Leydig cell metabolic disorder act as a new mechanism affecting for focal spermatogenesis in Klinefelter syndrome patients: a real world cross-sectional study base on the age.

Background: Klinefelter's syndrome (KS) was once considered infertile due to congenital chromosomal abnormalities, but the presence of focal spermatozoa changed this. The key to predict and promote spermatogenesis is to find targets that regulate focal spermatogenesis. Objective: To explore the trend of fertility changes in KS patients at different ages and identify potential therapeutic targets. Methods: Bibliometric analysis was used to collect clinical research data on KS from the Web of Science Core Collection (WoSCC) from 1992 to 2022. A cross-sectional study was conducted on 75 KS patients who underwent microscopic testicular sperm extraction (mTESE) from 2017 to 2022 in the real world. The reproductive hormones, testicular histopathology, androgen receptors, insulin-like factor 3 (INSL3) receptors and sperm recovery rate (SRR) were analyzed. Results: Male infertility, dysplasia, Sertoli cells, Leydig cells, testosterone and spermatogenesis were the research focuses related to KS. Luteinizing hormone (LH), testosterone, and INSL3 were evaluation indicators of Leydig cell function that fluctuate with age. Testosterone and LH peaked at ages 13-19 and 30-45, while INSL3 only peaked at ages 13-19. 27 patients (27/75) recovered sperm through mTESE and experienced SRR peaks at the ages of 20, 28, 34, and 37. The SRR of fibrosis patients was 46.15%, fatty degeneration was 7.14%, and melanosis was 40.00%. The INSL3 and androgen receptors were highly expressed and roughly balanced in focal spermatogenesis. Conclusion: Abnormal metabolism of Leydig cells led to imbalanced expression of INSL3 and androgen receptors, which might be a potential target for spermatogenesis in KS.

Treatment progress of cryptozoospermia with Western Medicine and traditional Chinese medicine: A literature review.

Background and Aims: Cryptozoospermia is an extreme oligozoospermia with an unsatisfactory treatment effect, with an incidence rate of approximately 8.73% in male infertility, whose effective solution has become the call of the times. Western Medicine has achieved certain effects through drugs, surgery, and assisted reproductive therapy, but this is still not ideal. Traditional Chinese medicine (TCM) has made many achievements in other disciplines; however, there is still a lack of evidence-based medical evidence to improve sperm production. Methods: The relevant literatures from the China National Knowledge Internet (CNKI) and PubMed in the past 10 years were collected in this article, of which the mechanisms, advantages, or current controversies of various treatment methods of Western Medicine and TCM were analyzed, to find new treatment methods and research directions. Results: With the development of modern science and technology, medical treatments for cryptozoospermia have become increasingly abundant; however, there is still no universally recognized unified and effective guiding plan. Although TCM has not been fully verified by evidence-based medicine, most TCM combined with Western Medicine can achieve unexpected results. Conclusion: The combination of TCM and Western Medicine may become a bane for cryptozoospermia and bring good news to infertile men worldwide.

"Seminal testosterone", rising viewpoint of local spermatogenesis in nonobstructive azoospermia: One center long-term bidirectional cohort study.

