Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I.

PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline PART II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]). CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

Ghrelin ameliorates adhesions in a postsurgical mouse model.

BACKGROUND: Peritoneal adhesion formation is a well-recognized consequence of abdominal and pelvic surgery, causing infertility, chronic pelvic pain, and intestinal obstruction. We hypothesized that ghrelin, a 28-amino acid peptide predominantly found in the stomach, plays an important role in preventing postoperative surgical adhesions. The purpose of this study was to develop a new surgical peritoneal adhesion model to define the role that ghrelin plays in wound healing and adhesion formation. MATERIALS AND METHODS: C57BL/6 wild-type mice (n = 40) and growth hormone secretagogue receptor-knockout (GHSR KO) mice (n = 20) underwent a midline laparotomy to establish a peritoneal adhesion model characterized by the combination of two different techniques: ischemic peritoneal buttons and cecal multiple abrasion. All mice received intraperitoneal injections with ghrelin (0.16 mg/kg) or saline twice daily for 20 d after surgery. Peritoneal ischemic buttons were harvested to determine protein expression of collagen (Masson trichrome, picrosirius red stain, and Western blot). RESULTS: The novel mouse model demonstrated consistent and easily reproducible formation of intra-abdominal adhesions. Ghrelin administration significantly reduced postoperative adhesion formation (P < 0.001) in wild-type mice. The antifibrotic effect of ghrelin in wild-type mice was confirmed by measuring collagen I protein levels via Western blot analysis. The anti-adhesion effect of ghrelin seen in wild-type mice was not detected in GHSR KO mice demonstrating that this effect is mediated by the GHSR-1a receptor. CONCLUSIONS: Ghrelin administration may improve surgical outcome by reducing peritoneal adhesion formation and fibrotic response in a mouse model.

Prognostic utility of erectile dysfunction for cardiovascular disease in younger men and those with diabetes.

Multiple published studies have established erectile dysfunction (ED) as an independent risk marker for cardiovascular disease (CVD). In fact, incident ED has a similar or greater predictive value for cardiovascular events than traditional risk factors including smoking, hyperlipidemia, and family history of myocardial infarction. Here, we review evidence that supports ED as a particularly significant harbinger of CVD in 2 populations: men <60 years of age and those with diabetes. Although addition of ED to the Framingham Risk Score only modestly improved the 10-year predictive capacity of the Framingham Risk Score for myocardial infarction or coronary death data in men enrolled in the Massachusetts Male Aging Study, other epidemiologic studies suggest that the predictive value of ED is quite strong in younger men. Indeed, in the Olmstead County Study, men 40 to 49 years of age with ED had a 50-fold higher incidence of new-incident coronary artery disease than those without ED. However, ED had less predictive value (5-fold increased risk) for coronary artery disease in men 70 years and older. Several studies, including a large analysis of more than 6300 men enrolled in the ADVANCE study, suggest that ED is a particularly powerful predictor of CVD in diabetic men as well. Based on the literature reviewed here, we encourage physicians to inquire about ED symptoms in all men more than 30 years of age with cardiovascular risk factors. Identification of ED, particularly in men <60 years old and those with diabetes, represents an important first step toward CVD risk detection and reduction.

Case of malignant priapism and review of the literature.

Malignant priapism, or priapism secondary to locally invasive or metastatic cancer, is a rarely reported phenomenon with a very poor prognosis. We report on a case of malignant priapism secondary to metastasis of urothelial carcinoma of the bladder in a 73 year old gentleman who underwent a radical cystectomy with negative margins but positive nodal disease three months prior to presentation. The rapid progression of disease and resultant demise of this patient is unusual even when compared to the limited available literature. Rapid progression to muscle invasion despite intravesical immunotherapy, histologic involvement of the prostate and seminal vesicles with extensive lymphovascular invasion, and the rapid development of metastasis are all consistent with the aggressive nature of a cancer that has metastasized to the penis. Further, while conservative penile sparing therapy may be a goal in patients with limited life expectancy, ongoing pain and infectious concerns may force the physician to resort to a penectomy.

Iatrogenic male infertility: medical and surgical treatments that impair male fertility.

