Rises in Hematocrit Are Associated With an Increased Risk of Major Adverse Cardiovascular Events in Men Starting Testosterone Therapy: A Retrospective Cohort Claims Database Analysis.

PURPOSE: Elevated hematocrit (Hct) can result in increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy (TTh). However, the impact of the magnitude of the change in Hct from baseline after starting TTh has never been assessed. MATERIALS AND METHODS: To assess whether an increase in Hct after initiating TTh is associated with an increased risk of MACE within 3 and 24 months of initiating TTh, we queried the TriNetX Research network database for men over the age of 18 with Hct values obtained within 6 months before starting TTh, and who had follow-up Hct measurements within 3 and 24 months after beginning TTh from 2010 to 2021. Men with and without a subsequent increase in Hct after initiating TTh were propensity matched. MACE was defined as myocardial infarction, stroke, or death. RESULTS: After matching, 10,511 men who experienced an any increase in Hct after initiating TTh and an equal number of controls who did have an increase in Hct were included. Compared to controls who did not have an increase in Hct after starting TTh, the men who had an increase in subsequent Hct had a significantly increased risk of MACE compared to men with no change in Hct. CONCLUSIONS: We demonstrate that increases in Hct from baseline are associated with increased risk of MACE, compared to men whose Hct remains stable while receiving TTh.

Characteristics of systemic testosterone therapy for female hypoactive sexual desire disorder-a claims database analysis.

BACKGROUND: Testosterone therapy (TTh) is recommended for postmenopausal women with hypoactive sexual desire disorder (HSDD); however, there remain insufficient data to support use of TTh in premenopausal women with sexual dysfunction. AIM: In this study, we used a large national database to evaluate prescribing trends of TTh for women with HSDD. METHODS: We conducted a cohort analysis of information from electronic health records acquired from the data network TriNetX Diamond. The study cohort consisted of women 18-70 years of age with a diagnosis of HSDD. We analyzed trends of testosterone prescriptions, routes of testosterone administration, and coadministration of testosterone with estrogen. OUTCOMES: Despite an increase in rates of testosterone prescriptions for HSDD, there remains a high degree of variability in the duration of treatment, route of administration, and coadministration of estrogen with significant underprescription of testosterone. RESULTS: Our query of the TriNetX database led to the identification of 33 418 women diagnosed with HSDD at a mean age of 44.2 ± 10.8 years, among whom 850 (2.54%) women received a testosterone prescription. The testosterone prescriptions were highly variable with regard to duration and route of administration and coadministration with estrogen. For all patients until 2015, the prevalence of testosterone prescriptions for HSDD showed a positive quadratic relation was observed. Since 2015 a linear increase in prevalence was observed, with the highest rate of increase for patients aged 41-55 years. CLINICAL IMPLICATIONS: The findings of this study reveal a significant need for further research investigating the optimal use of TTh to enhance the sexual health of women with HSDD, and further studies on the long-term effects of testosterone use must be undertaken to ensure that patients have access to safe and effective treatment. STRENGTHS AND LIMITATIONS: Limitations to this study include patient de-identification and lack of availability of testosterone dosage data. However, this study also has many strengths, including being the first, to our knowledge, to characterize the prescribing trends of testosterone for women with HSDD. CONCLUSION: Testosterone therapy should be considered as a potential therapy for premenopausal female patients with HSDD. Further studies on the long-term effects of testosterone use must be undertaken to address disparities in the management of HSDD and to ensure patients can access treatment.

Testosterone therapy in females is not associated with increased cardiovascular or breast cancer risk: a claims database analysis.

BACKGROUND: Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results. AIM: To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database. METHODS: The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years). OUTCOMES: We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh. RESULTS: When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56 years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls. CLINICAL IMPLICATIONS: Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women. STRENGTHS AND LIMITATIONS: The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors. CONCLUSIONS: We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis.

Antidepressant nonadherence and sexual dysfunction among young adult males: the cross-sectional YAMAN study.

