Novel reference range values for serum testosterone: a cross-sectional study of 200,000 males.

PURPOSE: To better understand the effects of aging, metabolic syndrome, diurnal variation, and seasonal variation on serum testosterone levels in the context of current guideline statements on testosterone deficiency. METHODS: This cross-sectional study utilized the United Kingdom Biobank. Physical examination, anthropomorphic measurements, and laboratory evaluation were performed at the time of enrollment from 2006 to 2010. The primary outcomes were the effect of age, the presence of metabolic syndrome, the time of day, and the month of the year on serum testosterone levels. RESULTS: Among 197,883 included men, the 5th, 25th, 50th, 75th and 95th percentile testosterone levels in men without metabolic syndrome were significantly higher than those in men with metabolic syndrome at every decade of life (p < 0.001). The average testosterone level within each group (men without metabolic syndrome vs. men with) was clinically similar across decade of life (12.43 in 40's 12.29 in 50's 12.24 in 60's vs. 10.69 in 40's 10.56 in 50's 10.63 in 60's respectively). Average testosterone levels decreased with blood draws later in the day ranging from 10.91 to 12.74 nmol/L (p < 0.01). Similarly, there was seasonal variation in serum testosterone ranging from 11.86 to 12.18 nmol/L (p < 0.01). CONCLUSIONS: We found significant variation in serum testosterone according to the presence of metabolic syndrome and time of laboratory draw, but not according to age. These data challenge the prior dogma of age-related hypogonadism and favor an individualized approach towards serum testosterone measurement and interpretation. However, further studies are needed to correlate these population-based data with individuals' hypogonadal symptoms.

Urologist Access for the Male Population: An 18-Year Study on Population Trends.

INTRODUCTION: Our study examines the factors associated with urologist availability for younger and older men across the country over a period of 18 years from 2000 to 2018. METHODS: The Area Health Resource Files and US Census Data were analyzed from 2000, 2010, and 2018. The younger male population was defined as men aged 20 to 49, and the older male population was defined as ages 50 to 79. Urologist availability was determined by county at all time points. Logistic regression analysis and geographically weighted regression was completed. RESULTS: Over an 18-year period, overall urologist availability decreased for men by 19.6%. Access to urologist availability for men in metropolitan and rural counties decreased by 9.4% and 29.5%, respectively. Among the younger male cohort, urologist availability increased in metropolitan counties by 4%, but decreased by 16% in rural counties. There was an overall decrease in urologist availability of 28% and 43% in metropolitan and rural counties in the older male population. Multiple logistic regression analysis demonstrated that metropolitan status was the most significant factor associated with urologist availability for both male populations. The odds of each independent factor predicting urologist availability for the younger and older male population is dependent on geography. CONCLUSIONS: The majority of the male population has seen a decline in urologist availability. This is especially true for the older male residing in a rural county. Predictors of urologist availability depend on geographical regions, and understanding these regional drivers may allow us to better address disparities in urological care.

Assisted reproductive technology cycles involving male factor infertility in the United States, 2017-2018: data from the National Assisted Reproductive Technology Surveillance System.

Objective: To describe the prevalence and treatment characteristics of assisted reproductive technology (ART) cycles involving specific male factor infertility diagnoses in the United States. Design: Cross-sectional analysis of ART cycles in the National ART Surveillance System (NASS). Setting: Clinics that reported patient ART cycles performed in 2017 and 2018. Patients: Patients who visited an ART clinic and the cycles were reported in the NASS. The ART cycles included all autologous and donor cycles that used fresh or frozen embryos. Interventions: Not applicable. Main Outcome Measures: Analyses used new, detailed reporting of male factor infertility subcategories, treatment characteristics, and male partner demographics available in the NASS. Results: Among 399,573 cycles started with intent to transfer an embryo, 30.4% (n = 121,287) included a male factor infertility diagnosis as a reason for using ART. Of these, male factor only was reported in 16.5% of cycles, and both male and female factors were reported in 13.9% of cycles; 21.8% of male factor cycles had >1 male factor. Abnormal sperm parameters were the most commonly reported diagnoses (79.7%), followed by medical condition (5.3%) and genetic or chromosomal abnormalities (1.0%).Males aged ≤40 years comprised 59.6% of cycles with male factor infertility. Intracytoplasmic sperm injection was the primary method of fertilization (81.7%). Preimplantation genetic testing was used in 26.8%, and single embryo transfer was used in 66.8% of cycles with male factor infertility diagnosis. Conclusions: Male factor infertility is a substantial contributor to infertility treatments in the United States. Continued assessment of the prevalence and characteristics of ART cycles with male factor infertility may inform treatment options and improve ART outcomes. Future studies are necessary to further evaluate male factor infertility.

