Diagnosis of Testicular Torsion and Differentiation From Other Pathologies Using Near-Infrared Spectroscopy.

OBJECTIVE: To develop a near-infrared (NIR) spectroscopy device to diagnose testicular torsion with high sensitivity and specificity. Specifically, we aim to investigate the differentiation between testicular torsion from other pathologies such as orchidoepididymitis, varicocele, and hydrocele. METHODS: Two LEDs with wavelengths of 660 nm and 940 nm were used as light sources in the device. Each wavelength was sent to the testicle successively, and a photodiode detected back-reflected diffuse light. The ratio of the light intensities of 660 nm and 940 nm was used as a diagnostic parameter. A multi-center clinical trial was performed in 5 different hospitals. RESULTS: In total, 62 patients in urology clinics with acute testicular pain have been recruited for the study. The developed NIR spectroscopy correctly defined all 8 testicular torsion cases. Besides, 3 orchidoepididymitis, 1 varicocele, and 3 hydrocele cases were correctly distinguished from testicular torsion. Only 1 hydrocele case was misdiagnosed as torsion. The range of the ratio was between 0.14 and 1.16 overall measurements. The ratio varied between 0.14 and 0.3 for the testicle with torsion. The ratio was between 0.49 and 1.16 for the normal testicle and testicle with other pathologies mentioned above. CONCLUSION: We have chosen the threshold ratio of 0.4 to differentiate between the normal and torsion testis and diagnosed all the torsion cases among all normal and other pathologies. The developed optical device to diagnose testicular torsion is inexpensive, user-friendly, and works based on objective criteria with high sensitivity and specificity in real time.

Evolution of testicular asymmetry during puberty in adolescents without and with a left varicocele.

OBJECTIVES: To assess the evolution of the Testicular Atrophy Index (TAI) in adolescent boys with and without a left varicocele with special attention for the currently postulated cut-off value of 20%. SUBJECTS AND METHODS: During 2015-2019, 364 adolescent boys aged 11-16 years were recruited. Genital examination and scrotal ultrasonography were repeatedly performed (≥4 month intervals). Testicular volume (TV) was calculated using the Lambert formula (length × width × height × 0.71). TAI was calculated using the formula: [(TVright - TVleft)/TVlargest (right, left)] × 100. RESULTS: The final study population comprised 239 participants, 161 (67.36%) controls and 78 (32.64%) adolescent boys with left varicocele. The mean (sd) number of measurements per participant was 3.82 (1.08). A TAI of ≥20% at first measurement occurred in 9.94% and 35.90%, respectively. Of these, only 31.25% and 46.43% had a TAI of ≥20% at the last measurement, respectively. Nevertheless, the risk of ending up with a TAI of ≥20% was significantly higher if a TAI of ≥20% was recorded at first measurement (P = 0.041 and P = 0.002, respectively). The normalisation rate did not differ significantly between the groups (P = 0.182). Normalisation occurred most frequently in Tanner Stages III and IV. Normalisation was mostly (≥74%) due to catch-up growth of the left testis, in contrast to growth retardation of the right testis, in both groups. The TAI seems to be a fluctuating parameter. CONCLUSION: A TAI of ≥20% is a phenomenon seen in boys with and without varicocele but is more common in boys with varicocele. Although normalisation of a high TAI is frequently seen, both adolescent boys with and without a left varicocele who have an initial TAI of ≥20% have a higher risk of a TAI of ≥20% in the future. As the TAI is a fluctuating parameter during pubertal development, it's use as indicator for varicocelectomy based on a single measurement during pubertal development is questioned.

The Assessment of TikTok as a Source of Quality Health Information on Varicoceles.

