Gabapentin for Postoperative Pain Control and Opioid Reduction in Scrotal Surgery: A Randomized Controlled Clinical Trial.

PURPOSE: To assess the safety and efficacy of gabapentin in reducing postoperative pain among patients undergoing scrotal surgery for male infertility by conducting a randomized, double-blind, placebo-controlled trial. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, healthy men undergoing scrotal surgery with a single surgeon were randomized to receive either (1) gabapentin 600 mg given 2 hours preoperatively and 300 mg taken 3 times a day postoperatively for 3 days, or (2) inactive placebo. The primary outcome measure was difference in postoperative pain scores. Secondary outcomes included differences in opioid usage, patient satisfaction, and adverse events. RESULTS: Of 97 patients screened, 74 enrolled and underwent randomization. Of these, 4 men were lost to follow-up, and 70 were included in the final analysis (35 gabapentin, 35 placebo). Both differences in initial postoperative mean pain score (-1.14, 95% CI -2.21 to -0.08, P = .035) and final mean pain score differences (-1.27, 95% CI -2.23 to -0.32, P = .0097) indicated lower gabapentin pain compared to placebo. There were no statistically significant differences in opioid usage, patient satisfaction, or adverse events. CONCLUSIONS: These data suggest that perioperative gabapentin results in a statistically and clinically significant decrease in pain following scrotal surgery. While there was no evidence of an impact on opioid usage or patient satisfaction, given the low risk of adverse events, it may be considered as part of a multimodal pain management strategy.

Age, Sperm Retrieval, and Testicular Histology in Klinefelter Syndrome.

PURPOSE: We sought to examine sperm retrieval and testicular histology in males of different ages with Klinefelter syndrome. MATERIALS AND METHODS: We identified all males with Klinefelter syndrome who underwent microdissection testicular sperm extraction at our institution from 1995 to 2020. Patients were divided into adolescent (<20 years) and adult (≥20 years) cohorts. Histology and sperm retrieval were compared using chi-square statistics. Multivariable logistic regression models were used to examine factors associated with successful sperm retrieval. RESULTS: We identified 217 males with Klinefelter syndrome, of whom 59 were adolescents and 158 were adults. Adults were stratified into 10-year groupings (20-29 years, n = 62; 30-39 years, n = 88; ≥40 years, n = 8). Approximately 17% of adolescents had testis histology containing germ cells compared with 15% of the 20 to 29-year cohort, 14% of the 30 to 39-year cohort, and 0% over 40 years. In comparison to adolescents (53%), the sperm retrieval rate was significantly higher in the 20 to 29-year cohort (71%, P = .04) and lower in the ≥40-year cohort (13%, P = .03). In multivariable analysis, the presence of hypospermatogenesis on testis biopsy (OR 5.8, P = .03) was associated with higher odds of successful sperm retrieval. CONCLUSIONS: Younger males more frequently had germ cell-containing testis histology, however this finding was not associated with a higher odds of sperm retrieval. Reproductive urologists should counsel azoospermic males with Klinefelter syndrome that sperm retrieval during adolescence for fertility preservation is not required and can be performed in young adulthood.

Successful cryptozoospermia management with multiple semen specimen collection.

OBJECTIVE: To determine the prevalence of sperm suitable for intracytoplasmic sperm injection (ICSI) in fresh ejaculated semen samples provided by men scheduled for a microdissection testicular sperm extraction (mTESE) procedure. Secondary objectives included an evaluation of the effect of a short abstinence period on semen quality and ICSI outcomes for men with cryptozoospermia. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: All men were scheduled to undergo a mTESE procedure by a single, high-volume surgeon at an academic center from September 1, 2015, to May 1, 2021. INTERVENTION: Presence of sperm suitable for ICSI in the ejaculate on the day of scheduled mTESE. MAIN OUTCOME MEASURES: Prevalence of sperm suitable for ICSI in the ejaculate among previously diagnosed men with azoospermia. Secondary outcomes included changes in semen parameters, clinical pregnancy rate, and live birth rate. RESULTS: Of 727 planned mTESE procedures, 69 (9.5%) were canceled because sperm suitable for ICSI were identified in a fresh ejaculated sample produced on the day of scheduled surgery (typically one day before oocyte retrieval). Overall, 50 men (50/727, 6.9%) used these rare, ejaculated sperm for ICSI. Semen samples obtained with <24 hours of abstinence were more likely to have better motility than the sample initially provided on the day of the planned mTESE. The live birth rate per ICSI attempt using these rare, ejaculated sperm was 36% (19/53). CONCLUSION: Providing a fresh ejaculated semen sample on the day of mTESE allows nearly 10% of men with azoospermia to avoid surgery with satisfactory ICSI outcomes. Providing multiple ejaculated samples over a short period of time does not adversely affect sperm concentration and may enhance sperm motility in men with cryptozoospermia.

