Factors influencing the sperm retrieval rate of microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome / 亚洲男科学杂志(英文版)

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann‒Whitney U test or Student's t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.

Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation / 亚洲男科学杂志(英文版)

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

Clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection with fresh or cryopreserved sperm in patients with nonobstructive azoospermia / 亚洲男科学杂志(英文版)

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI) treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia (NOA). A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles (Group A). Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles (Group B). We compared patient characteristics, embryonic development, and pregnancy outcomes between Groups A and B. There was no statistical difference in the patient characteristics, and no differences were observed with fertilization or quality embryo rates between Groups A and B. The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B (both P < 0.05). In conclusion, fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.

Sperm retrieval rates and clinical outcomes for patients with different causes of azoospermia who undergo microdissection testicular sperm extraction-intracytoplasmic sperm injection / 亚洲男科学杂志(英文版)

The aim of our study was to compare the sperm retrieval rates (SRRs) and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection (micro-TESE-ICSI). We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing, China, from January 2014 to December 2017. This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI. Patients with azoospermia were classified into Group A (Klinefelter syndrome, n = 284, 125 cycles), Group B (azoospermia Y chromosome factor c [AZFc] microdeletion, n = 91, 64 cycles), Group C (cryptorchidism, n = 52, 39 cycles), Group D (previous mumps and bilateral orchitis, n = 23, 23 cycles), and Group E (idiopathic azoospermia, n = 319, 96 cycles). Clinical characteristics, SRR, embryonic development, and pregnancy outcomes of the patients were compared between all groups. Patients in Group D had the highest and most successful SRR. The average SRR for all patients was 46.0%. The rates of clinical pregnancy, implantation, and live birth in Group D were 78.3%, 65.0%, and 74.0%, respectively, which were higher than those in all other groups (P 0.05). Patients with orchitis had the highest SRR and best clinical outcomes. Although AZFc microdeletion patients had a higher SRR, their clinical outcomes were worse.

Altered microRNA profiles of testicular biopsies from patients with nonobstructive azoospermia / 亚洲男科学杂志(英文版)

Many studies have shown that microRNAs (miRNAs) play vital roles during the spermatogenesis. However, little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia (NOA). Using microarray technology, the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined. Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs. The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which were then validated with a larger sample size. Correlations between the miRNA expression levels and clinical characteristics were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia. Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups. Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis, cell cycle, and mitotic prometaphase. In the subsequent qRT-PCR assays, the selected miRNA expression levels were consistent with the microarray results, and similar validated results were obtained with a larger sample size. Some clinical characteristics were significantly associated with the expression of certain miRNAs. In particular, we identified a combination of two miRNAs (miR-10b-3p and miR-34b-5p) that could serve as a predictive biomarker of azoospermia. This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis. These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.

Transurethral seminal vesiculoscopy in treatment of oligoasthenozoospermia secondary incomplete ejaculatory duct obstruction: A report of 8 cases / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the utility of transurethral seminal vesiculoscopy with a slender ureteroscope in the treatment of severe oligoasthenozoospermia secondary incomplete ejaculatory duct obstruction (EDO).@*METHODS@#From March 2018 to September 2018, the clinical data of 8 patients with severe oligoasthenozoospermia secondary incomplete EDO treated by the technique of transurethral seminal vesiculoscopy in the Peking University Third Hospital Reproductive Center were analyzed. Preoperative routine included semen analysis, hormone determination, transrectal ultrasonography, pelvic magne-tic resonance examination and other examinations. All the patients were diagnosed with severe oligoasthenozoospermia secondary to incomplete EDO. All the patients were operated by the same surgeon with multiple cases of experience in transurethral surgery, and 1 year follow-up was conducted to evaluate the surgical effect.@*RESULTS@#The average age of the 8 patients was 29 years, and the average operation time was 32 min. Preoperative transrectal ultrasound indicated 6 cases of ejaculatory duct cyst or Mullerian cyst, 1 case of prostate calcification and bilateral seminal vesicle dilatation. The average maximum transverse diameter of the right seminal vesicle in pelvic MRI was 33.60 mm (24.63-42.28 mm), the average maximum transverse diameter of the left seminal vesicle was 32.85 mm (25.91-44.89 mm), the ave-rage maximum antero-posterior diameter was 27.99 mm (21.36-33.12 mm), the average maximum width of the seminal vesicle duct was 10.53 mm (5.93-19.39 mm). There were 5 cases of ejaculatory duct cyst, 2 cases of seminal vesicle hemorrhage, and 1 case of Mullerian cyst. The semen volume [(2.64±0.80) mL], the sperm concentration [(49.76±8.50)×106/mL], and the motility (grade a+b) [(25.76±6.48)%] in postoperation were significantly higher than those in preoperation [(1.46±0.50) mL, (28.78±5.17)×106/mL, and (2.88±0.93)%, P < 0.05]. Two patients conceived naturally during the follow-up of 6 months after surgery. There were no severe complications, such as retrograde ejaculation, urinary incontinence or rectal injury.@*CONCLUSION@#The technique of transurethral seminal vesiculoscopy is safe and effective for treating severe oligoasthenozoospermia secondary to incomplete EDO. However, due to the small sample size of this study, short follow-up time, and the uncertainty in seminal vesicle surgery, it still needs to be further confirmed by long-term follow-up studies with large samples.

