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Objective: Up to 40% of infertile men remain without a recognized cause (i.e., idiopathic infertility). We aimed to identify, categorize, and report the supposed causes of male infertility in a cohort of white-European men presenting for primary couple's infertility, by using a thorough and extensive baseline diagnostic work-up., Material and Methods: Cross-sectional study of 1,174 primary infertile men who underwent a thorough diagnostic work-up including: detailed medical history, physical examination, hormonal assessment, genetic testing, semen analyses; semen and urine cultures; testis color Duplex US. Men without any identified causal factor were considered as idiopathic. Six different etiological categories were established, and their prevalence was estimated. Logistic regression models estimated the risk of missing causal identification., Results: A possible causal factor was identified in 928 (81%) men. Hypogonadism was the most frequent identified cause (37%), followed by varicocele (27%). Genetic abnormalities were found in 5% of patients. A causal factor was more easily identifiable for the more severe infertility cases, and azoospermic men were those less likely to be defined as idiopathic (OR and 95% CIs: 0.09; 0.04-0.20). Relative proportion of identified causes remained constant during the 10-year study period (p>0.43)., Conclusions: Due to a more comprehensive and extensive diagnostic work-up, at least one underlying cause of male infertility factor in 4 out of 5 infertile men can be identified. Men with a less severe phenotype remain a clinical challenge in terms of establishing a possible etiologic factor. Further studies are needed to assess which subset of infertile men deserves a more extensive work-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ventimiglia, Pozzi, Capogrosso, Boeri, Alfano, Cazzaniga, Matloob, Abbate, Viganò, Montorsi and Salonia.)

Objective: To assess the relationship between the duration of infertility (DI) and the seminal parameters of a cohort of White-European primary infertile men., Patients and Methods: Data from 1644 infertile men were analysed. Patients were grouped according to the self-reported DI into 12-month time frames. Semen analysis values were assessed based on 2010 World Health Organisation reference criteria. Descriptive statistics tested the difference in clinical, hormonal and seminal parameters between groups. Logistic regression models assessed the impact of DI on semen parameters., Results: A DI of <12, 13-24, 25-36, 37-48, 49-60 and >60 months was found in 207 (12.6%), 651 (39.6%), 387 (23.5%), 168 (10.2%), 92 (5.6%) and 139 (8.4%) men, respectively. Patient's age (P < 0.001) and body mass index (P < 0.001) significantly increased along with DI. Hormonal values were similar across groups. Sperm concentration significantly decreased with DI (P = 0.01). Similarly, a higher rate of non-obstructive azoospermia (NOA) was more frequently found in men with a longer DI (P = 0.03). There were no differences in semen volume, sperm progressive motility, total motile sperm count (TMSC), and normal morphology across groups. Multivariable logistic regression analysis showed that DI was significantly associated with the risk of oligozoospermia (P < 0.001), TMSC <5 × 10 6 (P < 0.001), and NOA (P < 0.001)., Conclusions: This cross-sectional study showed that DI had a negative impact on semen parameters in primary infertile men. Sperm concentration was negatively associated with DI and patients with a longer DI reported higher rates of azoospermia. Furthermore, DI was significantly associated with a higher risk of oligozoospermia, low TMSC, and NOA., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Background: Infertile men have a worse overall health status than their fertile counterparts. Objective: We aimed to (1) compare kidney function in men presenting for primary couple's infertility with that of fertile men and (2) assess kidney function impairment toward sperm quality in infertile men. Materials and methods: In this case–control study, 387 consecutive white‐European infertile men were matched by age with 134 same‐ethnicity fertile men. Complete clinical and laboratory data were available for each patient. The Chronic Kidney Disease Epidemiology Collaboration function was used for estimated glomerular filtration rate calculation. Kidney functional impairment was defined as an estimated glomerular filtration rate <90 mL/min per 1.73 m2, according to the Kidney Disease Improving Global Outcomes criteria. Multivariable logistic regression analysis was used to (1) assess the association between kidney function impairment and infertility status and (2) investigate the association between kidney function and semen analysis abnormalities in infertile men. Results: After matching, 34 (8.8%) infertile men depicted at least a mild unknown impairment of kidney function compared to only four (3%) fertile men, with four (3%) of the infertile presenting with an overt kidney function impairment (estimated glomerular filtration rate <60 mL/min per 1.73 m2). There were no differences in terms of age, body mass index and rate of comorbidities between the two groups (all p > 0.05). After adjusting for major confounders, infertility status was associated with a higher risk of reduced estimated glomerular filtration rate (odds ratio 3.20; 95% confidence interval 1.21–5.2; p = 0.002). Conversely, estimated glomerular filtration rate was not associated with sperm abnormalities in infertile men. Conclusions: Mild kidney function impairment was found in 9% of asymptomatic and unaware men presenting for primary couple's infertility investigation. This novel finding corroborates growing data on a significant association of male infertility with a poorer overall male health status and the need for tailored preventive strategies. [ABSTRACT FROM AUTHOR]

