Altered regional brain activity and functional connectivity in primary intravaginal anejaculation patients revealed by resting-state fMRI.

ABSTRACT: Ejaculation is regulated by the central nervous system. However, the central pathophysiology of primary intravaginal anejaculation (PIAJ) is unclear. The present study aimed to examine the changes in regional brain activity and functional connectivity underlying PIAJ. A total of 20 PIAJ patients and 16 healthy controls (HCs) were enrolled from September 2020 to September 2022 in the Department of Andrology, Nanjing Drum Tower Hospital (Nanjing, China). Magnetic resonance imaging data were acquired from all participants and then were preprocessed. The measures of fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) were calculated and compared between the groups. PIAJ patients showed increased fALFF values in the left precuneus compared with HCs. Additionally, PIAJ patients showed increased ReHo values in the left precuneus, left postcentral gyrus, left superior occipital gyrus, left calcarine fissure, right precuneus, and right middle temporal gyrus, and decreased ReHo values in the left inferior parietal gyrus, compared with HCs. Finally, brain regions with altered fALFF and ReHo values in PIAJ patients showed increased FC with widespread cortical regions, which included the frontal, parietal, temporal, and occipital regions, compared with HCs. In conclusion, increased regional brain activity in the parietal, temporal, and occipital regions, and increased FC between these brain regions, may be associated with PIAJ occurrence.

Application of the sexual therapy combined with vacuum negative pressure hydropneumatic/pneumatic bubble massage in primary intravaginal anejaculation.

INTRODUCTION: Primary intravaginal anejaculation (PIAJ) is a relatively uncommon male sexual dysfunction characterized by an inability to achieve intravaginal ejaculation during all sexual intercourse. Effective treatment options for this condition are lacking. We aimed to explore the clinical effect of the sexual therapy combined with vacuum negative pressure hydropneumatic/pneumatic bubble massage (VNPHP/PBM) on primary intravaginal anejaculation, and its possible mechanism. METHODS: A total of 95 PIAJ patients were randomly divided into three groups, including group A with 32 patients treated with the sexual therapy combined with VNPHP/PBM, group B with 32 patients treated with the sexual therapy and group C with 31 patients treated with VNPHP/PBM. The efficacy of therapeutic regimes, latency of the somatosensory evoked potentials of dorsal nerve (DNSEP), glans penis (GPSEP) and penile shaft sensory threshold (PSST), measures of sexual behavior of patients, as well as the self-rating anxiety scale (SAS) sores of patients and their partners, were compared before and after treatment among three groups. RESULTS: The total effective rate of group A (84.38%) was higher than those of groups B and C (53.13% and 41.94%), however, no differences were found between groups B and C. The ratios of patients and their partners with anxiety, frequency of observing erotic films of patients, ratios of patients with special self-masturbation and frequency of masturbation decreased significantly in the three groups after the treatment. The decrease in the ratios of patients and their partners with anxiety, frequency of observing erotic films of patients in groups A and B were higher than those of group C, however, no differences were identified between groups A and B. The decrease in the ratios of patients with special self-masturbation and frequency of masturbation in group A were higher than those of group B, however, no differences were found between groups A and C, B and C. There were no differences in the latency of DNSEP, GPSEP, and PSST among the three groups before and after treatment. CONCLUSION: The sexual therapy combined with VNPHP/PBM has good therapeutic effects on PIAJ, which might be achieved by reducing the anxiety level of patients and their partners, improving sexual behavioral patterns, rather than increasing the sensitivity of penis including dorsal nerve and glans penis.

Hepatitis E virus infects human testicular tissue and Sertoli cells.

Globally, hepatitis E virus (HEV) infections are prevalent. The finding of high viral loads and persistent viral shedding in ejaculate suggests that HEV replicates within the human male genital tract, but its target organ is unknown and appropriate models are lacking. We aimed to determine the HEV tropism in the human testis and its potential influence on male reproductive health. We conducted an ex vivo culture of human testis explants and in vitro culture of primary human Sertoli cells. Clinically derived HEV genotype 1 (HEV1) and HEV3 virions, as well as rat-derived HEV-C1, were used for inoculation. Transcriptomic analysis was performed on testis tissues collected from tacrolimus-treated rabbits with chronic HEV3 infection. Our findings reveal that HEV3, but not HEV1 or HEV-C1, can replicate in human testis explants and primary human Sertoli cells. Tacrolimus treatment significantly enhanced the replication efficiency of HEV3 in testis explants and enabled successful HEV1 infection in Sertoli cells. HEV3 infection disrupted the secretion of several soluble factors and altered the cytokine microenvironment within primary human Sertoli cells. Finally, intratesticular transcriptomic analysis of immunocompromised rabbits with chronic HEV infection indicated downregulation of genes associated with spermatogenesis. HEV can infect the human testicular tissues and Sertoli cells, with increased replication efficiency when exposed to tacrolimus treatment. These findings shed light on how HEV may persist in the ejaculate of patients with chronic hepatitis E and provide valuable ex vivo tools for studying countermeasures.

