Improvements in semen parameters in men treated with clomiphene citrate-A retrospective analysis.

Clomiphene citrate (CC) is commonly used off-label for the treatment of male infertility, yet there is limited data to guide patient selection. To identify a subset of patients more likely to benefit from CC, we aimed to define predictors of improvement in semen parameters among men receiving CC. We retrospectively analysed 151 men treated with at least 25 mg CC daily for male infertility and/or hypogonadism at two institutions between 2004 and 2014. Men previously on testosterone were excluded. The primary outcome was change in semen parameters. Variables included baseline patient characteristics, pre-treatment hormone profiles and pre-treatment semen analyses. A total of 77 men met inclusion criteria. Median length of therapy was 2.8 months. There was significant improvement in sperm concentration (14-21 million/ml; p = 0.002) and total motile count (TMC; 13-28 million; p = 0.04). One third of patients who began with fewer than 5 million motile spermatozoon improved to a TMC > 5 million, increasing reproductive options to include intrauterine insemination. Patient characteristics, pre-treatment hormone profile and degree of oligozoospermia did not predict treatment response. While no predictors of improvement were identified, clinically useful response rates are described for use in shared decision-making.

Contemporary management of ejaculatory dysfunction.

Although erectile dysfunction is the most common disorder of male sexual health, ejaculatory dysfunction is the most common form of sexual dysfunction experienced by men. Ejaculatory dysfunction covers a broad range of disorders that we have divided into four main categories: premature ejaculation, delayed ejaculation (DE)/anorgasmia, unsatisfactory sensation of ejaculation (including painful ejaculation and ejaculatory anhedonia), and absent ejaculate (including retrograde ejaculation and aspermia). We also cover several special scenarios including hematospermia, spinal cord injury and fertility with anejaculation. In this paper, we will review the anatomy and pathophysiology of normal ejaculation to establish the baseline knowledge of how this pathway can go awry. We will then briefly review the critical diagnostic criteria, pertinent steps in evaluation, risk factors, and causes (if known) for each of the ejaculatory disorders. Finally, the bulk of the paper will discuss current management strategies of each disorder.

Frontiers in hormone therapy for male infertility.

For a significant number of couples worldwide, infertility is a harsh reality. As specialists in male infertility, much of our armamentarium lacks definitive, evidence-based therapies. For years, we have relied on manipulation of the male hormonal axis to treat those men who help carry the burden of infertility in their partnerships. Indeed, male factor infertility is the sole component of infertility in at least 20% of couples. Further compounding this dilemma is that 25% to 50% of males with infertility have no identifiable etiology and thus present a true management conundrum. This manuscript is an attempt to clarify what therapies exist for the treatment of male factor infertility. We have reviewed the relevant infertility literature honing, our focus on hormonal anomalies and their subsequent impact on fertility. Many of the therapies discussed have been utilized in practice for generations. Thus, this article attempts to provide the evidence-based literature to support the continued use of the current treatment paradigm. Furthermore, we recognize that any review beckons a discussion of what challenges and therapies await on the horizon. For instance, there has been significant interest in restoring spermatogenesis after testosterone replacement therapy (TRT). We explore the adverse long-term spermatogenic outcomes associated with TRT, which with the widespread use of TRT, will inevitably present a great challenge for male infertility specialists. Moreover, we discuss the role of varicocelectomy in the treatment of hypogonadism and infertility, review the association between growth hormone (GH) and male fertility and address the challenges presented by the rising prevalence of obesity.

Acquired von Willebrand Disease Secondary to Clear Cell Renal Cell Carcinoma.

Background: Acquired von Willebrand disease (AvWD) is a rare and often underdiagnosed disease that typically is associated with lymphoproliferative, cardiovascular disease, and myeloproliferative disease. It is challenging to diagnose as it requires a hemostatic challenge to present itself. Case Presentation: This is a 46-year-old male with a history of multiple sclerosis complicated by neurogenic bladder who presented with intermittent gross painless hematuria. He underwent a gross hematuria workup. Cystoscopy demonstrated active bleeding from the right ureteral orifice. CT Urogram showed a filling defect in the right renal pelvis and endophytic 3 cm solid, enhancing left kidney mass. The patient underwent diagnostic cystourethroscopy, bilateral retrograde pyelogram demonstrating no filling defects bilaterally. Right ureteropyeloscopy demonstrated diffuse patchy erythema of the infrarenal collecting system with biopsies obtained. His postoperative course was complicated by gross hematuria requiring cystoscopy which demonstrated no upper tract bleeding and small pulsatile bleeding vessel in the bladder requiring cauterization. Hematology was consulted to rule out bleeding diathesis with workup demonstrating a von Willebrand deficiency (vWD). He had no family history of vWD and an AvWD was suspected. Hematologic workup was consistent with AvWD, type 2B vWD also known as a platelet-type von Willebrand disease. Renal pelvis biopsies were negative for pathology. Further investigation of the left renal mass confirmed a biopsy-proven clear cell renal cell carcinoma (ccRCC). He underwent a laparoscopic left radical nephrectomy with final pathology demonstrating pT1 ccRCC with negative margins. Postoperatively his repeat laboratories demonstrated normal factor VIII activity, ristocetin cofactor, and vWF antigen with normalized activated partial thromboplastin time. Follow-up imaging demonstrated no further evidence of disease supporting the hypothesis of a paraneoplastic syndrome from his ccRCC that caused an AvWD. Conclusion: This is the first case report to our knowledge of a paraneoplastic AvWD secondary to ccRCC. This should be on your differential when there is abnormal bleeding in the setting of renal masses.