Real-world practice in Peyronie's disease management: Results from a national survey of urologists.

BACKGROUND: Despite many available treatments for Peyronie's disease (PD), practice patterns of available therapeutics are not well characterized. OBJECTIVE: We conducted a national survey of urologists to characterize real-world practice patterns of PD management and to characterize the use of therapies discouraged by the American Urological Association guidelines on PD management. MATERIALS AND METHODS: A 34-item survey was distributed via RedCap to urologists who treat patients with PD in all American Urological Association sections. Questions elicited demographic information as well as practices in the diagnosis and treatment of PD. Comparisons were made with Pearson's chi-squared test. The primary outcome was reported use of therapies discouraged by the American Urological Association guidelines on PD. RESULTS: A total of 145 respondents completed the survey, of whom 19% were fellowship trained in andrology/sexual medicine, 36% practiced in an academic setting, and 50% had at least 20 years in practice. Only 60% of respondents reporting performing in-office curvature assessment prior to commencing intralesional injection or surgical treatment, with higher prevalence in andrology/sexual medicine fellowship-trained versus non-fellowship-trained urologists (85% vs. 54%, p = 0.003). The most popular treatment modalities were collagenase clostridium histolyticum (61% of respondents), phosphodiesterase-5 inhibitors (54%), and penile traction (53%). Twenty-one percent of respondents reported currently using a treatment that is explicitly discouraged by the American Urological Association guidelines (extracorporeal shockwave therapy for curvature, L-carnitine, omega-3 fatty acids, or vitamin E). DISCUSSION: Patients seeking PD treatment may be offered different therapies, some of which are not evidence-based, depending on the treating urologist. This study is limited by self-selection and response bias. Its strength is that it represents a cross-sectional overview of real-world practice patterns in PD management, which has not been previously described. CONCLUSIONS: A significant proportion of urologists reported PD management practices that are not evidence-based and not guideline-supported.

The '-ics' of male reproduction: genomics, epigenetics, proteomics, metabolomics, and microbiomics.

PURPOSE OF REVIEW: To review the most current findings, from the past 2 years, in various '-ics' fields in male infertility, with a specific focus on nonobstructive azoospermia, the most severe form, and varicocele, the most common correctable cause of male infertility. RECENT FINDINGS: Recent studies confirm previously identified causes and identify previously unknown genetic mutations as causes for nonobstructive azoospermia and varicocele. SUMMARY: Infertility is a common problem for couples with approximately half of cases attributable to male factor infertility. Although advances in assisted reproductive technology have permitted many more men with infertility to father biological children, the majority of infertile men continue to have unknown causes. The recent explosion of the '-ics' fields, including genomics, epigenetics, proteomics, metabolomics, and microbiomics, has shed light on previously unknown causes for various diseases. New information in these fields will not only shed light on the pathogenesis of these conditions but also may shift the paradigm in clinical testing that may allow clinicians to provide more precise counseling and prognostic information for men with infertility.

Trends in Antimicrobial Prophylaxis for Inflatable Penile Prosthesis Surgery From a Large National Cohort.