A global perspective: characteristics of infertility-related randomized clinical trials.

BACKGROUND: Infertility is a prevalent global condition, and emerging reproductive technologies may enhance its evaluation and treatment. Understanding the current features of randomized clinical trials in infertility is crucial for improving study design and ensuring the translation of results for patient benefits. OBJECTIVES: To investigate the primary characteristics of randomized clinical trials related to infertility and areas where require improvement. MATERIALS AND METHODS: We conducted a search on the International Clinical Trials Registry platform for eligible infertility trials between 2003 and 2022. The distribution ratio of various characteristics uploaded by infertility-related studies on the platform was analyzed and compared according to sex and registration year. RESULTS: Out of the total trials, 85.3% (1,906) included only women, 8.6% (192) included only men, and 6.1% (136) included couples. The majority of retrieved trials followed a parallel arm design (91.0%) and were non-industry-funded (92.2%), with a median planned sample size of 131 patients (interquartile range 75-270). Among these trials, 54.5% (1,217) were conducted in Asia. The most common primary purpose of infertility-related trials was treatment (88.8%), with over half of the investigated interventions focusing on medication (57.9%). DISCUSSION: Asia is the leading region for research, and the drug therapy is still widely used and updated. However, support care for infertile couples has also received some preference. Areas that require improvement and promotion include addressing male infertility and focusing on underserved regions like Africa. The results also highlight deficiencies in trial registration and masking methods, emphasizing the need for better regulation and facilitation of infertility trials in the post-COVID-19 era. CONCLUSION: Based on the current status of infertility RCT studies, greater attention should be paid to infertile men and populations in underdeveloped regions like Africa in future studies, together with a standardized registration and implementation procedures.

ADSCs labeled with SPIONs tracked in corpus cavernosum of rat and miniature pig by MR imaging and histological examination.

Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

Decreased grey matter volume in dorsolateral prefrontal cortex and thalamus accompanied by compensatory increases in middle cingulate gyrus of premature ejaculation patients.

INTRODUCTION: The prefrontal-cingulate-thalamic areas are associated with ejaculation control. Functional abnormalities of these areas and decreased grey matter volume (GMV) in the subcortical areas have been confirmed in premature ejaculation (PE) patients. However, no study has explored the corresponding GMV changes in the prefrontal-cingulate-thalamic areas, which are considered as the important basis for functional abnormalities. This study aimed to investigated whether PE patients exhibited impaired GMV in the brain, especially the prefrontal-cingulate-thalamic areas, and whether these structural deficits were associated with declined ejaculatory control. METHODS: T1-weighted structural magnetic resonance imaging (MRI) data were acquired from 50 lifelong PE patients and 50 age-, and education-matched healthy controls (HCs). The PE diagnostic tool (PEDT) was applied to assess the subjective symptoms of PE. Based on the method of voxel-based morphometry (VBM), GMV were measured and compared between groups. In addition, the correlations between GMV of brain regions showed differences between groups and PEDT scores were evaluated in the patient group. RESULTS: PE patients showed decreased GMV in the right dorsolateral superior frontal gyrus (clusters = 13, peak T-values = -4.30) and left thalamus (clusters = 47, T = -4.33), and increased GMV in the left middle cingulate gyrus (clusters = 12, T = 4.02) when compared with HCs. In the patient group, GMV of the left thalamus were negatively associated with PEDT scores (r = -0.35; P = 0.01). Receiver operating characteristic (ROC) analysis showed that GMV of the right dorsolateral superior frontal gyrus (AUC = 0.71, P < 0.01, sensitivity = 60%, specificity = 78%), left thalamus (AUC = 0.72, P < 0.01, sensitivity = 92%, specificity = 46%) and middle cingulate gyrus (AUC = 0.69, P < 0.01, sensitivity = 50%, specificity = 90%), and the combined model (AUC = 0.84, P < 0.01, sensitivity = 78%, specificity = 80%) all had the ability to distinguish PE patients from HCs. CONCLUSION: Disturbances in GMV were revealed in the prefrontal-cingulate-thalamic areas of PE patients. The findings implied that decreased GMV in the dorsolateral prefrontal cortex and thalamus might be associated with the central pathological neural mechanism underlying the declined ejaculatory control while increased GMV in the middle cingulate gyrus might be the compensatory mechanism underlying PE.

It is easy and effective to locate adrenal gland during retroperitoneal laparoscopic left adrenalectomy by the landmark of left PFSV.

