Longitudinal semen parameter assessments and live birth: variability and implications for treatment strategies.

OBJECTIVE: To examine whether semen parameters are associated with live birth among couples seeking infertility treatment after accounting for semen parameter variability. DESIGN: Folic Acid and Zinc Supplementation Trial (FAZST) prospective cohort. SETTING: Four US reproductive endocrinology and infertility care study centers, 2013-2017. PATIENT(S): Couples (n = 2,369) seeking fertility consultations at 4 US infertility care study centers. INTERVENTION(S): Semen volume, pH, sperm viability, morphology, progressive and total motility, concentration, count, and total and progressive motile count assessed at baseline and at 2, 4, and 6 months after enrollment. MAIN OUTCOME MEASURE(S): Log-binomial models stratified by fertility treatment received (in vitro fertilization [IVF], intrauterine insemination [IUI], ovulation induction [OI], or no treatment) estimated risk differences (RDs) between semen parameter quartiles and live birth and accounted for multiple semen assessments per person. We accounted for abstinence time, the biological interdependence of semen parameters, and potential selection bias because of loss to follow-up. RESULT(S): Among couples using OI only or no treatment, 39% had a live birth, and relative to the highest quartile, the lowest quartiles of morphology (RD, -19 [95% CI, -23 to -15] per 100 couples), motility (RD, -13 [95% CI, -17 to -9]), concentration (RD, -22 [95% CI, -26 to -19]), and total motile count (RD, -18 [95% CI, -22 to -14]) were associated with fewer live births. For IUI, 26% had a live birth, and the lowest quartiles of volume (RD, -6 [95% CI, -11 to -0.4]), concentration (RD, -6 [95% CI, -11 to -0.1]), count (RD, -10 [95% CI, -15 to -4]), and total motile count (RD, -7 [95% CI, -13 to -1]) were associated with fewer live births. For IVF, 61% had a live birth, and only morphology (Q1 RD, -7 [95% CI, -14 to 0.2]; Q2 RD, -10 [95% CI, -17 to -2.2]) was associated with live birth. CONCLUSION(S): Semen parameters are critical in couples undergoing OI/IUI. Only low morphology was important for live birth after IVF. Although data supporting the use of semen parameters are fragmented across differing populations, current findings are generalizable across the range of male fertility and couple fertility treatments, providing evidence about which semen parameters are most relevant in which settings. CLINICAL TRIAL REGISTRATION NUMBER: NCT#01857310.

Masculinizing gender-affirming surgery for trans men and non-binary individuals: what you should know.

Gender dysphoria, the discordance between one's gender identity and anatomy, affects nearly 25 million people worldwide, and the prevalence of transgender and non-binary identities is increasing because of greater acceptance and awareness. Because of the improved accessibility to gender-affirming surgery (GAS), many providers will care for patients during and after gender transition. For trans men (female-to-male), GAS represents a combination of procedures rather than a single surgery. The particular combination of masculinizing procedures is chosen on the basis of informed patient-provider discussions regarding the patient's goals and anatomy and implemented through a multidisciplinary team approach. In this review, we describe the common procedures comprising masculinizing GAS to improve delivery of specialized care for this patient population.

A Prospective Cohort Study to Evaluate the Impact of Diet, Exercise, and Lifestyle on Fertility: Design and Baseline Characteristics.

Diet, lifestyle, and psychosocial factors might influence fertility for men and women, although evidence is mixed, and couple-based approaches are needed for assessing associations with reproductive outcomes. The Impact of Diet, Exercise, and Lifestyle (IDEAL) on Fertility Study is a prospective cohort with contemporaneous detailed follow-up of female partners of men enrolled in the Folic Acid and Zinc Supplementation Trial studying couples seeking infertility treatment (2016-2019). Follow-up of men continued for 6 months, while female partners were followed for 9 months while attempting pregnancy and throughout any resulting pregnancy (up to 18 months). Longitudinal data on diet, physical activity (including measurement via wearable device), sleep, and stress were captured at multiple study visits during this follow-up. A subset of women (IDEALplus) also completed daily journals and a body fat assessment via dual-energy x-ray absorptiometry. IDEAL enrolled 920 women, and IDEALPlus enrolled 218. We demonstrated the ability to enroll women in a prospective cohort study contemporaneous to a partner-enrolled randomized trial. In combination with data collected on male partners, IDEAL data facilitates a couple-based approach to understanding associations between lifestyle factors and infertility treatment outcomes. We describe in detail the study design, recruitment, data collection, lessons learned, and baseline characteristics.

