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.

Factors Impacting Postoperative Opioid Use Among Patients Undergoing Implantation of Inflatable Penile Prosthesis.

BACKGROUND: While there is an increasing burden of chronic postoperative opioid use and opioid abuse in the United States, opioid use following inflatable penile prosthesis (IPP) surgery has not been well described. AIM: Describe postoperative opioid use following IPP surgery. METHODS: Seventy-four consecutive patients undergoing IPP implantation by a single surgeon were enrolled. Self-reported diaries tracked the type and amount of medication taken for 2 weeks following IPP surgery. High opioid consumers were defined as those consuming more than the median amount (10 mg) of opioids during the first 2 weeks postoperatively. Multivariate analyses were performed using stepwise backward elimination. OUTCOMES: Quantification of opioid use postoperatively and factors related to high opioid use. RESULTS: Fifty-six patients were included after 7 were excluded for preoperative opioid use and 11 were excluded for inability to contact. Median age was 67.5. Devices used were Boston Scientific (41, 73%) and Coloplast (15, 27%). All patients received local anesthetic. Most surgeries (44, 79%) were performed as outpatient. Preoperative analgesia with acetaminophen, celecoxib, and pregabalin was administered in 44 (78%), 44 (78%), and 28 (50%) of cases respectively; 32 (57%) of patients received 2 medications, 21 (36%) received three medications. In hospital median morphine equivalents was 7.5 (interquartile range [IQR] 0-7.5). Oxycodone prescribed at discharge was 50 mg (29, 52%), 75 mg (4; 7%), and 100 mg (23; 41%). Median milligrams of oxycodone used was 10 mg (IQR 0-23.5) at 7 days and 10 (IQR 0-37.5) at 14 days postdischarge. On univariate analysis, factors associated with an increased likelihood of high opioid use were morphine equivalents utilized in hospital (odds ratio [OR] 1.13, P < .05) and milligrams oxycodone prescribed at discharge (OR 1.05, P < .001) while patient demographics, procedure characteristics, and analgesic types were not found to be predictive of high opioid use. On multivariate analysis, milligrams oxycodone prescribed at discharge (OR 1.04, P < .005) were associated with an increased likelihood of high opioid use after discharge. CLINICAL IMPLICATIONS: Increased understanding of opioid use after IPP surgery may improve prescribing patterns after discharge. STRENGTHS & LIMITATIONS: This study quantified post discharge opioid use over the first 14 postoperative days. It is limited by single surgeon, small sample size, and retrospective design. CONCLUSION: Provider opioid prescribing patterns were associated with high opioid consumption postoperatively and a substantial amount of opioids prescribed at discharge remain unused by patients, suggesting that we can reduce or replace the amount of opioids that are prescribed. Ehlers ME, Mohan CS, Akerman JP, et al. Factors Impacting Postoperative Opioid Use Among Patients Undergoing Implantation of Inflatable Penile Prosthesis. J Sex Med 2021;18:1915-1920.

The relationship of plasma antioxidant levels to semen parameters: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial.

PURPOSE: The understanding of the role of plasma antioxidant levels in male fertility in the USA is limited. In a secondary analysis of the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial, we sought to determine whether serum levels of vitamin E (α-tocopherol), zinc, and selenium were correlated with semen parameters and couple fertility outcomes. METHODS: This study is a secondary analysis of the MOXI clinical trial. The primary endpoints in this secondary analysis include semen parameters, and DNA fragmentation and clinical outcomes including pregnancy and live birth. Analyses were completed using Wilcoxon's rank-sum test and linear regression models. RESULTS: At baseline, the analysis included plasma labs for vitamin E (n = 131), selenium (n = 124), and zinc (n = 128). All baseline plasma values were in the normal ranges. There was no association between selenium, zinc, or vitamin E levels and semen parameters or DNA fragmentation. Baseline antioxidant levels in the male partners did not predict pregnancy or live birth among all couples. Among those randomized to placebo, baseline male antioxidant levels did not differ between those couples with live birth and those that did not conceive or have a live birth. CONCLUSIONS: Among men attending fertility centers in the USA, who have sufficient plasma antioxidant levels of zinc, selenium, or vitamin E, no association was observed between vitamins and semen parameters or clinical outcomes in couples with male infertility. Higher levels of antioxidants among men with circulating antioxidants in the normal range do not appear to confer benefit on semen parameters or male fertility.

