REVIEW


New Insights beyond Established Norms: A Scoping Review of Genetic Testing for Infertile Men

Hamid Kalantari, Marjan Sabbaghian, Paraskevi Vogiatzi, Giovanni M. Colpi, Mohammad Ali Sadighi Gilani

Urology Journal, Vol. 20 (2023), 25 Dey 2022, Page 8008
https://doi.org/10.22037/uj.v20i.8008

Purpose‎: From a diagnostic standpoint, certain approaches to genetic screening in clinical practice remain ambiguous in ‎the era of assisted reproduction. Even the most current guidelines do not provide definite guidance on testing ‎protocols, leaving clinicians to carefully determine which tests best serve patients struggling with infertility.‎ The lack of uniformity in the current practice of male fertility evaluation can prove to be quite costly, thus necessitating healthcare practitioners to carefully appraise the necessity and weigh the advantages against potential economic and psychological detriments. The objective of this review is to map the existing literature on the general topic of the clinical indications of routine karyotyping and/or AZF screening in infertile men, identify key concepts, determine where the gaps are, and lastly, provide an overview of the conclusions drawn from a body of knowledge that varies widely in terms of methodologies or disciplines.

Materials and Methods‎: A thorough search was conducted for the published findings up until July 2023, utilizing PubMed (MEDLINE). This comprehensive search involved the use of specific search keywords, ‎either individually or in combination. The search terms employed were as follows: “Karyotype”, "Klinefelter" or "KS" ‎or "47,XXY", "AZF" or "Azoospermi*" and/or "microdeletion*" in the title or ‎abstract. Once the titles and abstracts of selected articles were obtained, the complete texts of linked ‎papers were meticulously scrutinized.‎

Results‎: A total of 191 records were identified from PubMed. During screening, 161 records (84.3%) were ‎eliminated. Finally, 30 papers were included in this scoping review, which was conducted in 18 ‎countries. The number of sequence tag sites (STSs) used in the studies varied from 5 to 59. The rate of AZF deletions ‎among patients with NOA ranged from 1.3% to 53%. The mean frequency was estimated to be 5.6%. ‎The rate of YCM among patients with XXY karyotype was nil in 19 out of 30 studies (63%), whilst, in the ‎remaining studies, the rate varied from 0.8% to 67%.‎

Conclusion‎: This review provides insights into managing male infertility. The presence of spermatozoa in ejaculation and successful ‎surgical retrieval cannot be excluded for individuals with AZFb/AZFbc microdeletions. Screening for Y ‎chromosome microdeletions is not needed for mosaic or classic KS. Only 1% of individuals with sperm ‎concentration exceeding 1×106 sperm/mL and less than 5×106 sperm/mL exhibit AZF microdeletions; therefore, testing ‎referral for such populations may need reassessment. Individuals with mosaic monosomy X karyotype and ‎certain chromosomal anomalies should be referred for AZF deletion screening. These findings have implications ‎for male infertility management and future research.‎

Procedure-Specific Thromboprophylaxis in Urological Surgeries: A Narrative Review

Behnam Shakiba, Ali Faegh, Sepideh Emami, Kazem Heidari, Robab Maghsoudi

Urology Journal, Vol. 20 (2023), 25 Dey 2022, Page 8068
https://doi.org/10.22037/uj.v20i.8068

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a serious complication that can occur after urological surgeries. It is a leading cause of preventable hospital-related morbidity and mortality in surgical patients [1]. In urological surgeries, VTE remains a serious complication and a significant challenge [2] and PE is considered as the most common cause of postoperative death in patients undergoing major urologic surgery [3]. The decision to use thromboprophylaxis in urological surgeries involves weighing the reduction in VTE risk against the potential increase in perioperative bleeding [4]. However, there is a lack of procedure-specific evidences about thromboprophylaxis in urologic surgeries. Therefore, we have reviewed the available evidence on thromboprophylaxis in urological surgeries and we have tried to summarized these evidences in a procedure specific context.

