Effect of varicoceles on spermatogenesis.

Varicoceles are dilated veins within the spermatic cord and a relatively common occurrence in men. Fortunately, the large majority of men are asymptomatic, however, a proportion of men with varicoceles can suffer from infertility and testosterone deficiency. Sperm and testosterone are produced within the testis, and any alteration to the testicular environment can negatively affect the cells responsible for these processes. The negative impact of varicoceles on testicular function occurs mainly due to increased oxidative stress within the testicular parenchyma which is thought to be caused by scrotal hyperthermia, testicular hypoxia, and blood-testis barrier disruption. Management of varicoceles involves ligation or percutaneous embolization of the dilated veins. Repair of varicoceles can improve semen parameters and fertility, along with serum testosterone concentration. In this review, we discuss the pathophysiology of varicoceles, their impact on testicular function, and management.

Targeting COVID-19 and varicocele by blocking inflammasome: Ligand-based virtual screening.

COVID-19 is a new generation of outbreaks that invade not only local emerging region, continental but also the whole globe. Varicocele on the other hand, is a testicular vascular disease that underlies 40 % of male infertility cases. Fortunately, the two diseases can be blocked through targeting one common target, NLRP3 inflammasome. Upon searching for similar drugs that gained FDA-approval in ChEMBL library along with examining their potential blockade of the receptor through docking using CB-DOCK-2, three potential approved drugs can be repurposed, ChEMBL 4297185, ChEMBL 1201749, ChEMBL 1200545 which had binding energy of -9.8 and -9.7 kcal/mol (stronger than the reference inhibitor, -9.3 kcal/mol). Also, ADME profile of the top 3 drugs showed better attributes. Also, the simulated proteins exhibited stable pattern with strong free binding energies. Among the potential inhibitor drugs ChEMBL 4297185 was found to remain inside the binding site of the protein during the 200 ns simulation time. Hence, it is anticipated to have the highest binding and thus inhibition potential against the protein. The suggested drugs, especially ChEMBL 4297185, are potentially repurposable toward treating COVID-19 and varicocele which deserve further experimental validation.

Robotic-assisted versus conventional laparoscopic ICG-fluorescence lymphatic-sparing palomo varicocelectomy: a comparative retrospective study of techniques and outcomes.

PURPOSE: This study aimed to compare techniques and outcomes of robotic-assisted varicocelectomy (RAV) and laparoscopic varicocelectomy (LV). METHODS: The medical records of 40 patients, who received RAV and LV over a 2-year period, were retrospectively analyzed. Palomo lymphatic-sparing varicocelectomy using ICG fluorescence was adopted in all cases. Three 5-mm trocars were placed in LV, whereas four ports, three 8-mm and one 5-mm, were placed in RAV. The spermatic vessels were ligated using clips in LV and ligatures in RAV. The two groups were compared regarding patient baseline and operative outcomes. RESULTS: All patients, with median age of 14 years (range 11-17), had left grade 3 varicocele according to Dubin-Amelar. All were symptomatic and 33/40 (82.5%) presented left testicular hypotrophy. All procedures were completed without conversion. The average operative time was significantly shorter in LV [20 min (range 11-30)] than in RAV [34.5 min (range 30-46)] (p = 0.001). No significant differences regarding analgesic requirement and hospitalization were observed (p = 0.55). At long-term follow-up (30 months), no complications occurred in both groups. The cosmetic outcome was significantly better in LV than RAV at 6-month and 12-month evaluations (p = 0.001). The total cost was significantly lower in LV (1.587,07 €) compared to RAV (5.650,31 €) (p = 0.001). CONCLUSION: RAV can be safely and effectively performed in pediatric patients, with the same excellent outcomes as conventional laparoscopic procedure. Laparoscopy has the advantages of faster surgery, smaller instruments, better cosmesis and lower cost than robotics. To date, laparoscopy remains preferable to robotics to treat pediatric varicocele.

Sperm DNA fragmentation and infertility: a narrative review.

