Genitourinary Infections Related to Circumcision and the Potential Impact on Male Infertility.

Male circumcision (MC) is one of the oldest surgical procedures still completed today. Medical indications for MC include phimosis, recurrent balanitis, cosmesis, and infection prevention. In this review, we mainly focus on the role of MC in the prevention of human immunodeficiency virus, human papillomavirus, herpes simplex virus, gonorrhea, chlamydia, chancroid, and syphilis, and the subsequent impact of these genitourinary infections on male fertility. Overall, many compelling data support that MC may play an essential role in both genitourinary infection prevention and male fertility.

Use of 4K3D Video Microscope in Male Infertility Microsurgery.

OBJECTIVE: To evaluate a 4K3D video microscope in the operating room of an outpatient surgical center during male infertility microsurgery procedures. DESIGN: Video presentation. SETTING: University of Miami outpatient surgical center. PATIENTS: All patients undergoing microsurgical procedures who signed a written, informed consent for video and audio recording. INTERVENTIONS: vasovasotomy, vasoepididymostomy, varicocele repair, microsurgical testicular sperm extraction. MAIN OUTCOME MEASURES: Operating room times and surgeon fatigue. RESULTS: This video demonstrates the potential advantages of a 4K3D video microscope in the operating room compared to the standard optical operating microscope (SOM), as well as robotic assisted microsurgery. Operating times for all varicocele repair cases performed with the 4k3D video microscope during the 4-week trial period (6), were compared to the 6 most recent varicocelectomies done with a SOM. We observed a decrease in the median operating room times (74.5 minutes vs 96.5 minutes) for those surgeries involving the 4k3D video microscope. Mann Whitney U test was used to compare median operating times, however, because of our small sample size this was not statistically significant (p=0.092) (Figure 1). Additionally, between cases, the transport of microscope from room to room, draping and setup of the 4k3D video microscope required less time and was less strenuous for the OR staff. The 4k3D video microscope allows the surgeon to operate in a more ergonomic position compared to the SOM and comes at a price point which is more reasonable than a surgical robot (DaVinci). CONCLUSION: The 4K3D video microscope offers potential ergonomic and logistical advantages over the SOM and robotically assisted surgery. Future studies with larger sample sizes are needed to evaluate these potential advantages and objectively study the ergonomic improvements that the 4k3D video microscope offers over the SOM.

[Microsurgical management of obstructive azoospermia: Progress and prospects].

In the past two decades, with the rapid development of assisted reproductive technology and particularly the technological advances in male infertility microsurgery, many obstructive azoospermia-related infertile couples can now acquire the chances of natural pregnancy via reconstruction of the seminal tract. This article highlights the latest advances in surgical reconstruction of the seminal tract for the treatment of obstructive azoospermia, such as the application of laparoscopic and robotic techniques, with a discussion on microsurgical epididymal sperm aspiration and preservation, potential use of absorbable sutures or the bio-suture tape for microsurgical anastomosis in the management of obstructive azoospermia.

Novel Devices for Adolescent and Adult Male Circumcision.

There is an abundance of devices for adolescent and adult male circumcision (MC). It has been shown that the safety and efficacy of device-assisted MC are equal to or better than those for MC via conventional surgery. MC devices have the potential to simplify the procedure and increase the acceptability of circumcision among patients.

A novel experience of deferential vessel-sparing microsurgical vasoepididymostomy.

