Purpose: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). Materials and Methods: Data from 1,230 consecutive men presenting for primary couple’s infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. Results: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34–41 years] vs. 36.0 years [31–40 years]); had smaller testicular volume (TV) (12 mL [10–15 mL] vs. 15 mL [12–20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9–11.0 million/mL] vs. 13.8 million/mL [3.1–36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%–25.3%] vs. 20.0% [7.0%–36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. Conclusions More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Purpose: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). Materials and Methods: Data from 1,230 consecutive men presenting for primary couple’s infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. Results: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34–41 years] vs. 36.0 years [31–40 years]); had smaller testicular volume (TV) (12 mL [10–15 mL] vs. 15 mL [12–20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9–11.0 million/mL] vs. 13.8 million/mL [3.1–36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%–25.3%] vs. 20.0% [7.0%–36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. Conclusions More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Purpose: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). Materials and Methods: Data from 1,230 consecutive men presenting for primary couple’s infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. Results: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34–41 years] vs. 36.0 years [31–40 years]); had smaller testicular volume (TV) (12 mL [10–15 mL] vs. 15 mL [12–20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9–11.0 million/mL] vs. 13.8 million/mL [3.1–36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%–25.3%] vs. 20.0% [7.0%–36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. Conclusions More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Purpose: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). Materials and Methods: Data from 1,230 consecutive men presenting for primary couple’s infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. Results: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34–41 years] vs. 36.0 years [31–40 years]); had smaller testicular volume (TV) (12 mL [10–15 mL] vs. 15 mL [12–20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9–11.0 million/mL] vs. 13.8 million/mL [3.1–36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%–25.3%] vs. 20.0% [7.0%–36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. Conclusions More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Purpose: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). Materials and Methods: Data from 1,230 consecutive men presenting for primary couple’s infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. Results: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34–41 years] vs. 36.0 years [31–40 years]); had smaller testicular volume (TV) (12 mL [10–15 mL] vs. 15 mL [12–20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9–11.0 million/mL] vs. 13.8 million/mL [3.1–36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%–25.3%] vs. 20.0% [7.0%–36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. Conclusions More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Purpose: To assess the relationship between clinical and semen characteristics and assisted reproductive technology (ART) outcomes with different birth weight (BW) categories in a cohort of infertile men. Materials and Methods: Data from 1,063 infertile men were analyzed. Patients with BW ≤2,500, 2,500–4,000, and ≥4,000 g were considered as having low BW (LBW), normal BW (NBW), and high BW (HBW), respectively. Testicular volume (TV) was assessed with a Prader orchidometer. Serum hormones were measured in all cases. Semen analyses were categorized based on 2021 World Health Organization reference criteria. Sperm DNA fragmentation (SDF) was tested in every patient and considered pathological for SDF >30%. ART outcomes were available for 282 (26.5%) patients. Descriptive statistics and logistic regression analyses detailed the association between semen parameters and clinical characteristics and the defined BW categories. Results: Of all, LBW, NBW, and HBW categories were found in 79 (7.5%), 807 (76.0%), and 177 (16.5%) men, respectively. LBW men had smaller TV, presented higher follicle-stimulating hormone (FSH) but lower total testosterone levels compared to other groups (all p<0.01). Sperm progressive motility (p=0.01) and normal morphology (p<0.01) were lower and SDF values were higher (all p<0.01) in LBW compared to other groups. ART pregnancy outcomes were lower in LBW compared to both NBW and HBW categories (26.1% vs. 34.5% vs. 34.5%, p=0.01). At multivariable logistic regression analysis, LBW was associated with SDF >30% (odd ratio [OR] 3.7; p<0.001), after accounting for age, Charlson Comorbidity Index (CCI), FSH, and TV. Similarly, LBW (OR 2.2; p<0.001), SDF >30% (OR 2.9; p<0.001) and partner’s age (OR 1.3; p=0.001) were associated with negative ART outcomes, after accounting for the same predictors. Conclusions LBW was associated with impaired clinical and semen characteristics in infertile men compared to both NBW and HBW. SDF and ART outcomes were significantly worse in the LBW group.

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.

Infertility is a prevalent issue affecting many couples during their reproductive years, with a significant number facing challenges in conceiving despite regular unprotected intercourse. Male factor infertility (MFI) contributes significantly to these cases, with a significant proportion of men lacking an identifiable etiology. As such, a thorough assessment of MFI has become increasingly vital for personalized management. This position paper from the Andrology team at IRCCS Ospedale San Raffaele emphasizes a comprehensive and individualized approach to MFI work-up, addressing the evolving challenges encountered in clinical practice. Our approach involves a thorough diagnostic work-up to identify the underlying causes of MFI, integrating insights from extensive literature review and our proprietary data. Our data demonstrates that an extensive diagnostic assessment allows us to identify at least one underlying cause of MFI in most infertile men. However, challenges persist in diagnosing less severe phenotypes with unclear etiology. We discuss the importance of individualized MFI work-up and its implications for developing rational therapeutic protocols. Lastly, this paper highlights the necessity for a personalized diagnostic assessment, addressing the daily clinical challenges and emphasizing tailored approaches to try to improve outcomes among couples seeking first medical help for infertility.

Infertility is a prevalent issue affecting many couples during their reproductive years, with a significant number facing challenges in conceiving despite regular unprotected intercourse. Male factor infertility (MFI) contributes significantly to these cases, with a significant proportion of men lacking an identifiable etiology. As such, a thorough assessment of MFI has become increasingly vital for personalized management. This position paper from the Andrology team at IRCCS Ospedale San Raffaele emphasizes a comprehensive and individualized approach to MFI work-up, addressing the evolving challenges encountered in clinical practice. Our approach involves a thorough diagnostic work-up to identify the underlying causes of MFI, integrating insights from extensive literature review and our proprietary data. Our data demonstrates that an extensive diagnostic assessment allows us to identify at least one underlying cause of MFI in most infertile men. However, challenges persist in diagnosing less severe phenotypes with unclear etiology. We discuss the importance of individualized MFI work-up and its implications for developing rational therapeutic protocols. Lastly, this paper highlights the necessity for a personalized diagnostic assessment, addressing the daily clinical challenges and emphasizing tailored approaches to try to improve outcomes among couples seeking first medical help for infertility.

Infertility is a prevalent issue affecting many couples during their reproductive years, with a significant number facing challenges in conceiving despite regular unprotected intercourse. Male factor infertility (MFI) contributes significantly to these cases, with a significant proportion of men lacking an identifiable etiology. As such, a thorough assessment of MFI has become increasingly vital for personalized management. This position paper from the Andrology team at IRCCS Ospedale San Raffaele emphasizes a comprehensive and individualized approach to MFI work-up, addressing the evolving challenges encountered in clinical practice. Our approach involves a thorough diagnostic work-up to identify the underlying causes of MFI, integrating insights from extensive literature review and our proprietary data. Our data demonstrates that an extensive diagnostic assessment allows us to identify at least one underlying cause of MFI in most infertile men. However, challenges persist in diagnosing less severe phenotypes with unclear etiology. We discuss the importance of individualized MFI work-up and its implications for developing rational therapeutic protocols. Lastly, this paper highlights the necessity for a personalized diagnostic assessment, addressing the daily clinical challenges and emphasizing tailored approaches to try to improve outcomes among couples seeking first medical help for infertility.