OBJECTIVE: To assess changes in antibiotic prophylaxis for inflatable penile prosthesis surgery following publication of the American Urological Association (AUA) Best Practice Statement in April 2008. MATERIALS AND METHODS: The Premier Healthcare Database was queried for inflatable penile prosthesis surgeries from January 2000 to March 2020. The primary outcome was administration of an AUA-adherent antimicrobial regimen and secondary outcome was 90-day explant. Piecewise linear regression was used to compare antimicrobial trends before vs after guideline publication. Multivariable logistic regression models were constructed for primary and secondary outcomes. RESULTS: A total of 26,574 patients who underwent inflatable penile prosthesis surgery were identified, of whom 17,754 (67%) received AUA-adherent antibiotics. After guideline publication, there was a 42% relative increase in AUA-adherent regimen usage, with an increase in the usage trend on piecewise linear regression (from 0.1% to 0.8% of encounters per quarter, R2 = 0.75, P < .001). Increased usage trends were also observed for gentamicin (from 0.0% to 1.0% of encounters per quarter, R2 = 0.84, P < .001) and vancomycin (0.1%-0.7%, R2 = 0.77, P < .001). On multivariable regression, odds of AUA-adherence increased after guideline publication (OR: 1.67, 95% CI: 1.54-1.80, P < .001) and with surgery by a high-volume surgeon (OR: 2.21, 95% CI: 2.07-2.35, P < .01). Nonadherence to an AUA-recommended regimen with use of nonstandard antibiotics (OR: 1.16, 95% CI: 0.78-1.71, P = .5) or excess antibiotics (OR: 0.91, 95% CI: 0.62-1.30, P = .6) was not independently associated with increased risk of 90-day explant. CONCLUSIONS: Publication of the AUA Best Practice Statement was associated with subsequent increases in the usage of guideline-adherent antibiotic regimens, particularly vancomycin and gentamicin, despite absence of level-1 evidence supporting this combination.

Genetic Implications of Male-Reproductive-Health-Associated Comorbidities.

Male infertility is a common problem. There is growing evidence that infertile men may harbor significant illness and disease. Many of the genetic causes of male fertility have implications on other systemic illnesses. This review aims to discuss various genetic conditions and gene mutations and alterations associated with male infertility and evidence for associated systemic conditions. These findings highlight the importance of a thorough workup in men presenting for a fertility assessment.

The use of fresh compared to frozen ejaculated sperm has no impact on fresh embryo transfer cycle reproductive outcomes.

PURPOSE: To compare the reproductive outcomes of fresh embryo transfer (ET) cycles utilizing fresh versus frozen ejaculated sperm. METHODS: First autologous fresh embryo transfer cycles at a single high-volume academic institution between 2013 and 2019 were retrospectively reviewed. IVF cycles using ejaculated sperm were included, and cycles using donor or surgically retrieved sperm were excluded. Sperm concentration was stratified as ≥ 5 and < 5 million/ml. The primary outcome was live birth, and the secondary outcomes were clinical intrauterine pregnancy (IUP) and miscarriage. A multivariable logistic regression model for the aforementioned outcomes was adjusted a priori for sperm concentration as well as maternal and paternal age. RESULTS: A total of 6128 couples were included. Of these, 5780 (94.3%) utilized fresh sperm, and 348 (5.7%) frozen sperm. A total of 5716 (93.2%) had sperm concentrations ≥ 5 million/ml and 412 (6.7%) had sperm concentrations < 5 million/ml. On multivariable logistic regression, the use of freshly ejaculated sperm was not associated with significantly different odds of clinical IUP, miscarriage, or live birth when compared to cycles using frozen sperm. CONCLUSION: For couples conceiving via fresh ET, the use of fresh versus frozen ejaculated sperm is not associated with reproductive outcomes.

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.

Current updates and future perspectives in the evaluation of azoospermia: A systematic review.