Microsurgical longitudinal intussusception vasoepididymostomy (LIVE) has been widely used to treat epididymal obstructive azoospermia since 2004. Although the deferential vasculature plays an important role in supplying blood to the testis and epididymis, little attention has been paid to the potential benefits of sparing the deferential vessels during the anastomosis in LIVE. This study aimed to evaluate the efficacy and safety of deferential vessel-sparing LIVE in humans. From December 2013 to December 2015, 69 azoospermic men with epididymal obstruction due to a genital infection, trauma, or idiopathic factors underwent deferential vessel-sparing LIVE in the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. The outcomes of these patients were analyzed retrospectively. The mean age was 31.1 years for men and 28.3 years for their partners. Fifty-nine (85.5%, 59/69) men were followed up after surgery for approximately 16 months. Patency was noted and confirmed by semen analysis (>10 000 sperm/ml) in 83.1% (49/59) of men. The natural pregnancy rate was 40.7% (24/59) by the end of the study, with 87.5% (21/24) of these natural pregnancies achieved within 12 months after surgery. No severe adverse events or complications were observed. In this study, we present a novel technique for sparing the deferential vessels during LIVE. The preliminary outcomes show this technique to be safe with favorable patency and pregnancy rates.

Field study of adult male circumcision using the ShangRing in routine clinical settings in Kenya and Zambia.

BACKGROUND: Circumcision devices can facilitate adult voluntary medical male circumcision programs for HIV prevention. The World Health Organization recommends field studies to confirm the safety of devices in local settings. METHODS: We evaluated the safety of the ShangRing device in routine service delivery by measuring adverse event (AE) rates overall and by HIV status. We enrolled men aged 18-54 years and scheduled them for 2 post-circumcision follow-up visits at day 7 for device removal and days 35-42. Men were examined to document AEs and healing and to ascertain client acceptability. Provider preferences were also assessed. RESULTS: We enrolled 1163 men (557 in Kenya and 606 in Zambia); the as-treated analysis population comprised 1149 men, including 84 HIV-positive men. There were no serious AEs and 2 severe AEs: 1 severe wound dehiscence and 1 severe pain, both of which resolved with treatment. There were 18 moderate/severe AEs among 16 men (1.4% of men; 95% confidence interval: 0.8% to 2.3%). The most common AE was wound dehiscence (9 men, 0.8%). Healing was similar between HIV-infected and uninfected men, with 85.7% and 87.3% completely healed at days 35-42. Most men (94.8%) were very satisfied with post-circumcision appearance of the penis, and almost all would recommend a ShangRing procedure. Nineteen of 21 providers preferred the ShangRing over conventional surgery. CONCLUSIONS: The ShangRing has an excellent safety profile with few hemorrhagic and infectious complications. The ShangRing is well accepted by clients and preferred by providers, making it a potential boon to the scale-up of adult voluntary medical male circumcision in African countries.

Randomized controlled trial of the shang ring versus conventional surgical techniques for adult male circumcision: safety and acceptability.

OBJECTIVE: To compare clinical profiles of Shang Ring versus conventional circumcisions. DESIGN: Parallel group open-label randomized controlled trial with one-to-one allocations in 2 sites. METHODS: We enrolled HIV-negative men aged 18-54 years in Homa Bay, Kenya, and Lusaka, Zambia and followed them at 2, 7, 14, 21, 28, 42, and 60 days after Shang Ring versus conventional circumcision. We compared the duration of surgery, postoperative pain using a visual analog scale, adverse events rates, time to complete wound healing by clinical assessment, participant acceptability, and provider preferences between circumcision groups. RESULTS: We randomized 200 men to each group; 197 and 201 contributed to the Shang Ring and conventional surgery analyses, respectively. Adverse event rates were similar between groups. Pain scores at most time points were similar, however, the Shang Ring group reported higher scores for worst pain during erections (3.5 ± 1.9 vs. 2.3 ± 1.7; P < 0.001). Significantly more men were satisfied with the cosmetic appearance following Shang Ring male circumcision (MC), 95.7% versus 85.9% (P = 0.02) in Kenya, and 96.8% versus 71.3% (P < 0.01) in Zambia. Although median time to complete wound healing was 43 days in both groups, conventional circumcisions healed on average 5.2 days sooner (P < 0.001). Shang Ring procedures took one-third the time of conventional MC, 7 versus 20 minutes. All circumcision providers preferred the Shang Ring. CONCLUSIONS: Safety profiles of the 2 techniques were similar, all MC providers preferred the Shang Ring technique, and study participants preferred the Shang Ring's cosmetic results. The Shang Ring should be considered for adult MC as programs scale-up.