OBJECTIVE: To evaluate the quality of varicocele information on TikTok, a popular video platform that adolescent patients are now turning to as a source of medical information before visiting a doctor. METHODS: Using the key word "varicocele," we retrieved the top 225 videos listed on TikTok in May 2022. We extracted general video and engagement data. Video information was coded and analyzed for the completeness of different types of content (definition, symptoms, evaluation, management, and outcomes). The quality of consumer health information was rated using the DISCERN instrument. RESULTS: Thirty-six videos met inclusion criteria; 17 were created by general users, 16 by healthcare professionals or systems (2 by urologists), and 3 by scientific communities. Healthcare professionals had more views than non-healthcare (P = .05). The quality of health information using the DISCERN instrument was "poor" from health care professional videos and "very poor" from non-health care professionals. However, the quality of information provided by healthcare professionals was statistically better than that of non-healthcare (P< .05). Video content mainly focused on symptoms: 50% of videos from healthcare providers had some or extensive content and 41% of non-healthcare had some content. 23% of videos had misinformation. CONCLUSION: The overall quality of information for varicoceles on TikTok is not acceptable and does not meet patient needs. It is imperative that urologists create robust, accurate content, and partner with these platforms to connect users with higher quality information. TikTok users should also be mindful that information may not be medically accurate.

Long lasting effect on testes following methylene blue injection in laparoscopic lymphatic sparing varicocelectomy.

OBJECTIVE: Injection of methylene blue to testis has been shown to have adverse effect in animal studies but it is still being used frequently as lymphatic mapping agent during lymphatic sparing varicocelectomy in adolescent varicoceles. We aim to report postoperative ultrasound changes after subaortic injection of methylene blue in human testes. STUDY DESIGN: A retrospective observational study of consecutive patients under 18 years old undergoing laparoscopic varicocelectomy from August 2017 to August 2021 was performed. Demographics such as age, symptoms, pre-operative testicular volume was collected. Primary outcome was change on testicular ultrasound at 3, 6, 12 months after the operation. Secondary outcome was testicular volume difference between affected and unaffected testes, and growth rate of affected testis at 1 year after the operation. RESULTS: Fifty-eight patients were included, with median age of 15 years old (IQR 11-18 years). Thirty-one patients had non-lymphatic sparing varicocelectomy (Group A) and 27 patients had lymphatic sparing varicocelectomy (Group B). There was no statistical difference between the mean testicular volume difference between the two groups, but hydrocele rate was significantly higher in Group A (16% vs 0%, p = 0.03). In group B, 6 patients (22.2%, p = 0.005) developed testicular change detectable by ultrasound. No statistical difference could be demonstrated for median testicular size difference (between affected and unaffected testes) at 1 year between group with and without ultrasound change (-23% vs 0%, p = 0.36). Median follow up time was 20.4 months (IQR 5-32 months). DISCUSSION: Varicocele treatments improve testicular volume and increase total sperm concentration and lymphatic sparing surgery significantly decreased post-operative hydrocele rates [2]. Different agents have been used to delineate lymphatic vessels and one commonly used agent is methylene blue [10,15-16]. However it has been shown in other animal studies that intraparenchymal injection of methylene blue to rat testis result in degenerative changes [18]. Our study is the first to describe post-operative changes of human testes on imaging after lymphatic sparing varicocelectomy with subdartoic injection of methylene blue. Six patients (22.2%) demonstrated new onset testicular changes on post-operative ultrasound. Although no statistically significant testicular volume reduction was seen in the group with change on imaging, these observations may serve as a surrogate marker for testicular injury or reduced testicular function. It will be desirable for future studies if we can investigate it further with hormonal markers or semen analysis after puberty has been reached. CONCLUSION: Lymphatic sparing procedure reduced post-operative hydrocele in adolescent varicocele, however long-lasting effect on testis is evident with subdartoic injection of methylene blue. This agent must be used with caution and long term follow up of these patients are needed.

Clinical parameters as predictors for sperm retrieval success in azoospermia: experience from Indonesia.