Ambient ozone pollution is associated with decreased semen quality: longitudinal analysis of 8945 semen samples from 2015 to 2018 and during pollution-control period in Beijing, China / 亚洲男科学杂志(英文版)

Previous studies suggest that air pollution has a negative effect on semen quality. However, most studies are cross-sectional and the results are controversial. This study investigated the associations between air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3) and semen quality among sperm donation candidates, especially when the air pollution was artificially controlled in Beijing, China. We analyzed 8945 semen samples in the human sperm bank of Peking University Third Hospital (Beijing, China) from October 2015 to May 2018. Air pollution data during the entire period (0-90 days prior) and key stages (0-9, 10-14, and 70-90 days prior) of sperm development were collected from the China National Environmental Monitoring Centre. The association between air pollutants and semen parameters (sperm concentration and progressive motility) was analyzed by a mixed model adjusted for age, abstinence duration, month, and average ambient temperature. Only O3during key stages of 0-9 days and 10-14 days and the entire period was negatively associated with sperm concentration between 2015 and 2018 (P < 0.01). During the period of air pollution control from November 2017 to January 2018, except for the increase in O3concentration, other five pollutants' concentrations decreased compared to those in previous years. In this period, the sperm concentration decreased (P < 0.001). During the pollution-control period, O3exposure 10-14 days prior was negatively associated with sperm concentration (95% CI: -0.399--0.111; P < 0.001). No significant association was found between the other five pollutants and semen quality during that period. Our study suggested that only O3exposure was harmful to semen quality. Therefore, O3should not be neglected during pollution control operation.

Analysis of intratesticular condition in micro-dissection testicular sperm extraction era / 北京大学学报(医学版)