Purpose: In industrialized countries, air pollutants levels have been monitored closely for environmental and research issues. Using Italian data, we aimed to investigate the association between air pollutants levels and semen parameters in a cohort of non-Finnish white-European men presenting for couple’s infertility. Materials and Methods: Complete demographic and laboratory data from 1,152 infertile men consecutively assessed between January 2015 and January 2018 were analyzed. Semen analyses were based on the 2010 World Health Organization reference criteria. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). We analyzed the annual average level of the three main markers of air pollution (Pm10, Pm2.5, and NO2) between 2014 and 2018. Descriptive statistics, linear and logistic regression analyses tested the association between air pollutants levels and semen parameters. Results: Of 1,152 men, 87 (7.55%) had normal sperm parameters at first semen analysis. Of 1,065 patients with abnormal semen analyses, 237 (22.25%), 324 (30.42%), and 287 (26.95%) patients presented 1, 2 or 3 abnormalities, respectively, and 217 (20.38%) were azoospermic. At linear regression analysis, Pm10, Pm2.5, and NO2 were negatively associated with sperm morphology (Pm10: β=-0.5288 µg/m³, p=0.001; Pm2.5: β=-0.5240 µg/m³, p=0.019; NO2: β=-0.4396 µg/m3, p<0.0001). Furthermore, the adjusted odds of normal sperm morphology <4% were 1.06 (95% confidence interval [CI], 1.03–1.09; p=0.007) for Pm10, 1.07 (95% CI, 1.03–1.11; p=0.007) for Pm 2.5, and 1.03 (95% CI, 1.02–1.05; p=0.001) for NO2, respectively. Conclusions: In a large homogenous cohort of infertile men, Pm10, Pm 2.5, and NO2 levels were negatively associated with sperm morphology. Conversely, no clear association was observed with other macroscopic sperm parameters. [ABSTRACT FROM AUTHOR]

Purpose: Overall, male factor infertility (MFI) accounts for up to 50% of etiologies of couple’s infertility, with almost 30% of MFI cases being idiopathic in nature. Idiopathic MFI does not support a tailored treatment work-up in clinical practice. To investigate rates of and characteristics of men presenting for idiopathic versus unexplained primary infertility as compared with same-ethnicity, age-comparable fertile men. Materials and Methods: Demographic, clinical and laboratory data from 3,098 primary infertile men consecutively evaluated were analyzed and compared with those of 103 fertile controls. Idiopathic male infertility (IMI) was defined for abnormality at semen analysis with no previous history of diseases affecting fertility and normal findings on physical examination and genetic and laboratory testing. Unexplained male infertility (UMI) was defined as infertility of unknown origin with completely normal findings at semen analysis. Descriptive statistics and logistic regression models tested the association between clinical variables and idiopathic infertility status. Results: Overall, 570 (18.5%) and 154 (5.0%) patients depicted criteria suggestive for either IMI or UMI, respectively. Groups were similar in terms of age, BMI, CCI, recreational habits, hormonal milieu, and sperm DNA fragmentation indexes. Conversely, testicular volume was lower in IMI (p<0.001). Vitamin D3 levels were lower in IMI vs. UMI vs. fertile controls (p=0.01). At multivariable logistic regression analysis only vitamin D3 deficiency (OR, 9.67; p=0.03) was associated with IMI. Characteristics suggestive for IMI versus UMI were observed in almost 20% and 5% of men, respectively. Overall, clinical differences between groups were slightly significant and certainly not supportive of a tailored management work-up. Conclusions: Current findings further support the urgent need of a more detailed and comprehensive assessment of infertile men to better tailoring their management work-up in the everyday clinical setting. [ABSTRACT FROM AUTHOR]