The Potential Role of Urinary Microbiota in Bladder Carcinogenesis: A Systematic Review

Amir Ghabousian, Ashkan Shafigh, Sona Tayebi, Hanieh Salehi-Pourmehr, Hadi Mostafaei, Ursula Lemberger, Keiichiro Mori, Fatemeh Sadeghi-Ghyassi, Hoora Hassanzadeh, Sakineh Hajebrahimi, Shahrokh F. Shariat

Urology Journal, Vol. 20 (2023), 25 Dey 2022, Page 8036
https://doi.org/10.22037/uj.v20i.8036

Purpose: The quantitative objective of the current systematic review was to identify the potential role of urinary microbiota in bladder cancer (BC) carcinogenesis, invasiveness, progression, and metastasis.

Materials and Methods: The proposed systematic review was conducted in accordance with critical review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, and the Joanna Briggs Institute (JBI) methodology for systematic reviews. The search strategy aimed to find both published and unpublished studies up to the January 2024. A JBI appraisal checklist was used to assess possible biases.

Results: This systematic review was centered on 27 studies comprising 926 BC patients. Overall, 412 control individuals were compared with BC patients. The most common sampling method was midstream urine collection. Regarding microbial alpha diversity, there was no statistically significant difference between cancerous and healthy samples (n=8), recurrent and not recurrent (n=1), responders versus non-responders(n=1), tumor grades (n=1), and collection methods (n=1). However, five studies reported higher diversity in controls, and five other studies reported, conversely, high levels of alpha diversity in BC patients or recurrent cases. Furthermore, a responder (RE) to treatment and a non-muscle invasive bladder cancer (NMIBC) groups demonstrated significant difference with non-responder (NR) and muscle invasive bladder cancer (MIBC), respectively. In terms of beta-diversity, nine studies reported significant diversity between BC patients and controls, one article demonstrated difference between recurrent and not recurrent patients, a study reported significant difference in RE and NR groups whereas another showed opposite, and others (n=4) did not find any difference between BC, controls, MIBC and NMIBC patients, or between tumor grades. One study reported a difference between the collection method and beta-diversity in males and another reported the difference in females.

Conclusion: The included studies demonstrate that the composition of urinary microbiota is altered in patients with BC. However, the differentially enriched genera in the urine of these patients vary between studies, and there is too much heterogeneity across studies to make any reliable and valid conclusions. Furthermore, well-designed research is necessary to assess the role of microbiota in the carcinogenesis and progression of BC.

Purpose: This review presents a clinical approach to genetic issues in male infertility. Unlike other related reviews that discuss different types of genetic diseases (such as Klinefelter and Down syndrome), this review focuses on the clinical features that result from these genetic problems (such as azoospermia and oligospermia).

Methods: A narrative review of the clinical literature in PubMed was conducted using keywords related to male infertility, recurrent pregnancy loss, recurrent in vitro fertilization failure, and genetics. The search included articles with English reviews published online after 2020. Headlines were defined based on the available literature, and after a critical review of each manuscript, clinical facts were classified under the corresponding headlines, and a primary draft was written.

Results: 29 relevant articles were selected from the search. According to the literature, there are clinical genetic approaches for azoospermia, severe oligospermia, severe teratospermia, severe asthenospermia, recurrent miscarriage, and recurrent in vitro fertilization failure.

Conclusion: Although many mutations that can affect male fertility and spermogram have been identified, only a few have clinical predictive value.

 

ORIGINAL PAPER (ENDOUROLOGY AND STONE DISEASE)


Purpose: To establish a prediction model for repeated shockwave lithotripsy (SWL) efficacy to help choose an appropriate treatment plan for patients with a single failed lithotripsy, reducing their treatment burden.

Patients and Methods: The clinical records and imaging data of 304 patients who underwent repeat SWL for upper urinary tract calculi (UUTC) at the Urology Centre of Shiyan People’s Hospital between April 2019 and April 2023 were retrospectively collected. This dataset was divided into training (N = 217; 146 males [67.3%] and 71 females [32.7%]) and validation (N = 87; 66 males [75.9%] and 21 females [24.1%]) sets. The overall predictive accuracy of the models was calculated separately for the training and validation.  Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. The normalized importance of each independent variable (derived from the one-way analyses) in the input layer of the artificial neural network (ANN) model for the dependent variable (success or failure in repeat SWL) in the output layer was plotted as a bar chart.