Intrauterine insemination performance characteristics and post-processing total motile sperm count in relation to live birth for couples with unexplained infertility in a randomised, multicentre clinical trial.

STUDY QUESTION: Are intrauterine insemination (IUI) performance characteristics and post-processing total motile sperm count (TMC) related to live birth rate in couples with unexplained infertility? SUMMARY ANSWER: Patient discomfort with IUI and lower inseminate TMC were associated with a reduced live birth rate, while time from hCG injection to IUI, sperm preparation method and ultrasound guidance for IUI were not associated with live birth success. WHAT IS ALREADY KNOWN: We previously determined that some baseline characteristics of couples with unexplained infertility, including female age, duration of infertility, history of prior loss and income, were related to live birth rate across a course of ovarian stimulation and IUI treatment. However, the relationship between treatment outcomes and per-cycle characteristics, including ultrasound guidance for IUI, timing of IUI relative to hCG injection, difficult or painful IUI and inseminate TMC, are controversial, and most prior investigations have not evaluated live birth outcome. STUDY DESIGN, SIZE, DURATION: This was a secondary analyses of 2462 cycles from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) clinical trial. This prospective, randomised, multicentre clinical trial determined live birth rates following IUI after ovarian stimulation with clomiphene citrate, letrozole or gonadotropins in 854 couples with unexplained infertility. It was conducted between 2011 and 2014, and couples could undergo up to four consecutive treatment cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: AMIGOS was an NIH-sponsored Reproductive Medicine Network trial conducted at 12 clinical sites. Participants were women with unexplained infertility who were between 18 and 40 years of age. Cluster-weighted generalised estimating equations (GEE), which account for informative clustering of multiple IUI treatment cycles within the same patient, were used to determine associations between IUI performance characteristics, including inseminate TMC, and live birth rate. Efficiency curves were also generated to examine the relationship between inseminate TMC and live birth rate. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for treatment group and baseline factors previously associated with live birth across a course of OS-IUI treatment, patient discomfort during the IUI procedure was associated with a reduction in live birth rate (aRR 0.40 (0.16-0.96)). Time from hCG trigger injection to IUI was not significantly associated with outcome. Higher TMC was associated with greater live birth rate (TMC 15.1-20.0 million (14.8%) compared to ≤5 million (5.5%)) (aRR 2.09 (1.31-3.33)). However, live births did occur with TMC ≤ 1 million (5.1%). LIMITATIONS, REASONS FOR CAUTION: This investigation is a secondary analysis, and AMIGOS was not designed to address the present question. Since timed intercourse was allowed as part of the AMIGOS trial, we cannot rule out the possibility that any given pregnancy resulted from intercourse rather than IUI. WIDER IMPLICATIONS OF THE FINDINGS: Most factors associated with the performance of IUI were not significantly related to obtaining live birth. Our findings suggest that higher TMC inseminated leads to an increase in live birth rate up to TMC ~20 million. However, there may be no reasonable threshold below which live birth is not possible with IUI. STUDY FUNDING/COMPETING INTEREST(S): Funding was received through grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10 HD055925. This research was made possible by funding by the American Recovery and Reinvestment Act. Dr Hansen reports grants from NIH/NICHD and Yale University during the conduct of the study, grants from Roche Diagnostics and grants from Ferring International Pharmascience Center US outside the submitted work. Dr Peck reports support from Ferring Pharmaceuticals outside the submitted work. Dr Coward has nothing to disclose. Dr Wild reports grants from NICHD during the conduct of the study. Dr Trussell has nothing to disclose. Dr Krawetz reports grants from NICHD during the conduct of the study, grants from Merck and support from Taylor and Frances and from Springer, outside the submitted work. Dr Diamond reports grants from NIH/NICHD, Yale University, during the conduct of the study and support from Advanced Reproductive Care AbbVie, Bayer and ObsEva, outside the submitted work. Dr Legro reports support from Bayer, Kindex, Odega, Millendo and AbbVie and grants and support from Ferring, outside the submitted work. Dr Coutifaris reports grants from NICHD/NIH and personal fees from American Society for Reproductive Medicine, outside the submitted work. Dr Alvero has nothing to disclose. Dr Robinson reports grants from NIH during the conduct of the study. Dr Casson has nothing to disclose. Dr Christman reports grants from NICHD during the conduct of the study. Dr Santoro reports grants from NIH during the conduct of the study. Dr Zhang reports grants from NIH during the conduct of the study and support from Shangdong University outside the submitted work. TRIAL REGISTRATION NUMBER: n/a.