Identification of spermatogenesis in a rat sertoli-cell only model using Raman spectroscopy: a feasibility study.

PURPOSE: We determined whether Raman spectroscopy could identify spermatogenesis in a Sertoli-cell only rat model. MATERIALS AND METHODS: A partial Sertoli-cell only model was created using a testicular hypothermia-ischemia technique. Bilateral testis biopsy was performed in 4 rats. Raman spectra were acquired with a probe in 1 mm3 samples of testicular tissue. India ink was used to mark the site of spectral acquisition. Comparative histopathology was applied to verify whether Raman spectra were obtained from Sertoli-cell only tubules or seminiferous tubules with spermatogenesis. Principal component analysis and logistic regression were used to develop a mathematical model to evaluate the predictive accuracy of identifying tubules with spermatogenesis vs Sertoli-cell only tubules. RESULTS: Raman peak intensity changes were noted at 1,000 and 1,690 cm(-1) for tubules with spermatogenesis and Sertoli-cell only tubules, respectively. When principal components were used to predict whether seminferous tubules were Sertoli-cell only tubules or showed spermatogenesis, sensitivity and specificity were 96% and 100%, respectively. The ROC AUC to predict tubules with spermatogenesis with Raman spectroscopy was 0.98. CONCLUSIONS: Raman spectroscopy is capable of identifying seminiferous tubules with spermatogenesis in a Sertoli-cell only ex vivo rat model. Future ex vivo studies of human testicular tissue are necessary to confirm whether these findings can be translated to the clinical setting.

[Update of genetic evaluation for male infertility].

Men with azoospermia or severe oligospermia (< 5 x 10(6)/ml) should have genetic testing to identify the reason for male infertility before treatment. Identification of obstructive azoospermia (OA) or non-obstructive azoospermia (NOA) is essential because genetic testing differs for OA (which has normal testicular function, testicular volume, and FSH) versus NOA (which has small, soft testes and increased FSH). Among patients with NOA, history and physical examination along with laboratory testing is required to choose genetic testing specifically for primary testicular failure or congenital hypogonadotropic hypogonadism (HH). Genetic testing options include cystic fibrosis transmembrane conductance regulator (CFTR) testing for men with OA due to congenital absence of the vas, while karyotype, Y chromosome microdeletions (YCMD), and other specific genetic tests may be indicated if patient has severe oligospermia or NOA. These genetic tests help to identify which patients may benefit from medical and/or surgical intervention. The most recent techniques for genetic analysis will improve diagnosis and management of male infertility.

Microsurgical denervation of rat spermatic cord: safety and efficacy data.

OBJECTIVE: To describe a microsurgical technique for denervation of the spermatic cord and use of multiphoton microscopy (MPM) laser to identify and ablate residual nerves after microsurgical denervation. To evaluate structural and functional changes in the rat testis and vas deferens after denervation. MATERIALS AND METHODS: Nine Sprague-Dawley rats were divided into three experimental groups: sham, microsurgical denervation of the spermatic cord (MDSC), and MDSC immediately followed by laser ablation with MPM. At 2 months after surgery, we assessed testicular volume, functional circulation of the testicular artery with Doppler, patency of the vas deferens, and histology of the testis and vas deferens. RESULTS: There was a significant decrease in the median number of nerves remaining around the vas deferens with MDSC alone (3.5 nerves) or MDSC with MPM (1.5 nerves) compared with sham rats (15.5 nerves) (P = 0.003). Although, MDSC with MPM resulted in the fewest remaining nerves, this result was similar to MDSC alone (P = 0.29). No deleterious effects on spermatogenesis or vas patency were seen in the experimental groups when compared with the sham rats. CONCLUSION: A microsurgical approach can be used to effectively and safely denervate the rat spermatic cord with minimal changes to structure and function of the testis and vas deferens. MPM can be used as an adjunct to identify and ablate residual nerves after MDSC.