PURPOSE: Selective serotonin reuptake inhibitors are associated with high rates of nonadherence and sexual dysfunction, yet the correlation between these findings in young adult men is poorly characterized. We aimed to evaluate if young adult men are less willing to adhere to antidepressant treatment due to intolerable side effects, such as sexual dysfunction. METHODS: Deidentified, compensated survey that assessed baseline demographics, PHQ-8 and GAD-7 scores, attitudes towards antidepressant medication side effects, and perceptions of antidepressant medications including selective serotonin reuptake inhibitors, bupropion, and mirtazapine. RESULTS: From 665 delivered surveys, 505 respondents completed their survey (response rate: 76%), of which 486 were included for final analysis. After seeing common side effect profiles, our sample's willingness to take sexual function-sparing agents, such as bupropion or mirtazapine, was significantly greater than selective serotonin reuptake inhibitors (p < 0.001), with no significant difference between bupropion and mirtazapine (p = 0.263). The negative influence of erectile dysfunction and anorgasmia scored significantly higher than other common antidepressant side effects like weight gain, nausea, and dry mouth (range: p < 0.001, p = 0.043). With the exception of insomnia, participants indicated that experiencing sexual dysfunction while taking an antidepressant medication would lead to nonadherence at a significantly higher frequency than any other side effect assessed (range: p < 0.001, p = 0.005). CONCLUSION: The risk of experiencing sexual side effects when taking antidepressants could lead young adult men to become nonadherent to these medications. Strategies to augment the effectiveness of antidepressants, such as shared decision-making and the use of sexual function-sparing agents, are critical.

Association between comorbidities and longitudinal changes in total testosterone among men from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Previous cross-sectional and longitudinal studies have described decreasing testosterone levels with age in men, without consideration of acquired comorbidities in aging males. AIM: We evaluated the longitudinal association between age and testosterone levels as well as the impact of several comorbidities on this relationship using multivariate panel regression analysis. METHODS: Participants were selected from the Baltimore Longitudinal Study of Aging. Data were obtained on the presence of several comorbidities and total testosterone level during each follow-up visit. A multivariate panel regression analysis was performed to determine the impact of age on testosterone level while controlling for individual comorbidities. OUTCOMES: The primary outcomes were strength of association between age and various comorbidities, and testosterone level. RESULTS: A total of 625 men were included in this study, with a mean age of 65 years and a mean testosterone level of 463 ng/dL. On multivariable-adjusted panel regression analysis, age was not significantly associated with testosterone decline, while anemia, diabetes mellitus, heart failure, obesity, peripheral artery disease, and stroke were inversely associated with total testosterone level. We report no association between cancer and total testosterone. CLINICAL IMPLICATIONS: This study indicates that a decline in testosterone levels over time may be due to the presence of various comorbidities, which affects the medical management of hypogonadism in aging men. STRENGTHS AND LIMITATIONS: The strengths of this study include the standardized acquisition of testosterone tests and uniform collection of variables, while limitations include the lack of follow-up data from 205 patients and the limited racial/ethnic diversity in the cohort. CONCLUSIONS: In this large longitudinal study, we found that when adjusted for the presence of concomitant comorbidities, age does not predict a significant decline in testosterone level. With the overall increase in life expectancy and the simultaneous rise in the incidence of comorbidities such as diabetes and dyslipidemia, our findings may help optimize screening and treatment for late-onset hypogonadism in patients with multiple comorbidities.

A comparison of adverse pregnancy events between ureteral stents and percutaneous nephrostomy tubes in the treatment of nephrolithiasis during pregnancy: A propensity score-matched analysis of a large multi-institutional research network.

PURPOSE: To investigate rates of adverse pregnancy events associated with the use of percutaneous nephrostomy tubes (PCN) versus ureteral stents in the treatment of nephrolithiasis during pregnancy. METHODS: We queried the TriNetX Diamond Network database to evaluate pregnant women (ICD-10 Z34, O09) with a history of nephrolithiasis (N20-23) who underwent a PCN (CPT 50432) or ureteral stent (52332) placement up to 6 months before delivery (O80-82). We controlled for the following potentially confounding variables through propensity score matching: age, race, ethnicity, acute pyelonephritis (N10), infections of the genitourinary tract in pregnancy (O23.0), and other sepsis (A41) at the time of stent or PCN placement. RESULTS: We identified 2,999 pregnant women who underwent ureteral stent placement and 321 who underwent PCN. Following propensity score matching, we found there to be no significant difference in the rate of premature labor or delivery (aOR 1.08, 95% CI 0.735-1.588), premature rupture of membranes (0.889, 0.453-1.743), intrauterine infection (0.906, 0.379-2.165), or c-Sect. (0.825, 0.408-1.667). Within 6 months of their initial procedure, women with a ureteral stent experienced a significantly decreased rate of subsequent urinary tract infection (UTI) or pyelonephritis (0.52, 0.38-0.71), inpatient hospital stay (0.40, 0.26-0.64), emergency department visit (0.65, 0.48-0.89), and repeat exchange procedure (0.70, 0.51-0.96). CONCLUSION: In the treatment of nephrolithiasis during pregnancy, PCN versus ureteral stent placement does not confer a significant difference in rates of adverse pregnancy events. However, ureteral stent placement was associated with a lower incidence of hospital admissions, emergency department visits, exchange procedures, and new UTIs or pyelonephritis.