Objective: Reproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method, seminal reproductive hormones were studied. Methods: A bidirectional cohort study was performed. A total of 126 infertile men from 2018 to 2019 were retrospectively analyzed. They were divided into nonobstructive azoospermia (NOA), oligozoospermia (OLZ) and normal (NOR) groups. A prospective study was conducted on patients in the NOA and OLZ groups for 2 years. Microscopic testicular sperm extraction was performed for NOA patients, who were divided into a focal spermatogenesis group (FS) and an idiopathic azoospermia group (IA). Drug treatment was for OLZ patients, who were divided into a valid group (VA) and an invalid group (IN). The differences in sperm parameters and reproductive hormones were compared. ANOSIM analysis was used between and within groups. Pearson correlation analysis, CO inertia analysis and Proctor's analysis were for relationships. ROC curve for the specificity and sensitivity. Time series analysis was for the trends between hormones and time. Results: The b-FSH, b-LH, s-T and ΔT in the NOA group were significantly higher than those in the OLZ and NOR groups. However, the s-FSH, s-E2, s-P, ΔFSH, ΔLH, ΔP and ΔE2 were lower. Thirty-one NOA patients underwent MTSE, of whom 12 had sperm (FS) and 19 had no sperm (IA). The s-FSH and s-E2 of the FS group were higher than those of the IA group. Twenty-six OLZ patients completed 30 days of treatment, of which 11 had an improved sperm count (VA) and 15 had no (IN). The ΔT of the VA group was higher than that of the IN group. After follow-up for 2 years, 18 patients' results showed that b-FSH, b-LH and s-T were different over time, with delays of 19, 3 and -19 days. SC is closely related to pH, s-FSH, s-LH, s-E2, s-P, s-T, b-FSH, b-LH, ΔFSH, ΔLH, ΔP, ΔE2 and ΔT. There were complex common trends and relationships between different kinds of hormones. s-FSH, s-LH, s-E2, s-P, s-T, b-FSH and b-LH were useful to judge spermatogenesis, of which s-T, b-FSH and b-LH were more sensitive. If s-T, b-FSH and b-LH reached 64.4, 9.4 and 4.7, respectively, their prediction performance was the strongest. Conclusion: Seminal testosterone is sensitive for judging local spermatogenesis in nonobstructive azoospermia patients, which may be the direction of local spermatogenesis in nonobstructive azoospermia. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200060463.

Jiawei Runjing Decoction Improves Spermatogenesis of Cryptozoospermia With Varicocele by Regulating the Testicular Microenvironment: Two-Center Prospective Cohort Study.

Objective: The aim of the study was to explore the evidence of JWRJD in the treatment of cryptozoospermia. Methods: A total of 162 cryptozoospermia patients with varicocele who refused to undergo surgery were included from January 2021 to December 2021. They were divided into the Jiawei Runjing Decoction group (group A), tamoxifen group (group B), and no treatment group (group C), and after the follow-up for 3 months, therapeutic effectiveness was compared. Network pharmacology was used to analyze and validate the effects and mechanisms of JWRJD. Results: Fifty-eight patients were treated with JWRJD, 55 with tamoxifen, and 49 without any treatment. After treatment, five patients were lost: one in group A, one in group B, and three in group C. The sperm count and the decrease of FSH in group A were significantly higher, but the degree of decline in the testicular volume and the degree of vein expansion have decreased significantly, which were closely related to the testicular volume (TV) [especially changes in the left testicular volume (ΔL-TV)], citric acid (CC) and its changes (ΔCC), and the vein width (VW) [especially left spermatic vein width (L-VW) and mean vein width (M-VW) and their changes (ΔL-VW and ΔM-VW)], as well as the sperm count before the treatment (bSC), which were the significant indexes to predict the therapeutic effect, especially for patients >35 years old and with grade III varicoceles. Network pharmacological analysis verifies that it can be regulated by fluid shear stress and the atherosclerosis pathway to improve the testicular microenvironment for spermatogenesis. Conclusion: JWRJD may promote spermatogenesis in cryptozoospermia patients with varicocele, which may be closely related to improving the testicular microenvironment, especially for >35 year olds and grade III varicocele patients.

Risk Prediction of Ureaplasma urealyticum Affecting Sperm Quality Based on Mathematical Model and Cross-Sectional Study.