Fertility Related Quality of Life, Gonadal Function and Erectile Dysfunction in Male Partners of Couples with Unexplained Infertility.

PURPOSE: We sought to determine whether lower fertility related quality of life or depression in men of couples with unexplained infertility is associated with low total testosterone levels, abnormal semen quality or erectile dysfunction. MATERIALS AND METHODS: This study is a secondary analysis of a large, multicenter, randomized controlled trial in couples with unexplained infertility. Male partners underwent baseline semen analysis with measurement of fasting total testosterone and gonadotropin. They also completed surveys, including the FertiQOL (Fertility Quality of Life), the PHQ-9 (Patient Health Questionnaire-9) and the IIEF (International Index of Erectile Function). The primary study outcomes were total testosterone with low total testosterone defined as less than 264 ng/dl, semen parameters and the IIEF score. We performed multivariable logistic regression analyses adjusted for patient age, race, body mass index, education, smoking, alcohol use, infertility duration and comorbidity. RESULTS: A total of 708 men with a mean ± SD age of 34.2 ± 5.6 were included in study. Of the men 59 (8.3%) had a PHQ-9 score of 5 or greater, which was consistent with depression, 99 (14.0%) had low total testosterone and 63 (9.0%) had mild or worse erectile dysfunction. Neither the FertiQOL score nor depression was associated with total testosterone or any semen parameter. The FertiQOL score was inversely associated with erectile dysfunction (for every 5-point score decline AOR 1.30, 95% CI 1.16-1.46). Depressed men were significantly more likely to have erectile dysfunction than nondepressed men (AOR 6.31, 95% CI 3.12-12.77). CONCLUSIONS: In men in couples with unexplained infertility lower fertility related quality of life and depression are strongly associated with erectile dysfunction. However, neither is associated with spermatogenesis or testosterone levels. Erectile dysfunction in infertile men merits longitudinal investigation in future studies.

Innovating Incrementally: Development of the Modern Inflatable Penile Prosthesis.

PURPOSE OF REVIEW: The inflatable penile prosthesis (IPP) was introduced in 1973. Since that time, the fundamental design of the IPP has not changed, but numerous improvements to the device, surgery, and peri-operative management have resulted in a modern IPP with excellent reliability, infection control, safety profile, and user experience. RECENT FINDINGS: We describe important modifications to the IPP and review available data assessing the impact of these changes. We also discuss possible changes to the IPP that would result in continued improvement. Since its introduction in 1973, changes to the penile prosthesis have resulted in significant improvements in reliability, infection control, safety, and user experience. Design changes are anticipated to continue, resulting in a better and more versatile penile prosthesis.

Demographic and Practice Trends of Rural Urologists in the U.S.: Implications for Workforce Policy.

INTRODUCTION: There is a shortage in the number of urologists needed to satisfy the needs of an aging U.S. POPULATION: The urologist shortage may have a pronounced impact on aging rural communities. Our objective was to describe the demographic trends and scope of practice of rural urologists using data from the American Urological Association Census. METHODS: We conducted a retrospective analysis of American Urological Association Census survey data over a 5-year period (2016-2020), including all U.S.-based practicing urologists. Metropolitan (urban) and nonmetropolitan (rural) practice classifications were based on rural-urban commuting area codes for the primary practice location zip code. We conducted descriptive statistics of demographics, practice characteristics and specific rural-focused survey items. RESULTS: In 2020, rural urologists were older (60.9 years, 95% CI 58.5-63.3 vs 54.6 years, 95% CI 54.0-55.1) and were in practice longer (25.4 years, 95% CI 23.2-27.5 vs 21.2 years, 95% CI 20.8-21.5) than urban counterparts. Since 2016, mean age and years in practice increased for rural urologists but remained stable for urban urologists, suggesting an influx of younger urologists to urban areas. Compared with urban urologists, rural urologists had significantly less fellowship training and more frequently worked in solo practice, multispecialty groups and private hospitals. CONCLUSIONS: The urological workforce shortage will particularly impact rural communities and their access to urological care. We hope our findings will inform and empower policymakers to develop targeted interventions to expand the rural urologist workforce.

