Testicular volume is a noninvasive predictor of sperm retrieval failure in idiopathic nonobstructive azoospermia.

ABSTRACT: We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia (iNOA). We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction. The Chi-square test and Mann-Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons. A logistic regression analysis was conducted to identify predictors of retrieval failure. Area under the receiver operating characteristic curve for each variable was evaluated, and the net clinical benefit was calculated using a clinical decision curve. Patients with iNOA had a lower sperm retrieval rate than those with known causes. Moreover, testicular volume was an independent factor affecting sperm extraction outcomes (odds ratio = 0.79, P < 0.05). The testicular volume cut-off value was 6.5 ml (area under the curve: 0.694). The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed. The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution. There was also a significant association between a uniform tubule distribution and testicular volume. In conclusion, a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.

Comparative evaluation of double- and single-armed two-suture longitudinal intussusception techniques in microsurgical vasoepididymostomy: An updated systematic review and meta-analysis.

BACKGROUND: This study aimed to compare the outcomes of double-armed two-suture longitudinal intussusception microsurgical vasoepididymostomy (LIVE) and single-armed two-suture LIVE techniques in patients with epididymal obstructive azoospermia (EOA). The main outcomes assessed were patency rates, patency time, semen quality and natural pregnancy rates. METHODS: Data from patients with EOA who underwent two-suture LIVE were obtained from databases including PubMed, EMBASE, and Web of Science. Weighted data were analyzed using a random-effects model, and weighted mean differences were reported. RESULTS: A total of 1574 patients with EOA from 24 studies were included. The overall patency rate was approximately 68% (95% confidence interval [CI]: 63-72%), with a patency time of approximately 4.63 months (95% CI: 4.15-5.12). The sperm concentration reached 26.90 million/ml and the sperm motility was 23.74%. The natural pregnancy rate was 38% (95% CI: 31-46%). The different definitions of patency do not seem to have any meaningful impact when comparing patency rates. There was no significant difference in patency rates, patency time, semen quality and natural pregnancy rates between the double-armed and single-armed LIVE techniques. CONCLUSION: The single-armed LIVE is a potential alternative surgical option when high quality double-needle sutures are not easily accessible.

Efficacy of various surgical approaches in treating hematospermia using transurethral seminal vesiculoscopy.

PURPOSE: To explore the efficacy of different approaches of seminal vesiculoscopy surgery and the predictive factors of good treatment outcome. MATERIALS AND METHODS: A retrospective analysis of 68 patients who underwent seminal vesiculoscopy for hematospermia in our hospital from January 2015 to January 2021. According to different surgical approaches, they were divided into three groups: natural ejaculatory ducts (method A, 45 cases), assisted transurethral resection/incision of ejaculatory ducts (method B, 14 cases), fenestration in prostatic utricle (method C, 9 cases). We analyzed the recurrence rate of the three surgical approaches and the predictive factors of treatment efficacy. RESULTS: The total recurrence rate after the seminal vesiculoscopy for hematospermia in this group was 32.35%. The postoperative recurrence rates of the three methods were 24.44% for method A, 50.00% for method B and 44.44% for method C, and there was no significant difference among the three methods (P > 0.05). The data of five predictors of 45 cases in method A group were included in the Univariate Logistic analysis, the results suggest that whether complicated with seminal tract stones/cysts was an effective predictor (OR 0.250, P = 0.022), which was still an effective predictor in the Multivariate Logistic analysis model (OR 0.244, P = 0.010). CONCLUSIONS: The Transurethral seminal vesiculoscopy technique demonstrates a low postoperative recurrence rate in treating hematospermia. Among the various approaches, the intraoperative use of natural orifices through the ejaculatory duct exhibits the lowest recurrence rate. Additionally, seminal tract stones/cysts effectively predict favorable postoperative outcomes.

TENT5D disruption causes oligoasthenoteratozoospermia and male infertility.