Objective: To explore the risk of Ureaplasma urealyticum (UU) affecting sperm quality. Methods: Prospective cross-sectional study was conducted. In total, 340 semen samples were collected. According to whether they were infected with UU, the samples were divided into the UU-positive group (observation group) and UU-negative group (control group). The patients with UU-positive were followed up to obtain treatment and collected the semen again after treatment. The semen characteristics and sperm parameters were detected and compared, and the relationship of UU and the sperm quality was analyzed by mathematical models. Results: There were 104 UU-positive semen samples in all, with an overall infection rate of 30.6%, which was highest in 31 to 40-year-old men, and over 40-year-old men were the lowest. The pH, PR, VCL, VSL, and STR in the observation group were significantly lower than those in the control group (allP < 0.001), while SV, NP, and WOB were significantly higher (allP < 0.001). After treatment, the pH, VSL, LIN, WOB, and STR in the observation group were significantly higher than before (allP < 0.001), while SV and VCL were significantly lower (allP < 0.001). UU infection was closely correlated with pH, PR, NP, VCL, VSL, WOB, and STR. During the treatment, pH, PR, VSL, WOB, and STR increased, but NP and VCL decreased. 7 major factors that would affect SQ were extracted, of which VAP, LIN, and UU were the first three main factors. The risk of SQ declining after UU infection increased nearly twice with the change of PR and VCL and increased 0.08 times with STR. Conclusion: UU may approximately double the risk of altering the sperm's curvilinear movement rate and straightness to affect the sperm quality.

Effects of varicocele and microsurgical varicocelectomy on the metabolites in semen.

The influence of varicocele and microsurgical varicocelectomy on semen quality remains unclear. Few studies have investigated the relationship between semen metabolism and the abnormalities in reproductive function caused by varicocele, however, there is no study on the changes of semen metabolism after microsurgical varicocelectomy. Here, we used the non-targeted and targeted metabolic analysis to investigate the different metabolites in seminal plasma within normal, varicocele, and varicocelectomy groups. We clearly showed that varicocele significantly affects semen metabolism, and microsurgical varicocelectomy can reverse this metabolic abnormality. Moreover, we characterized the landscape of three dipeptides in the seminal plasma of patients with varicocele that have not been identified previously in human tissues or biofluids. Interestingly, the levels of these three dipeptides decreased after microsurgical varicocelectomy coincident with an improvement in semen quality. Western blotting confirmed the downregulation of DPEP3 (dipeptidase 3) in the varicocele group and the upregulation of DPEP3 in the varicocelectomy group. Furthermore, we found that eight metabolites may be helpful to distinguish varicocele patients from normal subjects. Our results may be applied to earlier diagnosis or to predict the outcome of microsurgery for varicocele.

"Dancing Coins?" Unexpected Finding During microsurgery and Potential Risk of Sperm Damage: Intrascrotal Calculi: A Retrospective Analysis.

Objective: Microsurgery of andrology always brings unexpected findings. Scrotal calculi are rare and unique, which are easily confused with tumor. To understand its etiology and harm, our study retrospectively analyzed the clinical characteristics of men with scrotal calculi to provide a reference for clinical practice. Methods: The clinical data of patients who underwent microscopic testicular sperm extraction (MTESE) and microscopic epididymal sperm aspiration (MESA) from January 1, 2018 to December 31, 2021 were retrospectively analyzed. Data screening was performed on cases in which calculi were found or not, and the relationship between calculi and spermatogenesis was analyzed. Results: A total of 405 patients were recruited. After screening, 218 nonobstructive azoospermia (NOA), 83 obstructive azoospermia (OA), and 13 cryptozoospermia (CZ) patients were included in the study. Calculi were found in 3 patients [incidence was 0.74% (3/405)], in which 2 patients had obstructive azoospermia (1 was epididymal calculi, 1 was intrascrotal calculi) and 1 patient had cryptozoospermia (intrascrotal calculi). Pathological results showed that chronic granuloma with abscess infiltration appeared in epididymal tissue, basement membrane thickening and fibrosis appeared in seminiferous tubules, and fibrous hyperplasia with calcium deposition was found in scrotal calculus. White blood cells, lymphocytes, red blood cells, abstinence time and urethritis were closely related to the occurrence of calculi. While abstinence time might be a potential predictor, which increased the risk by approximately 1.2 times. Conclusion: Disturbance of the testicular microenvironment caused by lymphocyte infiltration may be the main reason for scrotal calculi and ultimately cause spermatogenesis disorders. Prolonged sexual abstinence was a potential risk.