Background: Azoospermia is the most severe type of male infertility. This study aimed to identify useful clinical parameters to predict sperm retrieval success. This could assist clinicians in accurately diagnosing and treating patients based on the individual clinical parameters of patients. Methods: A retrospective cohort study was performed involving 517 patients with azoospermia who underwent sperm retrieval in Jakarta, Indonesia, between January 2010 and April 2023. Clinical evaluation and scrotal ultrasound, serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were evaluated before surgery. Multivariate analyses were conducted to determine clinical parameters that could predict overall sperm retrieval success. Further subgroup analysis was performed to determine the factors that the diagnosis of non-obstructive azoospermia (NOA) diagnosis and sperm retrieval success among patients with NOA. Results: A total of 2,987 infertile men attended our clinic. Men with azoospermia (n=517) who met the inclusion criteria and did not fulfil any exclusion criteria were included in the study. The overall sperm retrieval success was 47.58%. Logistic regression revealed that FSH 7.76 mIU/mL (sensitivity: 60.1%, specificity: 63.3%, p<0.001); longest testicular axis length 3.89 cm (sensitivity: 33.6%, specificity: 41.6%); and varicocele (p<0.001) were independent factors for overall sperm retrieval. The FSH cutoff of 7.45 mIU/mL (sensitivity: 31.3%, specificity: 37.7%, p<0,001); longest testicular axis length 3.85 cm (sensitivity: 76.7%, specificity: 65.4%, p<0.001); and varicocele (p<0.001) were independent factors for NOA diagnosis. Varicocele was the only clinical parameter that significantly predicted the success of sperm retrieval in patients with NOA. Conclusions: FSH, LH, longest testicular axis, and varicocele are among the clinical parameters that are useful for predicting overall sperm retrieval success and NOA diagnosis. However, varicocele is the only clinical parameter that significantly predicts sperm retrieval success in patients with NOA. High-quality studies are required to assess the other predictors of sperm retrieval success.

Effects of alpha-lipoic acid on sperm quality in patients with varicocele-related male infertility: study protocol for a randomized controlled clinical trial.

BACKGROUND: Varicocele is a high incidence and is considered to be the most common and correctable cause of male infertility. Oxidative stress (OS) plays a central role in the pathogenesis of varicocele-related male infertility. In addition to varicocelectomy, antioxidant supplementation seems to be an effective scheme for the treatment of varicocele-related male infertility, but it is still controversial. The purpose of this study is to determine the effects of alpha-lipoic acid (ALA) supplementation on sperm quality in patients with varicocele-related male infertility. METHODS: In this randomized controlled clinical trial, we will randomize 80 patients with varicocele-related male infertility from Guilin People's Hospital. The non-surgical observation group (n = 20) will receive ALA, the non-surgical control group (n = 20) will receive vitamin E, the surgical observation group (n = 20) will receive ALA after the operation, and the surgical control group (n = 20) will receive vitamin E after the operation. The course of treatment will be 3 months. The results will compare the changes in semen parameters, sex hormones, testicular volume, sperm DNA fragment index (DFI), seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) between the groups at baseline and after 3 months of antioxidant supplementation. DISCUSSION: Whether it is necessary to use antioxidants in varicocele-related male infertility, how potent antioxidants should be used, postoperative application or non-surgical independent application still needs to be explored. This study attempts to compare the effects of two antioxidants (ALA and vitamin E) on sperm quality in patients with varicocele-related male infertility (surgical or non-surgical) and attempted to answer the above questions. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100054958. Registered on 29 December 2021.

Doppler Ultrasonography - An Important Tool in Managing Patients With Varicocele and Secondary Infertility.

BACKGROUND/AIM: Doppler ultrasound was successfully implemented as part of the diagnostic plan of medical emergencies in scrotal pathology. This study aimed to investigate whether it could play an important role in managing not only varicocele, but patients with secondary infertility as well. PATIENTS AND METHODS: The current study included 135 patients with varicocele and infertility. Surgery was performed in 18 cases with painful varicocele, 15 cases with testicular hypotrophy, and 48 cases with infertility. RESULTS: Among cases with infertility who underwent surgery, aged between 19 and 36 years old, 80% showed a significant improvement in the spermogram after curing the varicocele. In patients over 36 years of age, only 42% had some improvement in the spermogram after surgery. In addition, after surgery, antispermatic antibodies showed a significant decrease in all patients. CONCLUSION: Varicocele and secondary infertility are a well-known pathology. While the role of Doppler ultrasonography is established in varicocele diagnosis, we found an important pool of patients with secondary infertility and asymptomatic varicocele that would not have been diagnosed in the absence of Doppler ultrasound investigations. Since the best results in fertility were observed in patients younger than 36 years of age, we reiterate the importance of Doppler ultrasonography in addressing infertility.

