Follicle-stimulating hormone modestly predicts improvement in semen parameters in men with infertility treated with clomiphene citrate.

Clomiphene citrate is a commonly prescribed empiric medical therapy for male infertility, but outcomes data and response rates remain incompletely understood. We retrospectively reviewed our single-institutional experience of infertile men prescribed clomiphene. Clomiphene treatment in the final cohort of 140 men was associated with a modest increase in median sperm concentration from 2.2 to 2.5 million/ml (p < 0.001). A total of 46/140 (33%) of men upgraded according to World Health Organization concentration categories. Clomiphene treatment in 26/113 (23%) of previously ineligible men became eligible for intrauterine insemination. Using both univariate and multivariable regression, pre-treatment follicle-stimulating hormone was inversely associated with change in semen concentration with clomiphene treatment. On binary logistic regression, follicle-stimulating hormone level was inversely related to World Health Organization concentration category upgrade (p = 0.01). Unfortunately, 17/140 (12%) of men paradoxically worsened on clomiphene, but no predictors for this could be identified. In summary, clomiphene citrate confers a clinically relevant but modest benefit in a subset (1/3rd ) of infertile men, particularly those with lower pre-treatment follicle-stimulating hormone levels. Men with elevated follicle-stimulating hormone over 15 IU/ml are less likely to benefit from treatment and should be counselled on other relevant treatment alternatives.

Assessing online price transparency of sperm cryopreservation across the United States.

Although the lack of information on the costs and pricing of healthcare services prevails throughout the medical industry, empiric observations have demonstrated that pricing information is even more obscured in the sperm cryopreservation market. Thus, the objectives of our study are to assess and compare online price transparency and the price of sperm cryopreservation across various healthcare settings in the United States. This study examined online pricing published by facilities that have an active registration to store spermatozoa with the Food and Drug Administration. Less than one-fifth of registered facilities display any pricing information online. Price transparency also varies among census regions and facility types. Nationally, the median initial bank fee and annual price of storage are $350 and $385 respectively. Although there were no differences in the initial fee by facility type and census region, the annual price of storing spermatozoa is highest in the Northeast, which could be attributed to laboratory techniques, demographic patterns or insurance coverage. Guidelines from professional societies or different legislation and regulatory requirements across different US states can increase price transparency, which can promote consumer decision-making and decrease the barrier for men seeking fertility preservation.

Conventional semen analysis and advanced sperm function tests in diagnosis and management of varicocele.

Clinical varicoceles are a common cause of male infertility and affect sperm parameters as measured in a conventional semen analysis. Varicocelectomy has been shown in prospective studies to improve semen parameters in men with a clinical varicocele. Clinical varicoceles are also a well-known source of oxidative stress which may affect the quality of spermatozoa. Spermatozoa are particularly susceptible to oxidative stress due to a limited capacity for DNA repair. The susceptibility of spermatozoa to oxidative stress is modulated by a balance between ROS and antioxidants, which can be quantified by various laboratory assays. Varicocelectomy has been consistently shown to reduce both ROS and sperm DNA fragmentation, and various assays should be utilised in the diagnosis and treatment of infertile men with a clinical varicocele.

Pathophysiology and treatment options of varicocele: An overview.

Varicocele is the most common correctable cause for male infertility, but not all men with varicocele are affected equally by this condition. The pathophysiology of varicocele-induced fertility remains ill-defined. While evidence suggests that oxidative stress remains a central factor, other mechanisms likely include scrotal hyperthermia, reflux of metabolites, hypoxia and cadmium accumulation. Microsurgical varicocelectomy remains the gold standard treatment option for infertile men with a clinically palpable varicocele and abnormal semen parameters. Newer evidence suggests a potential role for antioxidant supplementation and a meaningful role of varicocelectomy for patients destined for ART to improve pregnancy outcomes.

