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.

ShangRing versus Mogen clamp for early infant male circumcision in eastern sub-Saharan Africa: a multicentre, non-inferiority, adaptive, randomised controlled trial.

BACKGROUND: Use of medical devices represents a unique opportunity to facilitate scale-up of early infant male circumcision (EIMC) across sub-Saharan Africa. The ShangRing, a circumcision device prequalified by WHO, is approved for use in adults and adolescents and requires topical anaesthesia only. We aimed to investigate the safety and efficacy of the ShangRing versus the Mogen clamp for EIMC in infants across eastern sub-Saharan Africa. METHODS: In this multicentre, non-inferiority, open-label, randomised controlled trial, we enrolled healthy male infants (aged <60 days), with a gestational age of at least 37 weeks and a birthweight of at least 2·5 kg, from 11 community and referral centres in Kenya, Tanzania, and Uganda. Infants were randomly assigned (1:1) by a computer-generated text message service to undergo EIMC by either the ShangRing or the Mogen clamp. The primary endpoint was safety, defined as the number and severity of adverse events (AEs), analysed in the intention-to-treat population (all infants who underwent an EIMC procedure) with a non-inferiority margin of 2% for the difference in moderate and severe AEs. This trial is registered with Clinical. TRIALS: gov, NCT03338699, and is complete. FINDINGS: Between Sept 17, 2018, and Dec 20, 2019, a total of 1420 infants were assessed for eligibility, of whom 1378 (97·0%) were enrolled. 689 (50·0%) infants were randomly assigned to undergo EIMC by ShangRing and 689 (50·0%) by Mogen clamp. 43 (6·2%) adverse events were observed in the ShangRing group and 61 (8·9%) in the Mogen clamp group (p=0·078). The most common treatment-related AE was intraoperative pain (Neonatal Infant Pain Scale score ≥5), with 19 (2·8%) events in the ShangRing and 23 (3·3%) in the Mogel clamp group. Rates of moderate and severe AEs were similar between both groups (29 [4·2%] in the ShangRing group vs 30 [4·4%] in the Mogen clamp group; difference -0·1%; one-sided 95% CI upper limit of 1·7%; p=0·89). No treatment-related deaths were reported. INTERPRETATION: Use of the ShangRing device for EIMC showed safety, achieved high caregiver satisfaction, and did not differ from the Mogen clamp in other key measures. The ShangRing could be used by health systems and international organisations to further scale up EIMC across sub-Saharan Africa. FUNDING: Bill & Melinda Gates Foundation.

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.

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.

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.

Technological Advancements in Male Infertility Microsurgery.

There have been significant advancements in male infertility microsurgery over time, and there continues to be significant promise for new and emerging techniques, technologies, and methodologies. In this review, we discuss the history of male infertility and the evolution of microsurgery, the essential role of education and training in male infertility microsurgery, and new technologies in this space. We also review the potentially important role of artificial intelligence (AI) in male infertility and microsurgery.

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 impact of SARS-CoV-2 and COVID-19 on male reproduction and men's health.

Many couples initially deferred attempts at pregnancy or delayed fertility care due to concerns about coronavirus disease 2019 (COVID-19). One significant fear during the COVID-19 pandemic was the possibility of sexual transmission. Many couples have since resumed fertility care while accepting the various uncertainties associated with severe acute respiratory syndrome coronavirus 2, including the evolving knowledge related to male reproductive health. Significant research has been conducted exploring viral shedding, tropism, sexual transmission, the impact of male reproductive hormones, and possible implications to semen quality. However, to date, limited definitive evidence exists regarding many of these aspects, creating a challenging landscape for both patients and physicians to obtain and provide the best clinical care. This review provides a comprehensive assessment of the evolving literature concerning COVID-19 and male sexual and reproductive health, and guidance for patient counseling.

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.

No evidence of severe acute respiratory syndrome-coronavirus 2 in semen of males recovering from coronavirus disease 2019.

