Factors affecting patency time and semen quality in a single-armed microsurgical vasoepididymostomy.

ABSTRACT: Although microsurgical vasoepididymostomy (MVE) is an effective treatment for epididymal obstructive azoospermia, some patients may experience delayed patency or suboptimal semen parameters after patency. However, research into patency time, semen quality postpatency, and associated influencing factors remains limited. This study aimed to address these issues by evaluating 181 patients who underwent at least one-sided MVE employing asingle-armed longitudinal intussusception vasoepididymostomy technique, with a follow-up period of over 12 months for 150 patients. The overall patency rate was 75.3%, with 86.0% of patients achieving patency within 6 months following MVE. Unexpectedly, factors such as age, history of epididymitis, duration of surgery, side of anastomosis, sperm motility in epididymal fluid, and the site of anastomosis showed no correlation with patency time. Nonetheless, our univariate and multivariate linear regression analysis indicated that only the site of anastomosis was positively correlated with and could independently predict postoperative total motile sperm count. Therefore, the site of anastomosis might serve as a predictor for optimal postoperative semen quality following the MVE procedure.

Comparison of clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with or without concurrent vas-deferens obstruction.

BACKGROUND: Microsurgical vasoepididymostomy is an effective surgical method for treating epididymal obstructive azoospermia but the surgical outcomes can be affected in some non-vasectomized epididymal obstructive azoospermia patients with concurrent vas-deferens obstruction. This study aimed to explore the clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with versus without concurrent vas-deferens obstruction. STUDY DESIGN: Retrospective study. OBJECTIVE: To explore the clinical characteristics and surgical outcomes in non-vasectomized epididymal obstructive azoospermia patients with versus without concurrent vas-deferens obstruction, aiming to identify predictive factors for concurrent vas-deferens obstruction and evaluate the efficacy of microsurgical vasoepididymostomy in patients with epididymal obstructive azoospermia and concurrent short-segment vas-deferens obstruction. MATERIALS AND METHODS: A retrospective analysis of 225 epididymal obstructive azoospermia cases was conducted at the First Affiliated Hospital of Fujian Medical University from November 2016 to March 2023. All patients underwent a comprehensive preoperative evaluation. During surgery, the vas deferens were assessed to determine the presence and extent of obstruction. Depending on the obstruction length, either a standard microsurgical vasoepididymostomy was performed, or the obstructed segment was resected followed by microsurgical vasoepididymostomy. If the remaining length post-resection was insufficient for anastomosis, the procedure was discontinued. Data on patient clinical characteristics, operative findings, and outcomes were collected and analyzed. Logistic regression was used to identify predictive factors for concurrent vas-deferens obstruction, and comparative analysis assessed patency and pregnancy rates between patients with and without concurrent vas-deferens obstruction. RESULTS: Of the 225 patients in the study, 77 (34.22%) presented with epididymal obstructive azoospermia and concurrent vas-deferens obstruction. Logistic regression analysis revealed that "the history of epididymitis" was a significant predictive factor for epididymal obstructive azoospermia patients with concurrent vas-deferens obstruction (odds ratio = 9.06, p < 0.001). The average length of vas deferens obstruction amenable to microsurgical vasoepididymostomy post-resection was 1.31 ± 0.54 cm (range from 0.50 to 2.50 cm). In contrast, cases unsuitable for microsurgical vasoepididymostomy presented an average obstruction length of 15.26 ± 5.79 cm (p < 0.001). The patency rates were 82.17% in epididymal obstructive azoospermia patients without concurrent vas-deferens obstruction and 74.14% in those with concurrent vas-deferens obstruction. The pregnancy rates followed a similar trend, at 34.11% and 34.48%, respectively. These differences were not statistically significant (p > 0.05 for both). However, epididymal obstructive azoospermia patients with vas-deferens obstruction exhibited a decreased likelihood of bilateral microsurgical vasoepididymostomy (p < 0.001). DISCUSSION AND CONCLUSION: Our study identifies a noticeable occurrence of concurrent vas-deferens obstruction in non-vasectomized epididymal obstructive azoospermia patients, with approximately one-third of the cases (34.22%) exhibiting vas-deferens obstruction during surgical interventions. Notably, a small fraction (6.67%) of these individuals chose not to proceed with any microsurgical vasoepididymostomy, even on one side, due to the extensive length of the obstruction. Through logistic analysis, we have demonstrated that "the history of epididymitis" is a critical predictive factor for the presence of vas-deferens obstruction, underscoring its significance in preoperative evaluations. Furthermore, our research confirms that microsurgical vasoepididymostomy is still an effective treatment for epididymal obstructive azoospermia patients with concurrent short-segment vas-deferens obstruction, achieving significant patency and favorable pregnancy rates compared to those patients without vas-deferens obstruction. These insights are pivotal for enhancing surgical strategies and improving fertility outcomes in this patient cohort.

