Search

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]

Background: A severe male infertility factor has been associated with both lower health status and increased mortality in infertile men. Objectives: To investigate reproductive factors associated with health status impairment in infertile men over a 10‐year time frame since the first clinical evaluation. Materials and methods: Data from 899 infertile men were analysed at baseline between 2003 and 2010. Health‐significant comorbidities were scored with the Charlson Comorbidity Index. Patients were followed up yearly recording any worsening in their health status until 2019. Cox regression models were used to estimate hazard ratios and 95% confidence intervals of Charlson Comorbidity Index score increase. Results: At a median follow‐up of 136 months (Interquartile range: 121, 156), 85 men (9.5%) depicted an increase of their baseline Charlson Comorbidity Index score of at least one point. The most frequent reason for Charlson Comorbidity Index upgrade was cancer (34%), cardiovascular diseases (29%) and diabetes mellitus (22%). Compared to patients without a Charlson Comorbidity Index increase, patients with a Charlson Comorbidity Index increase presented with higher body mass index and follicle‐stimulating hormone values, a higher rate of baseline Charlson Comorbidity Index ≥ 1 (all p < 0.01) and a greater proportion of non‐obstructive azoospermia (p < 0.001). In the Cox regression model, the patient's BMI (p < 0.001), baseline Charlson Comorbidity Index ≥ 1 (p < 0.01) and azoospermia status (p = 0.001) were found to be independently associated with Charlson Comorbidity Index increases. Conclusions: Almost 10% of men presenting for primary infertility had a decrease of the overall health status already in the relatively short 10‐year time frame after the first presentation. Non‐obstructive azoospermic men showed the worst health status impairment and should be strictly followed‐up regardless of their fertility status. [ABSTRACT FROM AUTHOR]

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. [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]

STUDY QUESTION Are the European Association of Urology (EAU) guidelines for performing semen culture accurate enough for detecting a positive semen culture in Caucasian-European infertile men? SUMMARY ANSWER The majority (80%) of asymptomatic infertile men with a positive sperm culture may miss a proper diagnostic assessment when relying on EAU guidelines; no single parameter can assist in medical decision-making. WHAT IS KNOWN ALREADY The EAU guidelines suggest performing semen culture in case of increased leukocytes in semen (>106 peroxidase positive white blood cells/ml, i.e. leukocytospermia). STUDY DESIGN, SIZE, DURATION A cross-sectional validation study including 523 infertile men was carried out during 2010–2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Infertile men who were asymptomatic for genital infections were enrolled at a single academic center, and a semen culture was obtained in every case. A concentration of >103 cfu/ml urinary tract pathogens in the ejaculate was considered indicative of significant bacteriospermia. Semen analysis values were assessed on the basis of 2010 World Health Organization reference criteria. EAU guidelines for semen culture were used to predict positive semen culture in our cohort and thus validated. Moreover, we tested the predictive performance and accuracy of several clinical parameters and compared them to EAU guidelines. MAIN RESULTS AND THE ROLE OF CHANCE A positive semen culture was found in 54 men (10%). The application of EAU guidelines would have missed 43 out of 54 (80%) positive semen cultures with 120/131 (92%) useless examinations. EAU guidelines specificity, sensitivity and discrimination were 74%, 20% and 47%, respectively. When trying to improve positive semen culture prediction, we were unable to find any informative baseline parameter except for serum neutrophil-to-lymphocyte ratio (odds ratio 1.70 (95% CI 1.04–2.77)), although without any improvement in terms of discrimination (P  = 0.10). LIMITATIONS, REASONS FOR CAUTION The study was limited by the lack of a control group of fertile men its retrospective nature. Moreover, monoclonal antibodies were not used for leukocyte assessment. WIDER IMPLICATIONS OF THE FINDINGS Since it is not possible to identify infertile men at risk of semen infection, further studies are needed to tailor the execution of semen culture. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this study. There are no competing interests. [ABSTRACT FROM AUTHOR]

