Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Subsets of preoperative sex hormones in testicular germ cell cancer: a retrospective multicenter study.

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: 'neutral' (n = 228) with normal sex hormone homeostasis, 'testicle' (n = 91) with elevated T and E2, low pituitary hormones, and finally 'pituitary' subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Sexual function in male cancer survivors is not correlated to sperm quality.

PURPOSE: Both infertility and erectile dysfunction (ED) are known long-term consequences of cancer treatment in young male cancer survivors. In the present study, we aimed to assess whether sperm quality and sexual function in male cancer survivors are associated. METHODS: In this prospective study, n = 244 patients male cancer survivors who underwent sperm analysis and cryopreservation between 2008 and 2018 prior to the initiation of gonadotoxic treatment were invited. In total n = 50 had a follow-up sperm analysis and completed two questionnaires, the Aging Males' Symptom Scale (AMS) and the International Index of Erectile Function (IIEF-EF). Differences between the individual parameters were analyzed using the Wilcoxon or Mann Whitney test. RESULTS: Azoospermia was present in n = 16/50 (32.0%) patients at time of follow-up. ED occurred in n = 9/43 (20.9%) patients and was observed more frequently in patients with oligo- or azoospermia than in those with normospermia, even though this association was not statistically significant. Sperm parameters (total sperm count, sperm concentration, progressive motility) did not differ between time of cryopreservation and time of follow-up. Mean total, somatic, psychological, and sexual AMS score was 23.6, 9.9, 6.6, and 6.8, respectively. Mean total IIEF-EF score was 27.3, indicating mainly mild ED. CONCLUSIONS: More than one-third of cancer patients suffered from azoospermia, and ED was primarily present in this subgroup. We recommend implementing the screening of sexual dysfunction in the annual sperm testing that should be offered to all men after gonadotoxic treatment. Our study highlights the importance of counseling young cancer patients on both aspects-future infertility and sexual function-prior to treatment and at follow-up visits.

Diagnosis and Therapy Before Assisted Reproductive Treatments. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Register Number 015-085, February 2019) - Part 1, Basic Assessment of the Woman.

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German/Austrian/Swiss interdisciplinary S2k guideline on "Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)" was published in February 2019. This guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aims One third of the causes of involuntary childlessness are still unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. At present, there is no standard treatment concept, as currently no standard multidisciplinary procedures exist for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnostic workup and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations The first part of this guideline focuses on the basic assessment of affected women, including standard anatomical and endocrinological diagnostic procedures and examinations into any potential infections. Other areas addressed in this guideline are the immunological workup with an evaluation of the patient's vaccination status, an evaluation of psychological factors, and the collection of data relating to other relevant factors affecting infertility. The second part will focus on explanations of diagnostic procedures compiled in collaboration with specialists from other medical specialties such as andrologists, human geneticists and oncologists.

Diagnosis and Treatment Before Assisted Reproductive Treatments. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Register Number 015-085, February 2019) - Part 2, Hemostaseology, Andrology, Genetics and History of Malignant Disease.

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German-language interdisciplinary S2k guideline on "Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)" was published in February 2019. The guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aim In one third of cases, the cause of involuntary childlessness remains unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. There is no standard treatment concept for these patients at present, as there are currently no standard multidisciplinary procedures for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnosis and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations This second part of the guideline describes the hematological workup for women as well as additional diagnostic procedures which can be used to investigate couples and which are carried out in cooperation with physicians working in other medical fields such as andrologists, geneticists and oncologists.

Effect of tadalafil once daily on prostate blood flow and perfusion in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: a randomized, double-blind, multicenter, placebo-controlled trial.

OBJECTIVE: To assess effects of tadalafil vs placebo on prostatic blood flow measured by transrectal ultrasonography in men aged ≥45 years with moderate-to-severe benign prostatic hyperplasia-lower urinary tract symptoms. METHODS: After screening and washout, patients were randomized to placebo (n = 50) or tadalafil 5 mg (n = 47) once daily for 8 weeks. Transrectal ultrasonography was performed at baseline, 4, and 8 weeks. The primary efficacy measure was the prostate transition zone (TZ) resistive index (RI). Secondary efficacy measures were RI in the peripheral zone and bladder neck, color pixel intensity (CPI), and color pixel density (CPD) in all 3 regions. Outcomes were assessed using mixed-model repeated-measures analyses. RESULTS: The overall treatment effect (tadalafil vs placebo) for the change from baseline through week 8 in prostate TZ RI was not statistically significant (least squares mean change: placebo, -0.01; tadalafil, 0.00; P = .118), nor was the change from baseline in prostate TZ CPI (P = .564) or CPD (P = .592). Results were similar for all flow measures in prostate peripheral zone and bladder neck. The adverse event profile was consistent with previous studies with no new safety findings. CONCLUSION: Tadalafil for 8 weeks in men with BPH-LUTS did not result in detectable decreases in arterial RI or increases in CPI or CPD in the prostate or bladder neck. Detection of changes may not be possible because of already low baseline RI, insufficient sensitivity of techniques used, or may have been confounded by methodologic variability across sites. Alternatively, other possible mechanisms not assessed in this study may be more prominently involved.