Fourteen-Core Systematic Biopsy That Includes Two Anterior Cores in Men With PI-RADS Lesion ≥ 3 is Comparable With Magnetic Resonance Imaging-ultrasound Fusion Biopsy in Detecting Clinically Significant Prostate Cancer: A Single-institution Experience.

INTRODUCTION: Magnetic resonance imaging (MRI)-ultrasound fusion targeted prostate biopsy (FB) has been advocated by many experts as a replacement for the standard template biopsy. Herein, we compared pathology results and cancer detection rates of FB with our standard 14-core systematic prostate biopsy (SB) that includes 2 anterior cores. MATERIALS AND METHODS: One hundred two men with elevated prostate-specific antigen and suspicious lesions on multiparametric MRI, Prostate Imaging Reporting And Data System (PI-RADS) v2 score ≥ 3, underwent FB. Each target lesion was biopsied 3 times; our SB was performed concurrently. Biopsy results were compared for overall and clinically significant (cs), defined as Gleason score ≥ 7, cancer detection. RESULTS: Fifty-two percent of patients had positive biopsy results, and of those, 44 had cs prostate cancer (PCa). The overall detection rates for FB and SB were 39% and 50%, respectively, and there was no statistical difference in the detection rate of csPCa detection rate (P = .42). Of 17 patients diagnosed with a high-risk PCa, defined as Gleason score ≥ 8, SB identified 15, whereas FB identified 10. Within the SB group, 21 had positive anterior core biopsies, of which 11 were cs. CONCLUSION: Expanding the standard template prostate biopsies to include 2 anterior horn sampling may be just as effective as FB in men with PI-RADS lesion ≥ 3, thereby mitigating the increased cost associated with FB.

Culture-independent Next Generation Sequencing of Urine and Expressed Prostatic Secretions in Men With Chronic Pelvic Pain Syndrome.

OBJECTIVE: To compare standard cultures and next-generation sequencing (NGS) in men with chronic prostatitis/chronic pelvic pain syndrome (CPPS). CPPS shares clinical features with urinary tract infections, but bacteria are seldom found. NGS is more sensitive than standard cultures. MATERIALS AND METHODS: Men diagnosed with CPPS (National Institute of Health Category III) underwent traditional cultures and NGS of their urine and expressed prostatic secretions (EPS). Characteristics between groups were compared statistically. RESULTS: Thirty-one men with CPPS were included (mean age 44.5). All standard urine cultures were negative, and 3 EPS cultures were positive. Seventy-eight unique microbes were detected with NGS, including uropathogens in 10 of the men. There were no bacteria identified by NGS in EPS that were not also found in the urine. Men with positive NGS did not differ from those without in age, symptom severity or phenotype. Men with typical urinary tract infection symptoms (eg, dysuria, chills) were more likely to have uropathogens detected on NGS relative to men without such symptoms. Nine patients were prescribed antibiotics based on their NGS findings, but only 1 exhibited symptom improvement (11%). CONCLUSION: NGS commonly identified bacteria in CPPS patients, but these did not localize to the prostate. NGS positivity did not correlate with symptom severity and antibiotic therapy was seldom effective. NGS detected uropathogens more frequently in those with clinical symptoms suggestive of urinary tract infection. Clinical trials are needed to examine the utility of NGS-guided antibiotics in this subpopulation.

Prolactin-to-Testosterone Ratio Predicts Pituitary Abnormalities in Mildly Hyperprolactinemic Men with Symptoms of Hypogonadism.