The Effect of Route of Testosterone on Changes in Hematocrit: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Trials.

PURPOSE: We sought to compare testosterone formulations and determine the degree that hematocrit increases vary by testosterone therapy formulation. As head-to-head trials are rare, network meta-analysis of the contemporary studies is the only way to compare hematocrit changes by testosterone type, including topical gels and patches, injectables (both short-acting and long-acting) and oral tablets. MATERIALS AND METHODS: We conducted a thorough search of listed publications in Scopus®, PubMed®, Embase®, Cochrane CENTRAL, and ClinicalTrials.gov. A total of 29 placebo-controlled randomized trials (3,393 men) met inclusion criteria for analysis of mean hematocrit change after testosterone therapy. Randomized controlled trial data for the following formulations of testosterone were pooled via network meta-analysis: gel, patch, oral testosterone undecanoate, intramuscular testosterone undecanoate, and intramuscular testosterone enanthate/cypionate. RESULTS: All types of testosterone therapies result in statistically significant increases in mean hematocrit when compared with placebo. Meta-analysis revealed all formulations, including gel (3.0%, 95% CI 1.8-4.3), oral testosterone undecanoate (4.3%, 0.7-8.0), patch (1.4%, 0.2-2.6), intramuscular testosterone enanthate/cypionate (4.0%, 2.9-5.1), and intramuscular testosterone undecanoate (1.6%, 0.3-3.0) result in statistically significant increases in mean hematocrit when compared with placebo. When comparing all formulations against one another, intramuscular testosterone cypionate/enanthate were associated with a significantly higher increase in mean hematocrit compared to patch, but no differences in hematocrit between other formulations were detected. CONCLUSIONS: All types of testosterone are associated with increased hematocrit; however, the clinical concern of this increase remains questionable, warranting future studies. This is the first network meta-analysis to quantify mean hematocrit change and compare formulations, given the absence of head-to-head trials.

Testosterone Therapy is Associated With Depression, Suicidality, and Intentional Self-Harm: Analysis of a National Federated Database.

BACKGROUND: Long-term use of testosterone can be associated with mood destabilizing effects. Most studies investigating psychiatric complications of anabolic steroids have used small samples, but a comprehensive assessment of the risk of developing mental health disorders after testosterone use has not been performed at the population level. AIM: To determine whether testosterone therapy is associated with major depressive disorder or suicide attempts in men. METHODS: We conducted a retrospective cohort study of 70.3 million electronic health records collected from 46 healthcare organizations encompassing flagship hospitals, satellite hospitals, and outpatient clinics since 2008 to determine whether testosterone use is associated with major depressive disorder and suicide attempts in a large population. We included men 18 or older who either used testosterone or did not, defined by reported use, insurance claim, or prescription use of testosterone documented in the electronic health record. We propensity-score matched by age, race, ethnicity, obesity, and alcohol-related disorder. Additionally, a sub-group analysis was performed in testosterone deficient (<300 ng/dL) men comparing those with TD on testosterone therapy to a control group of men with TD who are not using testosterone. OUTCOMES: We determined measures of association with a new diagnosis of major depressive disorder and suicide attempt or intentional self-harm following testosterone use within 5 years. RESULTS: A total of 263,579 men who used testosterone and 17,838,316 men who did not were included in the analysis. Testosterone use was independently associated with both Major Depressive Disorder (OR 1.99, 95% CI 1.94-2.04, P < .0001) and Suicide Attempt/Intentional Self-Harm (OR 1.52, 95% CI 1.40-1.65, P < .0001). Results remained significant in testosterone deficient sub-group analysis. CLINICAL IMPLICATIONS: Men who use testosterone should be screened for and counseled about risks of depression and suicidality. STRENGTHS AND LIMITATIONS: Strengths of this study include a large sample size, the ability to account for chronology of diagnoses, the use of propensity score matching to control for potentially confounding variables, and the consistency of results with sub-group analyses. Limitations include the potential for incorrect coding within the electronic health record, a lack of granular information regarding testosterone therapy adherence, the possibility that unrecorded testosterone or anabolic steroid use were prevalent but not captured within the control group, and a lack of data regarding testosterone withdrawal. CONCLUSION: Testosterone use is independently associated with new-onset mental health disorders. Future studies are necessary to elucidate the role that androgen withdrawal plays and whether a causal relationship exists. Nackeeran S, Patel MS, Nallakumar DT, et al. Testosterone Therapy is Associated With Depression, Suicidality, and Intentional Self-Harm: Analysis of a National Federated Database. J Sex Med 2022;19:933-939.

