Effect of varicoceles on spermatogenesis.

Varicoceles are dilated veins within the spermatic cord and a relatively common occurrence in men. Fortunately, the large majority of men are asymptomatic, however, a proportion of men with varicoceles can suffer from infertility and testosterone deficiency. Sperm and testosterone are produced within the testis, and any alteration to the testicular environment can negatively affect the cells responsible for these processes. The negative impact of varicoceles on testicular function occurs mainly due to increased oxidative stress within the testicular parenchyma which is thought to be caused by scrotal hyperthermia, testicular hypoxia, and blood-testis barrier disruption. Management of varicoceles involves ligation or percutaneous embolization of the dilated veins. Repair of varicoceles can improve semen parameters and fertility, along with serum testosterone concentration. In this review, we discuss the pathophysiology of varicoceles, their impact on testicular function, and management.

Testicular Torsion and Spermatogenesis.

Testicular torsion (TT) is a common urologic emergency that can occur at any age. It is most common in newborns and during puberty. Prompt evaluation and management is required to salvage the testis following an episode of torsion. TT brings about damage to testicular tissue and spermatogenesis through various hypothesized mechanisms; however there is a consensus that the effects of ischemia, ischemia-reperfusion injury, and oxidative stress account for the most destructive effects. Numerous studies have examined the effects of various agents and therapies in limiting the effects of TT on the testis.

The Kinetics of Sperm Return and Late Failure Following Vasovasostomy or Vasoepididymostomy: A Systematic Review.

PURPOSE: Vasovasostomy and vasoepididymostomy are technically challenging microsurgical reconstructive procedures necessary for men with obstructive azoospermia at the level of the vas deferens or epididymis. Patency rates following vasovasostomy or vasoepididymostomy have been widely described in the literature. However, few reports have discussed the timing of sperm return to the ejaculate after reconstruction as well as the proportion of men in whom late failure develops following vasovasostomy or vasoepididymostomy. Therefore, the objective of this article was to review the rates and predictors associated with late failure and the timing of sperm returning to the ejaculate after vasovasostomy and vasoepididymostomy. MATERIALS AND METHODS: A literature search was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines via the PubMed®/MEDLINE® database. We included relevant articles published in English in peer reviewed journals from 1960 to 2017 which reported outcomes regarding time to patency, time to late failure or the late failure rate after vasovasostomy or vasoepididymostomy. Macroscopic reconstructions were excluded from study. RESULTS: A total of 24 articles were included in the review. Mean time to patency after vasovasostomy and vasoepididymostomy ranged from 1.7 to 4.3 and 2.8 to 6.6 months, respectively. The late failure rate after microsurgical vasovasostomy and vasoepididymostomy ranged from 0% to 12% and 1% to 50%, respectively. Mean time to late failure after vasovasostomy and vasoepididymostomy ranged from 9.7 to 13.6 and 6 to 14.2 months, respectively. There was significant heterogeneity in the available data, limiting comparisons between series. CONCLUSIONS: Sperm returns to the ejaculate sooner in men who undergo vasovasostomy compared to vasoepididymostomy. Late failures are heterogeneously defined in the literature but they occur at a rate that is not insignificant. Thus, clinicians should discuss considerations for sperm cryopreservation.

Spermatogenesis in humans and its affecting factors.

Spermatogenesis is an extraordinary complex process. The differentiation of spermatogonia into spermatozoa requires the participation of several cell types, hormones, paracrine factors, genes and epigenetic regulators. Recent researches in animals and humans have furthered our understanding of the male gamete differentiation, and led to clinical tools for the better management of male infertility. There is still much to be learned about this intricate process. In this review, the critical steps of human spermatogenesis are discussed together with its main affecting factors.

[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.

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.

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.

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.

[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.

[The making of a good male infertility microsurgeon: learning experience at Weill Cornell Medical College of Cornell University].

Male infertility microsurgery represents the fastest growing sub-specialty in urology and clinical andrology over the past two decades. The importance of microsurgery for male infertility has risen as a part of the urologist's armamentarium in the medical and surgical management of male infertility. Despite the advances in male infertility microsurgery in China, the lack of standardized and well-organized training programs for male infertility microsurgery remains a serious problem affecting its development. In this article, Zhao and Peng have shared their experience with the learning curve of male infertility microsurgery at the Center for Male Reproductive Medicine and Microsurgery, Weill Medical College of Cornell University, which centers on how to pay attention to the details and basic principles of microsurgery. Male infertility microsurgery is physically, technically and mentally challenging, and must be first learned in the laboratory. Clinical success depends heavily upon appropriate training in a microsurgical laboratory. Good training can significantly reduce operation time and surgical errors as well as improve the quality of outcomes.

[Clinical studies of shang ring male circumcision in China and Africa].