PURPOSE: We aimed to identify predictor variables associated with pituitary abnormalities in hypogonadal men with mild hyperprolactinemia. We also sought to develop a decision-making aid to select patients for evaluation with pituitary magnetic resonance imaging. MATERIALS AND METHODS: We retrospectively examined men with mild hyperprolactinemia (15.1-50.0 ng/ml) who presented with symptoms of hypogonadism and underwent pituitary magnetic resonance imaging. Demographics, laboratory values and clinical data were obtained from the electronic medical record. Selected predictor variables were included in multivariable logistic regression and partitioning models. Cost avoidance analysis was performed on models achieving sensitivities ≥90%. RESULTS: A total of 141 men were included in the study, of whom 40 (28%) displayed abnormalities on pituitary magnetic resonance imaging. Patients with pituitary abnormalities exhibited higher prolactin (p=0.01), lower testosterone (p=0.0001) and lower luteinizing hormone (p=0.03) levels than those with normal anatomy, as well as higher prolactin-to-testosterone ratios (p <0.0001) and lower luteinizing hormone-to-follicle-stimulating hormone ratios (p=0.0001). These serological variables were identified as the best performing predictor variables. The partition incorporating a prolactin-to-testosterone ratio cutoff of 0.10 and prolactin cutoff of 25 ng/ml achieved 90% sensitivity and 48% specificity, and reduced diagnostic expenses by 28%. CONCLUSIONS: Hypogonadal men presenting with mild hyperprolactinemia and pituitary abnormalities declare themselves via endocrine studies routinely ordered to evaluate these conditions. The prolactin-to-testosterone ratio is the best independent predictor of finding a pituitary abnormality on magnetic resonance imaging, although sensitivity improves by referencing additional serological parameters. Significant cost avoidance may result from screening this population prior to ordering pituitary magnetic resonance imaging.

Failure of testosterone replacement therapy to improve symptoms correlates with burden of systemic conditions.

BACKGROUND: The symptoms of hypogonadism are non-specific and restoring testosterone (T) to physiologic levels may not lead to clinical improvement. In men with a high burden of systemic illness, it is difficult to assess whether hypogonadism is a primary contributing factor of their symptoms. Given that testosterone replacement therapy (TRT) is not without risk, it is important to understand which patients will benefit from treatment. Therefore, we hypothesize that men with a higher burden of systemic illness would be less likely to continue with TRT. METHODS: We performed a retrospective review of our men's health registry for men who started TRT and adhered to follow up labs and visits within the first year. We restricted treatment to Testopel pellets due to reliable early T levels. Men were classified as yes/no for continued TRT based on whether they felt their presenting symptoms improved on therapy and they chose to continue TRT. The previously validated ACTIONS men's health phenotype was calculated as a composite systemic disease score grading severity [0-2] for each of anxiety, cardiovascular disease, low testosterone, diabetes, obesity, neurologic disease and obstructive sleep apnea (total score 0-14). RESULTS: Sixty men were identified with a mean age of 59.5 (range, 33-81) years and mean starting total testosterone of 215 [48-332] ng/dL. Thirty-nine men (65%) felt symptomatic benefit and continued therapy for a median of 40.4 (20.5-76.4) months vs. 21 men without benefit treated for a median of 4.1 months (2.9-10.7, P<0.0001). Those who stopped TRT had a higher ACTIONS score than those who continued (8±2.5 vs. 4.1±1.6, P<0.0001). Age weakly correlated with total ACTIONS score (r=0.28, P=0.03) but age had no impact on continuing TRT and the relationship between continuing TRT and ACTIONS score held true regardless of age. CONCLUSIONS: Patients with a greater burden of systemic disease were less likely to have symptomatic improvement with TRT and more likely to stop therapy within a year. As several hypogonadal symptoms are non-specific, it is imperative that patients be counseled on the likelihood of success with TRT, particularly if they have multiple comorbidities. Ideal outcomes may come from multimodal therapy that includes lifestyle modification, and optimization of conditions such as diabetes, cardiovascular disease and sleep apnea.

Factors Associated With Receipt of Partial Nephrectomy or Minimally Invasive Surgery for Patients With Clinical T1a and T1b Renal Masses: Implications for Regionalization of Care.