The future of male contraception: a fertile ground.

The continued and rapid expansion of the Earth's population mandates the need for safe and effective measures of contraception. While a plethora of options exist for women, methods of contraception for the male partner are limited to condoms and vasectomy. The sequela of this discrepancy has led to the family planning burden falling disproportionately on the female partner. For the past several decades, extensive research has been undertaken exploring the feasibility of hormonal male contraception. This proposed method of contraception has focused on suppressing spermatogenesis by exploiting the hypothalamic-pituitary-gonadal (HPG) axis. Beginning with proof of concept studies in the early nineties, administration of testosterone in healthy male subjects has been shown to be an efficacious method of inducing sterility. Owing to ethnic differences in spermatogenesis suppression and the comparatively low rate of azoospermia in Caucasian men with androgen-only regimens, investigators have explored the addition of progestins to further enhance the efficacy of hormonal contraception. Though studies have revealed promise with androgen-progestin regimens, the lack of long-term studies has precluded the development of a marketable product. Recently, more research has been directed towards identifying non-hormonal alternatives to male contraception. These non-hormonal options have ranged from the development of devices facilitating reversible occlusion of the vas deferens lumen to medications disrupting various pathways in the process of spermatogenesis. Underlying the development of hormonal and non-hormonal strategies is the shared enthusiasm men and women have towards these male directed methods. The willingness of couples to pursue these alternatives combined with the global need to reduce the psychological and socioeconomic implications of unintended pregnancy ensures that research will continue to bring this goal to fruition.

Melanotic Xp11 Translocation Renal Cancer Managed With Radical Nephrectomy and IVC Tumor Thrombectomy.

Melanotic Xp11 translocation renal cancer is a rarely observed neoplasm primarily affecting adolescents and young adults. Given the paucity of data describing this malignancy, its natural history and subsequent long-term management are not well understood. We report a case of melanotic Xp11 translocation with tumor thrombus extension managed with radical nephrectomy and inferior vena cava (IVC) tumor thrombectomy. To our knowledge, this is the first case report to describe use of conventional tumor thrombectomy techniques in a patient with melanotic Xp11 translocation renal cancer.

Treatment of Urethral Strictures from Irradiation and Other Nonsurgical Forms of Pelvic Cancer Treatment.

Radiation therapy (RT), external beam radiation therapy (EBRT), brachytherapy (BT), photon beam therapy (PBT), high intensity focused ultrasound (HIFU), and cryotherapy are noninvasive treatment options for pelvic malignancies and prostate cancer. Though effective in treating cancer, urethral stricture disease is an underrecognized and poorly reported sequela of these treatment modalities. Studies estimate the incidence of stricture from BT to be 1.8%, EBRT 1.7%, combined EBRT and BT 5.2%, and cryotherapy 2.5%. Radiation effects on the genitourinary system can manifest early or months to years after treatment with the onus being on the clinician to investigate and rule-out stricture disease as an underlying etiology for lower urinary tract symptoms. Obliterative endarteritis resulting in ischemia and fibrosis of the irradiated tissue complicates treatment strategies, which include urethral dilation, direct-vision internal urethrotomy (DVIU), urethral stents, and urethroplasty. Failure rates for dilation and DVIU are exceedingly high with several studies indicating that urethroplasty is the most definitive and durable treatment modality for patients with radiation-induced stricture disease. However, a detailed discussion should be offered regarding development or worsening of incontinence after treatment with urethroplasty. Further studies are required to assess the nature and treatment of cryotherapy and HIFU-induced strictures.

Contemporary diagnosis and management of Fournier's gangrene.