Infertility Counseling and Misattributed Paternity: When Should Physicians Become Involved in Family Affairs?

Infertility specialists may be confronted with the ethical dilemma of whether to disclose misattributed paternity (MP). Physicians should be prepared for instances when an assumed father's evaluation reveals a condition known for lifelong infertility, for example, congenital bilateral absence of vas deferens (CBAVD). When there is doubt regarding a patient's comprehension of his diagnosis, physicians must consider whether further disclosure is warranted. This article describes a case of MP with ethics analysis that concludes that limited nondisclosure is most consistent with a physician's principled duties to inform, to respect patients' autonomy, and to employ nonmaleficence (including the avoidance of psychosocial harms).

18-Year Population Trends Determine Factors Associated with Future Access to Urologists.

INTRODUCTION: Our study evaluated urologist availability by United States county since 2000 relative to regional changes in the general population to identify factors associated with access to care. METHODS: County-level data from 2000, 2010 and 2018 from the Department of Health and Human Services, U.S. Census and American Community Survey were analyzed. Availability of urologists by county was defined as urologists per 10,000 adults. Multiple logistic and geographically weighted regression were performed. A predictive model was formulated with tenfold cross-validation (AUC=0.75). RESULTS: Despite a 6.95% increase in urologists over 18 years, local urologist availability declined 13% (-0.03 urologists/10,000 individuals, 95% CI 0.02-0.04, p <0.0001). On multiple logistic regression, metropolitan status was the greatest predictor of urologist availability (OR 1.86, 95% CI 1.47-2.34), followed by prior urologist presence (OR 1.49, 95% CI 1.16-1.89), defined as a higher number of urologists in 2000. The predictive weight of these factors varied by U.S. region. All regions experienced worsening overall urologist availability, with rural areas suffering the most. Large population shifts away from the Northeast to the West and South were outpaced by urologists leaving the Northeast, the only region with a decreasing number of total urologists (-1.36%). CONCLUSIONS: Urologist availability declined in every region over nearly 2 decades likely due to an increasing general population and inequitable regional migration. Predictors of urologist availability differed by region, and thus it will be necessary to investigate regional drivers influencing population shifts and urologist concentration to prevent worsening disparities in care.

One size does not fit all: variations by ethnicity in demographic characteristics of men seeking fertility treatment across North America.

OBJECTIVE: To compare racial differences in male fertility history and treatment. DESIGN: Retrospective review of prospectively collected data. SETTING: North American reproductive urology centers. PATIENT(S): Males undergoing urologist fertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographic and reproductive Andrology Research Consortium data. RESULT(S): The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, <1% Native Hawaiian/Other Pacific Islander, and 21% "Other". White males sought evaluation sooner (3.5 ± 4.7 vs. 3.8 ± 4.2 years), had older partners (33.3 ± 4.9 vs. 32.9 ± 5.2 years), and more had undergone vasectomy (8.4% vs. 2.9%) vs. all other races. Black males were older (38.0 ± 8.1 vs. 36.5 ± 7.4 years), sought fertility evaluation later (4.8 ± 5.1 vs. 3.6 ± 4.4 years), fewer had undergone vasectomy (3.3% vs. 5.9%), and fewer had partners who underwent intrauterine insemination (8.2% vs. 12.6%) compared with all other races. Asian/Indo-Canadian/Indo-American patients were younger (36.1 ± 7.2 vs. 36.7 ± 7.6 years), fewer had undergone vasectomy (1.2% vs. 6.9%), and more had partners who underwent intrauterine insemination (14.2% vs. 11.9%). Indian/Native males sought evaluation later (5.1 ± 6.8 vs. 3.6 ± 4.4 years) and more had undergone vasectomy (13.4% vs. 5.7%). CONCLUSION(S): Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.