BACKGROUND: Oligoasthenoteratozoospermia (OAT) is one of the most complex aggregators of male gametic problems. However, the genetic etiology of OAT is still largely unknown. OBJECTIVES: To reveal the new genetic factors responsible for male infertility owning to OAT and reveal the outcomes of the affected patients from intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: Two infertile men with typical OAT were recruited in 2018 and retrospected a cohort that included 47 patients with OAT from 2013 to 2021. Fifty healthy men with proven fertility served as control subjects. To identify the novel pathogenic variants, whole-exome sequencing and Sanger sequencing were used. In silico analysis revealed the affecting of the variants. Field emission scanning electron microscopy was employed to observe the morphological defects of the spermatozoa. Immunofluorescence was used to analyze the expression and localization of the related protein. CRISPR/Cas9 was used to generate the mouse model. ICSI was used as a treatment for the patients and to assess the effects of the pathogenic variant on fertilization and embryo development. RESULTS: We identified a loss-of-function mutation NM_001170574.2:c.823G > T (p.Glu275*) in X-linked TENT5D from two patients with OAT. This variant is highly deleterious and has not been found in the human population. The count of patients' spermatozoa is dramatically decreased and displays multiple morphologic abnormalities with poor motility. Tent5d knockout mice are infertile and exhibit parallel defects. ICSI could rescue the infertility of the Tent5d knockout male mice. Moreover, the proband was treated with ICSI and achieved a successful pregnancy outcome for the first time. Subsequent mutation screening identified no TENT5D mutations among 47 additional patients with OAT and 50 control subjects. CONCLUSION: Mutation in TENT5D results in OAT and male infertility, and this terrible situation could be rescued by ICSI.

Discontinuation Rates of Tadalafil Alone and in Combination with a-Blockers in the Treatment of Male Lower Urinary Tract Symptoms with or without Coexisting Erectile Dysfunction: A Systematic Review and Meta-Analysis.

Purpose: We examined the discontinuation rates of tadalafil alone and in combination with a-blockers (ABs) for the treatment of male lower urinary tract symptoms (LUTS), with or without erectile dysfunction (ED). Materials and Methods: We searched the EMBASE, PubMed, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases for studies published until May 15, 2022. The discontinuation rates associated with LUTS medications were subsequently analyzed by meta-analysis. Results: Forty-four studies, including 1724 discontinued patients, were included. The combined discontinuation rate was 12.78% (95% confidence interval (CI) 9.89-15.98%), and the discontinuation rates because of adverse events and lack of efficacy were 4.56% (95% CI 3.39-5.90%) and 3.30% (95% CI 1.53-5.72%), respectively. Conclusions: The discontinuation rate of tadalafil alone or in combination with ABs for LUTS with or without ED was relatively low and varied according to the study type. Patients receiving monotherapy or combination therapy were similarly likely to abandon treatment. Treatment with a fixed-dose combination was associated with better persistence than with a free-dose combination. These data may help guide clinicians in selecting drug regimens when making decisions. Factors associated with treatment withdrawal need to be determined through high-quality clinical studies to reduce the drug discontinuation rate, which will ultimately reduce healthcare costs and improve patient outcomes.

Silencing CAMK2D Promotes the Proliferation of Spermatogonia in the Testis of Experimental Varicocele Rats.

Varicocele is regarded as the main factor that contributes to male infertility. This study aimed to explore the effect of CAMK2D on spermatogonia in the testis of experimental varicocele rats. The experimental varicocele model was established in rats and treated using different ligation methods. mRNA expression profile analysis was performed on the left testicular tissue isolated from different groups, and differentially expressed genes (DEGs) were analysed by bioinformatics methods and identified by qRT-PCR. The effect of CAMK2D, the screened DEG, on the proliferation of spermatogonia was evaluated by CCK-8 assay. The expression level of the c-kit was measured by the immunofluorescence assay and the expression levels of CAMKII, FOXO1, and ß-catenin were detected by qRT-PCR and western blotting. Five DEGs (i.e., TMCC3, FLNB, CAMK2D, OPLAH, and EGR1) were screened using the comprehensive analysis of mRNA high-throughput sequencing data. TMCC3 and FLNB were significantly downregulated, and CAMK2D, OPLAH, and EGR1 were dramatically upregulated in the testicular tissue of varicocele rats. The target DEG CAMK2D was obtained through identification by using qRT-PCR. In vitro assays revealed that the proliferation of spermatogonia was significantly facilitated by the silencing of CAMK2D, which resulted in the downregulation of CAMKII, FOXO1, and ß-catenin. In conclusion, silencing CAMK2D facilitated the proliferation of spermatogonia in the testis of experimental varicocele rats.

Intercellular transfer of P-glycoprotein mediates the formation of stable multi-drug resistance in human bladder cancer BIU-87 cells.