HIV/STIs remain a major global public health problem. One of the global strategies for the prevention and control of HIV/STIs is to interrupt their transmission, which requires the public health methods based on scientific evidence and cost-effectiveness. The scale-up of male circumcision services in the priority countries of the HIV-prevention project in sub-Saharan Africa has been hampered by the scarcity of trained providers and relative technical difficulty of male circumcision techniques recommended by WHO and UNAIDS. Shang Ring is an innovative and disposable device for male circumcision, which has been safely used for over 600 000 males in China since 2006. Clinical studies of more than 3 000 cases of Shang Ring circumcision in China, Kenya, Zambia, and Uganda have demonstrated its safety, effectiveness, acceptability and ease of use. The most obvious advantages of Shang Ring include short procedure time (3-6 min), excellent postoperative cosmesis, low rate of complications, high acceptance by clients and providers, ease of use, and standardization for reliable performance. As an innovative technique, Shang Ring has a great potential for facilitating the safe and effective scale-up of circumcision services. This article comprehensively reviews the clinical studies of Shang Ring male circumcision in China and Africa.

[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.

Comparison of the penile microbiome in infant male circumcision: Mogen clamp versus Shangring.

BACKGROUND: This study aimed to characterise the infant penile (coronal sulcus) microbiome and the effects of early infant male circumcision (EIMC), following a standard surgical method (Mogen Clamp) and a non-surgical alternative (ShangRing). METHODS: We collected coronal sulcus swabs at baseline and on days 7 and 14 post-circumcision from infants assigned to receive EIMC by Mogen Clamp (n = 15) or ShangRing (n = 15), in a randomised trial in Rakai and Kakuuto, Uganda. We used 16S rRNA gene-based sequencing and broad-coverage qPCR to characterise the infant penile microbiome and assess the effects of EIMC in both study arms. FINDINGS: Prior to EIMC, the infant penile microbiome had a mixture of facultative and strict anaerobes. In both study arms, EIMC caused penile microbiome proportional abundance changes characterised by decreases in penile anaerobes [ShangRing Prevotella: -15.0%, (SD = 19.1); Mogen clamp Prevotella: -3.6% (11.2); ShangRing Veillonella: -11.3% (17.2); Mogen clamp Veillonella: -2.6% (11.8)] and increases in skin-associated facultative anaerobes [ShangRing Corynebacterium: 24.9%, (22.4); Mogen clamp Corynebacterium: 4.7% (21.3); ShangRing Staphylococcus: 21.1% (20.5); Mogen clamp Staphylococcus: 18.1% (20.1)]. Clostridium tetani was not detected during the study. INTERPRETATION: Mogen Clamp and ShangRing EIMC both changed the composition of the infant penile microbiome by reducing the proportional abundances of anaerobes and uropathogens, which is consistent with medical male circumcision findings in adults. C. tetani was not increased by either EIMC method. FUNDING: Bill and Melinda Gates Foundation.

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.

Timing for maximum anaesthetic effect of topical cream during early infant circumcision (EIC) in Rakai, Uganda.

Objectives: The objective of this study is to determine the optimal timing for device-based infant circumcision under topical anaesthesia. Subjects/patients: We include infants aged 1-60 days who were enrolled in a field study of the no-flip ShangRing device at four hospitals in the Rakai region of south-central Uganda, between 5 February 2020 and 27 October 2020. Methods: Two hundred infants, aged 0-60 days, were enrolled, and EMLA cream was applied on the foreskin and entire penile shaft. The anaesthetic effect was assessed every 5 min by gentle application of artery forceps at the tip of the foreskin, starting at 10 min post-application until 60 min, the recommended time to start circumcision. The response was measured using the Neonatal Infant Pain Scale (NIPS). We determined the onset and duration of anaesthesia (defined as <20% of infants with NIPS score >4) and maximum anaesthesia (defined as <20% of infants with NIPS score >2). Results: Overall, NIPS scores decreased to a minimum and reversed before the recommended 60 min. Baseline response varied with age, with minimal response among infants aged 40 days. Overall, anaesthesia was achieved after at least 25 min and lasted 20-30 min. Maximum anaesthesia was achieved after at least 30 min (except among those aged >45 days where it was not achieved) and lasted up to 10 min. Conclusion: The optimal timing for maximum topical anaesthesia occurred before the recommended 60 min of waiting time. A shorter waiting time and speed may be efficient for mass device-based circumcision.

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.

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.

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.

Future of Male Infertility Evaluation and Treatment: Brief Review of Emerging Technology.

Over the past few decades, there have been significant advances in male infertility, particularly in the development of novel diagnostic tools. Unfortunately, there remains a substantial number of patients that remain infertile despite these improvements. In this review, we take heed of the emerging technologies that will shape the future of male infertility diagnosis, evaluation, and treatment. Improvement in computer-assisted semen analyses and portability allow males to obtain basic semen parameters from the comfort of their home. Additionally, breakthrough ultrasound technology allows for preoperative prediction of potential areas of spermatogenesis within the testes, high-resolution optics permits better visualization during microdissection testicular sperm extraction (mTESE), and artificial intelligence improves sperm selection and identification.