Objectives: To investigate which infertile men with semen parameters above WHO reference limits at first semen analysis deserve a second semen test. Materials and methods: Data from 1358 consecutive infertile men were analysed. Patients underwent two consecutive semen analyses at the same laboratory. Descriptive statistics and logistic regression models tested the association between clinical variables and semen parameters. A new predicting model was identified through logistic regression analysis exploring potential predictors of semen parameters below WHO reference limits after a previously normal one. Diagnostic accuracy of the new model was compared with AUA/ASRM and EAU guidelines. Decision curve analyses (DCA) tested their clinical benefit. Results: Of 1358, 212 (15.6%) infertile men had semen parameters above WHO reference limits at first analysis. Of 212, 87 (41.0%) had a second semen analysis with results above WHO reference limits. Men with sperm parameters below reference limits at second analysis had higher FSH values, but lower testicular volume (TV) (all p<0.01) compared to men with a second semen analysis above WHO limits. At multivariable logistic regression analysis, lower TV (OR 0.9, p = 0.03), higher FSH (OR 1.2, p<0.01), and lower total sperm count (OR 0.9, p<0.01) were associated with second semen analyses below WHO limits. DCA showed the superior net benefit of using the new model, compared to both AUA/ASRM and EAU guidelines to identify those men with a second semen sample below WHO limits after a previously normal one. Conclusions: Approximately 60% of infertile men with a first semen analysis above WHO limits have a second analysis with results below limits. The newly identified risk model might be useful to select infertile men with initial semen results above WHO limits who deserve a second semen analysis. [ABSTRACT FROM AUTHOR]

Background: Alfa‐fetoprotein (AFP) is a serum glycoprotein highly produced during fetal development. While AFP synthesis drops dramatically after birth, AFP production only persists or returns under specific pathological condition. Objective: We sought to investigate the rate of and the potential meaning of high AFP serum levels in men seeking first medical attention for couple's primary infertility. Materials and methods: Socio‐demographic and clinical data from 1803 non‐Finnish, White‐European primary infertile men were retrospectively analysed. AFP was routinely measured in each patient (high AFP was defined as >7 ng/ml). Men with history of liver diseases, testicular cancer, or other known causes of increased AFP levels were excluded from the final analysis. Semen analyses were based on the 2010 World Health Organization reference criteria. Descriptive statistics and logistic regression models tested the association between serum AFP and clinical variables. Possible nonlinear relationships were graphically explored with locally estimated scatterplot smoothing method. Results: Overall, high serum AFP level was found in 29 (1.7%) patients. Normal versus high AFP levels patients were comparable in terms of body mass index (BMI), Charlson Comorbidity Index, waist circumference, smoking habits, history of cryptorchidism, testicular volume, and serum hormones (i.e., follicle‐stimulating hormone, luteinizing hormone, and total testosterone). Conversely, men with higher AFP levels were older (p = 0.02), had lower sperm concentration (p = 0.003), and were more frequently oligozoospermic and azoospermic (all p ≤ 0.03). At multivariate analysis, high AFP levels were independently associated with oligozoospermia (OR 3.79; p = 0.033) and azoospermia (OR 3.29; p = 0.006). Likewise, if AFP levels increase, patients were found to be older, with higher BMI and to have more comorbidities (all p < 0.05). Discussion: Unexplained high AFP levels account for almost 2% of cases in primary infertile patients without a previous history of associated disorders. Higher serum AFP levels are linked with aberrant sperm counts, older age, obesity, and a greater amount of comorbid conditions. Conclusion: Despite the need for additional validation, these data suggest that serum AFP measurement might have a multifaceted role over the diagnostic work‐up of males presenting for couple's infertility. [ABSTRACT FROM AUTHOR]