Microsurgical rat varicocele model.

PURPOSE: A rat varicocele model using partial occlusion of the left renal vein was described previously. Reproducibility in creating this model has met with varied success. Alternate routes of testicular venous drainage may negate the effect of partial renal vein occlusion on varicocele creation. We hypothesized that varicocele induction would be more effective if microsurgical ligation of the gonadal venous drainage to the common iliac vein was combined with partial occlusion of the left renal vein. MATERIALS AND METHODS: We randomly assigned a total of 36 rats to 3 groups, including sham surgery, partial renal vein occlusion alone (the classic technique) and microsurgical ligation. Half of the rats in each group were evaluated at 5 and 12 weeks, respectively. We evaluated internal gonadal vein and spermatic cord diameter, testicular weight, cauda epididymal sperm concentration and motility and testicular histology using the Johnsen score as well as serum and intratesticular testosterone and dihydrotestosterone. RESULTS: Five weeks after varicocele creation the microsurgical ligation group had a larger spermatic cord diameter and lower Johnsen scores than rats in the classic technique and sham surgery groups. At 12 weeks the microsurgical ligation group had a larger spermatic cord diameter, lower cauda epididymal sperm concentration, lower sperm motility and worse histology than the classic technique and sham surgery groups. There was no difference in serum androgen outcomes but the microsurgical ligation group had lower intratesticular androgens. CONCLUSIONS: Adding microsurgical ligation of testicular vein collaterals in the pelvis to partial renal vein occlusion appears to improve the effectiveness of creating a rat varicocele model.

[Long-term benefit of male circumcision to the reduction of urinary tract infections and genitourinary cancers in China].

Increasingly accumulated results from randomized controlled trials and other clinical studies have demonstrated that male circumcision reduces the risks of acquisition and transmission of HIV, HPV, HSV-2, and other sexually transmitted infections, and thus has a potential role in preventing cervical cancer, penile cancer and prostate cancer. The prevalence of male circumcision in China is currently less than 5%. The clinical evaluation studies and randomized controlled trials of the Shang Ring device showed excellent safety profiles, extremely high acceptability, and satisfaction among the participants and service providers in Africa and China. Given the recent recommendations by the World Health Organization and the Joint United Nations Program on HIV/AIDS (UNAIDS), voluntary medical male circumcision should be promoted in China at the national level as an important alternative intervention to reduce reproductive tract infections and prevent both males and females from reproductive tract cancers. More emphasis is required on the studies of the long-term health benefits of male circumcision in uro-andrology.

Clinical and investigative applications of Raman spectroscopy in Urology and Andrology.

Raman spectroscopy (RS) is an optical technique that allows for real-time interrogation of biologic tissues with chemical specificity. Using a diode laser, incident photons are scattered on the tissue of interest and the spectral wavelength output is a reflection of the tissues' molecular fingerprint. Naturally, this technology has come into clinical usage to evaluate benign versus malignant tissue. Within the field of Urology, RS has seen tremendous growth as an optical biopsy tool for the real-time evaluation of diseases of the bladder, prostate, kidney, and testis. With such growing fervor for this emerging spectroscopic modality, we present a current summary of clinical studies utilizing RS within Urology and Andrology to highlight its potential applications.

Clinical trials using the Shang Ring device for male circumcision in Africa: a review.