A possible case of primary renal lymphoma: a case report.

INTRODUCTION: The entity primary renal lymphoma is controversial and rare. CASE PRESENTATION: We report a case in a 60-year-old man. Computed tomography revealed a large, homogeneous, retroperitoneal mass with 14.8 x 11.5 cm size arising from the right kidney. An ultrasound guided percutaneous biopsy was performed and the tumour was diagnosed histopathological as non-Hodgkin lymphoma. The patient was treated by systemic chemotherapy and thereafter a nephrectomy was performed. CONCLUSION: Primary renal lymphoma is a controversial and infrequent disease. However, there is growing evidence that it does exist.

Ureteroiliac fistula: a case report review of the literature.

INTRODUCTION: Ureteroiliac fistulas are rare but potentially life-threatening. Risk factors to develop a fistula are chronic indwelling ureteral stents, previous pelvic surgery and radiotherapy. CASE PRESENTATION: We report a case of a patient with intermittent gross hematuria after previous abdominal surgery, radiotherapy and indwelling ureteric stents. After several diagnostic and therapeutic procedures an ureteroiliac fistula could be finally identified and treated by endovascular stenting. CONCLUSION: Ureteroiliac fistula should be considered in any patient with intermittent gross hematuria and any of the known risk factors.

Sonographic detection of renal and ureteral stones: value of the twinkling sign

Purpose: To compare the detection of urinary stones using standard gray scale ultrasound for diagnostic accuracy using the color Doppler "twinkling sign". Material and Methods: Our study population consisted of forty-one patients who demonstrated at least one urinary stone on unenhanced CT evaluation of the kidneys or ureters. Each patient was evaluated using gray scale ultrasound and color Doppler imaging by an observer who was blinded to the CT results. Results: Seventy-seven stones were present in 41 patients, including 47 intrarenal stones, 5 stones in the renal pelvis, 8 stones at the ureteropelvic junction, 5 ureteral stones and 12 stones at the ureterovesical junction. Based upon gray scale sonography the diagnosis of stone was made with confidence in 66 percent (51/77) of locations. Based upon Doppler sonography using the twinkling sign, the diagnosis of stone was made with confidence in 97 percent (75/77) of locations. Clustered ROC analysis demonstrated that the Doppler twinkling sign (Az = 0.99) was significantly better than conventional gray scale criteria (Az = 0.95) for the diagnosis of urinary stones (p = 0.005, two-sided test). Conclusions: The color Doppler twinkling sign improves the detection, confidence and overall accuracy of diagnosis for renal and ureteral stones with minimal loss of specificity.

Adult stem cell therapy of female stress urinary incontinence.

OBJECTIVES: To investigate the efficacy of transurethral ultrasound (TUUS)-guided injections of autologous myoblasts and fibroblasts in women with incontinence. METHODS: Between January and June 2005, 20 female patients suffering from stress urinary incontinence (SUI) were included. Skeletal muscle biopsies were taken from the left arm to obtain cultures from autologous fibroblasts and myoblasts. By TUUS guidance the fibroblasts were injected into the urethral submucosa and the myoblasts were injected into the rhabdosphincter. A defined incontinence score, quality-of-life score and urodynamic, electromyographic, and laboratory parameters, as well as morphology and function of urethra and rhabdosphincter were evaluated before and up to 2 yr after therapy. RESULTS: Eighteen of 20 patients were cured 1 yr after injection of autologous stem cells and in 2 patients SUI was improved. Two years after therapy 16 of the 18 patients presented as cured, 2 others were improved, and 2 were lost to follow-up. Incontinence and quality-of-life scores were significantly improved postoperatively. The thickness of urethra and rhabdosphincter as well as activity and contractility of the rhabdosphincter were also statistically significantly increased after therapy. CONCLUSIONS: Clinical results demonstrate that SUI can be treated effectively with autologous stem cells. The present data support the conclusion that this therapeutic concept represents an elegant and minimally invasive treatment modality to treat SUI.

Urethral support with PelviSoft after artificial urinary sphincter erosion at revision procedures.