Efficacy and Safety of Common Ingredients in Aphrodisiacs Used for Erectile Dysfunction: A Review.

INTRODUCTION: Erectile dysfunction (ED) is the inability to attain or sustain an erection for sexual intercourse. Affected men endorse difficulties with intimacy and feelings of guilt and shame. Although medical treatments are available, patients are reluctant to discuss ED with physicians and often use dietary supplements to attempt to treat their ED. As such, there is a need to better understand the effects of ingredients used in nutraceuticals for ED treatment. OBJECTIVES: To summarize the literature on the efficacy and safety of the most common ingredients used in ED supplements. METHODS: 10 of the most common ingredients in ED supplements were reviewed using PubMed-indexed literature to assess their efficacy and safety in treating ED. Key findings were summarized to include historical use, active ingredients, prior animal studies, human studies, and toxicity. RESULTS: Nutraceuticals used in ED treatment include a variety of ingredients. Although L-arginine is a safe supplement with clinical data supporting improved erectile function, limited data exist on the efficacy of other ingredients in the treatment of ED. CONCLUSION: Despite the growing use of supplements for treatment of sexual dysfunction, ED supplements remain poorly studied, with limited data demonstrating efficacy of individual ingredients. Further study is required to definitively determine the efficacy of nutraceuticals in ED treatment. Srivatsav A, Balasubramanian A, Pathak UI, et al. Efficacy and Safety of Common Ingredients in Aphrodisiacs Used for Erectile Dysfunction: A Review. J Sex Med 2020;8:431-442.

An Analysis of Popular Online Erectile Dysfunction Supplements.

INTRODUCTION: Erectile dysfunction supplements (ED-Ss) are featured on online marketplaces like Amazon.com, with dedicated pages and claims that they naturally treat ED. However, their efficacy and safety are largely unknown, limiting the ability to counsel patients regarding their use. AIM: To evaluate the highest rated and most frequently reviewed ED-Ss on Amazon.com to facilitate patient counseling regarding marketing myths, ingredient profiles, and evidence for product efficacy and safety. METHODS: The Amazon marketplace was queried using the key term "erectile dysfunction" with default search settings and ranking items based on relevance. The top 6 ED-S products identified on September 29, 2018, were reviewed based on price, ratings, reviews, manufacturer, and ingredients. Consumer reviews were categorized using subtopics within the International Index of Erectile Function (IIEF) questionnaire to better understand ED-S efficacy and then reanalyzed following filtration of untrustworthy comments using ReviewMeta.com, a proprietary Amazon review analysis software. OUTCOMES: Quantitative and qualitative evaluation of ED-S products sold on Amazon.com. RESULTS: The top 6 ED-Ss had an average of 2,121 ± 1,282 reviews and a mean rating of 3.92 ± 0.42 stars. A total of 21 ingredients were identified in these ED-Ss. Ginseng, horny goat weed, L-arginine, and tongkat ali were the most popular ingredients included in the analyzed products. Our literature review identified 413 studies involving the 21 identified ingredients, of which 59 (16%) involved human subjects. Among these 69 human studies, only 12 (17%) investigated supplement ingredients individually and reported improvement in ED. Analysis of top-ranked customer reviews from the first 2 pages of reviews for each supplement revealed differences in IIEF scores before and after ReviewMeta.com filtration. After filtration, we observed a 77% decrease in reviews reporting improved erection strength, an 83% decrease in reviews reporting improved ability to maintain erection, a 90% decrease in reviews reporting increased sexual satisfaction, an 88% decrease in reviews reporting increased enjoyment with intercourse, and an 89% decrease in reviews reporting increased erection confidence. STRENGTHS & LIMITATIONS: Study strengths include a novel approach to ascertaining consumers' perceptions and satisfaction with ED-Ss and practical summary information that clinicians can provide to patients. Limitations include selection bias, the small number of supplements analyzed, and the proprietary nature of the Amazon review analysis software. CONCLUSIONS: Our investigation revealed that human studies evaluating the efficacy of ED-S ingredients are limited and have yielded no definitive findings of the effects on ED. Patients considering ED-S use should receive appropriate counseling, given the prevalence of disingenuous reviews and the ready availability of Food and Drug Administration-approved drug therapies. Balasubramanian A, Thirumavalavan N, Srivatsav A, et al. An Analysis of Popular Online Erectile Dysfunction Supplements. J Sex Med 2019;16:843-852.