Many medical and surgical treatments result in impaired male fertility. Sometimes impairments are permanent, while other times they may be reversible. Clinicians who treat urologic and nonurologic problems, as well as those of us who treat male and female infertility should understand what treatments affect which aspects of reproduction and what options for management are available. Conditions for which treatment may impair fertility range from benign prostatic hyperplasia to cancer to behavioral health issues. This month's Views and Reviews summarizes these conditions, the mechanisms of fertility impairment as well as preemptive and posttreatment approaches for management.

Highly conserved sperm function-related transcripts across three species: human, rat and mouse.

Assessing male reproductive toxicity of environmental and therapeutic agents relies on the histopathology of the testis and epididymis in a pre-clinical setting. Animal histopathology poorly correlates with human sperm parameters, and none of these current methods are strong indicators of sperm health or reproductive potential. Therefore, there is an urgent need to identify a translatable, non-invasive and reliable approach to monitor environmental and therapeutic agents' effects on male reproductive health. mRNA sequences were analyzed in mouse, rat and human sperm samples to identify sperm transcriptomic similarities across species that could be used as biomarkers to predict male reproductive toxicity in animal models. Semen specimens were collected from men aged 18 to 55 years with proven fertility. Rat and mouse semen specimens were collected via needle punctures of the cauda epididymides. Sperm RNAs were extracted using an optimized sperm RNA isolation protocol and subjected to polyA-purified mRNA-sequencing. Bioinformatics analyses, including differential abundance and gene set enrichment analysis, were used to investigate the biological and molecular functions of all shared and differentially abundant transcripts across species. Transcriptome profiling identified 6,684 similarly expressed transcripts within the three species of which 1,579 transcripts were found to be involved in spermatogenic functions. Our findings have shown that sperm transcriptome is highly species dependent, however, there are some key similarities among transcripts that are required for fertility. Based on these similarities, sperm mRNA biomarker may be developed to monitor male reproductive toxicity where rodent models would make suitable laboratory substitutes for human.

Diagnosis and treatment of infertility in men: AUA/ASRM guideline part II.

PURPOSE: The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. (Table 1) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm. (Figure 1) CONCLUSION: Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I.

PURPOSE: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated. MATERIALS/METHODS: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. (Table 1) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. RESULTS: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm. (Figure 1) CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

Sperm DNA damage in male infertility: etiologies, assays, and outcomes.

Male factor infertility is the sole cause of infertility in approximately 20% of infertile couples, with an additional 30% to 40% secondary to both male and female factors. Current means of evaluation of male factor infertility remains routine semen analysis including seminal volume, pH, sperm concentration, motility, and morphology. However, approximately 15% of patients with male factor infertility have a normal semen analysis and a definitive diagnosis of male infertility often cannot be made as a result of routine semen analysis. Attention has focused on the role of sperm nuclear DNA integrity in male factor infertility. Here we review the structure of human sperm chromatin, the etiology and mechanisms of sperm DNA damage, current tests available to assess sperm DNA integrity, and effect of sperm DNA integrity on reproductive outcomes.

Telemedicine in reproductive medicine-implications for technology and clinical practice.

The COVID-19 pandemic has caused the rapid adoption of telemedicine in most medical practices. This series of articles address issues that are often not well considered, such as the types of technological platforms available, the effects of telemedicine on staffing, space requirements, and the financial impact of remote visits. In addition, the limits of telemedicine compared to in-office visits are discussed, as well as the effects on trainees and possibilities for the future.

Introduction: Rare and unusual andrologic syndromes that clinicians should be aware of.

There are conditions that are rare and that most providers are unaware of or conditions that consist of a series of symptoms for which there is no agreement that they are even a medical condition. These include painful nocturnal erections, post-orgasmic illness syndrome, body dysmorphic disorder, and post-finasteride syndrome. While some have a psychiatric basis, others clearly have an organic pathophysiology, while for others, there remains much controversy. This month's Views and Reviews will inform the reader of these conditions so they may recognize affected patients and direct them towards appropriate resources for their care.

Brown Urology: A Historical Perspective.

The first Urology Residency Program in the United States was founded at the Johns Hopkins Hospital in the wake of the first structured surgery residency as established by Dr. William Halsted in the early 20th Century.1 Dr. Hugh Hampton Young was selected to lead the Genitourinary Division and the foundation for the first urology residency training program was established.2 The Brown University Medical School, initially opened in 1811, effectively closed circa 1827, and re-established in the 1970s, has a long tradition in training surgeons.3,4 The Rhode Island Hospital Urology Residency Training Program was organized in the early 1950s and will be explored in this article. Brown University affiliated with the residency program in the mid-1980s to establish the first and only academic urology residency program in Rhode Island. Today, this program provides state-of-the-art urologic care for thousands of patients in the state.