Aim: To assess the prevalence of isolated teratozoospermia (iTZS) in a cohort of infertile and fertile men; explore the relationship between iTZS, inflammatory parameters and sperm DNA fragmentation index (SDF) in the same cohort. Materials and methods: 1824 infertile men and 103 fertile controls. Semen analysis, the neutrophil-to-lymphocyte ratio (NLR) and serum hormones were investigated. DFI was tested in infertile men only. According to 2010 WHO semen analysis, patients were categorized in 3 sub-groups of isolated sperm defects: isolated oligozoospermia (iOZS), isolated asthenozoospermia (iAZS) and iTZS. Descriptive statistics and linear regression models tested the association between clinical variables and inflammatory markers. Results: Among infertile men, iAZS, iTZS, and iOZS were found in 13.9%, 11.9% and 4.1% participants, respectively. iTZS was found in 37 (35.9%) fertile men. Infertile men with iTZS had higher NLR values than those with iOZS, iAZS and men with normal semen parameters (all p<0.001). FSH and LH were higher and inhibin B lower in iOZS infertile men compared to all other groups (p≤0.001). Hormonal characteristics were similar between iTZS infertile and fertile men. Similarly, iTZS infertile men had higher SDF than all other groups (all p<0.001). Infertile men with iTZS had higher NLR values than fertile men with iTZS (p<0.01). Linear regression analysis showed that, in infertile men, iTZS was associated with SDF and NLR (all p≤0.01). Conclusions: iTZS was found in 11.9% of infertile men but it was even more prevalent in fertile controls. Infertile men with iTZS had higher NLR than fertile controls and increased SDF values than infertile participant with iAZS, iOZS, or normal semen parameters. No differences in hormonal characteristics were found between infertile and fertile men with iTZS. [ABSTRACT FROM AUTHOR]

Background: Trends of male factor causes of couples' infertility over time have been poorly investigated. Objective: We investigated trends in the causes of pure male factor infertility (MFI) throughout the last 10 years in a tertiary‐referral academic andrology center. Material and Methods: Baseline characteristics at first presentation from a cohort of 1647 consecutive male factor infertility patients belonging to primary infertile couples between 2008 and 2018 have been comprehensively collected over time. Seven major causes of male factor infertility were identified: varicocoele; history of cryptorchidism; hypogonadism (primary and secondary); obstructive azoospermia; genetic abnormalities; other causes (large group including the remnant conditions of known causes); and idiopathic infertility. Rates of different male factor infertility causes over the study period were analyzed. Multivariable logistic regression models tested the likelihood of male factor infertility causes over time. Estimated trends were explored graphically. Results: Of all, varicocoele was found in 615 (37.3%), cryptorchidism in 124 (7.5%), genetic abnormalities in 61 (3.7%), hypogonadism in 165 (10%), obstructive conditions in 55 (3.3%), other causes in 129 (7.8%) patients, and idiopathic infertility in 498 (30.3%) patients, respectively. Over time, a reduction in the proportions of cryptorchidism and varicocoele (all P < 0.001) cases was observed, along with an increase in the proportions of hypogonadism, other causes of MFI and idiopathic cases (all P ≤ 0.01). Rates of genetic and obstructive cases remained stable. The observed trends were confirmed at logistic regression models. Discussion and Conclusions: A decreasing trend in the proportions of varicocoele and cryptorchidism at first presentation was observed over the last 10 years; conversely, the proportions of idiopathic cases, hypogonadal patients, and infertile men presenting with other male factor infertility causes significantly increased over the same time frame at a single tertiary‐referral academic andrology center. [ABSTRACT FROM AUTHOR]