Prediction of semen analysis parameter improvement after varicocoelectomy using 1 H NMR-based metabonomics assays.

BACKGROUND: Varicocoele is the most common correctable cause of male infertility; however, predicting varicocoelectomy outcomes is difficult. "Omics" techniques have been increasingly used to develop new diagnostic and prognostics tools for several male infertility causes, and could be applied to study varicocoele. OBJECTIVES: The objective is to create metabolomics models capable of segregating men who improved semen analysis (SA) parameters or achieved natural pregnancy after microsurgical varicocoelectomy (MV) from those who did not, using hydrogen-1 nuclear magnetic resonance (1 H NMR) spectra of seminal plasma of pre-operative samples. MATERIAL AND METHODS: We recruited 29 infertile men with palpable varicocoele. 1 H NMR spectra of seminal plasma were obtained from pre-operative samples and used to create metabonomics models. Improvement was defined as an increase in the total motile progressive sperm count (TMC) of the post-operative SA when compared to the baseline, and pregnancy was assessed for 24 months after MV. RESULTS: Using linear discriminant analysis (LDA), we created a model that discriminated the men who improved SA from those who did not with accuracy of 93.1%. Another model segregated men who achieved natural pregnancy from men who did not. We identified seven metabolites that were important for group segregation: caprylate, isoleucine, N-acetyltyrosine, carnitine, N-acetylcarnitine, creatine, and threonine. DISCUSSION: We described the use of metabonomics model to predict with high accuracy the outcomes of MV in infertile men with varicocoele. The most important metabolites for group segregation are involved in energy metabolism and oxidative stress response, highlighting the pivotal role of these mechanisms in the pathophysiology of varicocoele. CONCLUSIONS: 1 H NMR spectroscopy of seminal plasma can be used in conjunction with multivariate statistical tools to create metabonomics models useful to segregate men with varicocoele based on the reproductive outcomes of MV. These models may help counseling infertile men with varicocoele regarding their prognosis after surgery.

Varicocele at High Altitude; Venous Outflow Restriction by Hypobaric Hypoxia.

BACKGROUND: Testicular aches have been reported to occur on exposure to high altitude (HA). As a painful expression of venous congestion at the pampiniform plexus, varicocele (VC) might be a consequence of cardiovascular adjustments at HA. Chile's National Social Security Regulatory Body (SUSESO) emphasized evaluating this condition in the running follow-up study "Health effects of exposure to chronic intermittent hypoxia in Chilean mining workers." OBJECTIVES: This study aimed at investigating the prevalence of VC in a population usually shifting between sea level and HA, thereby intermittently being exposed to hypobaric hypoxia. METHODOLOGY: Miners (n=492) agreed to be examined at their working place by a physician, in the context of a general health survey, for the presence of palpable VC, either visible or not. Among them was a group exposed to low altitude (LA) <2,400 m; n=123; another one exposed to moderate high altitude (MHA) working 3,050 m; n=70, and a third one exposed to very high altitude (VHA) >3,900 m, n=165. The Chi2 test and Kruskal-Wallis test were used for the descriptive analyses, and logistic regression was applied to evaluate the association of VC with exposure to HA. The Ethics Committee for Research in Human Beings, Faculty of Medicine, University of Chile, approved this project. RESULTS: VC prevalence (grades 2 and 3) was found to be 10% at LA, 4.1% at MHA, and 16.7% at VHA (p≤0.05). Hemoglobin oxygen saturation (SaO2) was lower, and hemoglobin concentrations were higher in workers with high-grade VC at VHA compared to LA and MHA (Wilcoxon tests, p<0.001). Odds ratios (OR) for the association of VC with HA were 3.7 (95%CI: 1.26 to 12.3) and 4.06 (95%CI: 1.73 to 11.2) for MHA and VHA, respectively. CONCLUSION: Association of VC with HA, a clinically relevant finding, may be related to blood volume centralization mediated by hypobaric hypoxia.