Surgically Extracted Epididymal Sperm from Men with Obstructive Azoospermia Results in Similar In Vitro Fertilization/Intracytoplasmic Sperm Injection Outcomes Compared with Normal Ejaculated Sperm.

PURPOSE: Controversy exists around the use of epididymal sperm for in vitro fertilization and intracytoplasmic sperm injection for couples with obstructive azoospermia, and the ability to reliably predict fertility outcomes with surgically extracted epididymal sperm remains limited. To provide additional clinical context, we sought to compare in vitro fertilization/intracytoplasmic sperm injection outcomes of epididymal sperm from couples with obstructive azoospermia to outcomes of couples using normal, ejaculated sperm. MATERIALS AND METHODS: We performed a case-control analysis of 40 couples who underwent office based epididymal sperm retrieval for obstructive azoospermia followed by in vitro fertilization/intracytoplasmic sperm injection compared with a control group of 38 female, age matched couples with no evidence of female factor infertility who underwent in vitro fertilization/intracytoplasmic sperm injection with normal, ejaculated sperm. Primary outcome was live birth on the initial embryo transfer. RESULTS: Epididymal samples yielded a median total motile sperm count of 9.1 million, compared to 81 million for ejaculated sperm. On the primary embryo transfer fertilization rate (71% vs 77%, p=0.2), blastulation rate (48% vs 59%, p=0.09), clinical pregnancy rate (70% vs 58%, p=0.4), and live birth rate (58% vs 47%, p=0.4) did not differ between epididymal and ejaculated sperm groups. CONCLUSIONS: For couples with a male partner with obstructive azoospermia epididymal sperm in vitro fertilization/intracytoplasmic sperm injection outcomes compare similarly with age matched controls undergoing in vitro fertilization/intracytoplasmic sperm injection using normal, ejaculated sperm. These results may help reproductive surgeons provide reassurance about the use of obstructed epididymal sperm as well as help guide discussions about anticipated outcomes of in vitro fertilization/intracytoplasmic sperm injection.

Access to male fertility preservation information and referrals at National Cancer Institute Cancer Centers.

Cancer treatment can lead to infertility, which is a significant source of financial and emotional distress for cancer patients and survivors. Given that future fertility and sexual function are critical quality of life issues, we hypothesise that access to subspecialist care is not uniformly distributed. Therefore, we sought to identify access gaps in male sexual health and infertility care at NCI cancer centres across US Census Regions. All 64 clinical NCI cancer centre websites were examined for language related to male sexual health and fertility. A phone-based survey was used to establish cancer centre referral patterns to andrologists and sperm banks. We utilised the Society for the Study of Male Reproduction member directory to determine geographic locations for andrologists relative to each centre. We found that the presence of information regarding male sexual health information was not associated with region. The presence of andrologists within 5-miles of a CC was significantly higher in the Northeast compared to all other census regions. Our work describes the access gap in fertility services at NCI cancer centres and how this differs by region of the country. These data can inform patients, and encourage centres to provide improved access to oncofertility care.

Elevated sperm DNA fragmentation does not predict recurrent implantation failure.

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9-105.5] million. Overall median DFI% and HDS% was 12 [7.1-18.9] and 9.6 [6.5-14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98-1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94-1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99-1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99-1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.

Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function.