OBJECTIVE: To describe detection of severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) in seminal fluid of patients recovering from coronavirus disease 2019 (COVID-19) and to describe the expression profile of angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) within the testicle. DESIGN: Observational, cross-sectional study. SETTING: Tertiary referral center. PATIENT(S): Thirty-four adult Chinese males diagnosed with COVID-19 through confirmatory quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) from pharyngeal swab samples. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets. RESULT(S): Six patients (19%) demonstrated scrotal discomfort suggestive of viral orchitis around the time of COVID-19 confirmation. Severe acute respiratory syndrome-CoV-2 was not detected in semen after a median of 31 days (interquartile range, 29-36 days) from COVID-19 diagnosis. Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression. CONCLUSION(S): Severe acute respiratory syndrome-CoV-2 was not detected in the semen of patients recovering from COVID-19 1 month after COVID-19 diagnosis. Angiotensin-converting enzyme 2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression. The long-term effects of SARS-CoV-2 on male reproductive function remain unknown.

No-flip ShangRing circumcision in 10-12 year old boys: Results from randomized clinical trials in Kenya.

BACKGROUND: Attention has recently turned toward the use of device-assisted male circumcision to help scale up male circumcision services in sub-Saharan Africa, with increasing emphasis on younger age groups. We assessed the use of the ShangRing for circumcising the subset of boys aged 10 to 12 years who were enrolled in two randomized clinical trials in Kenya. METHODS: We performed a sub-analysis of outcomes in 197 boys aged 10 to 12 years; a subset who were enrolled in two randomized clinical trials to assess the use of the no-flip ShangRing circumcision technique in men and boys. One trial assessed spontaneous detachment vs. planned removal of the ShangRing 7 days post-circumcision. The second trial compared the use of topical vs. injectable anesthesia with ShangRing circumcision. Aside from baseline characteristics, data was collected and analyzed for each trial separately. RESULTS: All participants were successfully circumcised. Duration of circumcision, participants requiring a dorsal slit, rate of adverse events, time to complete wound healing, and participant satisfaction were similar between the two groups in each trial. Mean time required for spontaneous ShangRing detachment was 14.82±3.76 days. Topical anesthesia showed a significantly lower mean pain score at the time of application (0.64±1.71 vs. 1.55± 2.21, p = 0.03) as well as postoperatively (0.54±0.88 vs. 1.72±1.56, p<0.0001). Median dwell time of the topical anesthetic was 43 (IQR: 35.5-60) minutes, while the median time it took the injectable anesthetic to take effect was 2.04 (IQR: 1.72-3.09) minutes. CONCLUSION: No-flip ShangRing circumcision had a positive safety profile among young adolescent boys, specifically ages 10-12 years. The use of spontaneous device detachment and topical anesthesia with the procedure have shown promising outcomes in this age group. This may have the potential to further increase the acceptability of ShangRing circumcision, and therefore accelerate the scle up of male circumcision services in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov registration # NCT02390310.

Management of Ejaculatory Duct Obstruction by Seminal Vesiculoscopy: Case Report and Literature Review.

Ejaculatory duct obstruction is a rare condition identified in up to 5% of infertile men. Patients with ejaculatory duct obstruction can present with aspermia, azoospermia or oligoasthenospermia, painful ejaculation, hematospermia, prostatic pain, or male infertility. Semen analysis, transrectal ultrasonography, pelvic computerized tomography and magnetic resonance imaging are often used in the diagnostic work up, but with limited accuracy. While transurethral resection of the ejaculatory ducts has good efficacy for distal duct obstruction, results for proximal obstruction are less impressive, and it might cause severe complications, such as rectal injury and urinary incontinence. Recently, the use of high quality endourological devices and an improved understanding of ejaculatory ducts anatomy gleaned through the use of sophisticated imaging tools have led to the development of novel minimally invasive treatment options for this condition. The present study aims to report an index case of ejaculatory ducts obstruction managed with seminal vesiculoscopy, and review the current literature regarding this topic.

Use of topical versus injectable anaesthesia for ShangRing circumcisions in men and boys in Kenya: Results from a randomized controlled trial.