Erectile dysfunction is not independently associated with cardiovascular death: data from the vitamins and lifestyle (VITAL) study.

INTRODUCTION: Erectile dysfunction (ED) is a significant problem among aging men. ED is independently associated with cardiovascular (CV) events (angina, myocardial infarction, and stroke). AIM: We sought to determine if ED was associated with CV death. MAIN OUTCOME MEASURES: Risk of CV death in men with ED. METHODS: Exactly 31,296 men in Washington aged 50-76 completed a questionnaire in 2000-2002 on supplements, diet, exercise, personal health, and ED. ED was determined by one question: "Have you experienced impotence in the last year?" We excluded patients with a history of coronary artery disease or stroke. Participants linked yearly through 2008 to the Washington State Death Certificate System. CV death was defined by death certificates listing CV-related deaths (International Classification of Diseases 10th Revision [ICD-10] codes: I00-I15, I20-I52, and I60-I99). We performed multivariate Cox proportional hazard regression adjusting for age, marital status, race, education, self-rating of health, body mass index (BMI), antihypertensive/lipid-lowering drug use, diabetes, family history of CV disease, smoking, and exercise. RESULTS: About 7,762 men had ED and there were 486 CV deaths over 7.8-year average follow-up. The typical man who suffered CV death was older, single, reporting poor health, taking antihypertensives, higher BMI, a smoker, a diabetic, and had a family history of CV disease. When adjusting for age, marital status, and education only, men with ED had a 23% increased risk of CV death (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.01, 1.49). With further adjustment for known risk factors for CV disease (diabetes, treatment for hypertension or hyperlipidemia, family history of myocardial infarction/stroke, BMI, and exercise), ED no longer predicted CV death (HR 0.93, 95% CI 0.76, 1.15). CONCLUSIONS: In this community-based cohort, ED was not independently associated with an elevated risk of CV death. These data do not contradict prior data associating ED and CV events but rather suggest that ED may be a manifestation of other known risk factors for CV disease.

Long-term use of supplemental vitamins and minerals does not reduce the risk of urothelial cell carcinoma of the bladder in the VITamins And Lifestyle study.

PURPOSE: Urothelial carcinoma has the highest lifetime treatment cost of any cancer, making it an ideal target for preventative therapies. Previous work has suggested that certain vitamin and mineral supplements may reduce the risk of urothelial carcinoma. We used the prospective VITamins And Lifestyle cohort to examine the association of all commonly taken vitamin and mineral supplements as well as 6 common anti-inflammatory supplements with incident urothelial carcinoma in a United States population. MATERIALS AND METHODS: A total of 77,050 eligible VITAL participants completed a detailed questionnaire at baseline on supplement use and cancer risk factors. After 6 years of followup 330 incident urothelial carcinoma cases in the cohort were identified via linkage to the Seattle-Puget Sound SEER cancer registry. We analyzed use of supplemental vitamins (multivitamins, beta-carotene, retinol, folic acid, and vitamins B1, B3, B6, B12, C, D and E), minerals (calcium, iron, magnesium, zinc and selenium) and anti-inflammatory supplements (glucosamine, chondroitin, saw palmetto, ginkgo biloba, fish oil and garlic). For each supplement the hazard ratios (risk ratios) for urothelial carcinoma comparing each category of users to nonusers, and 95% CIs, were determined using Cox proportional hazards regression, adjusted for potential confounders. RESULTS: None of the vitamin, mineral or anti-inflammatory supplements was significantly associated with urothelial carcinoma risk in age adjusted or multivariate models. CONCLUSIONS: The results of this study do not support the use of commonly taken vitamin or mineral supplements or 6 common anti-inflammatory supplements for the chemoprevention of urothelial carcinoma.