Biomarkers of Stress and Male Fertility.

To study if stress, as measured by salivary alpha-amylase and cortisol, negatively impacts male fertility, as measured by semen parameters, pregnancy, and live birth rates. Prospective, cohort study of men enrolled in the Males, Antioxidants, and Infertility (MOXI) trial. One-hundred twelve infertile men provided first-morning salivary and semen samples at baseline. Salivary samples were analyzed for alpha-amylase and cortisol. Couples attempted to conceive naturally (months 1-3) and with clomiphene citrate/intrauterine insemination (months 4-6). The association between stress-related biomarkers and semen parameters including DNA fragmentation was assessed using linear regression models adjusting for male age. Salivary levels were dichotomized at the 80th percentile. Pregnancy/live birth rates in couples in the upper quintile were compared to remaining subjects using chi-square testing. Salivary levels of alpha-amylase were not associated with semen parameters or DNA fragmentation. Salivary cortisol levels were not correlated with DNA fragmentation or normal morphology. For every 1-unit increase in salivary cortisol, total sperm count increased by 13.9 million (95% CI: 2.5, 25.3) and total motile sperm count increased by 9.9 million (95% CI: 3.2-16.6). Couple pregnancy rates and live birth rates did not differ for males in the highest quintile of alpha-amylase (27% and 28%, p = 0.96; 23% and 21%, p = 0.87) or cortisol (40% and 26%, p = 0.22; 35% and 19%, p = 0.12), compared to males with lower values. Physiologic measures of high stress may not harm but actually improve semen parameters among men with male-factor infertility.

Poor reproducibility of percentage of normally shaped sperm using the World Health Organization Fifth Edition strict grading criteria.

Objective: To determine the reproducibility of the World Health Organization Fifth Edition (WHO5) strict grading methodology by comparing the percentage of morphologically normal sperm (PNS) recorded by the core laboratory with results obtained at the fertility centers participating in a multisite clinical trial. Design: Secondary cohort analysis of data from the Males, Antioxidants, and Infertility trial. Setting: Fertility centers. Patients: Semen values of 171 men participating in a multicenter, double-blind, randomized, placebo-controlled trial evaluating the effect of antioxidants on male fertility. Interventions: Not applicable. Main Outcome Measures: Strict morphology expressed as PNS as determined at each fertility center and the core central laboratory for the same semen sample. Results: No correlation was found in the PNS values for the same semen sample between the core laboratory and fertility center laboratories either as a group or by individual site. Interobserver agreement was similarly low (κ = 0.05 and 0.15) between the core and fertility laboratories as a group for strict morphology, categorized by the WHO5 lower reference limits of 4% and 0, respectively. Moderate agreement was found between the core and 2 individual fertility laboratories for the cutoff value of 0 (κ = 0.42 and 0.57). The remainder of the comparisons demonstrated poor to fair agreement. Conclusions: Strict morphology grading using the WHO5 methodology demonstrated overall poor reproducibility among a cohort of experienced fertility laboratories. This lack of correlation and agreement in the PNS values calls into question the reproducibility, and thereby the potential applicability, of sperm strict morphology testing.

Sperm retrieval and intracytoplasmic sperm injection outcomes in men with cystic fibrosis disease versus congenital bilateral absence of the vas deferens.