SCROTAL THERMOGRAPHY IN THE EVALUATION OF SURGICAL OUTCOME AFTER VARICOCELE REPAIR: A CASE REPORT.

Scrotal thermography is a diagnostic method for varicocele. In short, there are five diagnostic thermographic criteria for varicocele, i.e., pattern of scrotal thermographic image indicative of varicocele, temperature at pampiniform plexus ≥34 C°, temperature difference between left and right pampiniform plexus ≥0.5 C°, enhancement of image during Valsalva maneuver, and temperature at pampiniform plexus ≥ temperature at ipsilateral thigh. Three or more positive signs are indicative of varicocele. The aim of this report is to present the use of digital thermography as a diagnostic method to evaluate the outcome of varicocele repair. We present a case of a student diagnosed with varicocele grade III, and assessed preoperatively and followed up postoperatively by scrotal thermography. According to thermographic indicators, our patient was positive for varicocele diagnosis before surgical treatment. Three months after varicocele repair, the patient did not show positive thermographic indicators of varicocele while physical examination and color Doppler ultrasound were equivocal. This case report suggests that infrared digital thermography of scrotum could be very valuable for monitoring patients in the period after surgery for varicocele, however, it should be confirmed in a larger number of patients.

Exosomes as Potential Biomarkers for Erectile Dysfunction, Varicocele, and Testicular Injury.

INTRODUCTION: Optimal male reproductive health is dependent upon critical mediators of cell-cell communication: exosomes or extracellular vesicles. These vesicles are nano-sized particles released into a variety of bodily fluids, such as blood and semen. Exosomes are highly stable and can carry genetic and other molecules, including DNA, RNA, and proteins, which provide information about their origin cells. OBJECTIVE: To identify exosomes as potential biomarkers or therapeutic mediators in male sexual and reproductive disorders like erectile dysfunction (ED), varicocele, and testicular injury. METHODS: A PubMed search was performed to highlight all articles available relating to exosomes and extracellular vesicles in the pathogenesis of different male sexual and reproductive disorders, and their importance in clinical use as both diagnostic markers and potential therapeutic mediators. RESULTS: Various male reproductive system disorders, such as ED, varicocele, and testicular injury, are linked to increased or decreased levels of exosomes. Exosomes have a higher number of molecules such as DNA, RNA, and proteins, which can give a more precise and comprehensive result when compared to other biomarkers. Exosomes can be considered as plausible diagnostic biomarkers for male sexual and reproductive diseases, with considerable advantages over other diagnostic procedures such as invasive tissue biopsy. Exosomes can carry cargo such certain drugs and therapeutic molecules making them a promising therapeutic approach. Several studies have begun to test treating various male sexual reproductive disorders with exosomes. CONCLUSION: Exosomes deliver many components that can regulate gene expression and target signaling pathways. Understanding how extracellular vesicles can be utilized as biomarkers in diagnosing men, particularly those with idiopathic erectile dysfunction, will not only aid in diagnosis but also help with making therapeutic targets. Khodamoradi K, Golan R, Dullea A, et al. Exosomes as Potential Biomarkers for Erectile Dysfunction, Varicocele, and Testicular Injury. Sex Med Rev 2022;10:311-322.

Management of adolescent varicocele.

Varicocele is defined as an abnormal dilation and tortuosity of the internal spermatic veins found within the pampiniform plexus. It is a common finding in adolescents and adult men alike, however its diagnosis in the adolescent population poses different dilemmas in regard to indications for treatment than in adults. Failed Paternity is a clear-cut indication for repair in adult men attempting to father children. In adolescents, the physicians, family and patients must consider potential for future fertility problems which may or may not actually become of concern. Assessing the degree of negative effect of the varicocele on an adolescent's testicular health can also be difficult as teenagers typically are not asked to provide semen for analysis and thus surrogate markers for testicular health such as testicular size differentials must be used. Treatment options for the adolescent varicocele are similar to options in adult populations. While risks and benefits of various techniques can be considered, the gold standard for varicocele repair in adolescents has not been clearly defined. We aim to discuss diagnosis of varicocele, considerations for initiating treatment of varicocele in the adolescent, and techniques for management.