Background: A number of studies showed that obesity may negatively impact on sperm quality and consequently couple's fertility. Recently, specific attention was given to a clinical condition known as metabolically healthy obesity (MHO). Objectives: To evaluate the effects of MHO on semen and hormonal parameters of men presenting for primary couple's infertility associated with pure male factor infertility (MFI). Materials and methods: Data from a homogenous cohort of 512 white‐European primary infertile men belonging to couples with pure MFI have been cross‐sectionally analyzed. Semen analysis was based on 2010 WHO reference criteria. Patients were segregated into eugonadal, secondary hypogonadal, primary hypogonadal, and compensated hypogonadal. The Harmonized International Diabetes Federation criteria were used to define metabolic syndrome (MetS). Based on BMI and MetS, patients were further segregated into the following: (a) metabolically healthy non‐obese (MHNO); (b) metabolically unhealthy non‐obese (MUNO) (c) metabolically healthy obesity (MHO); and, (d) metabolically unhealthy obesity (MUHO). Main outcome measures were the prevalence of MHO and the impact of MHO on semen and hormonal parameters in this cohort of MFI primary infertile men. Results: Overall, MHNO, MUNO, MHO, and MUHO were found in 462 (90%), 13 (2.5%), 27 (5.2%), and 10 (1.9%) men, respectively. MHO patients had lower total testosterone and SHBG levels (all P <.05) but higher E2 values (P <.005) compared with MHNO men. Groups did not differ in terms of semen parameters. At multivariable logistic regression, analysis MHO was associated with an increased risk of primary and secondary hypogonadism (all P ≤.02) compared with MHNO, after accounting for age and comorbid conditions. Discussion and conclusions: Metabolically healthy obesity is threefold more prevalent than unhealthy obesity in primary infertile men. Despite semen parameters are comparable among groups, MHO patients show worse endocrine parameters and a higher risk of primary and secondary hypogonadism compared with metabolically healthy normal infertile men. [ABSTRACT FROM AUTHOR]

We assessed the concomitant impact of cigarette smoking and alcohol consumption in men presenting for primary couple's infertility. Data from 189 infertile men were analyzed. Semen analysis, serum hormones, and sperm DNA fragmentation (SDF) were obtained. Smoking status was categorized as follows: current nonsmoker (-S), moderate smoker (+MS), and heavy smoker (+HS). Alcohol consumption was categorized as follows: abstainer (-D), moderate drinker (+MD), and heavy drinker (+HD). Descriptive statistics and logistic regression models were applied. Among all the participants, 132 (69.8%), 30 (15.9%), and 27 (14.3%) patients were -S, +MS, and +HS, respectively. In addition, 67 (35.4%), 77 (40.7%) and 45 (23.8%) men were -D, +MD and +HD, respectively. Regarding concomitant habits, 52 (27.5%) patients were nonsmokers and abstainers (-S/-D: Group 1), 91 (48.1%) had at least one recreational habit (-S/+D or +S/-D: Group 2), and 46 (24.3%) were both smokers and drinkers (+S/+D: Group 3). Sperm concentration and progressive motility were lower in +HS and +HD, compared with -S and -D (all P < 0.05), respectively. Similarly, both parameters were significantly lower in Group 3 than Groups 1 and 2 (all P < 0.05). SDF values were higher in Group 3 than Groups 1 and 2 (both P < 0.05). In multivariate analysis, follicle-stimulating hormone (FSH) levels and concomitant +S/+D status were independent predictors of impaired sperm concentration and progressive motility (all P < 0.05). Heavy smoking and heavy drinking were associated with worse seminal parameters than moderate smoking/drinking and nonsmoking/ abstaining. When concomitant, +S/+D status has an even greater detrimental effect on semen parameters. [ABSTRACT FROM AUTHOR]

Objective: To study the prevalence and the risk associated with prediabetes (PreDM) in primary infertile men. Patients and methods: Data from 744 infertile men were analysed. Health‐significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Serum hormones were measured in every man. Semen analysis was based on 2010 World Health Organization (WHO) reference criteria. PreDM was defined according to the clinical criteria detailed by the American Diabetes Association (Diabetes Care 2014; 37 (Suppl. 1): S81). Descriptive statistics and logistic regression analyses tested the association between PreDM status, hormonal milieu and seminal parameters. The predictive accuracy of all variables was evaluated using the area under the curve, and the clinical net benefit estimated by decision curve analysis (DCA). Results: Of the 744 men, PreDM was found in 114 (15.4%). Men with PreDM (+PreDM) were older, had higher CCI scores, lower total testosterone and sex hormone‐binding globulin but higher follicle‐stimulating hormone (FSH) and 17β‐oestradiol values compared to those without PreDM (−PreDM) (all P ≤ 0.04). Higher sperm DNA fragmentation index (DFI; P = 0.014) and idiopathic non‐obstructive azoospermia (iNOA; P < 0.001) were found more frequently in +PreDM men. At multivariable logistic regression analysis, older age, FSH and iNOA (all P ≤ 0.04) were significantly associated with +PreDM status. DCA demonstrated a clinical net benefit in discriminating men at higher risk of a +PreDM status. Conclusions: About 15% of primary infertile men had criteria suggestive of undiagnosed PreDM. A PreDM status was associated with a greater risk of hypogonadism, higher DFI values and iNOA status. Age, FSH values and iNOA status could be considered as useful parameters to recognise men with PreDM and implement early preventive interventions in those men at risk of the consequences from poor glycaemic control. [ABSTRACT FROM AUTHOR]