PURPOSE: The purpose of this narrative review is to provide a practical understanding of sperm DNA fragmentation (SDF) in the management of male infertility. METHODS: A search for systematic reviews and meta-analyses (SRMA) on SDF between April 1st, 2018 and April 1st, 2023 was performed using PubMed and articles were selected as per their relevance to the topic. Guidelines from major societies were also reviewed. Three clinical cases are reported and discussed. RESULTS: The search initially identified 80 articles. We selected 13 SRMAs based on their relevance to the topic. Of the 13 SRMAs, 7 evaluated the effect of SDF on assisted reproductive technology (ART) outcomes and recurrent pregnancy loss, 3 studied the effect of varicocele repair on SDF, and 3 evaluated the role of SDF involving lifestyle and environmental health factors including body mass index and male factor treatment strategies. CONCLUSION: Evidence suggests that increased SDF has a negative impact on natural pregnancy and ART outcomes. SDF testing may be particularly important in the infertility evaluation of men with varicoceles, idiopathic or unexplained infertility, recurrent pregnancy loss, or previous ART failure. Further studies are needed on SDF testing and the implications it can have on male factor infertility and pregnancy outcomes as well as its implementation in the setting of ART.

The role of the radiologist in the evaluation of male infertility: recommendations of the European Society of Urogenital Radiology-Scrotal and Penile Imaging Working Group (ESUR-SPIWG) for scrotal imaging.

OBJECTIVES: The Scrotal and Penile Imaging Working Group (SPIWG) of the European Society of Urogenital Radiology (ESUR) aimed to produce recommendations on the role of the radiologist in the evaluation of male infertility focused on scrotal imaging. METHODS: The authors independently performed an extensive literature Medline search and a review of the clinical practice and consensus opinion of experts in the field. RESULTS: Scrotal ultrasound (US) is useful in investigating male infertility. US abnormalities related to abnormal sperm parameters (sperm concentration, total count, motility, and morphology) are low testicular volume (TV), testicular inhomogeneity (TI), cryptorchidism, testicular microlithiasis (TML), high-grade varicocele, bilateral absence of vas deferens, bilateral dilation and echotexture abnormalities of the epididymis. The proposed ESUR-SPIWG recommendations for imaging in the evaluation of male infertility are therefore: to measure TV; investigate TI; perform annual (US) follow-ups up to age 55 in men with a history of cryptorchidism/orchidopexy and/or in men with TML plus "additional risk factors" or with "starry sky" TML; perform scrotal/inguinal US in men with nonpalpable testis; perform scrotal US in men with abnormal sperm parameters to investigate lesions suggestive of tumors; evaluate varicocele in a standardized way; evaluate the presence or absence of vas deferens; investigate the epididymis to detect indirect signs suggesting obstruction and/or inflammation. CONCLUSIONS: The ESUR-SPIWG recommends investigating infertile men with scrotal US focusing on TV, inhomogeneity, localization, varicocele, vas deferens, and epididymal abnormalities. Cryptorchidism, TML, and lesions should be detected in relation to the risk of testicular tumors. CLINICAL RELEVANCE STATEMENT: The ESUR-SPIWG recommendations on scrotal imaging in the assessment of male infertility are useful to standardize the US examination, focus on US abnormalities most associated with abnormal semen parameters in an evidence-based manner, and provide a standardized report to patients. KEY POINTS: So far, ESUR-SPIWG recommendations on scrotal imaging in the assessment of male infertility were not available. The ESUR-SPIWG recommends investigating infertile men with scrotal US focusing on testicular volume, inhomogeneity, localization, varicocele, vas deferens and epididymal abnormalities, and assessing cryptorchidism, testicular microlithiasis and lesions in relation to the risk of testicular tumors. The ESUR-SPIWG recommendations on scrotal imaging in the assessment of male infertility are useful to standardize the US examination, focus on US abnormalities most associated with abnormal sperm parameters in an evidence-based manner, and provide a standardized report to patients.

Impacts of non-coding RNAs in the pathogenesis of varicocele.