To evaluate the feasibility and clinical significance of the left perinephric fat sac vein (PFSV) as an anatomical landmark in locating left adrenal gland (LAD) during retroperitoneal laparoscopic left adrenalectomy (RLLA). In this study, a total of 36 patients who underwent RLLA were enrolled from February 2019 and March 2021. By following a vein vessel on the internal surface of perinephric fat sac (PFS), known as PFSV, LAD was searched finally along the upper edge of this vein. The demographic and clinical characteristics of these patients were acquired, including tumor features and perioperative outcomes (operating time, estimated blood loss, complications). The operations were successfully completed in all the 36 patients without conversion to open surgery. In addition, the LAD was successfully found along the upper edge of PFSV in 34 patients. For all operations, the mean operative time was 75 min (range 60-95) and the estimated blood loss was 20 ml (range 10-50). The median oral intake was 20.7 h (range 6-39). The median hospital stay was 6.3 days (range 4-9), and the median follow-up was 12.3 months (range 9-17). Moreover, no intraoperative complications were observed and no residual tumors were detected after 9 to 15 months follow-up. It may be a safe and efficient procedure to use PFSV as a landmark for searching LAD during RLLA, especially for beginners. However, more studies with larger sample size are need to be conducted to further evaluate the outcomes of this method and the significance of PFSV in searching LAD during RLLA.

Outcomes and affecting factors for ICSI and microTESE treatments in nonobstructive azoospermia patients with different etiologies: A retrospective analysis.

Introduction: Nonobstructive azoospermia (NOA) is a common and severe form of male infertility. Microdissection testicular sperm extraction (microTESE) combined with intracytoplasmic sperm injection (ICSI) is an optimal treatment for men with NOA. However, the outcomes and affecting factors of ICSI for NOA patients with different etiologies receiving microTESE treatment are still unclear. Methods: A total of 335 NOA patients undergoing microTESE from January 2017 to December 2021 were included in this retrospective analysis. The patients were divided into five groups (idiopathic, Klinefelter syndrome (KS), Y chromosome microdeletions (YCMDs), cryptorchidism and mumps orchitis) according to the etiologies. The clinical characteristics and outcomes of microTESE and ICSI were collected and comparisons were performed between clinical characteristics of patients who had successful sperm retrieval (SSR) and sperm retrieval failure (SRF). In addition, relationships between clinical characteristics and rates of SSR were explored by Kendall correlation analysis. Results: The overall SSR rate was 40.90%. SSR rate of the idiopathic group (31.22%) was the lowest and was much lower than that of other groups (KS: 48.65%, 28/58; YCMDs: 60.87%; cryptorchidism: 80.95%; mumps orchitis: 75.00%). The overall fertilization rate was 72.26%. No group differences were found among five groups (idiopathic: 73.91%; KS: 71.43%; YCMDs: 64.29%; cryptorchidism: 70.59%; mumps orchitis: 77.78%). The overall clinical pregnancy rate was 66.67%. No group differences were found among five groups (idiopathic: 68.63%; KS: 65.00%; YCMDs: 44.44%; cryptorchidism: 66.67%; mumps orchitis: 85.71%). The overall live birth rate was 66.67%. No group differences were found among five groups (idiopathic: 71.43%; KS: 53.85%; YCMDs: 50.00%; cryptorchidism: 75.00%; mumps orchitis: 66.67%). For SSR patients, the average age was significantly lower in the idiopathic group, while the average testicular volume was significantly greater in the cryptorchidism and mumps orchitis groups. However, no significant differences were found in the level of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) between patients who had SSR and SRF. In addition, negative relationships were found between age and rates of SSR in idiopathic NOA patients while positive relationships were found between testis volume and rates of SSR in patients with cryptorchidism and mumps orchitis. Conclusion: Patients with idiopathic NOA had lowest SSR. In addition, the age in idiopathic NOA patients was a predictor for SSR while testicular volume in NOA patients with cryptorchidism and mumps orchitis was a predictor for SSR. However, the relationships between clinical characteristics and clinical outcomes in NOA patients were preliminary, and further validation needed to be carried out in a larger sample to increase statistical capacity before a definitive conclusion could be drawn.

Altered Structural and Functional Connectivity Contribute to Rapid Ejaculation: Insights from a Multimodal Neuroimaging Study.

Little is known about how the aberrant structural and functional connectivity relates to the rapid ejaculation. Data of diffusion tensor imaging and resting state functional magnetic resonance imaging were acquired from 32 PE patients and 38 healthy controls (HCs). Firstly, we investigated the structural connectivity (SC) disruptions of PE patients using the method of graph theoretical analysis. Brain regions with impaired nodal strength were then defined as regions of interest (ROI). Secondly, the corresponding functional connectivity (FC) changes were explored. Finally, the correlation analyses were performed between brain areas with abnormal connectivity and clinical characteristics. Structural analysis revealed that PE patients had increased nodal strength in the right superior frontal gyrus (dorsolateral), left middle frontal gyrus, right superior frontal gyrus (medial), right superior frontal gyrus (medial orbital) and decreased nodal strength in the left amygdala. FC analysis revealed that PE patients had decreased FC values in the default mode network, visual recognition network and subcortical network, as well as increased FC values in the attention network. Moreover, correlation analysis revealed that the nodal strength of right superior frontal gyrus (dorsolateral) was negatively associated with the intra-vaginal ejaculation latency, while FC values between the left middle frontal gyrus and middle occipital gyrus were positively related to the total scores of the premature ejaculation diagnostic tool (PEDT). Our results indicated that PE might be associated with the abnormal SC of areas in the prefrontal-amygdala pathway and aberrant FC in certain functional brain networks, especially in default mode network.