Novel mutations in LRRC23 cause asthenozoospermia in a nonconsanguineous family.

ABSTRACT: The cause of asthenozoospermia (AZS) is not well understood because of its complexity and heterogeneity. Although some gene mutations have been identified as contributing factors, they are only responsible for a small number of cases. Radial spokes (RSs) are critical for adenosine triphosphate-driven flagellar beating and axoneme stability, which is essential for flagellum motility. In this study, we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23 ( LRRC23 ; c.1018C>T: p.Q340X and c.881_897 Del: p.R295Gfs*32) in a proband from a nonconsanguineous family with AZS and male infertility. Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology. Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella. Additionally, transmission electron microscopy showed the absence of RS3 in sperm flagella, which disrupts stability of the radial spoke complex and impairs motility. Following in vitro fertilization and embryo transfer, the proband's spouse achieved successful pregnancy and delivered a healthy baby. In conclusion, our study indicates that two novel mutations in LRRC23 are associated with AZS, but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Association between anti-Müllerian hormone concentrations and sperm retrieval outcomes in patients with idiopathic nonobstructive azoospermia: a systematic review and meta-analysis.

ABSTRACT: Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%-46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: -2.70; 95% CI: -3.94--1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies 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.

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

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.

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.

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.

Geographic and position-based variations in phyllospheric bacterial communities present on flue-cured tobacco.

Although tobacco leaves (TLs) contain abundant bacteria, how the geography and leaf position of TLs affect these bacteria is unclear. Here, TLs at different positions from Henan (HN, strong flavor style) and Yunnan (YN, fresh flavor style) provinces were collected, and the bacteria were characterized by Illumina sequencing at harvest and 1 year of storage. Bacterial communities were very different between TLs originating from different geographical areas and positions, and beta diversity analysis showed that leaf position was the most important factor for phyllospheric bacterial communities, followed by geographical area and storage time. At the genus level, Subdoligranulum, Thermus, and Acinetobacter were obviously more abundant in HN than in YN, while Blautia and Ruminococcus were significantly more abundant in YN. These differences in bacterial communities decreased after 1 year of storage, indicating that the microbiota tends to become similar during tobacco processing. Storage time also affected the phyllospheric bacteria of TLs, as the bacterial communities shifted significantly on both HN and YN TLs after 1 year of storage. Significant differences in the predicted genes were also observed between the different geographic locations and leaf positions. Potential human pathogens, including Acinetobacter, Methylobacterium, and Escherichia-Shigella, were greatly different between TLs originating from different areas and positions. These data suggested that geographic variations and positions were associated with phyllospheric bacterial communities on TLs, which may be related to not only the flavor style and quality of TLs but also the potential health risks to humans. KEY POINTS: • Tobacco leaf position and tobacco growth location affected bacterial communities. • Microbial communities of TLs shifted significantly after one year of storage. • Potential human pathogens differed at different leaf positions and growth locations.

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.

[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.