Two classes of non-coding RNAs, namely lncRNAs and miRNAs have been reported to be involved in the pathogenesis of varicocele. MIR210HG, MLLT4-AS1, gadd7, and SLC7A11-AS1 are among lncRNAs whose expression has been changed in patients with varicocele in association with the sperm quality. Animal studies have also suggested contribution of NONRATG001060, NONRATG002949, NONRATG013271, NONRATG027523 and NONRATG023747 lncRNAs in this pathology. Meanwhile, expression of some miRNAs, such as miR-210-3p, miR-21, miR-34a, miR-122a, miR-181a, miR-34c and miR-192a has been altered in this condition. Some of these transcripts have the potential to predict the sperm quality. We summarize the impacts of lncRNAs and miRNAs in the pathogenesis of varicocele.

Investigation of sperm hsa-mir-145-5p and MLH1 expressions, seminal oxidative stress and sperm DNA fragmentation in varicocele.

BACKGROUND: Mechanisms by which varicocele causes infertility are not clear and few studies have reported that some miRNAs show expression alterations in men with varicocele. Recently, sperm promoter methylation of MLH1 has been shown to be higher in men diagnosed with varicocele. This study aimed to assess the potential effects of miR-145, which was determined to target MLH1 mRNA in silico on sperm quality and function in varicocele. METHODS: Sperm miR-145 and MLH1 expressions of six infertile men with varicocele (Group 1), nine idiopathic infertile men (Group 2), and nine fertile men (control group) were analyzed by quantitative PCR. Sperm DNA fragmentation was evaluated by TUNEL and the levels of seminal oxidative damage and total antioxidant capacity were analyzed by ELISA. RESULTS: Our results have shown that sperm expression of miR-145 was decreased in Group 1 compared to Group 2 (P = 0.029). MLH1 expression was significantly higher in Group 2 than the controls (P = 0.048). Total antioxidant level and sperm DNA fragmentations of Group 1 and Group 2 were decreased (P = 0.001 and P = 0.011, respectively). Total antioxidant capacity was positively correlated with sperm concentration (ρ = 0.475, P = 0.019), total sperm count (ρ = 0.427, P = 0.037), motility (ρ = 0.716, P < 0.0001) and normal morphological forms (ρ = 0.613, P = 0.001) and negatively correlated with the seminal oxidative damage (ρ=-0.829, P = 0.042) in varicocele patients. CONCLUSION: This is the first study investigating the expressions of sperm miR-145 and MLH1 in varicocele patients. Further studies are needed to clarify the potential effect of miR-145 on male fertility.

Chlorogenic acid can improve spermatogenic dysfunction in rats with varicocele by regulating mitochondrial homeostasis and inhibiting the activation of NLRP3 inflammasomes by oxidative mitochondrial DNA and cGAS/STING pathway.

In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.

Successful pregnancy and delivery following microdissection testicular sperm extraction and intracytoplasmic sperm injection for non-obstructive azoospermia after microsurgical varicocelectomy: A case report and review of the literature.

Although surgical varicocele treatment is generally considered to result in improved reproductive outcomes, we encountered a rare case of postoperative azoospermia in an infertile male patient who underwent microsurgical varicocelectomy for a palpable left-sided varicocele with concomitant cryptozoospermia. More than 1 year after varicocelectomy, the patient still had not recovered from azoospermia. Thereafter, he underwent microdissection testicular sperm extraction (micro-TESE), allowing him and his partner to obtain one good quality blastocyst via intracytoplasmic sperm injection following oocyte retrievals. Finally, the couple had a successful pregnancy following a frozen embryo transfer, and a live male infant was subsequently delivered to them at 39 weeks and 5 days. In cases of severe testicular dysfunction, varicocelectomy may worsen the postoperative semen parameters until azoospermia. Therefore, it is important to consider preoperative sperm cryopreservation and to explore the possibility of subsequent TESE.

Significant reduction in left testicular volume shown by ultrasonography in infertile patients with left-side grade 2-3 varicocele as compared to less than grade 2: An evidence for indication of varicocelectomy.

