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. 21 No. 04 (2024), 9 Khordad 2024, Page 200-207
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.

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. 21 No. 04 (2024), 9 Khordad 2024, Page 208-220
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.

Procedure-Specific Thromboprophylaxis in Urological Surgeries: A Narrative Review

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

Urology Journal, Vol. 21 No. 04 (2024), 9 Khordad 2024, Page 226-233
https://doi.org/10.22037/uj.v20i.8068

Purpose: Postoperative pulmonary embolism is a leading cause of mortality in patients undergoing major urologic
surgeries, presenting a complex challenge in balancing the risks of venous thromboembolism (VTE) and perioperative bleeding. This study examines the current evidence on thromboprophylaxis in urological procedures, focusing on procedure-specific considerations.
Methods: Literature on thromboprophylaxis in urological procedures was reviewed during the past decade.
Results: Various mechanical thromboprophylaxis methods, such as compression stockings, pneumatic compression
devices, foot pumps, mobilization, and exercises, are available preventive measures. Additionally, unfractionated
heparin (UFH) and low molecular weight heparin (LMWH) are commonly used pharmacological agents
for VTE prevention, with the choice between mechanical, pharmacological, or combined approaches tailored to
individual patient characteristics and surgical requirements. Patient risk stratification into low, medium, and highrisk
categories based on age, BMI, and VTE history guides the selection of thromboprophylaxis strategies. Surgical
procedures are categorized as oncological or non-oncological, with uro-oncological surgeries posing a higher VTE
risk than non-oncological procedures. Consequently, a combination of pharmacological and mechanical prophylaxis
is typically recommended for uro-oncological patients, while pharmacological prophylaxis is reserved for
high-risk individuals undergoing non-oncological surgeries. Mechanical prophylaxis is advised for high-risk patients
undergoing procedures with elevated VTE risk.
Conclusion: This study summarized an optimal thromboprophylaxis protocol taking into account patient risk factors and the specific urological procedure.

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)


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. 21 No. 04 (2024), 9 Khordad 2024, Page 242-249
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.

LETTER


Why Discovery of PSA was not Granted a Nobel Prize?

Oktay ÖZMAN

Urology Journal, Vol. 21 No. 04 (2024), 9 Khordad 2024, Page 265-266
https://doi.org/10.22037/uj.v20i.7703

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.

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

Jalil Hosseini , Samin Khannejad, Armin Attar, Ali Goudarzikarim

Urology Journal, Vol. 21 No. 04 (2024), 9 Khordad 2024, Page 269-270
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.

Extra-peritoneal vs. Trans-peritoneal Radical Cystectomy pros and cons

Farzad Allameh, Amir Hossein Eslami

Urology Journal, Vol. 21 No. 04 (2024), 9 Khordad 2024, Page 271
https://doi.org/10.22037/uj.v20i.8140

One of the most common cancers of the urinary tract is bladder tumors. Bladder cancers are divided into two groups: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer. (1)

 Trans-Peritoneal  Radical Cystectomy (RC) with  pelvic lymphadenectomy is the standard technique in muscle invasive and high risk non-muscle invasive bladder cancer (2). and Urologist around the world are more familiar with trans-peritoneal technique.

In some articles extra-peritoneal Radical Cystectomy (RC) implied as an decreased  postoperative  complications techniques. In this letter we want to compare these two techniques and find out the pros and cons of these techniques.

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. 

Video


A Step-by-Step Guide to Double-Puncture Technique for Endoscopic Management of Ureterocele

Behnam Nabavizadeh, Reza Nabavizadeh, Abdol-Mohammad Kajbafzadeh

Urology Journal, Vol. 21 No. 04 (2024), 9 Khordad 2024, Page 273
https://doi.org/10.22037/uj.v16i7.6028

To date, the optimal surgical technique for treatment of ureterocele remains unclear and the available options are variable. The endoscopic techniques that are gaining popularity mostly share major drawbacks including low success rate, high probability of mandatory secondary surgery and de novo vesicoureteral reflux to the ureterocele moiety. The Double-Puncture technique is shown to have promising outcomes in terms of long-term success and low rate of complications. In this video, a step-by-step guide to this technique is presented.