC groups were calculated without selecting the WHO groups.

    “In view of the correlation between the WHO and TMSC classification, the ORs of the TMSC groups were calculated without selecting the WHO groups.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Because there is no specific WHO class with the poorest outcome, as the SOPRs among various WHO male infertility classes are comparable, it is questionable whether the WHO criteria can be used to determine the proper treatment strategy.

    “Because there is no specific WHO class with the poorest outcome, as the SOPRs among various WHO male infertility classes are comparable, it is questionable whether the WHO criteria can be used to determine the proper treatment strategy.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    IUI is much cheaper and less invasive.

    “As IUI is much cheaper and less invasive, this therapy should be offered as the first choice treatment (van Rumste et al., 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites van Rumste et al., 2014

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

37 of 37

  • The paper relies on this without support.

    A validated TMSC classification is missing.

    “Because a validated classification is missing, couples were divided into the following groups according to the degree of male infertility: group 1 TMSC ,1 × 10 6 spermatozoa, group 2 TMSC 1-5 × 10 6 , group 3 TMSC 5-10 × 10 6 and group 4 TMSC 10-20 × 10 6 .”

  • The paper relies on this without support.

    Only a few studies have evaluated the predictive value of the WHO criteria in an infertile population.

    “Thus far, only a few studies evaluated the predictive value of the WHO criteria in an infertile population.”

  • The paper relies on this without support.

    The WHO reference limits are determined in a large group of fertile men who recently fathered a child.

    “The WHO reference limits are determined in a large group of fertile men, who recently fathered a child.”

  • The paper relies on this without support.

    Pregnancies occurring during or after treatment are spontaneous.

    “spontaneous pregnancies which occur during and after treatments are not included”

  • The paper relies on this without support.

    The TMSC is easy to calculate.

    “In addition, the TMSC is easy to calculate.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Hormone levels were measured using validated assays (ElectroChemiLuminiscenceImmunoassay in cohort 2, automated fluorescence detection in cohort 1), and free testosterone was calculated according to a published method.

    “Levels of testosterone, luteinising hormone (LH), follicle‐stimulating hormone (FSH) and sex‐hormone binding globulin (SHBG) that were available from both cohorts, were measured in the second cohort by use of ElectroChemiLuminiscenceImmunoassay (Roche Cobas) as previously described in detail. 26 In the first cohort, recruited around year 2000, these hormones were measured by use of an automated”

    From Decreased sperm counts in Swedish users of oral tobacco (2022) · cites this paper as [26]

    The Fertility work-up section mentions a midluteal progesterone measurement, and the Semen analysis section describes sperm testing, but neither addresses the claimed hormone assays or free-testosterone calculation. Searches for ElectroChemiLuminiscenceImmunoassay, Roche Cobas, automated fluorescence detection, and free testosterone found no relevant passage in our copy (page numbers unavailable). (LLM, conf=0.75)

    Experimental — accuracy not yet measured

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.

  • Text omits a significant WHO group shown in Table II

    Minor

    The text says only OA, OAT and unexplained groups correlate with spontaneous pregnancy, but Table II also gives the O-T group a univariate P-value of 0.029, below the stated 0.05 significance threshold.

1 of 1

Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1016/j.fertnstert.2007.12.010

    Major

    The cited work was retracted on 2009-03-01 (notice 10.1016/j.fertnstert.2007.12.010), before this paper was published (2015-03-18). Its authors could have known.

    Cited work 10.1016/j.fertnstert.2007.12.010 · retracted 2009-03-01 · notice 10.1016/j.fertnstert.2007.12.010 · this paper published 2015-03-18

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Authors
Hamilton, J. A. M., Cissen, M., Brandes, M., Smeenk, J. M. J., de Bruin, J. P., Kremer, J. A. M., Nelen, W. L. D. M., & Hamilton, C. J. C. M.
Affiliations
  • Jeroen Bosch Ziekenhuis (NL)
  • Radboud University Medical Center (NL)
  • Elisabeth-TweeSteden Ziekenhuis (NL)
Corresponding author
Hamilton, J. A. M.
ORCID
Venue
Human Reproduction
Publisher
Oxford University Press (OUP)
Published
2015-03-18
Volume
30
Issue
5
Pages
1110-1121
ISSN
  • 0268-1161 (ISSN-L)
  • 1460-2350
DOI
10.1093/humrep/dev058
OpenAlex
W2125686250
Cited by
236
References
23
Citations by year
2026: 17 · 2025: 14 · 2024: 25 · 2023: 24 · 2022: 26 · 2021: 28 · 2020: 26 · 2019: 31 · 2018: 14 · 2017: 16 · 2016: 12 · 2015: 3
FWCI
14.74
Type
journal article
Language
en
Open access
Locations
  • Human Reproduction (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
  • Health Sciences › Health Professions › General Health Professions › Male Reproductive Health Studies
Keywords
total motile sperm count, male factor infertility, semen analysis, unexplained infertility, sperm motility, infertility treatment outcomes, intrauterine insemination, in vitro fertilization, intracytoplasmic sperm injection, expectant management, postcoital test
MeSH terms
Adult, Female, Humans, Infertility, Male, Longitudinal Studies, Male, Prognosis, Severity of Illness Index, Sperm Count, Sperm Motility, Spermatozoa, World Health Organization, Reproducibility of Results, Semen Analysis

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 ›

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