OBJECTIVES: Here we examine the association between shift work sleep disorder (SWSD) and erectile dysfunction (ED) in shift workers. METHODS: Men presenting to a single andrology clinic between January 2014 and July 2017 completed validated questionnaires: International Index of Erectile Function (IIEF), Patient Health Questionnaire-9 (PHQ-9), and the nonvalidated SWSD Questionnaire. Men were also asked about shift work schedule, comorbidities, phosphodiesterase 5 (PDE5) inhibitor use, and testosterone use. Serum total testosterone values were determined for each visit. Linear regression was performed controlling for testosterone use, testosterone levels, PDE5 inhibitor use, age, and comorbidities to determine the effect of SWSD on ED as assessed using the IIEF. RESULTS: Of the 754 men completing questionnaires, 204 reported nonstandard shift work (begins before 7 am or after 6 pm, regularly extends out of that frame, or rotates frequently) and 48 were found to have SWSD using a screening questionnaire. Nonstandard shift work alone did not result in worse IIEF-EF scores (P = .31), but those who worked nonstandard shifts and had SWSD demonstrated IIEF-EF scores 2.8 points lower than men without SWSD (P < .01). When assessing for the type of shift work performed, men who worked night shifts had IIEF-EF scores 7.6 points lower than men who worked during the day or evening (P < .01). Testosterone use improved IIEF-EF scores for men with SWSD by 2.9 points, ameliorating the effect of SWSD on ED. However, baseline testosterone levels were not associated with worse erectile function in this cohort. CONCLUSION: Men with SWSD have worse erectile function, with men who work night shifts having even poorer erectile function. These findings suggest that circadian rhythm disturbance may significantly impact erectile function. While testosterone therapy may partly reverse the effects of SWSD, shift work is a potential risk factor for ED and should be assessed for as part of the evaluation of men with ED. Rodriguez KM, Kohn TP, Kohn JR, et al. Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function. J Sex Med 2020;17:1687-1693.

The effect of tetrahydrocannabinol on testosterone among men in the United States: results from the National Health and Nutrition Examination Survey.

PURPOSE: To determine the association between tetrahydrocannabinol (THC) use and testosterone (T) levels among men in the United States. METHODS: Using the National Health and Nutrition Examination Survey (NHANES) data from the years 2011-2016, we identified all men 18 years and older who answered the substance use questionnaire and underwent laboratory testing for T. Regular THC users were defined as those who use THC at least one time per month, every month for at least 1 year. Multivariable linear regressions controlling for confounders were then used to determine the relationship between THC use and T levels. RESULTS: Among the 5146 men who met inclusion, 3027 endorsed using THC at least once in their life (ever-user). Nearly half of the THC ever-users (49.3%) were considered regular THC users. Multivariate analysis controlling for age, comorbidities, tobacco use, alcohol use, body mass index (BMI), exercise level, and race revealed a small but statistically significant increase in T among regular THC users at any measured level of use, compared to non-regular THC users (non-users). This increase was characterized by an inverse U-shaped trend with Regular THC users using two-three times per month demonstrating the greatest increase in T (+ 66.77 ng/dL) over non-users. CONCLUSION: THC use is associated with small increases in testosterone. This increase in T appears to decline as THC use increases, but nevertheless, T is still higher with any amount of regular use when compared to T in non-users. Prospective work is needed to validate the observed increase and to better elucidate the mechanism of impact THC use has on T levels.

Genetic testing in male infertility - reassessing screening thresholds.

PURPOSE OF REVIEW: Genetic testing in male infertility is an essential part of the process of diagnosis. Genetic abnormalities, such as Y-chromosome microdeletion, chromosomal abnormalities and mutations for cystic fibrosis, can all negatively impact a male's fertility and can be tested for during a fertility evaluation. Both Y-chromosome microdeletion and chromosomal abnormalities increase in prevalence as sperm concentrations decrease, and azoospermic men have the greatest frequency of genetic abnormalities. RECENT FINDINGS: These genetic abnormalities can also be found in oligospermic men; however, on the basis of several recent studies, the prevalence of genetic abnormalities is lower in oligospermic men than previously thought. SUMMARY: The current screening thresholds are devised from the previously determined prevalences and have not been revised based on the emerging data; thus, in this review of the literature, we will discuss this new evidence and whether screening thresholds should be changed.

Inflatable penile prosthesis outcomes after pelvic radiation.