PURPOSE: Testicular volume (TV) is known to be one of the main parameters for testicular function (TF). This study was conducted to re-evaluate the indications of a varicocelectomy based on a survey of preoperative TV results in left-side varicocele patients considered to reflect the detrimental effects of a varicocele on TF. METHODS: TV results of infertile patients determined using ultrasonography by a single expert physician were retrospectively evaluated. RESULTS: Of 590 examined patients, 424 had no varicocele findings (Group A), while 148 had a left-side varicocele (Group B). Group B was subdivided based on varicocele grade into Group B0 (subclinical), B1 (grade 1), B2 (grade 2), and B3 (grade 3). Comparisons of left-side TV showed no significant differences for grade among Group A, B0, and B1, whereas that for Group B2 and B3 was significantly lower as compared with Group A (p < 0.01, 0.02, respectively). The median TV of Group B I (composed of Groups B0 and B1) was 9.8 cm3, while that of Group B II (Groups B2 and B3) was significantly lower at 8.4 cm3 (p < 0.05). In contrast, a comparison of right TV values identified no significant differences among the groups (p = 0.918). CONCLUSION: A varicocelectomy should be performed for patients with a grade 2 and 3 varicocele for ameliorating testicular function.

Association between left-sided varicocele and epididymo-orchitis with sonographic findings.

OBJECTIVE: The aim of this study was to investigate the relationship between left-sided varicocele and epididymitis or epididymo-orchitis. MATERIALS AND METHODS: The study included 72 patients with left side epididymitis (EP) or epididymo-orchitis (EPO) (Group 1) and a control group of 72 patients without EP or EPO (Group 2). Those with right EP-EPO were excluded due to possible other underlying retroperitoneal pathologies causing varicocele. Groups were evaluated for presence of left side varicocele, varicocele grade and pampiniform plexus vein diameter. RESULTS: The average age was 38 ± 8.4 years (range, 18-50 years) in Group 1, and 36 ± 9.1 years (range, 16-47 years) in Group 2. Varicocele was significantly more common in patients with EP or EPO (p < 0.001). The rate of varicocele was 66.7% (48/72) in Group 1, and 22.3% (16/72) in Group 2. The median grade of varicocele was 2 in Group 1, and 0 in Group 2. Pampiniform plexus vein diameters were found to be significantly larger in patients with EP or EPO compare to patients without EP and EPO. The median vein diameter was 3.3 mm with the 25th and 75th percentiles at 2.7 and 3.8 mm, and was 1.9 mm with the 25th and 75th percentiles at 1.7 and 2.3 mm, respectively (p < 0.001). CONCLUSIONS: Left-sided varicocele was significantly more common in patients with EP or EPO and it is an important cause for the development of EP/EPO because of chronic venous stasis.

Video-Assisted Telescope Operating Monitor 3D System in Microsurgical Varicocelectomy: A Preliminary Report.

INTRODUCTION: Video-assisted telescope operating monitor (VITOM®) with 3D Visualization technology was developed and has been used with favorable results by several surgical specialties. Our study aims to be a preliminary report for initial experience using the VITOM® 3D system for microsurgical varicocelectomy on varicocele patients. METHODS: We performed 35 microsurgical varicocelectomy procedures using the VITOM® 3D system on varying types and grades of varicoceles. The surgeon had the option of using either a 2.5 or 3.5 magnifying loupe in addition to the exoscope for each operation evaluated. The exoscope is a standalone camera head with an integrated 3D telescope and remote control with zoom and focus functions. It is connected to the 3D monitor via a mechanical holding arm. During the procedure, surgeons, assistants, and observers were able to view the 3D high-definition stream displayed on a 26-inch 3D monitor at a convenient viewing angle and distance. The varicocele ligation was performed using a Carl Zeiss Meditec AG microscope. RESULTS: There were 35 patients with varicocele aged 31.51 years old on average, which were included in this report. Most patients had grade 3 bilateral varicocele (n = 13, 37.1%). All procedures were performed without any intraoperative complications. After the procedures, only a few patients suffered from postoperative complications. Three patients suffered scrotal edema (8.6%), while another had hydrocele (2.9%). The postoperative pain results were also very minimal from .89 1 day after the operation to .26 3 days after the operation. CONCLUSION: The VITOM® 3D system showed promise in microsurgical varicocelectomy.

Clinical application and nursing experience of the plan-do-check-act cycle in daytime varicocelectomy.