An artificial urinary sphincter cuff (AMS 800) is regarded the gold standard for surgically treating urinary incontinence without residual sphincter function. After erosion of an AMS 800 into the urethral lumen the whole system has to be explanted. When the urethral wall is supported and covered after healing with a porcine dermal acellular collagen matrix BioMesh (PelviSoft), a new artificial urinary sphincter may be implanted. The follow-up of up to two years seems promising in preventing erosion of the new cuff through the strengthened urethra wall, without compromising the functionality of the artificial urinary sphincter.

The value of three-dimensional transrectal ultrasonography in staging prostate cancer.

OBJECTIVE: To use three-dimensional transrectal ultrasonography (3D-TRUS) to reconstruct the prostate, and thus determine its value in staging clinically localized prostate cancer. PATIENTS AND METHODS: In all, 180 patients with newly diagnosed clinically localized prostate cancer were assessed using 3D-TRUS for staging. TRUS findings were compared with histopathological staging after radical prostatectomy. RESULTS: Pathological staging of specimens showed extracapsular extension in 69 patients, of whom 53 had pathological capsular perforation and 16 had seminal vesicle invasion. 3D-TRUS identified 58 patients with sites of extracapsular extension with 84% sensitivity, 96% specificity, 94% positive predictive value, 91% negative predictive value and an overall accuracy of 92%. Of the 16 patients with seminal vesicle invasion 14 were identified correctly on 3D-TRUS. Overall the 3D-TRUS staging sensitivity was 84%, specificity 96%, positive predictive value 93%, negative predictive value 91% and accuracy 91%. CONCLUSIONS: 3D-TRUS seems to be an accurate technique for staging localized prostate cancer. If 3D-TRUS indicates locally advanced disease, the probability of capsular perforation or seminal vesicle invasion is very high.

Gray scale and color Doppler sonography with extended field of view technique for the diagnostic evaluation of anterior urethral strictures.

PURPOSE: We compared the clinical relevance of radio urethrography with that of sonourethrography for evaluating male urethral strictures. MATERIALS AND METHODS: From 2002 to 2004, 93 men were referred to our institution for urethral strictures. Patients were evaluated by conventional voiding cystourethrography, retrograde urethrography, and gray scale and color Doppler sonourethrography. For sonourethrography the extended field of view technique was used to obtain 1 image of the whole anterior urethra. In all cases the urethra was evaluated cystoscopically or at open surgery. Radio urethrography and sonourethrography findings were compared with cystoscopy or surgery findings. RESULTS: All strictures were evaluated and treated cystoscopically with visual internal urethrotomy (34%) or at open operation (66%), which allowed comparison of the ability of each study to predict operative stricture length. Sonourethrography correctly identified the stricture and its site in all cases, whereas radio urethrography yielded 2 false-negative results. There was a significant difference between stricture length measured by radio urethrography compared to that measured by sonourethrography (correlation coefficient 0.72 vs 0.92, p<0.005). Mean+/-SD stricture length measured by radio urethrography was 1.5+/-1.3 cm and by sonourethrography it was 2.1+/-0.9 cm. Comparison of radio urethrography and sonourethrography stricture length with operative lengths demonstrated a good correlation in the penile urethra (correlation coefficient 0.91 vs 0.98), whereas a poor correlation was found in the bulbar urethra (correlation coefficient 0.65 vs 0.92). CONCLUSIONS: Gray scale and color Doppler sonourethrography using the extended field of view technique with a Siemens Sonoline Elegra is a promising tool for defining male urethral strictures. It seems to be superior to radio urethrography for treatment planning.

Persistent detrusor overactivity after transurethral resection of the prostate is associated with reduced perfusion of the urinary bladder.

OBJECTIVES: To elucidate, in patients with benign prostatic hyperplasia (BPH), how often detrusor overactivity (DOA) is persistent after transurethral resection of the prostate (TURP) and if perfusion of the lower urinary tract influences postoperative outcomes. PATIENTS AND METHODS: Fifty men with urodynamically confirmed DOA and bladder outlet obstruction due to BPH had a TURP. Before and 1 year after TURP the International Prostate Symptom Score (IPSS), quality of life (QoL) score, prostate-specific antigen (PSA) level and total prostatic volume (TPV) were evaluated. Also, the lower urinary tract was evaluated using pressure-flow studies and transrectal colour Doppler ultrasonography to assess the vascular resistive index (RI) as a variable of the perfusion of the lower urinary tract. RESULTS: After TURP the IPSS, QoL score, PSA level and TPV decreased. Cystometric measurements showed that in 15 (30%) patients DOA was persistent after TURP. The mean (sd) maximum urinary flow rate increased from 9.20 (4.03) to 15.98 (4.62) mL/s and postvoiding residual urine volumes decreased from 109.38 (73.71) to 29.24 (45.00) mL. When men with persistent DOA (15 patients; group 1) were compared with those with no DOA after TURP (35; group 2) there was a statistically significantly higher RI of the bladder vessels in group 1, at 0.86 (0.068) than in group 2, at 0.68 ( 0.055) (P < 0.001). CONCLUSIONS: Persistent DOA in men after TURP seems to be associated with increased vascular resistance of the bladder vessels with subsequent reduced perfusion and hypoxia.