Objective To evaluate the prevalence, and clinical and seminal impact of comorbidities in white European men presenting for couple infertility. Design Cross-sectional study. Setting Academic reproductive medicine outpatient clinic. Patient(s) Cohort of 2,100 consecutive infertile men (noninterracial infertile couples). Intervention(s) Obtaining complete demographic, clinical, and laboratory data from 2,100 consecutive infertile men with health-significant comorbidities scored via the Charlson comorbidity index (CCI; categorized 0 vs. 1 vs. ≥2) and semen analysis values assessed based on 2010 World Health Organization reference criteria. Main Outcome Measure(s) Assessment of the rate of comorbidities by means of CCI scores and possible associations between CCI, semen and hormonal parameters. Result(s) Descriptive statistics and regression models tested the associations among semen parameters, clinical characteristics, and CCI. When assessing general comorbidity prevalence, CCI 0, CCI 1, and CCI ≥2 was found in 1,921 (91.5%), 102 (4.9%), and 77 (3.6%) patients, respectively. Patient age and follicle-stimulating hormone levels increased as the general health status decreased. Conversely, the total testosterone levels and sperm concentration decreased as CCI scores increased. A higher rate of oligozoospermia and nonobstructive azoospermia was observed in patients with CCI ≥1. No differences were observed among the considered comorbidity groups in terms of testicular volume or further hormonal or seminal parameters. Both continuously coded and categorized sperm concentrations were independent predictors of CCI ≥1. Patients with sperm concentration <45.6 million/mL (most informative cutoff value) had a 2.74-fold increased risk of having a CCI ≥1. Conclusion(s) Decreased general health status appears to be associated with impaired male reproductive health, including lower sperm concentration, lower total testosterone levels, and higher follicle-stimulating hormone values. [ABSTRACT FROM AUTHOR]