Recent data suggest that cystic fibrosis transmembrane conductance regulator (CFTR) gene alterations negatively impact male fertility beyond obstruction. We sought to compare gene alterations, sperm retrieval rates, and intracytoplasmic sperm injection (ICSI) outcomes among men with cystic fibrosis (CF) disease and congenital bilateral absence of the vas deferens (CBAVD) only. We retrospectively evaluated all men who underwent surgical sperm retrieval at two academic, high-volume andrology centers from 2010 to 2018. Only men with documented CFTR alterations and obstructive azoospermia from either CBAVD or CF were included. Differences between groups for CFTR abnormality, sperm retrieval, and ICSI outcomes were statistically analyzed. Overall, 39 patients were included with 10 in the CF and 29 in the CBAVD groups. Surgical sperm retrieval rates were significantly lower in the CF group for sperm concentration (14.8 × 10[6] ml-1 vs 61.4 × 10[6] ml-1, P = 0.02) and total motile sperm count (2.9 million vs 11.4 million, P = 0.01). This difference was only predicted by homozygous delta F508 CFTR mutations (P < 0.05). The CF group also demonstrated a significantly higher rate of rescue testicular sperm extraction (70.0% vs 27.6%, P < 0.03) and lower fertilization rate with ICSI (32.5% vs 68.9%, P < 0.01). In conclusion, those with CF demonstrated lower sperm quality, greater difficulty with sperm retrieval, and worse ICSI outcomes compared with CBAVD-only patients. Homozygous delta F508 CFTR mutations appear to significantly impair spermatogenesis and sperm function.

Challenging Ethical Scenarios in the Surgical Treatment of Erectile Dysfunction: A Survey of High-Volume Penile Prosthesis Surgeons.

OBJECTIVE: To investigate how surgeons approach ethically challenging scenarios that arise in penile prosthesis surgery and identify patient-related factors that impact their approach. METHODS: A survey was distributed to the Society for Urologic Prosthetic Surgeons membership consisting of 6 ethically challenging scenarios: an HIV+ patient, a patient with cognitive disability, a registered sex offender, a nonverbal patient, a litigious patient, and an uncontrolled diabetic patient whose insurance will lapse soon. Additional clinical information was provided to assess how the likelihood to offer surgery might change. The primary outcome was the likelihood of offering surgery in each scenario. RESULTS: The response rate was 15.6% (n = 29). When compared to the baseline patient, respondents had a lower likelihood of offering surgery in all scenarios except the HIV+ patient, with the lowest likelihood of offering surgery to a sex offender (P < .01). Within each scenario, factors associated with an increased odds of offering surgery included knowledge that a patient with Down Syndrome is high functioning (odds ratio [OR] 5.0, confidence interval [CI]: 1.4-17.8), that a prior sex offender is currently married (OR 16.5, CI:3.5-99.8), that a litigious patient sued a surgeon for a retained sponge (OR 6.3, CI:1.7-24.3), and that a nonverbal patient had expressed prior interest in penile prosthesis surgery (OR 4.5, CI: 1.3-16.2). CONCLUSION: Ethical principles, including respect for autonomy, nonmaleficence, beneficence, and justice, are appropriately applied by urological prosthetic surgeons when ethical challenges arise. While the likelihood of offering penile prosthesis surgery is decreased with most ethical dilemmas, specific clinical factors often augment decision-making.

Sperm morphology from the actual inseminated sample does not predict clinical pregnancy following intrauterine insemination.

OBJECTIVE: To determine the effect of sperm morphology from the specific sample used for intrauterine insemination (IUI) on clinical pregnancy rates (CPR). DESIGN: Prospective cohort study. SETTING: Academic fertility clinic. PATIENTS: Couples undergoing IUI July 2016-January 2017. INTERVENTIONS: Morphology slides were prepared from the semen sample produced for IUI. MAIN OUTCOME MEASURES: CPR was measured by detection of cardiac activity. Multiple logistic regression modeling was performed to determine the association of sperm morphology with CPR, controlling for age, antimüllerian hormone level, and post-wash total motile sperm count. RESULTS: Semen analyses, including Kruger strict criteria for morphology from the actual sample inseminated, were reviewed for 155 couples, comprising 234 total treatment cycles. The percent normal morphology significantly differed between the preliminary semen analysis and the IUI sample (-2.0% +3.7% (95% CI -2.55, -1.53). Of the total 234 treatment cycles, 8.6% resulted in clinical pregnancy. When categorized by strict morphology >4%, <4%, and <1%, the CPR was 6.6%, 9.8%, and 10.9%, respectively. In couples with otherwise normal semen parameters (isolated teratospermia), CPR by >4%, <4%, and <1% normal forms was 7.2%, 9.8%, and 11.1%, respectively. There was no significant association between the percent normal morphology and CPR in multivariate analysis. CONCLUSIONS: This study evaluating the morphology of the actual inseminated sample did not find differences in CPR following IUI among couples with normal and abnormal sperm morphology, including severe teratospermia. Abnormal sperm morphology should not exclude couples from attempting IUI.