Tissue perfusion-controlled guided biopsies are essential for the outcome of testicular sperm extraction.

OBJECTIVE: To determine if there are areas of major and minor perfusion in a single testicle, and if the quality and quantity of sperm are correlated with the level of perfusion, we collected testicular tissue from areas with different levels of perfusion. DESIGN: Controlled clinical study. SETTING: Consecutive patients with azoospermia. PATIENT(S): Patients with azoospermia undergoing testicular sperm extraction (TESE) biopsy for the retrieval of sperm to be used in an assisted reproduction program. INTERVENTION(S): Perfusion mapping was performed with the use of color Doppler ultrasound. Areas with different levels of perfusion were marked with needles. After incision with radiofrequency cutting, the exposed tissue was examined with a laser Doppler flowmeter, and biopsies were taken for TESE and histology. Sperm were analyzed using World Health Organization criteria, and prepared for intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Correlation of sperm quality and quantity in testicular-tissue biopsies, with tissue-perfusion units (TPU) measured by laser Doppler flowmeter. RESULT(S): From 40 biopsies taken from 20 testicles of 12 patients, tissue was analyzed for sperm quality and quantity. Sperm quality was highest in areas of high tissue perfusion. In areas of 70 TPU, 72.3% progressive sperm were detected, whereas in areas of 10 TPU, only 13.3% progressive sperm and elevated numbers of precursor cells could be observed. The number of motile sperm isolated from tissue samples correlated well with the intensity of tissue perfusion. CONCLUSION(S): We have shown for the first time that in patients suffering from azoospermia, sperm quality and quantity depend on tissue perfusion within the testicle.

The use of three-dimensional computed tomography for assessing patients before laparoscopic adrenal-sparing surgery.

OBJECTIVE: To evaluate the efficacy of three-dimensional computed tomography (3D-CT) in delineating the relationship of the adrenal mass to adjacent normal structures in preparation for laparoscopic partial adrenalectomy. PATIENTS AND METHODS: Multislice CT (1 mm slices, 0.5 s rotation time) was used to evaluate 12 patients before adrenal-sparing surgery for aldosterone-producing adenoma or phaeochromocytoma. The CT data were reconstructed using two rendering techniques; (i) volume rendering with the modified VOLREN software (Johns Hopkins Hospital, Baltimore, MD, USA) which allowed interactive 3D examination of the whole data volume within a few minutes; (ii) surface representations only of the interesting structures (kidney, adrenal tumour, vessels) represented in different colours and depicted together in a 3D scene using the software package 3DVIEWNIX. RESULTS: In all, 14 adrenal masses in 12 patients were evaluated with 3D-CT; the number and location of lesions was accurate in all cases with both rendering techniques. The coloured surface-rendered images showed a consistently better delineation of the adrenal tumour from the normal tissue than did the volume-rendering technique. From this information all laparoscopic partial adrenalectomies could be completed as planned. CONCLUSIONS: Interactive visualization of volume-rendered CT images was helpful for the planning and successful performance of the procedure, but coloured surface-rendered CT provided more convenient, immediate and accurate intraoperative information.

Treatment of severe bilateral nerve pain after Pfannenstiel incision.

The lower transverse abdominal incision, as described by Hermann Johannes Pfannenstiel, cutting both skin and fascia in a transverse fashion was popularized in 1900. Nerve pain syndromes included invalidating pain involving neuroma formation or scar encasement of the ilioinguinal or iliohypogastric nerves. We report a case of a female patient who developed severe pain at the lateral wound edges of a Pfannenstiel incision. The diagnosis of pain of nerve origin was made by infiltration of local anesthetic, after which the pain immediately vanished temporarily. Only complete excision of the scar and involved part of the nerve stopped the pain.

Complete recovery after the removal of an ectopic testicle in a case of primary reninism and retroperitoneal hemangioma.

A 32-year-old man recovered completely from hypokalemic hypertension that had been caused by primary reninism after the ablation of an ectopic left testis, epididymis and ductus deferens. For several years, severe hypertension has been resistant to treatment, even the concurrent administration of up to seven antihypertensive agents. In this case, cryptorchidism was associated with an indirect inguinal hernia and an open peritoneo-vaginal process on both sides, aplasia of the posterior wall of the inguinal canal on the right side, an umbilical hernia, and a retroperitoneal tendrillar hemangioma.