Study Question: Given the relevant role of the extracellular microenvironment in regulating tissue homeostasis, is testicular bacterial microbiome (BM) associated with germ cell aplasia in idiopathic non-obstructive azoospermia (iNOA)?Summary Answer: A steady increase of dysbiosis was observed among testis with normal spermatogenesis vs. iNOA with positive sperm retrieval and iNOA with complete germ cell aplasia.What Is Known Already: Tissue-associated BM has been reported to be a biologically important extracellular microenvironment component for numerous body habitats, but not yet for the human testis.Study Design, Size, Duration: Cross-sectional study, investigating tissue-associated BM in the testis of (i) five men with iNOA and negative sperm retrieval at microdissection testicular sperm extraction (microTESE); (ii) five men with iNOA and positive sperm retrieval at microTESE; and (iii) five normozoospermic men upon orchiectomy. Every testicular specimen was histologically classified and analyzed in terms of bacterial community.Participants/materials, Setting, Methods: Massive ultra-deep pyrosequencing was applied to investigate testis microbiome. Metagenome was analyzed using Quantitative Insights Into Microbial Ecology (QIIME). Tissue-associated bacterial load was quantified by digital droplet PCR.Main Results and the Role Of Chance: Normozoospermic men showed small amounts of bacteria in the testis, with Actinobacteria, Bacteroidetes, Firmicutes Proteobacteria as the dominating phyla; iNOA individuals had increased amounts of bacterial DNA (P = 0.02), associated with decreased taxa richness due to the lack of Bacteroidetes and Proteobacteria (P = 2 × 10-5). Specimens with negative sperm retrieval at microTESE depicted complete germ cell aplasia and a further decrease in terms of Firmicutes and Clostridia (P < 0.05), a complete lack of Peptoniphilus asaccharolyticus, but increased amount of Actinobacteria.Limitations, Reasons For Caution: The limited number of specimens analyzed in this preliminary study deserves external validation. The paraneoplastic microenvironment could have an impact on the residential bacterial flora.Wider Implication Of the Findings: Human testicular microenvironment is not microbiologically sterile, containing low amounts of Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. A dysbiotic bacterial community was associated with iNOA and complete germ cell aplasia. Novel findings on testicular BM could support future translational therapies of male-factor infertility.Study Funding/competing Interest(s): This work was supported by URI-Urological Research Institute free funds. Authors declared no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Known genetic alterations play a major role in perturbing male reproductive health. We sought to retrospectively validate the European Association of Urology (EAU) guidelines for karyotype analysis (KA) in a homogenous cohort of 1168 White European men presenting for primary couple's infertility (noninterracial infertile couples only) and to develop a novel nomogram capable of predicting karyotype alterations. Overall, 742 (63.5%) patients would have deserved KA according to the EAU guidelines. Of those, 48 (6.9% of the assessable patients according to EAU guidelines) displayed any kind of alteration at KA. Conversely, hypothetically relying on the EAU criteria, 12 (20%) out of 60 patients with karyotype abnormalities would not have been candidates for the same genetic assessment. Overall, 694 (62.6%) patients would have been candidates for genetic workup despite having a normal karyotype. As a whole, the EAU guideline sensitivity, specificity, and discrimination were 80%, 37%, and 59%, respectively. We developed a novel nomogram, with a 2% probability cut-off, which allows for a more careful detection of KA alterations. Patient summary The application of the European Association of Urology guidelines for karyotype analysis does not ensure an adequate diagnostic process. In this regard, we propose a novel diagnostic tool to improve detection of alterations at karyotype analysis. [ABSTRACT FROM AUTHOR]

Individuals born with low birth weight (LBW) risk cardiometabolic complications later in life. However the impact of LBW on general health status and male reproductive function has been scantly analysed. We investigated the clinical and seminal impact of different birth weights (BW) in white-European men presenting for primary couple’s infertility. Demographic, clinical, and laboratory data from 827 primary infertile men were compared with those of 373 consecutive fertile men. Patients with BW ≤2500, 2500–4200, and ≥4200gr were classified as having LBW, normal (NBW), and high BW (HBW), respectively. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Testicular volume was assessed with a Prader orchidometer. Semen analysis values were assessed based on 2010 WHO reference criteria. Descriptive statistics and regression models tested associations between semen parameters, clinical characteristics and BW categories. LBW, NBW and HBW were found in 71 (8.6%), 651 (78.7%) and 105 (12.7%) infertile men, respectively. LBW was more frequent in infertile patients than fertile men (p = 0.002). Infertile patients with LBW had a higher rate of comorbidities (p = 0.003), lower mean testicular volume (p = 0.007), higher FSH (p = 0.02) and lower tT levels (p = 0.04) compared to other BW groups. Higher rates of asthenozoospermia (p = 0.02) and teratozoospermia (p = 0.03) were also found in LBW men. At logistic regression models, LBW was univariably associated with pathologic progressive motility (p≤0.02) and pathologic sperm morphology (p<0.005). At multivariable logistic regression analysis, LBW achieved independent predictor status for both lower sperm motility and pathologic sperm morphology (all p≤0.04). Only LBW independently predicted higher CCI values (p<0.001). In conclusion, we found that LBW was more frequent in infertile than in fertile men. Infertile individuals with LBW showed a higher rate of comorbidities and significantly worse clinical, endocrine and semen parameters compared to other BW groups. [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]

To evaluate the correlation between clinical and hormonal parameters and comorbidity burden in Caucasian women presenting for fertility treatment. Monocentric cross-sectional study including a cohort of 3163 Caucasian women seeking medical care for fertility treatment. All patients underwent centralized laboratory testing for hormonal assessment. Complete clinical and laboratory data from the entire cohort were retrospectively analysed. Comorbidity burden score was assessed by the Charlson Comorbidity Index (CCI; categorized as 0 versus 1 versus ≥2). Descriptive statistics and regression models tested the associations between clinical and laboratory parameters and CCI. Among the entire cohort of patients, a CCI = 0 was found in 2977 women (94.1%), and CCI = 1 and CCI ≥2 were found in 113 (3.6%) and 73 (2.3%) patients, respectively. Age (P = 0.009), gravidity (P = 0.001), anti-Müllerian hormone (AMH, P < 0.001) and TSH (P = 0.003) values were significantly different among CCI groups. In regression models, age at presentation and AMH emerged as independent indicators of CCI ≥ 1. Age at presentation <36 years (odds ratio [OR] 1.742, 95% confidence interval [CI] 1.284–2.364) and an AMH concentration ≤2.3 ng/ml (OR 1.864, 95% CI 1.29–2.69) were the most informative cut-off values for CCI ≥ 1 in the study population. A younger age at presentation and lower AMH concentrations are significant independent indicators of decreased general health in women requiring clinical evaluation for fertility treatment. As observed for sperm parameters in men, AMH might serve as a proxy of women's general health status. [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]