Factors associated with undergoing microdissection testicular sperm extraction among men with non-obstructive azoospermia following evaluation by a reproductive urologist.

Background: Microdissection testicular sperm extraction (mTESE) is the gold standard treatment for men with non-obstructive azoospermia (NOA). However, many men do not elect to pursue this surgical intervention. We aimed to identify factors associated with NOA patients undergoing mTESE after initial evaluation by a reproductive urologist (RU) through a retrospective cohort study. Methods: We retrospectively reviewed NOA patient who underwent evaluation by a RU between 2002-2018. Demographic and clinical data were collected. Our primary outcome was electing to undergo mTESE. Results: 44.4% (75/169) of NOA men underwent mTESE. These patients earned significantly higher median neighborhood income ($133,000 vs. $97,000, P<0.001), spent fewer years trying to conceive before seeking care {1.3 [interquartile range (IQR): 1-3] vs. 2.3 (IQR: 1-5), P=0.012}, and were more likely to be married (79.7% vs. 53.9%, P=0.001). On univariate analysis, married men [odds ratio (OR) 3.37, 95% confidence interval (CI): 1.67-6.79, P=0.001] and men with higher neighborhood income (OR 1.14, 95% CI: 1.06-1.21, P<0.001) were more likely to undergo mTESE, while couples attempting to conceive for a longer period of time prior to initial evaluation were less likely to undergo mTESE (OR 0.79, 95% CI: 0.68-0.92, P=0.003). On multivariable regression analysis, marital status and years attempting to conceive remained significantly associated with NOA patients undergoing mTESE (OR 4.61, 95% CI: 1.16-18.25, P=0.03; OR 0.67, 95% CI: 0.52-0.88, P=0.003, respectively). Conclusions: Higher neighborhood income and marital status were positively associated with patients undergoing mTESE, while couples who attempted to conceive for a longer period of time before seeking infertility care were less likely to undergo mTESE.

Characteristics of men who use direct-to-consumer men's health telemedicine services.

The characteristics of men who use direct-to-consumer (DTC) men's health services are not well understood. We conducted an online survey of adult men via ResearchMatch, assessing sociodemographic data, health behaviors, and concern for low testosterone and infertility. Logistic regression estimated the association between participant characteristics and familiarity with and reported use of DTC services such as Hims® and Roman®. Among 1276 men surveyed, 62.2% were concerned about low testosterone. While almost half (48.5%) were familiar with men's DTC health services, only 37 (2.9%) reported using these services. On multivariable analysis, men who used DTC men's health services were more likely to be younger (age 18-39: odds ratio [OR] 2.94, 95% confidence interval [CI] 1.03-8.38, p = 0.04; age 40-59: OR 3.26, CI 1.17-9.10, p = 0.02; referent age ≥60), have annual income between $75k and $100k (OR 5.25, CI 1.39-19.87.45, p = 0.02), and be concerned about low testosterone (OR 3.81, CI 1.46-9.96, p = 0.01). In conclusion, younger men and those with mid-range incomes were more likely to use online DTC men's health services compared to older or wealthier men. Likewise, men with concerns about low testosterone were more likely to use DTC services, but other health-conscious behaviors and frequency of doctor visits did not predict use.

Self-Reported Race/Ethnicity Is Not Associated with Abnormal Semen Parameters after Accounting for Body Mass Index and Socioeconomic Status.

PURPOSE: We evaluated whether consideration of body mass index (BMI) and socioeconomic status alters the reported association between race/ethnicity and abnormal semen parameters. MATERIALS AND METHODS: We conducted a retrospective review of all men who underwent semen analysis (SA) for fertility evaluation at an integrated academic health care system from 2002 to 2021. Men were excluded if they had a diagnosis of Klinefelter's syndrome, history of varicocele, prior testicular surgery, prior history of chemotherapy or radiation for cancer, or prior testosterone-modulating medication use. Chi-square and Kruskal-Wallis tests were used to analyze categorical and continuous variables across self-reported racial groups, respectively. Logistic regression was used to evaluate the association between race and abnormal semen parameters according to WHO 2010 criteria, controlling for potential confounders. RESULTS: Among 2,750 men meeting inclusion criteria, 2,037 (74.1%) identified as White Non-Hispanic, 207 (7.5%) as Black Non-Hispanic, 245 (8.9%) as Hispanic and 261 (9.5%) as Asian. Median age was 35 years (IQR 32-40). Black men had an older median age (37 years, IQR 33-42, p=0.002) than other groups at the time of index SA. While Black men had higher odds of abnormal sperm concentration (OR 1.46, 95% CI 1.06-2.02, p=0.02) and abnormal total motile sperm count (OR 1.65, 95% CI 1.21-2.25, p=0.001) compared to other men after adjusting for age alone, the association of race with abnormal semen parameters was rendered insignificant with the progressive inclusion of BMI, insurance status and neighborhood income as covariates. CONCLUSIONS: In men undergoing SA for fertility evaluation, we did not see evidence of an association between race/ethnicity and abnormal semen parameters after controlling for BMI, insurance status and neighborhood income.