BACKGROUND: Varicocele is the most prevalent correctable cause of male infertility. Currently, surgical treatment is the primary method to enhance fertility.For many young varicocele patients who have postponed surgery due to time constraints, daytime surgery is especially crucial. Thus, this study aims to investigate the clinical and nursing application value of the Plan-Do-Check-Act (PDCA) cycle in daytime varicocelectomy. METHODS: Retrospective collection of clinical data was conducted on 130 patients undergoing laparoscopic varicocelectomy in the Third Affiliated Hospital of Southern Medical University, Guangzhou,China.Among them, 65 patients who underwent daytime surgery were assigned to the observation group, while 65 patients who underwent routine hospital surgeries were assigned to the control group.The former also implemented PDCA cycle management.A comparison was made between the two groups regarding hospitalization time, hospitalization costs, and patient satisfaction. RESULTS: The observation group exhibited a shorter hospitalization time and lower hospitalization costs compared to the control group, with higher patient satisfaction and pre-discharge visual analog scale (VAS) scores noted (P < 0.05).No significant difference was observed in the incidence of postoperative complications between the two groups during hospitalization (P > 0.05). The implementation of the PDCA cycle in the observation group has demonstrated its effectiveness, ensuring the smooth conduct of the daytime varicocelectomy. CONCLUSION: In conclusion,daytime varicocelectomy can reduce hospitalization time,lower hospitalization costs, improve patient satisfaction. The PDCA Cycle enhances the rationality and efficacy of the daytime varicocelectomy procedure and is highly recommended. Furthermore, it offers valuable reference for the application of the PDCA Cycle in various other diseases and nursing management approaches. TRIAL REGISTRATION: The Trial Registration Number: ChiCTR2300077465;Date of registration: November 9, 2023.

[Construction of a predictive model for postoperative pain relief after microscopic spermatic cord surgery for spermatic cord pain].

OBJECTIVE: To explore the relevant factors affecting the efficacy of microscopic spermatic cord surgery and build a predictive model for postoperative pain relief. METHODS: A retrospective analysis was conducted on the clinical data of 324 patients with spermatic cord pain who visited the Department of Urology at Peking University People's Hospital between October 2015 and April 2023. This cohort included 212 patients with varicocele-related spermatic cord pain and 112 patients with idiopathic spermatic cord pain. All the patients underwent microsurgical procedures: varicocele-related pain was treated with microsurgical varicocelectomy, and idiopathic pain was treated with microsurgical denervation of the spermatic cord. The patients were categorized into effective and ineffective groups based on whether their pain had decreased by more than 50% six months post-surgery compared with pre-surgery levels. Baseline data were preliminarily screened for clinical indicators using t tests and univariate analysis. Clinical predictor variables [age, duration of pain, diameter of varicocele, patient health questionnaire-9 (PHQ-9) score, generalized anxiety disorder-7 (GAD-7) score] were selected using Lasso regression. A clinical prediction model for effective pain relief following microscopic spermatic cord surgery was constructed using Logistic regression and presented as a nomogram. The model's internal validation was performed using the bootstrap method. Its predictive power and clinical utility were evaluated through the concor-dance index, the area under the receiver operating characteristic curve, and calibration plots. RESULTS: Post-microscopic varicocele ligation, 156 patients (73.58%) experienced significant pain relief, as did 94 patients (83.93%) following microscopic denervation. Independent predictors for postoperative outcomes included age, PHQ-9 score, GAD-7 score, chronic pain duration, and varicocele diameter, differing slightly between varicocele-related and idiopathic pain groups. The models demonstrated excellent predictive ability, with areas under the curve of 0.909 and 0.913 for varicocele and idiopathic groups, respectively, and high concordance indices. CONCLUSION: The postoperative efficacy prediction model based on age, pain duration, PHQ-9 score, GAD-7 score, and varicocele diameter has good predictive ability and clinical applicability, and can be used in clinical practice.

Role of varicocele repair in the era of assisted reproductive technologies: Lessons from 2000 cases of microsurgical varicocele repair.