PURPOSE: To identify factors associated with receipt of partial nephrectomy (PN) and minimally invasive surgery (MIS) in patients with clinical T1 renal cell carcinoma (RCC) using the National Cancer Data Base (NCDB). METHODS: We queried the NCDB from 2010 to 2014 identifying patients treated surgically for cT1a-bN0M0 RCC. Logistic regression was used to examine associations between socioeconomic, clinical, and treatment factors, and receipt of MIS or PN within the T1 patient population. RESULTS: Our cohort included 69,694 patients (cT1a, n = 44,043; cT1b, n = 25,651). For cT1a tumors, 70% of patients received PN and 65% underwent MIS. For cT1b tumors, 32% of patients received PN and 62% underwent MIS. cT1a and cT1b patients with household income < $62,000, without private insurance, and treated outside academic centers were less likely to receive MIS or PN. cT1a patients traveling > 31 miles were more likely to undergo MIS. For both cT1a/b, the farther a patient traveled for treatment, the more likely a PN was performed. CONCLUSION: Data showed an increase in utilization of MIS and PN from 2010 to 2014. However, patients in the lowest socioeconomic groups were less likely to travel and were more likely to receive more invasive treatments. On the basis of these findings, additional research is needed into how regionalization of RCC surgery affects treatment disparities.

Impact of pathologic lymph node-positive renal cell carcinoma on survival in patients without metastasis: Evidence in support of expanding the definition of stage IV kidney cancer.

BACKGROUND: Stage III renal cell carcinoma (RCC) encompasses both lymph node-positive (pT1-3N1M0) and lymph node-negative (pT3N0M0) disease. However, prior institutional studies have indicated that among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease. The objective of the current study was to validate these findings using a large, nationally representative sample of patients with kidney cancer. METHODS: Patients with AJCC stage III or stage IV RCC were identified using the National Cancer Data Base (NCDB). Patients were categorized as having lymph node-positive stage III (pT1-3N1M0), lymph node-negative stage III (pT3N0M0), or stage IV metastatic (pT1-3 N0M1) disease. Cox proportional hazards models compared outcomes while adjusting for comorbidities. Kaplan-Meier estimates illustrated relative survival when comparing staging groups. RESULTS: A total of 8988 patients met the inclusion criteria, with 6587 patients classified as having lymph node-negative stage III disease, 2218 as having lymph node-positive stage III disease, and 183 as having stage IV disease. Superior survival was noted among patients with lymph node-negative stage III disease, but similar survival was noted between patients with lymph node-positive stage III and stage IV RCC, with 5-year survival rates of 61.9% (95% confidence interval [95% CI], 60.3%-63.4%), 22.7% (95% CI, 20.6%-24.9%), and 15.6% (95% CI, 11.1%-23.8%), respectively. CONCLUSIONS: Current RCC staging systems group pT1-3N1M0 and pT3N0M0 disease as stage III disease. However, the results of the current validation study suggest the need for further stratification and even placement of patients with pT1-3N1M0 disease into the stage IV category. Staging that accurately reflects oncologic prognosis may help clinicians better counsel and select patients who might derive the most benefit from lymphadenectomy, adjuvant systemic therapy, more rigorous imaging surveillance, and clinical trial participation.

Vasovasostomy: kinetics and predictors of patency.

OBJECTIVE: To assess the timing of patency and late failure (secondary azoospermia) after vasovasostomy (VV) using standardized kinetics definitions. DESIGN: Retrospective cohort study. SETTING: University-affiliated hospital. PATIENT(S): Patients with obstructive azoospermia. INTERVENTION(S): Vasovasostomy. MAIN OUTCOME MEASURE(S): Univariate and multivariate logistic regression assessed predictors of patency and late failure. Patency was defined as any sperm return to the ejaculate; and >2 million total motile sperm (TMS) in ejaculate. Late failure after VV was defined as azoospermia; or <2 million TMS in ejaculate. RESULT(S): 429 men underwent VV, with median follow up of 242 days. Mean time to patency was 3.25 months versus 5.29 months in the "any sperm" versus ">2 million TMS" groups. Finding sperm intraoperatively during VV significantly improved patency rates in multivariable analysis (odds ratio [OR] 4.22). This association was further boosted when sperm was found bilaterally (OR 6.70). Late failure rate (azoospermia) was 10.6% at mean time of 14.1 months and 23% for <2 million, at mean time of 15.7 months. When assessing predictors of late failure, intraoperative motile sperm bilaterally was a statistically significant protective factor on multivariate analysis (hazard ratio 0.22). CONCLUSION(S): Vasovasostomy remains highly efficacious in treating obstructive azoospermia. Young patients, shorter obstructive intervals, and sperm identified intraoperatively predict improved outcomes. Clinicians can expect VV patency in 3 months and late failure within the first 2 years after surgery. However, patency rates, late failure rates, and kinetics vary by definition.