Systematic Review and Meta-Analysis of Cycling and Erectile Dysfunction.

INTRODUCTION: Conflicting evidence exists on the relationship between bicycle riding and erectile dysfunction (ED). A major limitation to several prior studies is the lack of a validated measure of ED. OBJECTIVE: To assess the relationship between cycling and clinically validated ED based on existing literature. METHODS: We searched several major databases from database inception through 2018 using a variety of search terms relating to "cycling" and "erectile dysfunction." Studies were included if they were written in English, reported original data, compared ED between cyclists and non-cycling controls, and used a validated measure of ED, such as the International Index of Erectile Function or the subset Sexual Health Inventory for Men (SHIM). Age, SHIM score, and comorbidities were extracted for all groups. Primary outcomes for each group were mean SHIM score and presence of ED (SHIM ≤ 21). A generalized linear mixed-effects model was used to fit the collected data for meta-analysis. Main outcome measures were unadjusted odds ratios of ED for cyclists and non-cyclists, mean SHIM score difference between cyclists and noncyclists, and both of these measures adjusted for age and comorbidities. RESULTS: After a systematic evaluation of 843 studies, 6 studies met our inclusion criteria, encompassing 3,330 cyclists and 1,524 non-cycling controls. When comparing cyclists to non-cyclists in an unadjusted analysis, there were no significant differences in the odds of having ED or mean SHIM score. However, when controlling for age and comorbidities, cyclists had significantly higher odds of having ED (odds ratio: 2.00; 95% confidence interval: 1.57, 2.55). CONCLUSIONS: Limited evidence supports a positive correlation between cycling and ED when adjusting for age and several comorbidities. Heterogeneity among studies suggests that further investigation into certain populations of cyclists that may be more vulnerable to ED may be beneficial. Gan ZS, Ehlers ME, Lin FC, et al. Systematic Review and Meta-Analysis of Cycling and Erectile Dysfunction. Sex Med 2021;9:304-311.

Zika RNA and Flavivirus-Like Antigens in the Sperm Cells of Symptomatic and Asymptomatic Subjects.

Zika virus (ZIKV) RNA has been found to remain in human semen for up to one year after infection, but the presence of Flavivirus antigens in the different compartments of semen has been largely unexplored. Following the introduction of ZIKV in Nicaragua (2016), a prospective study of patients with clinical symptoms consistent with ZIKV was conducted in León to investigate virus shedding in different fluids. ZIKV infection was confirmed in 16 male subjects (≥18 years of age) by RT-qPCR in either blood, saliva or urine. Of these, three provided semen samples at 7, 14, 21, 28, 60 and 180 days postsymptom onset (DPSO) for Flavivirus antigens and RNA studies. These cases were compared with 19 asymptomatic controls. Flavivirus antigens were examined by immunofluorescence (IF) using the 4G2 Mabs, and confocal microscopy was used to explore fluorescence patterns. The three (100%) symptomatic subjects and 3 (16%) of the 19 asymptomatic subjects had Flavivirus antigens and viral RNA in the spermatozoa fraction. The percentage of IF Flavivirus-positive spermatozoa cells ranged from 1.9% to 25% in specimens from symptomatic subjects, as compared with 0.8% to 3.8% in specimens from asymptomatic controls. A marked IF-pattern in the cytoplasmic droplets and tail of the spermatozoa was observed. The sperm concentrations (45 × 106/mL vs. 63.5 × 106/mL, p = 0.041) and the total motility percentage (54% vs. 75%, p = 0.009) were significantly lower in specimens from ZIKV-positive than in those of ZIKV-negative. In conclusion, this study demonstrated the presence of Flavivirus antigens and RNA within a time frame of 28 DPSO in sperm cells of symptomatic and asymptomatic subjects during the ZIKV epidemic. These findings have implications for public health, in terms of nonarthropod-born, silent transmission facilitated by sperm cells and potential transmission from asymptomatic males to pregnant women, with consequences to the fetus.