Reproductive outcomes of intracytoplasmic sperm injection using testicular sperm and ejaculated sperm in patients with AZFc microdeletions: a systematic review and meta-analysis.

Studies have explored the assisted reproductive technology (ART) outcomes of Y-chromosome azoospermia factor c (AZFc) microdeletions, but the effect of sperm source on intracytoplasmic sperm injection (ICSI) remains unknown. To determine the ART results of ICSI using testicular sperm and ejaculated sperm from males with AZFc microdeletions, we searched Embase, Web of Science, and PubMed to conduct a systematic review and meta-analysis. The first meta-analysis results for 106 cycles in five studies showed no significant differences in the live birth rate between the testicular sperm group and the ejaculated sperm group (risk ratio: 0.97, 95% confidence interval [CI]: 0.73-1.28, P = 0.82). The second meta-analysis of 106 cycles in five studies showed no difference in the abortion rate between the testicular sperm group and ejaculated sperm group (risk ratio: 1.06, 95% CI: 0.54-2.06, P = 0.87). The third meta-analysis of 386 cycles in seven studies showed no significant difference in clinical pregnancy rates between the testicular sperm group and the ejaculated sperm group (risk ratio: 1.24, 95% CI: 0.66-2.34, P = 0.50). Inevitable heterogeneity weakened our results. However, our results indicated that testicular sperm and ejaculated sperm yield similar ART outcomes, representing a meaningful result for clinical treatment. More properly designed studies are needed to further confirm our conclusions.

[High-frequency ultrasonography for epididymal stasis after vasectomy].

OBJECTIVE: To explore the clinical application of high-frequency ultrasound in the diagnosis and treatment of epididymal stasis after vasectomy. METHODS: We retrospectively studied the sonographic characteristics of 23 cases of epididymal stasis treated by vasectomy, which were divided into a mild (n = 5), a moderate (n = 11) and a severe group (n = 7) according to the results of color Doppler flow imaging. We analyzed the significance of high-frequency ultrasonography in the treatment of epididymal stasis after vasectomy. RESULTS: High-frequency ultrasonography revealed 14 cases of increased bilateral epididymal volume, 6 cases of left epididymal thickening and 3 cases of right epididymal thickening, mainly the thickening of the epididymal body and tail. After conservative treatment, 18 of the epididymal stasis cases (5 mild, 11 moderate and 2 severe) were improved, and the other 5 severe cases significantly relieved and discharged from hospital following conservative treatment combined with vasectomy reversal. CONCLUSION: Post-vasectomy epididymal stasis has typical sonographic characteristics, and high-frequency ultrasonography has an extremely important application value in the clinical classification, diagnosis and treatment of the disease.

[The reconstruction of funnel chest deformity with the reversed transplantation of sternum-costicartilage flap carried by the abdominal rectus pedicle].

OBJECTIVE: To investigate the reconstructive operative procedures of funnel chest with "sternum-costicartilage" flap carried by the abdominal rectus pedicle. METHODS: (1) In accordance with the lesioned area of funnel-like depressed deformity of anterior thoracic wall, a perpendicular median incision was designed and made; (2) The "sternum-costicartilage" flap carrying the abdominal rectus pedicle was used and reversed and transplanted to reconstruct severe funnel chest deformity. RESULTS: The procedure was used in 7 cases from 1999 to 2005. The results of surgery were satisfactory. There were no recurrence after operation. CONCLUSIONS: The procedure reported here is rather safe, solid and sound with good therapeutic results, and is of great value in clinical practice.