INTRODUCTION Few studies have compared surgical outcomes after 3-piece inflatable penile prosthesis (IPP) surgery in patients exposed to pelvic radiation therapy (RT) compared to a radiation naïve control group. MATERIALS AND METHODS: A total of 715 consecutive patients underwent 3-piece IPP placement between 2007-2018. There were 101 men exposed to pelvic RT before or after IPP for a variety of malignancies and 153 men met inclusion criteria for the control group, which included men undergoing IPP surgery with a history of radical prostatectomy but no exposure to pelvic RT. RESULTS: Patients in the RT group had a higher body mass index (kg/m²) (28.7 versus 27.8, p = 0.003) and higher Charlson co-morbidity index score (6 versus 5; p < 0.001). At a median follow up of 5 years (IQR 2-8 years), there was an 18.4% surgical complication rate in the radiation group compared to 11.5% in the control group, though this was not statistically significant (p = 0.141). Timing of radiation, prior artificial urinary sphincter (AUS) status, co-implantation of an AUS, and brand of prosthesis were not associated with increased rate of complications. On multivariable logistic regression analysis, exposure to RT was not significantly associated with increased risks of complications (OR: 1.31; CI 0.55-3.12). CONCLUSIONS: This study shows no significant increase in risk of surgical complication in patients exposed to pelvic RT and supports the use of IPP in men with a history of RT and refractory erectile dysfunction.

Impact of Abnormal Sperm Morphology on Live Birth Rates Following Intrauterine Insemination.

PURPOSE: We evaluated the live birth rate and the prevalence of congenital anomalies in couples undergoing intrauterine insemination with abnormal sperm morphology (less than 4% normal forms). MATERIALS AND METHODS: We retrospectively reviewed intrauterine insemination outcomes from January 2012 to March 2015. Patients who were found to have an ultrasound confirmed clinical pregnancy were contacted to determine the live birth rate and the prevalence of congenital abnormalities. We used chi-square analysis to assess categorical variables and the Student t-test to assess continuous variables. Logistic regression was done to assess the odds of achieving pregnancy and the risk of spontaneous abortion while assessing female age, the total motile count and sperm morphology. RESULTS: In 984 intrauterine insemination procedures performed in a total of 501 couples we found no difference in the ultrasound clinical pregnancy rate in couples with sperm morphology less than 4% vs 4% or greater (12.3% vs 13.6%, p=0.59). We collected live birth and birth abnormality data on 95 of the 130 couples with ultrasound confirmed clinical pregnancy for a 73% response rate. We found no difference in the live birth rate or the spontaneous abortion rate after an ultrasound confirmed clinical pregnancy in couples with abnormal sperm morphology (less than 4% normal forms). There was also no increased risk of birth abnormalities for patients with abnormal sperm morphology. CONCLUSIONS: Abnormal sperm morphology impacted neither the pregnancy rate nor the live birth rate in couples undergoing intrauterine insemination. These results can be used to reassure couples who undergo intrauterine insemination that there is a minimal impact of abnormal sperm morphology on the live birth rate and the prevalence of birth abnormalities.

The risk of birth defects is not associated with semen parameters or mode of conception in offspring of men visiting a reproductive health clinic.