Male vitamin D status and male factor infertility.

OBJECTIVE: To determine the association between vitamin D levels in the male partner and fertility outcomes in couples with mild male factor infertility. DESIGN: Secondary analysis of a randomized, controlled trial. SETTING: Nine fertility centers in the United States. PATIENT(S): Men (n = 154) with sperm concentration between 5 and 15 million/mL, motility ≤40%, or normal morphology ≤4% were eligible. Female partners were ovulatory, ≤40 years old, and had documented tubal patency. INTERVENTION(S): Men provided semen and blood at baseline for semen analysis and 25-hydroxyvitamin D (25(OH)D) levels. They were randomly assigned to receive a vitamin formulation including vitamin D 2,000 IU daily or placebo for up to 6 months. Couples attempted to conceive naturally during the first 3 months and with clomiphene citrate with intrauterine insemination of the female partner in months 4 through 6. MAIN OUTCOME MEASURE(S): Primary: sperm concentration, motility, morphology, and DNA fragmentation at baseline. Secondary: cumulative pregnancy, miscarriage, and live birth rates. RESULT(S): Semen parameters and sperm DNA fragmentation were not statistically significantly different between men with vitamin D deficiency and men with 25(OH)D levels ≥20 ng/mL. In addition, clinical pregnancy and live birth rates were similar. Male 25(OH)D level <20 ng/mL was associated with a higher rate of pregnancy loss (adjusted odds ratio 9.0; 95% confidence interval 1.3 to 61.3). CONCLUSION(S): Vitamin D deficiency in the male partner did not significantly impact semen parameters or treatment outcomes. Further study is warranted to better characterize the rate of miscarriage in couples with male vitamin D deficiency.

Sperm deoxyribonucleic acid fragmentation: predictors, fertility outcomes, and assays among infertile males.

OBJECTIVE: To examine the factors associated with increased deoxyribonucleic acid fragmentation index (DFI), evaluate the pregnancy outcomes of men with increased DFI, and compare three independent DFI assays. DESIGN: Secondary analysis. SETTING: Nine US-based fertility centers. PATIENTS: Infertile men (N = 147) with sperm concentration ≤15 × 106/mL, motility ≤40%, or normal morphology ≤4% were enrolled. The female partners were ovulatory, ≤40 years old, and had documented tubal patency. INTERVENTIONS: At a baseline visit, the men provided a semen sample. The couples attempted conception without assistance for 3 months and with ovarian stimulation and intrauterine insemination in the subsequent 3 months. MAIN OUTCOME MEASURES: The DFI was analyzed using the sperm chromatin structure assay (SCSA) with increased DFI defined as >30%. The predictors of increased DFI were determined by a multivariable linear regression model. The pregnancy outcomes were compared using the χ2 test. The independent DFI assays (SCSA, deoxynucleotidyl transferase-mediated dUTP nick end labeling, and Comet) were compared with Pearson and Spearman correlations. RESULTS: The 19% of men with increased DFI were older (36.0 vs. 33.0 years) and had lower total sperm motility (38.2% ± 20.5% vs. 45.2% ± 15.6%). Increased male age was found to be a significant predictor of DFI (0.75, 95% confidence interval [0.06, 1.45]). Increased DFI was not associated with conception or live birth. There was a modest correlation of the deoxynucleotidyl transferase-mediated dUTP nick end labeling assay with the SCSA (r = 0.34) and Comet assay (r = 0.19). CONCLUSIONS: Older age was associated with increased DFI among infertile men. The DFI assays were only weakly correlated, indicating a standard definition of DFI is needed to truly interrogate how sperm deoxyribonucleic acid fragmentation impacts male fertility.