Results: This study included 304 patients, of whom 154 (50.7%) underwent successful repeat SWL. Predictive models were constructed in the training set and assessed in the validation set. Fourteen influencing factors were selected as input variables to build an ANN model: age, alcohol, body mass index, sex, hydronephrosis, hematuria, mean stone density (MSD), skin-to-stone distance (SSD), stone heterogeneity index (SHI), stone volume (SV), stone retention time, smoking, stone location, and urinary irritation symptom. The model’s AUC was 0.852 (95% confidence interval (CI): 0.8–0.9), and its predictive accuracy for stone clearance in the validation group was 83.3%. The order of importance of the independent variables was MSD > SV > SSD > stone retention time > SHI.

Conclusion: Establishing an ANN model for repeated SWL of UUTC is crucial for optimizing patient care. This model will be pivotal in providing accurate treatment plans for patients with an initial unsuccessful SWL treatment. Moreover, it can significantly enhance the success rate of subsequent SWL treatments, ultimately alleviating patients’ treatment burden.

ORIGINAL PAPER(UROLOGICAL ONCOLOGY)


Bladder cancer is diagnosed at older age compared to all other known cancer types. Radical cystectomy after neoadjuvant chemotherapy or tri-modality treatment (consist of TURB, concurrent chemo-radiation) are the standard treatments. Many of the patients cannot receive tri-modality treatment (concurrent chemo-radiation) because of medical comorbidities. The present study assessed the results of sequential use of chemotherapy and radiotherapy versus concurrent use of them in 266 muscle invasive bladder cancer patients. The results showed similar overall survival but lower disease-free survival in the sequential group. Recurrence rate was higher in the concurrent group. The results showed that sequential use of chemotherapy and radiotherapy provides comparable results to concurrent use of them and provides better results than less than tri-modality treatments.

 

Micro-RNA-371a-3p in Germ Cell Testicular Tumors on Diagnosis: A Prospective Case-Control Study in Turkish Population

Muzaffer Tansel Kılınç, Yunus Emre Göger, Mehmet Serkan Özkent, Özcan Kılıç, Betül Okur Altındaş, Mahmut Selman Yıldırım, Giray Karalezli

Urology Journal, Vol. 20 (2023), 25 Dey 2022, Page 8002
https://doi.org/10.22037/uj.v20i.8002

Purpose: We aimed to evaluate the diagnostic sensitivity and specificity of the miRNA-371a-3p for the primary diagnosis of germ cell tumors (GCT) and to investigate its relationship with pathological factors and clinical stage in the Turkish population.

Materials and Methods: In this prospective study, a total of 60 patients with GCTs, and 40 healthy male controls were examined for serum levels of miRNA-371a-3p before orchiectomy and again two weeks after surgery. The miRNA-371a-3p, alpha-fetoprotein (AFP), and beta-human chorionic gonadotropin (bHCG) levels in the preoperative and postoperative periods were compared at different clinical stages. Receiver operating characteristics curve analyses were performed to determine the sensitivity and specificity of miRNA-371a-3p. Clinical and pathological factors such as clinical stage (CS), tumor size, histology, rete testis invasion, and lymphovascular invasion, potentially impacting miRNA-371a-3p expression levels (relative quantity, RQ), were evaluated statistically.

Results: The sensitivity of miR-371a-3p in GCT patients was 98.3%, and the specificity was 95% (AUC = 0.997 [95%Cl:0.99–1], p < .001). miR-371a-3p expression was not detected in two patients with teratoma.

The median miR-371a-3p RQ was 489 times in GCT and 2.2 times in the Control group (p < .001). In the postoperative period, there was a significant decrease in AFP and bHCG levels in all CS-1 (p = .01) and 30% of the other CS (p = .3). Throughout this time there was a decrease of 19 times at the miR-371a-3p RQ in CS-1(p < .001) and 1.6 times in the other CS (p < .001). The miR-371a-3p RQs were correlated with tumor size and CS.