OBJECTIVE@#To summarizes the intratesticular condition of azoospermia patients, to understand azoospermia more intuitively, and improve the ability of clinical doctors to predict the success rate of microsperm extraction in azoospermia patients.@*METHODS@#Azoospermia patients (excluding Klinefelter's syndrome) who underwent a micro-TESE during January 2014 and January 2018 in a single center were enrolled. The types of seminiferous tubules were summarized, and the clinical characteristics of different types of seminiferous tubules compared with the success rates of sperm extraction. In this study, 472 cases of non-obstructive azoospermia (excluding Klinefelter's syndrome) were analyzed by SPSS 21.0 software package. Relevant data were expressed by median(minimum,maximum).t-test was used to compare the difference of success rate of sperm extraction between each group and the group with the lowest rate (a type).@*RESULTS@#The 472 patients with non-obstructive azoospermia underwent micro-TESE. The mean age of the patients was 31 (23, 46) years, the mean testicular size was 10 (1, 20) mL, the mean FSH was 15.4 (1.21, 68.4) IU/L, the mean T was 8.34 (0.69, 30.2) nmol/L, and totally 202 patients achieved success in micro-TESE (42.7%, 202/472). According to the seminiferous tubules seen during the operation, they were divided into the following six types: Class a, seminiferous tubules developed well and uniformly; Class b, seminiferous tubules developed well, occasionally slightly thick; Class c, seminiferous tubules were generally thin; Class d, seminiferous tubules basically atrophied, occasionally well-developed seminiferous tubules; Class e, all seminiferous tubules atrophied; Class f, seminiferous tubules were infiltrated by yellow substances. The success rate of micro-TESE varied greatly among different types of the patients. A total of 78 patients with type a were 29 (24, 40) years old, FSH 11.1 (1.21, 15.8) IU/L, T 10.2 (3.29, 26.5) nmol/L), and testicular size 12 (12, 20) mL. The successful rate of sperm extraction was 6.41%; 82 patients with type b were 31 (23, 42) years old, FSH 13.8 (3.23, 19.6) IU/L, T 9.44 (3.58, 30.2) nmol/L), and testicular size 12(8,15) mL. The successful rate of sperm extraction was 74.39%; There were 162 patients in group c, aged 31 (25, 40), FSH 19.6 (9.28, 26.6) IU/L, T 8.75 (5.66, 18.6) nmol/L, and testicular size 8 (5, 12) mL. The successful rate of sperm extraction was 45.06%. There were 36 patients in group d, aged 25 (23,38) years and FSH 28.5 (19.3, 45.6) IU/L, T 6.52 (2.12, 9.83) nmol/L, and testicular size 5 (3, 8) mL, and the success rate of sperm extraction was 94.44%. 26 patients with type e were 28(23, 46) years old, FSH 31.3 (18.5, 68.4) IU/L, T 6.72 (0.69, 18.2) nmol/L, and testicular size 5 (1, 8) mL. The success rate of sperm extraction was 45.38%. 88 patients with type f were 29 (24, 38) years old, FSH 18.5 (5.23, 31.6) IU / L, T 8.32 (3.58, 16.5) nmol/L, and testicular size 12 (6, 20) mL. The success rate of sperm extraction was 28.41%.@*CONCLUSION@#The success rate of micro-TESE in different types of seminiferous tubules in testis can be helpful to the judgement of the surgeon during the operation.

Nanotechnology-assisted adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury: In vivo cell tracking, optimized injection dosage, and functional evaluation / 亚洲男科学杂志(英文版)

Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell (ADSC) therapy for erectile dysfunction of cavernous nerve injury (CNI) by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage (2 × 105 cells) of ADSCs for intracavernous injection (ICI) and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs (NanoADSCs) were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction: interim results of a multicenter, randomized, open-label trial / 亚洲男科学杂志(英文版)

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

Collagenase clostridium histolyticum for Peyronie's disease: A new minimally invasive and effective treatment / 中华男科学杂志

The treatment of Peyronie's disease has been a challenge to urologists, as most of the current oral medications are considered hardly valid and the rest of the therapies require strict control of indications, some of which remain controversial, while the final surgical option may be associated with complications such as penile shortening or erectile dysfunction. Collagenase clostridium histolyticum has been proved to be effective in dissolving the penile cavernosal plaque and approved by the Food and Drug Administration of the USA as the first drug to be used for the treatment of Peyronie's disease. This article presents an introduction to the characteristics, safety, efficacy, and procedures of this new treatment, which may benefit urologists and the patients with Peyronie's disease.

Microdissection testicular sperm extraction for patients with nonmosaic Klinefelter syndrome: A report of 143 cases / 中华男科学杂志

Objective@#To investigate the clinical application and outcomes of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS).@*METHODS@#A total of 143 nonmosaic KS patients underwent micro-TESE in the Center of Reproductive Medicine of Peking University Third Hospital between July 2012 and August 2016. We analyzed their clinical and follow-up data and evaluated the outcomes.@*RESULTS@#Spermatozoa were successfully retrieved from the testicular tissue in 44.76% (64/143) of the patients, 84.4% (54/64) by unilateral and 15.6% (10/64) by bilateral micro-TESE. Seventy-five of the KS patients were followed up in the years of 2014 and 2015. Of the 34 patients with successful sperm retrieval, 73.52% (25/34) achieved clinical pregnancy and 8 boys and 8 girls were already born in 14 of the 25 cases.@*CONCLUSIONS@#The micro-TESE is a useful method for sperm retrieval in nonmosaic KS patients, with high rates of sperm retrieval, clinical pregnancy, and birth of biological offspring.