Renal parenchyma thickness: a rapid estimation of renal function on computed tomography.

PURPOSE: To define the relationship between renal parenchyma thickness (RPT) on computed tomography and renal function on nuclear renography in chronically obstructed renal units (ORUs) and to define a minimal thickness ratio associated with adequate function. MATERIALS AND METHODS: Twenty-eight consecutive patients undergoing both nuclear renography and CT during a six-month period between 2004 and 2006 were included. All patients that had a diagnosis of unilateral obstruction were included for analysis. RPT was measured in the following manner: The parenchyma thickness at three discrete levels of each kidney was measured using calipers on a CT workstation. The mean of these three measurements was defined as RPT. The renal parenchyma thickness ratio of the ORUs and non-obstructed renal unit (NORUs) was calculated and this was compared to the observed function on Mag-3 lasix Renogram. RESULTS: A total of 28 patients were evaluated. Mean parenchyma thickness was 1.82 cm and 2.25 cm in the ORUs and NORUs, respectively. The mean relative renal function of ORUs was 39%. Linear regression analysis comparing renogram function to RPT ratio revealed a correlation coefficient of 0.48 (p < 0.001). The linear regression equation was computed as Renal Function = 0.48 + 0.80 * RPT ratio. A thickness ratio of 0.68 correlated with 20% renal function. CONCLUSION: RPT on computed tomography appears to be a powerful predictor of relative renal function in ORUs. Assessment of RPT is a useful and readily available clinical tool for surgical decision making (renal salvage therapy versus nephrectomy) in patients with ORUs.

Introduction: Male fertility testing: the past, present, and future.

Semen analysis remains the initial laboratory evaluation for infertile men. The limitations of the standard semen analysis along with past attempts to improve the analysis of sperm are reviewed. Advances in genetic testing will lead to fewer diagnoses of idiopathic male infertility, and improvements in picking the best sperm offer hope of improved assisted reproduction outcomes. The development of simplified testing has opened up the availability of tests performed in settings without advanced laboratory facilities as well as by patients in their own homes.

Transurethral resection of the ejaculatory ducts: etiology of obstruction and surgical treatment options.

Ejaculatory duct obstruction is an uncommon but surgically correctable cause of male infertility. With the advent and increased use of high-resolution transrectal ultrasonography, anomalies of the ejaculatory ducts related to infertility have been well documented. Although there are no pathognomonic findings associated with ejaculatory duct obstruction, the diagnosis should be suspected in an infertile male with oligospermia or azoospermia with low ejaculate volume, normal secondary sex characteristics, testes, and hormonal profile, and dilated seminal vesicles, midline cyst, or calcifications on transrectal ultrasound (TRUS). Although additional larger prospective and comparative studies are needed, it appears that TRUS with aspiration is the most effective method for diagnosis. While intrusive, it is less invasive than vasography. The most robust and published evidence for treatment involves transurethral resection of ejaculatory duct (TURED). More recent experience with antegrade endoscopic approaches are promising and may also be considered. An alternative to surgeries for reversal of obstruction is sperm retrieval for in vitro fertilization/intracytoplasmic sperm injection. A thorough discussion of all alternatives, including risks and benefits, should be held with couples facing this uncommon condition to allow them to make informed decisions regarding management.

Erectile Dysfunction and Subclinical Cardiovascular Disease.