Conclusion: The miR-371a-3p seems to have higher diagnostic accuracy than classical serum tumor markers in GCT.

ORIGINAL PAPER (ANDROLOGY)


Melatonin Promotes Differentiation of Human Spermatogonial Stem Cells Cultured on Three-Dimensional Decellularized Human Testis Matrix

Maryam Salem, Farnaz Khadivi, Narjes Feizollahi, Mahshad Khodarahmian, Mojtaba Saedi Marghmaleki, Shimal Ayub, Raziye Chegini, Zahra Bashiri, Yasaman Abbasi, Mohammad Naji, Mehdi Abbasi

Urology Journal, Vol. 20 (2023), 25 Dey 2022, Page 7846
https://doi.org/10.22037/uj.v20i.7846

Purpose: The use of 3D (3-Dimensional) culture systems supported cell-to-cell and cell-to-extracellular matrix (ECM) interactions, proliferation, and differentiation of SSCs (Spermatogonial stem cells). The potential advantages of ECM-based scaffolds for in vitro spermatogenesis have been indicated in human and animal experiments. Furthermore, the strong antioxidant and anti-inflammatory activities of melatonin have improved in vitro manipulation of human SSCs in culture conditions.

Materials and Methods: SSCs were isolated from the testis of three dead-brain patients and then propagated for four weeks. The characterization of SSC colonies was done using real-time PCR (Polymerase chain reaction), ICC (Immunocytochemistry), and xenotransplantation to mice model. Decellularization of the human testis was performed using 0.3% sodium dodecyl sulfate (SDS) solution and 1% Triton X-100. Also, various characterizations of DTM (Decellularized testicular matrix ) were carried out using histological staining and DNA content analysis. The optimum dose of melatonin was selected by MTT (Methyl thiazol tetrazolium). SSCs were cultured in 4 groups: control, melatonin, ECM, and ECM-melatonin in a differentiation medium for four weeks. The expression of differentiation genes was evaluated by real-time polymerase chain reaction. In addition, the viability of cultured cells was assessed by MTT assay.

Results: The results of ICC and real-time PCR showed the expression of undifferentiated SSC markers (PLZF and GRFA1) in SSC colonies following the 2D culture of isolated SSCs. The presence of testicular ECM components after different staining methods; and the reduction of DNA content confirmed the proper decellularization process. Germ cell apoptosis significantly decreased in melatonin and ECM groups, and the higher viability of SSCs was seen in the ECM-melatonin group. The relative expression of GFRA1 and PRM2 decreased and increased in ECM and ECM-melatonin groups, respectively.

Conclusion: Our study showed that the addition of melatonin to the human naturally-derived ECM scaffold could provide a suitable platform for inducing the differentiation and preserving the viability of SSCs.

LETTER


We read with interest the recent paper by Hosseini et al detailing the management practice of Iranian Urologists towards the management of anterior urethral stricture disease. Please find our letter to the editor regarding this. 

Tele-Urology in the Era of COVID-19: an Experience of the Reconstructive Urology Department in Iran

Jalil Hosseini, Amir Hossein Eslami, Shahrzad Nematollahi, Rayka Sharifian, Arezoo Sheikh Milani, Alireza Fatemi

Urology Journal, Vol. 20 (2023), 25 Dey 2022, Page 8096
https://doi.org/10.22037/uj.v20i.8096

Introduction:The outbreak of coronavirus has put additional pressure on the health care systems of many countries; but telemedicine can be an important way to deal with it, especially for people whose health has been affected by the virus. The present study aims to investigate the Implementation of a Tele-urology Program for Reconstructive Urologic Referrals: Initial Results and Patient Satisfaction.