Reproductive urologic consultation in subfertile men: predictors of establishing care and patient perceptions after abnormal semen testing.

OBJECTIVE: To evaluate the predictors of establishing care with a reproductive urologist (RU) among men with abnormal semen analyses (SAs) ordered by nonurologists and examine patient perceptions of abnormal SAs in the absence of RU consultation. DESIGN: Retrospective cohort study with cross-sectional survey. SETTING: Large, integrated academic healthcare system during 2002-2019. PATIENT(S): We identified adult men undergoing initial SAs with nonurologists who had abnormalities. Patients with index SAs during 2002-2018 were included for the analysis of RU consultation. Men tested in 2019 were recruited for cross-sectional survey. INTERVENTION(S): Cross-sectional survey. MAIN OUTCOME MEASURE(S): RU consultation and accurate perception of abnormal SAs. RESULT(S): A total of 2,283 men had abnormal SAs ordered by nonurologists, among whom 20.5% underwent RU consultation. Mixed-effect logistic regression modeling identified oligospermia as the strongest predictor of RU care (odds ratio, 3.08; 95% confidence interval, 2.43-3.90) with a significant provider-level random intercept. We observed substantial provider-level heterogeneity among nonurologists with provider-specific rates of RU evaluation ranging from 3.7% to 35.8%. We contacted 310 men who did not undergo RU consultation with a 27.2% survey response rate. Of respondents, 6.7% reported receiving an RU referral. Among men with abnormal SAs not evaluated by RU, 22.7% appropriately perceived an abnormal SA. CONCLUSION(S): In men with abnormal SAs diagnosed by nonurologists, the rate of RU consultation was low and associated with substantial provider-level variation among ordering providers. Patients without RU consultation reported inaccurate perceptions of their SA. Multidisciplinary efforts are needed to ensure that subfertile men receive appropriate RU evaluation.

Prevalence of Hyperprolactinemia and Clinically Apparent Prolactinomas in Men Undergoing Fertility Evaluation.

OBJECTIVE: To determine prevalence of hyperprolactinemia and prolactinoma among men presenting for initial fertility evaluation. METHODS: We performed a retrospective review of men presenting for initial fertility evaluation at a tertiary care, academic health system between 1999 and 2018. Men with measured prolactin levels were analyzed to determine prevalence of hyperprolactinemia and prolactinoma. We compared clinical characteristics of men with and without hyperprolactinemia. Univariable and multivariable analysis were used to determine factors associated with hyperprolactinemia. We assessed effects of hyperprolactinemia and prolactinoma on testosterone levels, semen parameters and pregnancy outcomes after treatment. RESULTS: A total of 3101 men had serum prolactin level measured. 65 (2.1%) had hyperprolactinemia. Patients with hyperprolactinemia had lower testosterone (median 280 ng/dL vs 313 ng/dL, P = 0.038) and lower total motile sperm count (median 7.0 million vs 34.7 million, P = 0.001) compared to men without hyperprolactinemia. 43.1% of men with hyperprolactinemia had oligospermia vs 21.5% of men without hyperprolactinemia (P<0.001). Univariable analysis demonstrated that men with elevated luteinizing hormone (LH) (OR 1.077, P = 0.001) and follicle-stimulating hormone (FSH) (OR 1.032, P = 0.002) were more likely to have hyperprolactinemia. Men with oligospermia were more likely to have hyperprolactinemia (OR 2.334, P = 0.004). On multivariable analysis, neither hormone parameters nor oligospermia were associated with elevated prolactin (P>0.05). Of the 65 men with hyperprolactinemia, 11 (17%) were diagnosed with a prolactinoma, resulting in an overall prevalence of 11 in 3101 (0.35%). CONCLUSION: The overall prevalence of prolactinoma in our cohort of men undergoing fertility evaluation was 35-fold higher than the prevalence in the general male population.

The adverse association between stimulant use for attention deficit hyperactivity disorder (ADHD) and semen parameters.