Study question: we aimed to investigate the relationship between the tyg index and both semen and hormonal characteristics in a cohort of primary infertile men. Summary answer: almost one in two primary infertile men presented with a triglycerides/glucose index (tyg) suggestive of insulin resistance (ir). overall, patients with tyg suggestive of ir showed worse clinical, hormonal, and semen parameters. What is already known: male factor infertility (MFI) is often associated with metabolic disorders such as diabetes mellitus and metabolic syndrome, where insulin resistance (IR) plays a relevant pathological role. Recently, TyG has been suggested as a user-friendly IR marker. Study Design: serum hormones and the sperm DNA fragmentation index (SDF) were measured in every patient. The semen analysis was based on 2010 WHO reference criteria. Glucose and insulin levels were measured for every man after a 12-h overnight fast, and the homeostatic model assessment index (HOMA-IR) was then calculated and categorized using a 2.6 threshold. Similarly, fasting glucose and triglycerides levels were measured and the TyG index was calculated and categorized using an 8.1 threshold. Descriptive statistics and logistic regression models tested the association between the TyG and semen and hormonal characteristics. Participants: complete demographic, clinical, and laboratory data from 726 consecutive white European primary infertile men were considered for this analysis. Main results and the role of chance: the median (IQR) age was 39 (35–43) years. A TyG and HOMA suggestive for IR was found in 339 (46.6%) and 154 (21.2%) men, respectively. During the Spearman's test, the TyG index was highly correlated with HOMA-IR (rho = 0.46, p < 0.001). Compared to men with a normal TyG, men with TyG > 8.1 were older, had greater BMI and CCI scores, and lower total testosterone and sperm concentration, but higher DFI, and presented a greater proportion of NOA (all p < 0.01). The multivariable logistic regression analysis showed that men with TyG > 8.1 were at higher risk of SDF > 30 (OR 1.92 (CI: 1.2–2.9)) and NOA (OR 1.78 (CI: 1.1–2.8)). Wider implications of the findings: the Tyng index may act as a reliable marker of IR in the clinical work-up of primary infertile men in real-life settings. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively validate the American Society for Reproductive Medicine (ASRM) guidelines/recommendations concerning endocrine evaluation in a cohort of white European men presenting for couple's infertility.Design: Retrospective study.Setting: Academic reproductive medicine outpatient clinic.Patient(s): Cohort of 1,056 consecutive infertile men (noninterracial infertile couples).Intervention(s): Testicular volume was assessed with a Prader orchidometer. Serum hormones were measured (8-10 a.m.) in all cases. Hypogonadism was defined as total T < 3 ng/mL, according to the Endocrine Society definition. Semen analysis values were assessed based on the 2010 World Health Organisation reference criteria.Main Outcome Measure(s): ASRM indications for endocrine assessment in infertile men (sperm concentration <10 million/mL, impaired sexual function, and other clinical findings suggesting a specific endocrinopathy) were used to predict hypogonadism in our cohort. Moreover, a clinically user-friendly three-item nomogram was developed to predict hypogonadism and was compared to the ASRM guidelines assessment.Result(s): Biochemical hypogonadism was diagnosed in 156 (14.8%) men. Overall, 669 (63.4%) patients would have necessitated total T assessment according to the ASRM criteria; of these, only 119 (17.8%) were actually hypogonadal according to the Endocrine Society classification criteria. Conversely, 37 (23.7%) out of 156 patients with biochemical hypogonadism would have been overlooked. The overall predictive accuracy, sensitivity, and specificity of the ASRM guidelines was 58%, 76%, and 39%, respectively. Our nomogram was not reliable enough to predict hypogonadism, despite demonstrating a significantly higher predictive accuracy (68%) than the ASRM guidelines.Conclusion(s): The current findings show that the ASRM guidelines/recommendations for male infertility workup may not be suitable for application in white European infertile men. [ABSTRACT FROM AUTHOR]

Infertile men are at greater risk for oncological and nononcological chronic disease than fertile individuals. To investigate prostate-specific antigen (PSA) values in men presenting for primary couple's infertility compared with a cohort of fertile individuals, according to the recommendation of the European Association of Urology guidelines that a first PSA assessment should be done at 40–45 yr of age. This is a cross-sectional study. Data from 956 (90%) infertile men and 102 (9.6%) fertile participants were analysed. Circulating hormones, total PSA, and semen parameters were investigated in every man. Descriptive statistics, local polynomial smoothing, and linear regression models were used to test potential associations with PSA levels. Overall, PSA >1 ng/ml was found in 318 (30%) men. Serum PSA was higher (p = 0.02), while serum testosterone (p < 0.01) was lower in infertile than in fertile men. In participants younger than 40 yr, 176 (27%) men had PSA >1 ng/ml; of them, a greater proportion were infertile (28% infertile vs 17% fertile, p = 0.03). At multivariable linear regression analysis, infertile status (coefficient 0.21; 95% confidence interval 0.02–0.39) was associated with higher PSA values, after adjusting for age and serum testosterone level. This was a single-centre study, raising the possibility of selection biases. Infertile men have higher PSA values than fertile individuals. Of all, almost one out of three primary infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. In this study, we observed that (1) infertile men have higher prostate-specific antigen (PSA) values than fertile individuals and (2) a greater proportion of infertile men younger than 40 yr had total PSA >1 ng/ml at the first assessment. These data might be relevant to study the potential clinical impact of more rigorous screening in primary infertile men. Infertile men have higher prostate-specific antigen (PSA) values than fertile individuals. One out of three infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Serum PSA is related to worse semen quality in infertile men. [ABSTRACT FROM AUTHOR]