Objectives: To provide a summary of the current evaluation of azoospermia and insights into future perspectives in the evaluation and counselling of men with azoospermia. Methods: A search of PubMed, Cochrane Reviews and Web of Science databases was performed for full-text English-language articles published between 1943 and 2020 focussing on 'future perspectives', 'azoospermia' and 'evaluation'. Results: Azoospermia represents a severe form of male infertility characterised by sperm production so impaired that there are no sperm present in the ejaculate. The current evaluation of azoospermia focusses on patient history and physical examination with selected adjunctive laboratory investigations including serum hormones, a karyotype and screening for Y chromosome microdeletions. Future diagnostics are focussed on identifying the underlying genetic aetiologies for azoospermia, as well as a greater emphasis on screening for systemic illness that men with severe infertility may be predisposed to develop. Conclusion: Azoospermia represents an extreme form of male infertility, and evaluation relies heavily on history and physical examination, as genetic evaluations for these individuals remain limited. Future evaluation will focus on next-generation sequencing and more rigorous evaluation for possible co-existing and future risk of systemic disease. ABBREVIATIONS: ADGRG2, adhesion G protein-coupled receptor G2; ASRM: American Society of Reproductive Medicine; AZF: azoospermia factor; CBAVD: congenital bilateral absence of the vas deferens; CFTR: cystic fibrosis transmembrane conductance regulator; CRKL: CRK-like proto-oncogene; E2F1: E2F transcription factor 1; HAUS7: HAUS augmin-like complex subunit 7; HR: hazard ratio; KS: Klinefelter syndrome; MAZ, MYC-associated zinc finger protein; NGS: next-generation sequencing; NOA: non-obstructive azoospermia; OA: obstructive azoospermia; RHOX: reproductive homeobox on the X chromosome; SH2: SRC homology 2; TAF7L: TATA-box binding protein associated factor 7-like; TEX11: testis-expressed 11; WES: whole-exome sequencing.

Impact of duloxetine on male fertility: A randomised controlled clinical trial.

This study assessed the impact of duloxetine (serotonin and norepinephrine reuptake inhibitor) on semen parameters, sperm DNA fragmentation and serum hormones. We performed a double-blind, placebo-controlled, randomised clinical trial of duloxetine 60mg or placebo daily for 6 weeks (5 weeks full dose and 1 week taper). The primary outcome was the proportion of men with abnormal DNA fragmentation during and after duloxetine administration. Secondary outcomes were changes in semen parameters and hormones on treatment (2 and 6 weeks) and after discontinuation (8 and 10 weeks). Sixty-eight healthy males aged 18-65 were included. Duloxetine was not associated with an increase in the proportion of participants with abnormal sperm DNA fragmentation terminal deoxynucleotidyl transferase dUTP nick-end labelling scores (>25%) on treatment (p = 0.09) or after treatment (p = 0.56), nor did median sperm DNA fragmentation increase on treatment. Compared with placebo, there were no changes in bulk semen parameters during treatment. Limited changes in hormonal values were detected. This first published human study of a serotonin and norepinephrine reuptake inhibitor on male fertility revealed no clinically meaningful effects on sperm DNA fragmentation, semen parameters or serum hormones. Duloxetine, and possibly other serotonin and norepinephrine reuptake inhibitors, may be considered for men desiring fertility who require antidepressant treatment.

Quantifying Heterogeneity of Testicular Histopathology in Men with Nonobstructive Azoospermia.

PURPOSE: We sought to determine if testicular histopathological heterogeneity is associated with sperm retrieval rates (SRRs) in men with nonobstructive azoospermia (NOA) who are undergoing microdissection testicular sperm extraction (mTESE). MATERIALS AND METHODS: All patients undergoing mTESE by a single, high-volume surgeon at a tertiary infertility referral center between 2010 and 2020 were evaluated. Pathology reports from testis biopsy at the time of mTESE reported by fellowship-trained genitourinary pathologists were reviewed. Testicular heterogeneity was correlated to absolute SRRs. Logistic regression was used to determine if heterogeneity was associated with sperm retrieval. RESULTS: A total of 918 men with mTESE were included. Of these, 391 men (43%) had 1 pathology, 388 men (42%) had 2, 108 (12%) had 3, and 31 (3.4%) had 4. Overall, the most common histopathology was Sertoli-cell only, followed by maturation arrest. The overall SRR was 42% with a clinical intrauterine gestation rate of 30%. Increasing histopathological variety was associated with higher SRRs (p <0.01); a SRR of 33% was observed when one histopathological subtype was present vs 94% with 4 subtypes. Furthermore, men with any foci of spermatogenesis had higher SRRs. CONCLUSIONS: In men with NOA, increasing testicular histopathological heterogeneity is correlated with higher SRRs driven by the identification of focal areas of spermatogenesis. This is an important, although predictable, observation. While diagnostic biopsy is not routinely required, these findings emphasize the value of having histology to perhaps predict the chance of sperm retrieval for future mTESE procedures.

Reproductive Chances of Men with Azoospermia Due to Spermatogenic Dysfunction.