This study examined the relationship between stimulant medications used for the treatment of attention deficit hyperactivity disorder and semen parameters. We performed a retrospective cohort study at a large, academic institution between 2002 and 2020. We included men with a semen analysis without prior spermatotoxic medication use, empiric medical therapy exposure or confounding medical diagnoses (varicocele, Klinefelter's syndrome, cryptorchidism, cystic fibrosis, diabetes, cancer or cancer-related treatment, and azoospermia). Men were stratified by stimulant exposure (methylphenidate or amphetamines). A multivariable linear regression was fit to assess the association between individual semen parameters, age, stimulant exposure and non-stimulant medication use. Of 8,861 men identified, 106 men had active prescriptions for stimulants within 90 days prior to semen testing. After controlling for age and exposure to non-stimulant medications, stimulant use was associated with decreased total motile sperm count (ß: -18.00 mil/ejaculate and standard error: 8.44, p = 0.033) in the setting of decreased semen volume (ß: -0.35 ml, and standard error: 0.16, p = 0.035), but not sperm concentration, motility and morphology. These findings suggest a role for reproductive physicians and mental health providers to consider counselling men on the potential negative impact of stimulants prescribed for attention deficit hyperactivity disorder on semen volume during fertility planning.

Characterizing the Epidemiology and Provider Landscape of Male Infertility Care in the United States.

OBJECTIVE: To characterize the epidemiology of male factor infertility and identify which types of providers are treating infertile men in the United States. MATERIALS AND METHODS: The National Ambulatory Medical Care Survey was queried between 2006 and 2016 for all ambulatory care visits. Men with a diagnosis of infertility were identified by international classification of disease coding. Comorbidities, demographic and visit information were abstracted from the patients' medical record by a combination of trained surveyors and physicians. The survey data was weighted to create nationally representative estimates, and a combination of Chi-squared and Student's t-tests were utilized to determine significance. RESULT(S): Among the 8.7 billion patient visits between 2006 and 2016, there were 3,422,000 male encounters with a diagnosis of male factor infertility. The most common provider type for male factor infertility encounters was urology (42.12%) followed by primary care (39.79%), gynecology (7.05%) and all other provider types (11.01%). A significant number of men seen for infertility had comorbidities such as cancer (115,000 men, 3.36%) diabetes (267,000 men, 7.81%), depression (301,000 men, 8.8%), and active tobacco use (857,000 men, 30.3%). CONCLUSION: In a nationally representative sample, more than 50% of ambulatory care visits for male factor infertility were not seen by urologists. These men also had a significant number of comorbidities for a relatively young cohort, emphasizing the importance of multidisciplinary care for men with a diagnosis of infertility.

Understanding Students' Mental Well-Being Challenges on a University Campus: Interview Study.

BACKGROUND: Research shows that emerging adults face numerous stressors as they transition from adolescence to adulthood. This paper investigates university students' lived experiences of maintaining mental well-being during major life events and challenges associated with this transitional period. As we continue to design health technology to support students' mental health needs, it is imperative to understand the fundamental needs and issues particular to this phase of their life to effectively engage and lower the barriers to seeking help. OBJECTIVE: This study first aimed to understand how university students currently seek and receive support to maintain their mental well-being while going through frequent life events during this period of emerging adulthood. The study then aimed to provide design requirements for how social and technical systems should support the students' mental well-being maintenance practice. METHODS: Semistructured interviews with 19 students, including graduate and undergraduate students, were conducted at a large university in the Midwest in the United States. RESULTS: This study's findings identified three key needs: students (1) need to receive help that aligns with the perceived severity of the problem caused by a life event, (2) have to continuously rebuild relationships with support givers because of frequent life events, and (3) negotiate tensions between the need to disclose and the stigma associated with disclosure. The study also identified three key factors related to maintaining mental well-being: time, audience, and disclosure. CONCLUSIONS: On the basis of this study's empirical findings, we discuss how and when help should be delivered through technology to better address university students' needs for maintaining their mental well-being, and we argue for reconceptualizing seeking and receiving help as a colearning process.

4-1BB agonism: adding the accelerator to cancer immunotherapy.

The success of checkpoint inhibitors has validated immunomodulatory agents as a valuable class of anticancer therapeutics. A promising co-stimulatory immunologic target is 4-1BB, or CD137, a member of the tumor necrosis factor receptor superfamily. Ligation of 4-1BB induces an activating signal in CD8(+) T cells and natural killer cells, resulting in increased pro-inflammatory cytokine secretion, cytolytic function, and antibody-dependent cell-mediated cytotoxicity. Targeting 4-1BB with agonistic monoclonal antibody (mAb) therapy demonstrated potent antitumor effects in murine tumor models. While anti-4-1BB mAbs have entered clinical trials, optimal efficacy of 4-1BB-targeted agents will inevitably come from combination therapeutic strategies. Checkpoint blockade is a compelling combination partner for 4-1BB agonism. This novel immunotherapeutic approach has the potential to active antitumor immune effectors by a complementary mechanism: simultaneously "removing the brakes" via blocking inhibitory signaling and "stepping on the accelerator" via co-stimulation. While important considerations should be given to 4-1BB-mediated toxicities, the current understanding of 4-1BB biology suggests it may play a key role in advancing the capabilities of cancer combination therapy.