Standing Ultrasound Adds Clinical Utility for the Diagnosis of Varicoceles.

PURPOSE: We assessed the role of standing vs supine scrotal ultrasound (SUS) for varicocele assessment by evaluating differences in clinical outcomes. MATERIALS AND METHODS: We retrospectively reviewed men from 2008-2020 diagnosed with varicocele who had documented SUS with both supine and standing assessments with and without Valsalva. Clinical outcomes (semen parameters, TUNEL and serum testosterone [T]) after microsurgical varicocelectomy were compared among men who had varicoceles diagnosed by standing SUS (vein size >2.5 mm, vein size >3.0 mm or reversal of flow) to those who would have been missed on supine SUS only. RESULTS: A total of 349 men underwent varicocelectomy (right: 5 [1.4%]; left: 118 [33.8%]; bilateral: 226 [64.8%]). Disagreement between those with abnormal standing vs normal supine for vein size >2.5 mm was: 56 men (16.1%) on the right and 31 men (8.9%) on the left, for vein size >3.0 mm was: 64 men (18.3%) on the right, and 56 men (16.1%) on the left, and for flow reversal was: 36 (14.0%) on the right and 40 (15.4%) on the left. For those >2.5 mm, only T had significant improvements on the left (p=0.05). For those >3.0 mm significant differences were seen for sperm motility on the right (p=0.04), and TUNEL (p=0.04) and T (p <0.01) on the left. For flow reversal, significant differences were seen for sperm concentration (p <0.01), morphology (p=0.03) and volume (p=0.05) on the right and TUNEL on the left (p=0.02). CONCLUSIONS: Standing SUS identifies a greater number of men who would have been missed using supine SUS only.

Risk of herpes zoster infection in men with varicocele.

PURPOSE: Several diseases have been identified as stressful factors for herpes zoster (HZ) infection. In this study, we investigated the risk of HZ infection in men with varicocele. METHODS: We enlisted the data of patients with newly diagnosed varicocele between 2000 and 2012 from the Taiwanese National Health Insurance Research Database as case cohort. Four control patients were matched as per age and index year to a case patient. HZ diagnosis was the primary end point, and the follow-up period was considered as the time interval from the index date to the main outcome, withdrawal from the National Health Insurance program, or end of the study (31 December 2013). RESULTS: In total, 8720 patients were recruited (1744 with varicocele and 6976 controls); the overall mean age was 36 years. Majority (85%) of the participants were 20-49 years old. HZ incidence was higher in patients with varicocele (5.60 per 1,000 person-years) than in the control group (4.01 per 1,000 person years). Patients with varicocele were 1.37 times more likely to develop HZ than the controls after adjustment. Compared with the control cohort, the adjusted hazards ratio (HR) of the varicocele cohort was higher in patients younger than 49 years old (adjusted HR = 1.60). CONCLUSION: Men with varicocele had a higher risk of HZ development than those without varicocele, particularly those aged ≤49 years. Thus, stress from varicocele cannot be ignored in young men.

Molecular characteristics of varicocele: integration of whole-exome and transcriptome sequencing.