BACKGROUND: The ShangRing is a disposable, collar clamp circumcision device pre-qualified for use in men and boys 13 years and above. It has been shown to be faster than conventional circumcision with comparable adverse event (AE) rates and high client satisfaction. Voluntary medical male circumcision (VMMC) has been shown to dramatically reduce the risk of HIV acquisition in males. However, the fear of pain during circumcision is an important barrier to uptake. Use of topical anesthesia thus presents an opportunity to address this. OBJECTIVES: We sought to evaluate the safety, effectiveness and acceptability of the use of topical anaesthesia with ShangRing circumcision of men and boys 10 years of age and above. METHODS: Participants were randomised 2:1 to receive topical or injectable anaesthesia. All participants underwent no-flip ShangRing circumcision. The primary outcome measure was pain. Secondary outcomes included ease of use of topical versus injectable anaesthesia, AEs and participant satisfaction. RESULTS: Compared to the topical group, participants in the injectable group reported significantly more pain on administration of the anesthesia and at approximately 20 minutes after the procedure. In the topical group, sufficient anaesthesia with topical cream was not achieved in 21 (9.3%) cases before the start of the procedure; in another 6 (2.6%), supplementary injectable anaesthesia was required as the circumcision was being carried out. The AE rate was significantly lower (p<0.01) in the topical (0%) vs. the injectable group (4.2%). The most common AE was pain during the post-operative period. All AEs were managed conservatively and resolved without sequeale. 96.7% of participants were satisfied with the appearance of the healed penis and 100% would recommend the ShangRing to others. All seven male circumcision providers involved in the study preferred topical to injectable anaesthesia. CONCLUSIONS: Our results demonstrate the safety, improved clinical experience, effectiveness, and acceptability of the use of topical anaesthesia in ShangRing circumcision using the no-flip technique. Topical anaesthesia effectively eliminates needlestick pain from the clients' VMMC experience and thus has the potential to increase demand for the service. TRIAL REGISTRATION: ClinicalTrials.gov NCT02390310.

Microsurgical vasectomy reversal: contemporary techniques, intraoperative decision making, and surgical training for the next generation.

Men seeking fertility after elective sterilization can be treated with a wide array of interventions. Reconstruction of the reproductive tract remains the gold standard and most cost-effective option for the appropriately selected candidate. In the following review, the treatment algorithm for men desiring vasectomy reversal is outlined. Specifically, the current evidence basis for preoperative evaluation, intraoperative decision making, postsurgical management, and emerging advances to optimize outcomes will be discussed. Finally, the important role of microsurgical training and how the field can improve quality of care will be reviewed.

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.

Simplifying the ShangRing technique for circumcision in boys and men: use of the no-flip technique with randomization to removal at 7 days versus spontaneous detachment.

To assess safety of the no-flip ShangRing male circumcision technique and to determine clinical course and safety of spontaneous detachment (i.e., allowing the device to fall off), we conducted a case series of no-flip ShangRing circumcision combined with a randomized controlled trial of removal 7 days postcircumcision versus spontaneous detachment at two health facilities in Kenya. The primary outcome was the safety of the no-flip technique based on moderate and severe adverse events (AEs) during the procedure and through 42-day follow-up. A main secondary outcome was clinical course and safety of spontaneous detachment. Two hundred and thirty males 10 years and older underwent no-flip circumcision; 114 randomized to 7-day removal and 116 to spontaneous detachment. All circumcisions were successfully completed. Overall 5.3% (6/114) of participants in the 7-day group and 1.7% (2/116) in the spontaneous group had an AE; with no differences when compared to the 3% AE rate in historical data from African studies using the original flip technique (P = 0.07 and P = 0.79, respectively). Overall 72.4% (84/116) of participants in the spontaneous group wore the ShangRing until it detached. Among the remaining (27.6%; 32/116), the ring was removed, primarily at the participants' request, due to pain or discomfort. There was no difference in AE rates (P = 0.169), visit day declared healed (P = 0.324), or satisfaction (P = 0.371) between randomization groups. The median time to detachment was 14.0 (IQR: 7-21, range: 5-35) days. The no-flip technique and spontaneous detachment are safe, effective, and acceptable to boys and men 10 years and older. Phimosis and penile adhesions do not limit successful ShangRing circumcision with the no-flip technique.

[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.