Fournier's gangrene, an obliterative endarteritis of the subcutaneous arteries resulting in gangrene of the overlying skin, is a rare but severe infective necrotizing fasciitis of the external genitalia. Mainly associated with men and those over the age of 50, Fournier's gangrene has been shown to have a predilection for patients with diabetes as well as people who are long-term alcohol misusers. The nidus for the synergistic polymicrobial infection is usually located in the genitourinary tract, lower gastointestinal tract or skin. Early diagnosis remains imperative as rapid progression of the gangrene can lead to multiorgan failure and death. The diagnosis is often made clinically, although radiography can be helpful when the diagnosis or the extent of the disease is difficult to discern. The Laboratory Risk Indicator for Necrotizing Fasciitis score can be used to stratify patients into low, moderate or high risk and the Fournier's Gangrene Severity Index (FGSI) can also be used to determine the severity and prognosis of Fournier's gangrene. Mainstays of treatment include rapid and aggressive surgical debridement of necrotized tissue, hemodynamic support with urgent resuscitation with fluids, and broad-spectrum parental antibiotics. After initial radical debridement, open wounds are generally managed with sterile dressings and negative-pressure wound therapy. In cases of severe perineal involvement, colostomy has been used for fecal diversion or alternatively, the Flexi-Seal Fecal Management System can be utilized to prevent fecal contamination of the wound. After extensive debridement, many patients sustain significant defects of the skin and soft tissue, creating a need for reconstructive surgery for satisfactory functional and cosmetic results.

Electrosurgical management of Hunner ulcers in a referral center's interstitial cystitis population.

OBJECTIVE: To characterize electrocautery (EC) as a valid treatment option in interstitial cystitis (IC) patients with Hunner ulcers (HUs). METHODS: From 1997 to 2013, a single urologist's IC population was retrospectively reviewed to identify HU patients as well as their demographics, operative characteristics, and response to a 2-page questionnaire evaluating parameters of their experience with EC. Descriptive statistics, Pearson chi-square test, Student t test, and Pearson coefficient were used. RESULTS: Two hundred fourteen EC procedures were performed in 76 patients (87% women; mean age, 66 ± 1.67 years). Fifty-one patients (69%) who underwent multiple EC had mean initial bladder capacity of 438.62 ± 27.90 mL and final bladder capacity of 422.40 ± 30.10 mL. Mean number of EC procedures was 2.98 ± 0.25 (range, 1-11). Mean time between sessions was 14.52 ± 1.34 months (range, 1-121 months). Fifty-two patients (68%) completed our questionnaire, with 13.54 ± 1.28 years of symptoms and 10.66 ± 0.96 years since diagnosis. Ranking IC treatments, 37 patients (84%) reported EC most beneficial. On a 0-10 (none to worst possible) scale before and after EC, frequency improved from 9.04 ± 1.30 to 3.65 ± 2.75 (P <.001), urgency from 8.40 ± 2.38 to 3.28 ± 2.71 (P <.001), and pain from 8.62 ± 2.36 to 2.68 ± 2.55 (P <.001). Overall, 89.6% of patients noted some degree of symptom improvement after EC; 56.3% of patients had marked improvement. A total of 98% of patients would undergo EC again. CONCLUSION: EC of HU is an effective and safe procedure with high patient satisfaction that does not diminish bladder capacity.

Apremilast in the Treatment of Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Pilot Study.

OBJECTIVE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disease with an uncertain cause and limited effective treatments. Apremilast (Celgene Corporation, Summit, NJ, USA) is a selective phosphodiesterase type 4 (PDE4) inhibitor that modulates the immune system. An open-label, one-arm, pilot study was conducted to explore its potential for improving CP/CPPS symptoms. METHODS: Males ≥ 18 years of age were treated with 20 mg oral apremilast twice daily for up to 12 weeks. Outcomes were measured with Global Response Assessment (GRA), pain visual analog scale (VAS), Chronic Prostatitis Symptom Index (CPSI), Pittsburgh Sleep Quality Index (PSQI), SF-12 mental (MCS) and physical (PCS) health-related quality of life subscales, and voiding diaries. Repeated measures and paired t-tests evaluated changes from baseline to end of treatment, and at a final visit 4 weeks off the drug. RESULTS: Seventeen men (94% Caucasian; mean age 48.2 ± 10 years) were treated (mean 115.8 ± 56.1 doses). Mean VAS (3.4 ± 2.0 vs 1.8 ± 1.7; P = 0.0011), PSQI (9.4 ± 4.4 vs 7.4 ± 4.2; P = 0.037) and CPSI (26.1 ± 5.0 vs 17.2 ± 8.3; P = 0.0016) scores improved from baseline to end of treatment. Incontinence episodes per day improved slightly (P = 0.042). When only those completing at least 8 weeks of treatment were examined (n = 9), significant changes in CPSI, VAS, and PSQI were still observed. At the final visit, 8/9 (88.9%) men also reported some improvement in pain related to sex. Side-effects were generally mild and well tolerated. CONCLUSION: These results suggest that apremilast may improve CP/CPPS symptoms with only mild side-effects. However, placebo controlled studies are necessary to determine efficacy.