Backgrounds: In an era of advanced maternal age, there is less conclusive evidence regarding the treatment outcomes of varicocele repair for assisted reproductive technology (ART). Progress in basic research on varicocele is notable whereas there are many clinically relevant points to discuss. Methods: Based on our experience with more than 2000 cases of microsurgical varicocele repair, we focused on the effectiveness of varicocele repair, pathophysiology, surgical approaches, contributions to ART, sperm DNA fragmentation, and varicocele-associated azoospermia in this review with the aim of identifying clearer directions for basic and clinical research on varicocele. Results: Microsurgical low ligation for varicocele repair is expected to remain the gold standard for surgical therapy. Based on the findings from a number of systematic reviews and meta-analyses, negative opinions regarding the efficacy of microsurgical varicocele repair in male infertility treatment have become virtually nonexistent. However, the majority of evidence regarding surgical indications and effectiveness pertains to improvements in semen parameters or non-ART pregnancy rates. Conclusions: Further understandings regarding to pathophysiology of varicocele will likely be gained through comprehensive genetic, transcriptomic, and epigenetic analyses using blood and testicular samples from humans and we hope to develop new diagnostic methods and pharmacotherapy.

Prospective Randomized Controlled Trial Comparing Laparoscopic Palomo Surgery vs Scrotal Antegrade Sclerotherapy in Adolescent Varicocele.

PURPOSE: Varicocele is a common condition in adolescence and the most common correctable cause of infertility. This study aimed to analyze and compare the outcomes of scrotal antegrade sclerotherapy and laparoscopic Palomo surgery in a tertiary referral center. MATERIALS AND METHODS: Patients with left grade 3 varicocele indicated for surgery were prospectively enrolled and randomly allocated to the scrotal antegrade sclerotherapy and laparoscopic Palomo surgery groups, with their respective contralateral normal testes taken as controls. The primary outcome measures were clinical varicocele recurrence, testicular catch-up growth, and postoperative hydrocele. All patients were evaluated clinically and using Doppler ultrasound by radiologists. RESULTS: From 2015 to 2020, 113 patients completed the study and were statistically analyzed (scrotal antegrade sclerotherapy, n = 57; laparoscopic Palomo surgery, n = 56). All patients had significantly smaller testes preoperatively; the testicular volume differences with control testes were -23% in scrotal antegrade sclerotherapy and -19% in laparoscopic Palomo surgery. At 12-month follow-up, there were no statistically significant differences in clinical recurrences between the 2 groups (scrotal antegrade sclerotherapy = 5.3% vs laparoscopic Palomo surgery = 5.4%, P > .05, noninferiority test). Testicular catch-up growths were observed in both groups; the mean testicular volume difference between the treatment and control testes decreased from -23% to -8.1% in scrotal antegrade sclerotherapy (P < .001) and from -19% to -9.3% in laparoscopic Palomo surgery (P < .001) at 12-month follow-up. There was no postoperative hydrocele in the scrotal antegrade sclerotherapy group compared to 7 cases in the laparoscopic Palomo surgery group (0% vs 13%, P = .006). CONCLUSIONS: Both scrotal antegrade sclerotherapy and laparoscopic Palomo surgery are safe and effective procedures for treatment of adolescent varicocele with significant positive effect on testicular catch-up growth. Scrotal antegrade sclerotherapy is not inferior to laparoscopic Palomo surgery in terms of clinical recurrence rate and has significantly less postoperative hydrocele.

Apelin is found in human sperm and testis and is raised in inflammatory pathological conditions.