We investigated the biological characteristics of acquired drug-resistant cells (AqMDRs) formed by intercellular P-glycoprotein (P-gp) transfer and whether AqMDRs can form stable drug-resistant strains. Drug-sensitive BIU-87 cells were co-cultured with doxorubicin (DOX)-resistant derivative BIU-87/DOX cells in transwell chambers for up to 96 h. The presence of P-gp in recipient cell membranes (AqMDRs) was detected by confocal microscopy, CCK-8, western blot, and RT-PCR were used to detect resistance index (RI), P-gp expression and MDR1 mRNA expression in AqMDRs after 0, 4, 8, 16, and 20 passages and frozen/resuscitated twentieth generation AqMDRs. There was an increase in P-gp transfer with longer co-culture times of drug-resistant and sensitive strains. Without DOX, although the AqMDR numbers increased with each passage, the RI and P-gp expression decreased gradually, and the expression level of MDR1 mRNA did not change significantly. With DOX, the RI and P-gp expression increased slightly, and the MDR1 mRNA expression level gradually increased to the BIU-87/DOX level. AqMDRs can grow stably at drug concentrations slightly higher than the IC50 of sensitive strains, which sensitive strains cannot survive. P-gp transfer between cells gradually increases with longer co-culturing of drug-resistant and sensitive strains. The drug resistance of AqMDRs decreases without drug intervention, but with drug intervention, cells can maintain resistance and gradually develop into stable drug-resistant cells. This article has an associated First Person interview with the first author of the paper.

The role of TSG-6 and uroplakin III in bladder pain syndrome/ interstitial cystitis in rats and humans.

OBJECTIVES: We investigated the relationship between the expression of tumor necrosis factor-inducible gene 6 (TSG-6) with inflammation and integrity of the bladder epithelium in the bladder tissues of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and the mechanism of action using a rat model of BPS/IC. MATERIALS AND METHODS: Expression of TSG-6 and uroplakin III was determined by immuno- histochemistry of bladder biopsy samples from control human subjects and patients with verified BPS/IC. Our rat model of BPS/IC was employed to measure the perfusion of bladders with hyaluronidase, and assessment of the effect of TSG-6 administration on disease progression. Treatment effects were assessed by measurement of metabolic characteristics, RT-PCR of TGR-6 and interleukin-6, bladder histomorphology, and immunohistochemistry of TGR-6 and uroplakin III. RESULTS: The bladders of patients with BPS/IC had lower expression of uroplakin III and higher expression of TSG-6 than controls. Rats treated with hyaluronidase for 1 week developed the typical signs and symptoms of BPS/IC, and rats treated with hyaluronidase for 4 weeks had more serious disease. Administration of TSG-6 reversed the effects of hyaluronidase and protected against disease progression. CONCLUSION: Our results indicate that TSG-6 plays an important role in maintaining the integrity of the bladder epithelial barrier.

[Expressions of interleukin-17 and interleukin-8 in the prostatic tissue of the patients with BPH or BPH with inflammation].

OBJECTIVE: To investigate the expressions of interleukin-17 (IL-17) and interleukin-8 (IL-8) in benign prostatic hyperplasia (BPH) and BPH complicated with histological inflammation and their significance. METHODS: According to the results of HE staining, we divided 60 cases of BPH treated by transurethral resection of the prostate (TURP) into a BPH group (n = 23) and a BPH with inflammation group (n = 37). We analyzed the clinical data of the patients and determined the mRNA and protein expressions of IL-17 and IL-8 by immunohistochemistry, real-time fluorescence quantitative PCR, and Western blot, respectively. RESULTS: Compared with the BPH patients complicated with inflammation, the BPH group showed significantly lower International Prostate Symptom Score (IPSS) (29.1 ± 6.2 vs 21.6 ± 3.7), quality of life score (QoL) (5.4 ± 1.3 vs 4.4 ± 1.6), postvoid residual urine volume (RUV) (ï¼»198.6 ± 15.5ï¼½ vs ï¼»98.2 ± 19.3ï¼½ ml), prostate volume (ï¼»69.2 ± 24.1ï¼½ vs ï¼»49.8 ± 16.5ï¼½ ml), PSA level (ï¼»7.4 ± 1.9ï¼½ vs ï¼»2.8 ± 0.8ï¼½ µg/L) and serum c-reactive protein content (CRP) (ï¼»5.1±2.0ï¼½ vs ï¼»1.5±0.6ï¼½ mg/L), but a higher maximum urine flow rate (Qmax) (ï¼»4.7 ± 2.1ï¼½ vs ï¼»8.2 ± 1.8ï¼½ ml/s) (all P<0.05). The former group had a significantly higher incidence rate of urinary retention than the latter (32.4% ï¼»12/37ï¼½ vs 8.69% ï¼»2/23ï¼½), mRNA expressions of IL-17 (0.303 ± 0.076 vs 0.042 ± 0.019) and IL-8 (0.536 ± 0.059 vs 0.108 ± 0.025), and protein expressions of IL-17 (0.88 ± 0.10 vs 0.34 ± 0.05) and IL-8 (1.07 ± 0.08 vs 0.43 ± 0.04) (all P<0.05). CONCLUSIONS: The expressions of IL-17 and IL-8 are upregulated in the prostatic tissue of the BPH patients with inflammation, which may play a significant role in the development and progression of BPH.