Impact of Fellowship-Trained Andrology and Sexual Medicine Specialists on Performance on the Annual American Urological Association In-Service Examination.

OBJECTIVE: To demonstrate the distribution and impact of fellowship-trained andrology and/or sexual medicine urological specialists (FTAUS) on resident in-service examination (ISE) performance. METHODS: Residency program websites were accessed to create a database of FTAUS in the United States between 2007 and 2017. This database was reviewed by three separate FTAUS and cross referenced with membership lists to the Sexual Medicine of North America Society and the Society for the Study of Male Reproduction. De-identified ISE scores were obtained from the American Urological Association from 2007-2017 and scores from trainees at programs with a FTAUS were identified for comparison. Resident performance was analyzed using a linear model of the effect of a resident being at a program with an FTAUS, adjusting for post-graduate year. RESULTS: ISE data from 13,757 residents were obtained for the years 2007-2017. The number of FTAUS in the United States increased from 40-102 during this study period. Mean raw scores on the "Sexual Dysfunction, Endocrinopathy, Fertility Problems" (SDEFP) section of the ISE ranged from 52.1% ± 17.7% to 65.7% ± 16% (mean ± SD). Throughout the study period, there was no difference in performance within the SDEFP section (P < .01). Residents at a program with a FTAUS answered 0.95% more questions correctly in the SDEFP than those without a FTAUS (P < .001). For these residents, there was an improvement of approximately 0.66% on the percentage of questions answered correctly on the ISE overall (P < .001). Performance improved significantly as residents progressed from PGY-2-PGY-5. CONCLUSION: There is a small but statistically significant improvement in overall ISE and SDEFP sub-section performance.

The Impact of Physician Productivity Models on Access to Subspecialty Care: A White Paper From the Society for the Study of Male Reproduction and the Society for Male Reproduction and Urology.

Male infertility is a common disease. Male infertility is also a core competency of urology training and clinical practice. In this white paper from the Society for the Study of Male Reproduction and the Society for Male Reproduction and Urology, we identify and define different physician productivity plans. We then describe the advantages and disadvantages of various physician productivity measurement systems for male infertility practices. We close with recommendations for measuring productivity that we hope urologists and administrators can use when creating productivity plans for male infertility practices.

Eighteen-Year Review of Resident Performance on the American Urological Association In-Service Examination.

OBJECTIVE: To analyze national performance trends of urology residents on the American Urological Association In-Service Examination (ISE) over the last 18 years. METHODS: Trends in the national averages on the in-service examination for each year of residency training were collected and analyzed between the years 2000 and 2017. Mean and standard error were calculated for examination performance for each year of residency. Subject-specific performance was also determined for each given year of residency. Regression analysis was used to model trends in performance as a function of residency year. RESULTS: There was no significant difference in examination performance over 18 years with respect to each specific residency year. While there was an overall improvement in total scores with each advancing training year, year-over-year improvement in total examination performance began to plateau after Uro-2. Largest absolute performance improvement from Pre-Uro to Uro-4 were in subjects of "Urinary Diversion," "Obstructive Uropathy" and "Neoplasm." Scores in "Sexual Dysfunction, Endocrinopathy, Fertility Problems", and "Congenital Anomalies, Embryology, Anatomy" were consistently the lowest regardless of year of training. CONCLUSION: No significant change in performance was seen in each given year of residency over the 18-year period. There was improvement in overall scores as residents progressed through training, but scores plateaued after Uro-2 with minimal improvement between Uro-3 and Uro-4 years. Difference in subject scores suggests a disparity in educational focus in residency curricula and a potential need to improve the teaching strategies for subjects that tested less well throughout residency training.

Reproductive endocrinologists are the gatekeepers for male infertility care in North America: results of a North American survey on the referral patterns and characteristics of men presenting to male infertility specialists for infertility investigations.