Testicular torsion in brothers.

Testicular torsion is a common pediatric emergency. Predisposing factors and other risk factors for testicular torsion have not been fully elucidated. This case report highlights teenage brothers who each experienced right-sided testicular torsion at nearly the same age, just 1 year apart. Because of their parents' urgency in seeking medical attention, the affected testicles in both patients were salvaged. We also review the current literature in regards to etiology, inheritance, and patient and parental education.

Sperm granuloma masquerading as a supernumerary testis.

Sperm granuloma is a common finding following vasectomy, with majority of the lesions located at the site of the vasectomy defect. Sperm granulomas are typically small and asymptomatic. We describe a case in which the nodule presented similarly to a supernumerary testis by radiographic features.

Retroperitoneal Lymph Node Dissection as Primary Treatment for Men With Testicular Seminoma: Utilization and Survival Analysis Using the National Cancer Data Base, 2004-2014.

BACKGROUND: The role of retroperitoneal lymph node dissection (RPLND) as first-line treatment for testicular seminoma is less well defined than for testicular nonseminomatous germ-cell tumors. We describe utilization of primary RPLND in the United States and report on overall survival (OS) after surgery for these men. PATIENTS AND METHODS: Using 2004-2014 data from the National Cancer Data Base, we identified 62,727 men with primary testicular cancer, 31,068 of whom were diagnosed as having seminoma. After excluding men with benign, non-germ cell, and nonseminomatous germ-cell tumor histologies, those who did not undergo RPLND, those where clinical stage and survival data were unavailable, and those with testicular seminoma who underwent RPLND in the postchemotherapy setting (n = 47), 365 men comprised our final cohort. Descriptive statistics were used to summarize clinical and demographic factors. The Kaplan-Meier method was used to determine OS. RESULTS: A total of 365 men with testicular seminoma underwent primary RPLND. At a median follow-up of 4.1 years, there were 16 deaths in the entire cohort. Five-year OS was 94.2%. Subset analysis of men with stage I and IIA/B disease who underwent primary RPLND revealed 5-year OS rates of 97.3% and 92.0%, respectively (P = .035). OS did not significantly differ in patients with stage IIA versus IIB disease (91.8% vs. 92.3%, respectively, P = .907). CONCLUSION: Although RPLND is rarely used as primary therapy in testicular seminoma, OS rates appear to be comparable to rates reported in the literature for primary chemotherapy or radiotherapy. Ongoing prospective trials will clarify the role of RPLND in the management of testicular seminoma.

Reasons that should prompt a referral to a reproductive urologist: guidelines for the gynecologist and reproductive endocrinologist.

Obstetricians and gynecologists, and in particular reproductive endocrinologists (REIs), are typically the gatekeepers and first-line providers for couples initially seeking an infertility evaluation. A timely referral to a reproductive urologist may improve pregnancy outcomes in certain clinical scenarios. This review examines the evidence behind circumstances requiring referral and delivers practice-based recommendations on commonly encountered scenarios in the clinic. Scenarios that should prompt referral to a reproductive urologist include semen analysis (SA) abnormalities (e.g., asthenozoospermia, azoospermia, globozoospermia, leukocytospermia, necrozoospermia, oligospermia), recurrent intrauterine insemination (IUI)/in vitro fertilization (IVF) failure, and idiopathic recurrent pregnancy loss (RPL). Conversely, deferment is appropriate in the cases of isolated teratozoospermia and subclinical varicocele. Men with infertility are also at higher risk for other comorbid conditions and should have at least a baseline evaluation by a primary care physician. Coordination of care between a REI and reproductive urologist is critical in several clinical scenarios and expedient referral can improve reproductive outcomes.