Non-obstructive azoospermia (NOA), or lack of sperm in the ejaculate due to spermatogenic dysfunction, is the most severe form of infertility. Men with this form of infertility should be evaluated prior to treatment, as there are various underlying etiologies for NOA. While a significant proportion of NOA men have idiopathic spermatogenic dysfunction, known etiologies including genetic disorders, hormonal anomalies, structural abnormalities, chemotherapy or radiation treatment, infection and inflammation may substantively affect the prognosis for successful treatment. Despite the underlying etiology for NOA, most of these infertile men are candidates for surgical sperm retrieval and subsequent use in intracytoplasmic sperm injection (ICSI). In this review, we describe common etiologies of NOA and clinical outcomes following surgical sperm retrieval and ICSI.

Two Decades from the Introduction of Microdissection Testicular Sperm Extraction: How This Surgical Technique Has Improved the Management of NOA.

The treatment of men with non-obstructive azoospermia (NOA) has improved greatly over the past two decades. This is in part due to the discovery of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), but also significantly due to improvements in surgical sperm retrieval methods, namely the development of microdissection testicular sperm extraction (mTESE). This procedure has revolutionized the field by allowing for identification of favorable seminiferous tubules while simultaneously limiting the amount of testicular tissue removed. Improving sperm retrieval rates is imperative in this cohort of infertile men as there are a limited number of factors that are predictive of successful sperm retrieval. Currently, sperm retrieval in NOA men remains dependent on surgeon experience, preoperative patient optimization and teamwork with laboratory personnel. In this review, we discuss the evolution of surgical sperm retrieval methods, review predictors of sperm retrieval success, compare and contrast the data of conventional versus mTESE, share tips for optimizing sperm retrieval outcomes, and discuss the future of sperm retrieval in men with NOA.

Genetic implications of male-reproductive-health-associated comorbidities.

Male infertility is a common problem. There is growing evidence that infertile men may harbor significant illness and disease. Many of the genetic causes of male fertility have implications on other systemic illnesses. This review aims to discuss various genetic conditions and gene mutations and alterations associated with male infertility and evidence for associated systemic conditions. These findings highlight the importance of a thorough workup in men presenting for a fertility assessment.

Platelet-Reactive Antibodies in Patients after Ischaemic Stroke-An Epiphenomenon or a Natural Protective Mechanism.

Ischaemic brain damage induces autoimmune responses, including the production of autoantibodies with potential neuroprotective effects. Platelets share unexplained similarities with neurons, and the formation of anti-platelet antibodies has been documented in neurological disorders. The aim of this study was to investigate the presence of anti-platelet antibodies in the peripheral blood of patients after ischaemic stroke and determine any clinical correlations. Using a flow cytometry-based platelet immunofluorescence method, we detected platelet-reactive antibodies in 15 of 48 (31%) stroke patients and two of 50 (4%) controls (p < 0.001). Western blotting revealed heterogeneous reactivities with platelet proteins, some of which overlapped with brain proteins. Stroke patients who carried anti-platelet antibodies presented with larger infarcts and more severe neurological dysfunction, which manifested as higher scores on the National Institutes of Health Stroke Scale (NIHSS; p = 0.009), but they had a greater recovery in the NIHSS by the time of hospital discharge (day 7 ± 2) compared with antibody-negative patients (p = 0.043). Antibodies from stroke sera reacted more strongly with activated platelets (p = 0.031) and inhibited platelet aggregation by up to 30.1 ± 2.8% (p < 0.001), suggesting the potential to interfere with thrombus formation. In conclusion, platelet-reactive antibodies can be found in patients soon after ischaemic stroke and correlate with better short-term outcomes, suggesting a potential novel mechanism limiting thrombosis.

Clinical implications of Y chromosome microdeletions among infertile men.

Male factor infertility contributes significantly to couples facing difficulty achieving a pregnancy. Genetic factors, and specifically those related to the Y chromosome, may occur in up to 15% of men with oligozoospermia or azoospermia. A subset of loci within the Y chromosome, known as the azoospermia factors (AZFa, AZFb, and AZFc), have been associated with male infertility. Emerging evidence has demonstrated that microdeletions of at least a subset of these regions may also have impacts on systemic conditions. This review provides a brief review of male infertility and the structure of the Y chromosome, and further highlights the role of Y chromosome microdeletions in male infertility and other systemic disease.