Material and methods: All patients with a history of a urethral reconstructive surgery during last year was entered to our study and two nurses collected data of demographic and past medical history of patients by existed. Telephone visits:Fellowship of reconstructive urology was connected to patients during a phone call and filled the USS-PROM and COVID-19 questionnaires. Face to face visits: All patients were asked to answer the questionnaire about recent exposure and infection by corona virus, recent travel and other risk factors of COVID-19.

Results: Mean of USSPROM scale was calculated as 1.65 (+2.91) with a range of 0-15. Based on categorization for USSPROM scale, 74 patients (94.8%) had mild symptoms while 4 patients (5.1%) had moderate symptoms and needed further medical attention. Four patients with moderate USSPROM score were required to cystoscopic evaluation, which one patient with moderate USSPROM score had severe stricture and candidate for redo urethroplasty. Two other patients need for urethral stricture dilatation. Cost was calculated based on taxi-service fee. Accordingly, the average (+SD) cost for in-person visits to the physician was estimated as 4.80 + 4.32 million Rials. In terms of distance, the average distance for receiving medical services according to the patient`s residence area was 373.2 +348.79 kilometres.In terms of the patient`s opinion regarding virtual examination, inappropriateness of virtual visits for physical examination, and patient`s inability to explain the problem correctly, patient`s condition at the time of the virtual visit were the main challenges reported by the respondent.

Conclusion: Considering that the present COVID-19 emergency will likely last for months, telehealth could be the safest way to deliver urological care for a large percentage of the patients, such as those who are more at risk of unfavorable outcomes of COVID-19.

Management of Anterior Urethral Stricture: A Survey of Contemporary Practice of Iranian Urologists

Jalil Hosseini , Samin Khannejad, Armin Attar, Ali Goudarzikarim

Urology Journal, Vol. 20 (2023), 25 Dey 2022, Page 7886
https://doi.org/10.22037/uj.v20i.7886

Purpose: To evaluate Iranian urologists’ approach to urethral stricture and assess how often they select open urethroplasty over minimally invasive procedures.

Material and methods: This cross-sectional observational study was conducted via www.survey.porsline.ir among members of the Iranian urologists’ community. The urologists were contacted via email and social media applications (e.g., WhatsApp, Telegram), and data, including their demographic information and years of practice, as well as questions related to their attitude towards the management of urethral stricture, were collected.

Results: A total number of 376 patients were included in the current survey. The specialty of reconstructive urology was selected by less than 2% (n=5) as their field of interest. Only 6.64% (n=25) of the urologists stated that they received adequate training for management of urethral stricture. Only about 5% (n=19), believed that according to scientific resources, chose open urethroplasty as the initial management. Almost 94% (n=353) did not perform any urethroplasties during the past year and about 0.2% (n=2) performed more than 20 open urethroplasties. For diagnosing urethral stricture, almost 99% of them chose RUG+VCUG, 72% chose urethrocystoscopy, and 69% chose uroflowmetry in the third place. For evaluation of urethroplasty postoperative outcomes, 76% (n=269) used RUG+VCUG, 15% (n=56) used Rigid Cystoscopy, and 8% (n=29) used Flexible Cystoscopy,

Conclusion: Iranian urologists prefer minimally invasive procedures for treating urethral stricture, similar to other countries. This lack of urologists’ interest in open urethroplasty is greatly due to poor training during the residency years and little experience with urethral strictures. Therefore, further considerations in order to improve urologists’ knowledge and expertise for management of urethral stricture is recommended.

This essay draws attention to the prostate-specific antigen (PSA) discovery's lack of Nobel Prize acknowledgement despite its significance for prostate cancer (PCa) clinical practice. The Nobel Prize committee gives more weight to discoveries in basic research than to applications in medicine, which may account for PSA's lack of recognition. The prize has been dominated by the identification of cancer-causing viruses. Considering the subject from our -urologists- side, numerous pioneer researchers have uncovered PSA's presence and function, and its overuse in PCa screening has sparked debates about issues like overdiagnosis and overtreatment. We must concur that the factors contributing to PSA's underappreciation include the lack of a clear pioneer in its discovery and the contradictory opinions around its use. As a conclusion, PSA may have to wait for a better application before it receives recognition in the Nobel Prize.