Apelin/APJ receptor (R) is involved in many oxidative stress-induced pathological conditions. Since this system is not yet explored in male reproduction, we studied apelin/APJ-R in human semen and testis. Semen of 41 infertile patients with varicocele, genitourinary infections, unexplained infertility and 12 fertile men was analysed (WHO guidelines, 2021). Apelin was quantified by ELISA in seminal fluid and spermatozoa, interleukin (IL)-1ß in seminal fluid. Apelin/APJ-R were immunolocalized in spermatozoa and testis. Apelin was present in spermatozoa and its levels were negatively correlated with normal sperm morphology% (r = -0.857; p < 0.001), and positively with IL-1ß levels (r = 0.455; p < 0.001). Apelin and IL-1ß concentrations were increased in patients' samples with varicocele (apelin p < 0.01; IL-1ß p < 0.05) and infections (apelin p < 0.01; IL-1ß p < 0.001). By logistic regression analysis, apelin (OR 1.310; p = 0.011) and IL-1ß (OR 1.572; p = 0.005) were predictors of inflammatory diseases (varicocele, infections). Apelin and APJ-R immunofluorescence labels were weak in sperm tail of fertile men and intense along tail, cytoplasmic residues and post-acrosomal sheath of sperm from infertile men. In testis, apelin and APJ-R labels were evident in Leydig cells and weak inside the seminiferous tubule. Apelin/APJ-R system is present in human spermatozoa and testicular tissue and probably involved in human fertility.

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.

Postvaricocele Embolization Pain Syndrome: A Case Series Report and Review of Current Treatment Strategies.

BACKGROUND: Orchialgia is not an uncommon complaint among men with varicocele, but postvaricocele embolization-related testicular pain has not been widely investigated. This study evaluates the phenomenon of postvaricocele embolization pain (PVEP) syndrome and examines the current strategies to treat this unusual complication. METHODS AND MATERIALS: A prospectively collected database of patients with PVEP who presented to a tertiary center was analyzed between January 2011 and January 2020 following internal ethics approval. Patient demographics, including other complications related to embolization, analgesic requirements, and pain scores (on a 10-point visual analog score), treatment strategies, Patient Global Impression of Improvement (PGI-I) score and overall satisfaction score (on a 5-point scale), were reviewed. All patients were reviewed for a minimum of 12 months. RESULTS: A total of 20 men with a mean age of 33.8 (18-45) years old, presented with PVEP over 10 years. Most men received embolization on an average of 26.6 (18-48) months. The reasons for varicocele embolization include either isolated or combined orchialgia (15 men), subfertility (5 men), and cosmesis (6 men). Eighteen (90%) men underwent microscopic spermatic cord denervation (MSCD) and 2 patients elected for conservative measures. The average pain scores pre-MSCD and post-MSCD were 6.9 (4-9) and 1.4 (0-4) (p<0.001) with a significant reduction in analgesia requirements. Immediate improvement in pain score was reported in all the patients and this persisted at the 12 months review. Most men reported a high satisfaction score (of 4/5) and only one patient reported no change in symptoms after MSCD. CONCLUSION: PVEP is a unique complication and patients should be counseled on the potential risk of persistent orchialgia following embolization for varicocele. The MSCD appears to be an effective treatment option with high success and satisfaction rates.

Ergothioneine attenuates varicocele-induced testicular damage by upregulating HSP90AA1 in rats.

This study investigates the therapeutic effect and the underlying mechanisms of ergothioneine (EGT) on the testicular damage caused by varicocele (VC) in vivo, in vitro, and in silico. This preclinical study combines a series of biological experiments and network pharmacology analyses. A total of 18 Sprague Dawley (SD) male rats were randomly and averagely divided into three groups: the sham-operated, VC model, and VC model with EGT treatment (VC + EGT) groups. The left renal vein of the VC model and the VC + EGT groups were half-ligated for 4 weeks. Meanwhile, the VC + EGT group was intragastrically administrated with EGT (10 mg/kg). GC1 and GC2 cells were exposed to H2 O2 with or without EGT treatment to re-verify the conclusion. The structure disorder of seminiferous tubules ameliorated the apoptosis decrease in the VC rats receiving EGT. EGT can also increase the sperm quality of the VC model rats (p < 0.05). The exposure to H2 O2 decreased proliferation and increased apoptosis of GC1 and GC2 cells, which was revisable by adding EGT to the plates (p < 0.05). The network pharmacology and molecular docking were conducted to explore the potential targets of EGT in VC, and HSP90AA1 was identified as the pivotal gene, which was validated by western blot, immunohistochemistry, and RT-qPCR both in vivo and in vitro (p < 0.05). Overall, EGT attenuates the testicular injury in the VC model both in vivo and in vitro by potentially potentiating the expression of HSP90AA1.