Retinal Defects Three Months After Intravitreal Dexamethasone Implant.

Intravitreal dexamethasone implants are commonly used to treat macular edema and noninfectious uveitis, and side effects including glaucoma and cataract formation are frequently managed. Rarely, the implant can cause an impact injury. However, this case shows peripheral retinal defects in a vitrectomized eye with abutting dexamethasone intravitreal implant without a flap, operculum, or other evidence of traction, developing 3 months after insertion, excluding the chance of injury from impact. The presence of an intravitreal dexamethasone implant appeared to cause destruction of juxtaposed retinal tissue. This report describes evaluation and management of this previously unreported complication. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e211-e214.].

Accuracy of clinical nodal staging and factors associated with receipt of lymph node dissection at the time of surgery for nonmetastatic renal cell carcinoma.

INTRODUCTION: The benefit of lymph node dissection (LND) in renal cell carcinoma (RCC) remains poorly defined. Despite this uncertainty, the American Urological Association (AUA) guideline on localized renal cancer recommends that LND be performed for staging purposes when there is suspicion of regional lymphadenopathy on imaging. Using the National Cancer Database (NCDB), we sought to determine how much of a departure the new AUA guideline is from current practice. We hypothesized that practice patterns would reflect the "Expert Opinion" recommendation and that patients who are clinical lymph node (cLN) positive would receive a LND more often than those who are cLN negative. Additionally, we sought to determine factors that would trigger a LND as well the accuracy of clinical staging by examining the relationship between cLN and pathologic lymph node (pLN) status of patients who received a LND. MATERIALS AND METHODS: The NCDB was queried for patients with nonmetastatic RCC who underwent partial nephrectomy or nephrectomy from 2010 to 2014. Patient sociodemographic and clinical characteristics were extracted. Frequency distributions were calculated for patients with both cLN and pLN status available. Of patients who received a LND, sensitivity, specificity, and positive/negative predictive values (PPV/NPV) of cLN status for pLN positivity were calculated. Logistic regression models were used to examine association between clinical and socioeconomic factors and receipt of LND. Propensity score matching was used in sensitivity analyses to examine potential for reporting bias in NCDB data. RESULTS: We identified 110,963 patients who underwent surgery for RCC, of whom 11,867 (11%) had LND performed at the time of surgery. cLN and pLN information were available in 11,300 patients, of which 1,725 were preoperatively staged as having positive cLN. More LNDs were performed per year for patients who were cLN negative than cLN positive. Of patients who received a LND, the majority of patients were cLN negative across all clinical T (cT) stages. Multivariable analysis showed that all patients who had care at an academic/research institution (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.43-1.74) and had to travel >12.5 to 31.0 miles and >31.0 miles to a treatment center (OR: 1.08, 95%CI: 1.01-1.15 and OR: 1.28, 95%CI: 1.20-1.36, respectively) were more likely to get a LND. As cT stage increased from cT2-4, the risk of LND increased (OR range: 4.7-7.90, respectively). Patients who were cLN positive were more likely to receive a LND at the time of surgery (OR: 18.68, 95%CI: 16.62-21.00). Of the patients who received a LND, clinical staging was more specific than sensitive. CONCLUSION: More patients received a LND who were cLN negative compared to patients who were cLN positive. Patients who were cLN positive were more likely to receive a LND. Treatment center type, distance to treatment center, cT stage, and cLN positivity were factors associated with LND receipt.