Male circumcision (MC) reduces the risk of HIV and other sexually transmitted infections (STIs), including human papillomavirus (HPV) and herpes simplex virus type 2 (HSV-2), and is recommended as an important component of a comprehensive package of HIV prevention interventions. While computer modeling has demonstrated that substantial reductions in HIV could be achieved with rapid scale-up of MC services in sub-Saharan Africa, scale-up has lagged due to scarcity of trained providers coupled with relative technical difficulty of recommended surgical MC techniques. Simplified techniques, such as devices, have the potential to allow for a more rapid roll-out of MC. One such device is the Shang Ring, a novel disposable MC device that eliminates the need for suturing and has been on the Chinese market since 2005. Results from Chinese studies have demonstrated that the Shang Ring is both safe and easy to use. Since 2008, a series of studies using the Shang Ring for adult MC have been carried out in Kenya, Uganda and Zambia, according to guidelines established by World Health Organization (WHO) for clinical evaluation of new devices for adult MC. These include a proof of concept study, a study of delayed removal of the Shang Ring, two studies comparing Shang Ring circumcision to conventional surgical approaches, and a large field trial to evaluate safety of Shang Ring circumcision during routine service delivery. Results from these studies demonstrate that the Shang Ring has an excellent safety profile and that Shang Ring circumcision is relatively easy to teach and learn, making Shang Ring MC an appealing technique for use in sub-Saharan Africa where doctors are in short supply and non-physician providers such as nurses and clinical officers are playing a major role in providing MC through task shifting. Shang Ring MC and device removals were uneventfully performed by trained nurses and clinical officers, who preferred the Shang Ring to conventional surgical techniques. Adverse event rates were similar to those observed with conventional surgical circumcision and were managed with, at most, minor interventions, resolving with no long-term sequale. Perhaps one of the biggest advantages of the Shang Ring is the relatively short 3-6 minutes procedure time. Importantly, men also preferred the Shang Ring compared to conventional circumcision and satisfaction with cosmetic appearance of their circumcised penis was very high. The vast majority of participants in studies in Africa as well as China have reported few problems and little disruption to daily life while wearing the device. The Shang Ring holds great promise as an innovative technology that has the potential to facilitate the safe and effective scale-up of circumcision services in settings where MC is not widely used and where the burden of HIV-disease is high.

Male infertility microsurgical training.

A strong foundation in microsurgical techniques is imperative for urologists and clinical andrologists specializing in male infertility. Laboratory-based microsurgical training enhances surgical skills, improves surgeon confidence, and reduces stress and operating time, thereby benefiting both the patient and the surgeon. The laboratory environment additionally allows for the development of novel and innovative techniques. This review provides guidelines for setting up a microsurgical laboratory to develop and enhance microsurgical skills using synthetic and animal models.

Sex disparities in cancer mortality: the risks of being a man in the United States.

PURPOSE: In the United States more men are diagnosed with cancer than women. We quantified the differential mortality rates of nonsex specific cancers between the sexes and compared cancer stage distributions. MATERIALS AND METHODS: In this descriptive epidemiological study we obtained the incidence of new cancer cases, cancer deaths and stage distributions for the last 10 years in the United States from SEER (Surveillance, Epidemiology and End Results) program results. Sex specific cancers were excluded from study. We compared male-to-female relative mortality rate for all cancers as well as the average male-to-female relative mortality rate weighted by cancer incidence in the last 10 years. Sex specific stage distributions were also compared with the Kendall τ-c test. RESULTS: The male-to-female relative mortality rate for any cancer was 1.060 (95% CI 1.055-1.065). The average male-to-female relative mortality rate for the same cancer was 1.126 (95% CI 1.086-1.168). The discrepancy in incidence and mortality rates was stable for the last 10 years. Of the top 10 most common cancers men had an unfavorable stage distribution in all except colorectal, bladder and brain cancers. CONCLUSIONS: Men are more likely to have nonsex specific cancer than women and more likely to die of the cancer even after controlling for the incidence. This discrepancy has been stable for the last decade. For 7 of the 10 most commonly occurring nonsex specific cancers, representing 78% of all incident cancers, men are more likely to be diagnosed with advanced stage.

Pilot study of the correlation of multiphoton tomography of ex vivo human testis with histology.