OBJECTIVE: To characterize the referral patterns and characteristics of men presenting for infertility evaluation using data obtained from the Andrology Research Consortium. DESIGN: Standardized male infertility questionnaire. SETTING: Male infertility centers. PATIENT(S): Men presenting for fertility evaluation. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Demographic, infertility history, and referral data. RESULT(S): The questionnaires were completed by 4,287 men, with a mean male age of 40 years ± 7.4 years and female partners age of 37 years ± 4.9 years. Most were Caucasian (54%) with other races being less commonly represented (Asian 18.6%, and African American 5.5%). The majority (59.7%) were referred by a reproductive gynecologist, 19.4% were referred by their primary care physician, 4.2% were self-referred, and 621 (14.5%) were referred by "other." Before the male infertility investigation, 12.1% of couples had undergone intrauterine insemination, and 4.9% of couples had undergone in vitro fertilization (up to six cycles). Among the male participants, 0.9% reported using finasteride (5α-reductase inhibitor) at a dose used for androgenic alopecia, and 1.6% reported exogenous testosterone use. CONCLUSION(S): This broad North American patient survey shows that reproductive gynecologists are the de facto gateway for most male infertility referrals, with most men being assessed in the male infertility service being referred by reproductive endocrinologists. Some of the couples with apparent male factor infertility are treated with assisted reproductive technologies before a male factor investigation. The survey also identified potentially reversible causes for the male infertility including lifestyle factors such as testosterone and 5α-reductase inhibitor use.

An Evaluation of Reported Follicle-stimulating Hormone, Luteinizing Hormone, Estradiol, and Prolactin Reference Ranges in the United States.

OBJECTIVE: To characterize US clinical laboratory reference range reporting and testing methods of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and prolactin. METHODS: One hundred and seventeen US laboratories were surveyed. Outcomes measured were variation in lower and upper limits of normal male reference ranges for serum FSH, LH, estradiol, and prolactin, method of analysis and source of reference range RESULTS: The upper limit of normal reference ranges for FSH, LH, estradiol, and prolactin varied substantially across laboratories compared to the lower limits. The range of upper limits of FSH, LH, estradiol, and prolactin respectively are 7.9-20.0, 4.9-86.5, 37.7-77.0, and 7.4-25.0. Ninety-four percent of laboratories performed measurements on in-house high throughput analyzer utilizing immunoassays. Seventy percent of reported reference ranges for each hormone were based on validation studies of the analyzer's package insert values. Ten percent of laboratories derived their own reference ranges. Both the validation studies and derivations were based on a limited number of patient samples, ranging from 20 to 200. CONCLUSION: Current reference ranges are based on small population studies of men with unknown medical histories, sexual or reproductive function. Influence of race and age has not been evaluated and could potentially be important in normal variation. The absence of standard information has yielded a spectrum of upper and lower normal values, which could delay an appropriate male infertility evaluation. Our findings highlight the need for a large population study of males with known normal sexual and reproductive function to formulate more accurate clinical reference ranges.

Intracytoplasmic sperm injection use in states with and without insurance coverage mandates for infertility treatment, United States, 2000-2015.

OBJECTIVE: To compare indications and trends in intracytoplasmic sperm injection (ICSI) use for in vitro fertilization (IVF) cycles among residents of states with and without insurance mandates for IVF coverage. DESIGN: Cross-sectional analysis of the National Assisted Reproductive Technology Surveillance System from 2011 to 2015 for the main outcome and from 2000 to 2015 for trends. SETTING: IVF cycles performed in U.S. fertility clinics. PATIENT(S): Fresh IVF cycles. INTERVENTION(S): Residency in a state with an insurance mandate for IVF (n = 8 states) versus no mandate (n = 43 states, including DC). MAIN OUTCOME MEASURE(S): ICSI use by insurance coverage mandate status stratified by male-factor infertility diagnosis. RESULT(S): During 2000-2015, there were 1,356,377 fresh IVF cycles, of which 25.8% (n = 350,344) were performed for residents of states with an insurance coverage mandate for IVF. ICSI use increased significantly during 2000-2015 in states both with and without a mandate; however, for non-male-factor infertility cycles, the percentage increase in ICSI use was greater among nonmandate states (34.6% in 2000 to 73.9% in 2015) versus mandate states (39.5% in 2000 to 63.5% in 2015). For male-factor infertility cycles, this percentage increase was ∼7.3% regardless of residency in a state with an insurance mandate for IVF. From 2011 to 2015, ICSI use was lower in mandate versus nonmandate states, both for cycles with (91.5% vs. 94.5%), and without (60.3% vs. 70.9%) male-factor infertility. CONCLUSION(S): Mandates for IVF coverage were associated with lower ICSI use for non-male-factor infertility cycles.