STUDY QUESTION: What is the relationship between semen parameters and birth defect (BD) rates in offspring of men evaluated for infertility? SUMMARY ANSWER: Among men undergoing infertility evaluation, there is no significant relationship between semen parameters and defect rates in live or still births, even when considering mode of conception. WHAT IS KNOWN ALREADY: Approximately 15% of couples have fertility difficulties, with up to a 50% male factor contribution. An increased risk of BDs exists in couples using ART, particularly IVF and ICSI, but it is unknown if this related to the ART procedures or an underlying male factor. STUDY DESIGN, SIZE, DURATION: To determine if the severity of male factor infertilty, as assessed via sperm quality and mode of conception, is associated with BD rates, we performed a retrospective cohort study. Fathers with semen analysis data in the Baylor College of Medicine Semen Database (BCMSD) were linked with their offspring using Texas Birth Defects Registry (TBDFR) data between 1999 and 2009. In this 10-year period, a total of 1382 men were identified in linkage between the BCMSD and TBDFR. A total of 109 infants with and 2115 infants without BDs were identified. PARTICIPANTS/MATERIALS, SETTING, METHODS: To determine the association between BDs and semen parameters, we used hierarchical linear modeling to determine odds ratios between BD rates, semen parameters, and mode of conception before and after adjustment for paternal, maternal and birth covariates. Semen parameters were stratified based on thresholds defined by the WHO fifth edition laboratory manual for the examination and processing of human semen. MAIN RESULTS AND THE ROLE OF CHANCE: In total 4.9% of 2224 infants were identified with a BD. No statistically significant association was observed between BD rates and semen parameters, before or after adjustment for covariates. The association between sperm concentration and BDs demonstrated an odds ratio (OR) of 1.07 (95% confidence interval: 0.63-1.83); motility: OR 0.91 (0.52-2.22); and total motile count: OR 1.21 (0.70-2.08). Likewise, mode of conception, including infertility treatment and ART, did not affect BD rates (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: BDs recorded in the TBDFR only include live born infants or still births after 20 weeks, our study did not evaluate the effect of impaired semen parameters on developmental defects prior to 20 weeks of gestation. With 109 BDs, our statistical analysis was powered to detect moderate differences associated with particular semen parameters. Additionally, data about mode of conception was not available for 1053 of 2224 births. WIDER IMPLICATIONS OF THE FINDINGS: BD rates are not associated with semen quality or mode of conception. The current study suggests that the severity of male factor infertility does not impact the rate of congenital anomalies. This information is important when counseling couples concerned about the relationship between impaired semen quality and BDs. STUDY FUNDING/COMPETING INTEREST(S): Supported in part by the NIH Men's Reproductive Health Research (MRHR) K12 HD073917 (D.J.L.), the Multidisciplinary K12 Urologic Research (KURe) Career Development Program (D.J.L.), P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, NIH (D.J.L.), and by U01DD000494 from the Centers for Disease Control and Prevention and the Title V Block Grant to the Texas Department of State Health Services. A.W.P. is a National Institutes of Health K08 Scholar supported by a Mentored Career Development Award (K08DK115835-01) from the from the National Institute of Diabetes and Digestive and Kidney Diseases. This work is also supported in part through a Urology Care Foundation Rising Stars in Urology Award (to A.W.P.) None of the authors has a conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Impaired sleep is associated with low testosterone in US adult males: results from the National Health and Nutrition Examination Survey.

PURPOSE: Testosterone deficiency has been linked to several adverse health outcomes and recent data have suggested that abnormal sleep quality may result in lower testosterone levels. We assessed the effect of self-reported sleep patterns on serum testosterone while controlling for co-morbidities, and baseline demographics. MATERIALS AND METHODS: Using data collected from the 2011-2012 National Health and Nutrition Examination Survey (NHANES), we extracted serum total testosterone level, sleep duration, demographic, and co-morbidities for men aged 16 years and older. Univariate and multivariate linear regression was used to estimate the association of number of hours slept, co-morbidities, and demographics with serum testosterone. RESULTS: Among the 9756 individuals in the NHANES dataset, 2295 (23.5%) were males 16 years and older with a median (interquartile range) age of 46 years (29-62) who also had serum testosterone levels drawn. Median serum testosterone level was 377 ng/dL (IQR: 279-492 ng/dL). Median number of hours slept was 7 h (IQR: 6-8 h). On multivariate linear regression, we found serum testosterone decreased by 0.49 ng/dL per year of age (p = 0.04), 5.85 ng/dL per hour loss of sleep (p < 0.01) and 6.18 ng/dL per unit of body mass index (BMI) increase (p < 0.01). CONCLUSIONS: Among men aged 16-80 in the United States, we found increasing age, impaired sleep and elevated BMI is associated with low testosterone. It is important, therefore, that evaluation and treatment of reduced serum testosterone should also include improving sleep duration in combination with weight management.

Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles.

PURPOSE: To study the impact of advanced paternal age on embryo aneuploidy. METHODS: This is a multicenter international retrospective case series of couples undergoing assisted reproduction via in vitro fertilization using donor eggs to control for maternal factors and preimplantation genetic testing for aneuploidy via next-generation sequencing at Igenomix reproductive testing centers. The main outcome measure was the prevalence of embryo aneuploidy in egg donor cycles. Semen analysis data was retrieved for a small subset of the male patients. RESULTS: Data from 1202 IVF/ICSI egg donor cycles using ejaculated sperm (total 6934 embryos) evaluated using PGT-A between January 2016 and April 2018 in a global population across all Igenomix centers were included. No significant association was identified between advancing paternal age and the prevalence of embryo aneuploidy overall and when analyzing for each chromosome. There was also no significant association between advancing paternal age and specific aneuploid conditions (monosomy, trisomy, partial deletion/duplication) for all chromosomes in the genome. CONCLUSIONS: This is the largest study of its kind in an international patient population to evaluate the impact of advancing paternal age on embryo aneuploidy. We conclude there is no specific effect of paternal age on the prevalence of embryo aneuploidy in the context of embryo biopsies from egg donor cycles.