OBJECTIVE: To explore the exome and transcriptome characteristics potentially underlying the pathogenesis of varicocele (VE). DESIGN: Experimental study and cohort study. SETTING: Academic research laboratory and university-affiliated hospital. PATIENT(S): Eleven VE patients whose fathers also had VE, plus 151 additional patients and 324 healthy men for variants genotyping; for the rat model, eight Sprague-Dawley male rats. INTERVENTION(S): Partial ligation of renal vein was conducted to establish VE rat models for whole-transcriptome RNA sequencing (RNA-seq). MAIN OUTCOME MEASURE(S): Genes with differential expression and/or harboring potential pathogenic variants detected via RNA-seq and whole-exome sequencing (WES) then subjected to population-based survey to define candidate genes of VE and analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes to identify VE-involved pathways. RESULT(S): Whole-transcriptome RNA sequencing (RNA-seq) was performed using left spermatic veins of five rat VE models and three controls. We identified 9,688 genes and 18 pathways via RNA-seq, and via WES 160 genes harboring 279 potential deleterious variants and 16 pathways. Nine genes (AAMP, KMT2D, IRS2, SPINT1, IFT122, MKI67, DCHS1, LAMA2, and CBL) had variants in more than one patient who underwent WES, and six of these genes (AAMP, SPINT1, MKI67, IFT122, LAMA2, and DCHS1) showed differential expression. The population-based survey showed that AAMP, SPINT1, and MKI67 were strongly associated with VE risk. Together, two omic 67 data sets revealed four pathways potentially related to VE. CONCLUSION(S): For the first time, we have described the exome and transcriptome characteristics of VE. The bi-omics identified novel candidate genes and pathways involving the occurrence and development of VE.

Extensive Assessment of Underlying Etiological Factors in Primary Infertile Men Reduces the Proportion of Men With Idiopathic Infertility.

Objective: Up to 40% of infertile men remain without a recognized cause (i.e., idiopathic infertility). We aimed to identify, categorize, and report the supposed causes of male infertility in a cohort of white-European men presenting for primary couple's infertility, by using a thorough and extensive baseline diagnostic work-up. Material and Methods: Cross-sectional study of 1,174 primary infertile men who underwent a thorough diagnostic work-up including: detailed medical history, physical examination, hormonal assessment, genetic testing, semen analyses; semen and urine cultures; testis color Duplex US. Men without any identified causal factor were considered as idiopathic. Six different etiological categories were established, and their prevalence was estimated. Logistic regression models estimated the risk of missing causal identification. Results: A possible causal factor was identified in 928 (81%) men. Hypogonadism was the most frequent identified cause (37%), followed by varicocele (27%). Genetic abnormalities were found in 5% of patients. A causal factor was more easily identifiable for the more severe infertility cases, and azoospermic men were those less likely to be defined as idiopathic (OR and 95% CIs: 0.09; 0.04-0.20). Relative proportion of identified causes remained constant during the 10-year study period (p>0.43). Conclusions: Due to a more comprehensive and extensive diagnostic work-up, at least one underlying cause of male infertility factor in 4 out of 5 infertile men can be identified. Men with a less severe phenotype remain a clinical challenge in terms of establishing a possible etiologic factor. Further studies are needed to assess which subset of infertile men deserves a more extensive work-up.

Semen Biochemical Components in Varicocele, Leukocytospermia, and Idiopathic Infertility.

The evaluation of the seminal plasma plays a relevant role in the definition of male infertility and in assisted reproduction outcomes; for this reason, it would be recommended to find biochemical markers able to characterize sperm pathology. In this study, 53 infertile patients (grouped by the presence leukocytospermia, idiopathic infertility, or varicocele) and 10 fertile men were selected. Spermiogram was performed by light microscopy, and sperm ultrastructure was evaluated by transmission electron microscopy (TEM) mathematically elaborated. Testosterone (TESTO), estradiol (E2), ferritin (FERR), iron (Fe), transferrin (TRSF), triglycerides (TRG), cholesterol (CHOL), and isoprostanes (F2-IsoPs) were detected in seminal plasma. Sperm characteristics and biochemical components were correlated by Spearman's rank correlation coefficient in the whole population and in each group. The levels of TESTO and E2 were positively correlated with sperm quality in particular, and E2 was correlated with fertility index expressing the number of sperm free of ultrastructural defects evaluated by TEM. On the contrary, the indices of iron metabolism (FERR, Fe, and TRSF) were positively associated with low sperm quality and sperm necrosis, particularly in leukocytospermia and varicocele groups, pathologies in which an inflammatory status and oxidative stress condition are present. The study of the seminal plasma composition deserves attention because the levels of the various components seem to be associated with specific reproductive pathologies.