PURPOSE: Although microdissection testicular sperm extraction has become first line therapy for sperm retrieval in men with nonobstructive azoospermia, there are challenges to the procedure, including difficulty differentiating between seminiferous tubules with normal and abnormal spermatogenesis. Multiphoton microscopy illuminates tissue with a near infrared laser to elicit autofluorescence, which enables real-time imaging of unprocessed tissue without labels. We hypothesized that we could accurately characterize seminiferous tubular histology in humans using multiphoton microscopy. MATERIALS AND METHODS: Seven men with normal or abnormal spermatogenesis underwent testicular biopsies, which were imaged by multiphoton microscopy. We assessed these images in blinded fashion. The diagnosis rendered with multiphoton microscopy was then correlated with that of hematoxylin and eosin stained tissue. We evaluated the ability of multiphoton microscopy to differentiate normal from abnormal seminiferous tubules by examining autofluorescence characteristics and diameters, as imaged by multiphoton microscopy. Assessment was repeated with stained slides and results were compared. RESULTS: The overall concordance rate between multiphoton microscopy and stained slides was 86%. The seminiferous tubules of patients with nonobstructive azoospermia were smaller than those of controls when measured by multiphoton microscopy and staining (p <0.05). The proportion of normal tubules and the diameters obtained with multiphoton microscopy were not different from those obtained with hematoxylin and eosin (p >0.05). CONCLUSION: Multiphoton microscopy can be used to differentiate normal from abnormal spermatogenesis. Its characterization of seminiferous tubular architecture is similar to that provided by hematoxylin and eosin staining. Further investigation of the clinical applications of multiphoton microscopy may improve surgical sperm retrieval outcomes for patients with nonobstructive azoospermia.

Multiphoton imaging and laser ablation of rodent spermatic cord nerves: potential treatment for patients with chronic orchialgia.

PURPOSE: Microsurgical denervation of the spermatic cord has been done to treat chronic orchialgia. However, identifying the site of spermatic cord nerves is not feasible with an operating microscope or robotic stereoscope. We used multiphoton microscopy, a novel laser imaging technology, to identify and selectively ablate spermatic cord nerves in the rat. MATERIALS AND METHODS: The spermatic cords of adult male Sprague-Dawley® rats were initially imaged in vivo under a low power multiphoton microscopy laser. After assessing the number, diameter and site (vasal vs perivasal) of the nerves a higher power laser using the same objective was used to ablate the nerves. The precision of nerve ablation and the preservation of surrounding structures were determined by histological analysis. We assessed the heterogeneity of the number of nerves with the Wilcoxon signed rank test. RESULTS: The average number of nerves per spermatic cord was 10, which was similar bilaterally (p = 0.13). The vas and perivasal structures had a similar number of nerves (p = 0.4). The median diameter of all nerves was 32 µm. Confirmation of nerve ablation, and preservation of the vas deferens and vasculature were anatomically validated by histological analysis. CONCLUSIONS: Multiphoton microscopy can identify and ablate nerves selectively in vivo in the rat. It can potentially be used for spermatic cord denervation to treat chronic orchialgia. Such imaging may increase the efficacy of nerve ablation and can avoid the potential risks of testicular atrophy and hydrocele associated with spermatic cord microsurgical denervation.

Male circumcision: Africa and beyond?

PURPOSE OF REVIEW: Male circumcision has become an important component of HIV prevention strategies in Africa. Results of recent trials have renewed interest in this ancient procedure and its potential application in the reduction of sexually transmitted infections (STIs). With renewed interest comes controversy, which has always been a close companion to circumcision. RECENT FINDINGS: Following the three randomized trials in Africa demonstrating the protective effects of male circumcision on HIV infection, studies have reported other benefits of circumcision including protection from certain STIs, including human papillomavirus and herpes simplex virus 2. With data accumulating on the public health benefits of circumcision and the endorsement of circumcision from WHO, investigators have begun to evaluate the feasibility, safety and cost of implementation of large-scale circumcision programs. Limitations of circumcision have also been explored. SUMMARY: Male circumcision will likely play an important role in HIV/STI prevention programs in Africa; the inclusion of circumcision in the health policy of developed countries will require further investigation.