BACKGROUND: An association between erectile dysfunction (ED) and cardiovascular (CV) disease (CVD) has long been recognized, and studies suggest that ED is an independent marker of CVD risk. More significantly, ED is a marker for both obstructive and non-obstructive coronary artery disease (CAD) and may reveal the presence of subclinical CAD in otherwise asymptomatic men. AIM: To discuss the role of ED as an early marker of subclinical CVD; describe an approach to quantifying that burden; and propose an algorithm for the evaluation and management of CV risk in men 40-60 years of age with vasculogenic ED, those presumed to have the highest risk for a CV event. METHODS: A comprehensive review of original literature and expert consensus documents was conducted and incorporated into clinical recommendations for ED management in the context of CV risk. OUTCOMES: Assessment and management of ED may help identify and reduce the risk of future CV events. Initial evaluation should distinguish between vasculogenic ED and ED of other etiologies. RESULTS: For men with predominantly vasculogenic ED, we recommend that initial CV risk stratification be based on the 2013 American College of Cardiology/American Heart Association atherosclerotic CV disease risk score. Management of men with ED who are at low risk for CVD should focus on risk factor control; men at high risk, including those with CV symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo non-invasive evaluation for subclinical atherosclerosis. Evidence supports use of a prognostic markers, particularly coronary calcium score, to further understand CV risk in men with ED. CONCLUSIONS: Clinicians must assess the presence or absence of ED in every man >40 years of age, especially those men who are asymptomatic for signs and symptoms of CAD. We support CV risk stratification and CVD risk factor reduction in all men with vasculogenic ED. Miner M, Parish SJ, Billups KL, et al. Erectile Dysfunction and Subclinical Cardiovascular Disease. Sex Med Rev 2018;7:455-463.

Spermatozoal large RNA content is associated with semen characteristics, sociodemographic and lifestyle factors.

Semen analysis is one of the standard diagnostic tools currently used to assess male infertility and reproductive toxicity. However, semen analysis has a limited ability to separate fertile from infertile populations. Additional methods to detect impaired fertility are needed. The purpose of the present study was to evaluate how spermatozoal RNA content varies with sociodemographic and behavior/lifestyle factors, and to determine if spermatozoal large and small RNAs discriminate normal from abnormal spermatozoa. Semen specimens were collected from 133 men aged between 18 to 55 years undergoing semen analysis as part of couple infertility evaluation while 10 proven fertile donors were recruited as control group. Semen samples were classified as normal or abnormal according to World Health Organization (WHO) 2010 criteria. Sperm RNAs were extracted after somatic cells were lysed, and the association of large or small RNA content with semen quality and sociodemographic and behavioral/lifestyle factors was evaluated using a generalized additive model and one-way ANOVA. Inverse relationship was observed between large RNA content and sperm parameters such as sperm count, density and motility. Large RNA content per sperm was significantly increased in semen samples showing abnormal number of round cells. Furthermore, sperm motility was inversely associated with spermatozoal small RNA contents. Grouping donors by the number of semen abnormalities, we observed significant increased spermatozoal large and small RNA content in men with more than two semen abnormalities. Alcohol consumption was strongly associated with increased large RNA per sperm concentration after adjustment for age and BMI. Our study demonstrates a strong relationship between spermatozoal large RNA content and poor semen characteristics that may lead to a role in the assessment of male fertility, and may be used as an endpoint for reproductive toxicology risk assessment.

Comparison of outcomes of vasovasostomy performed in the convoluted and straight vas deferens.

PURPOSE: We compared postoperative semen analysis parameters and patency rates of vasovasostomy performed in the convoluted vs straight portion of the vas deferens. MATERIALS AND METHODS: Records of patients that underwent bilateral vasovasostomy in the straight and convoluted vas deferens by a single surgeon were retrospectively analyzed. Patient age, partner age, obstructive interval, gross and microscopic appearance of the intraoperative fluid aspirated from the testicular portion of the vas deferens, and postoperative semen analysis results were examined. Patency was defined as any sperm in the postoperative ejaculate and was compared for the 2 groups. RESULTS: A total of 42 and 64 patients underwent bilateral straight vasovasostomy and convoluted vasovasostomy, respectively. Mean patient age for straight and convoluted vasovasostomy was 38.5 and 40.3 years, respectively. Mean obstructive interval for straight vasovasostomy and convoluted vasovasostomy was 7.7 and 8.6 years, respectively. No significant differences in the postoperative semen analysis parameters of volume, total count, sperm density, motility or total motile count were found between the 2 groups. The patency rate was 98.1% and 97.3% for convoluted vasovasostomy and straight vasovasostomy, respectively, and was not statistically different. CONCLUSIONS: Although vasovasostomy in the convoluted vas deferens is considered technically more challenging than in the straight vas deferens, patency rates and postoperative semen analysis parameters for convoluted vasovasostomy and straight vasovasostomy are comparable.