Decreased embryo developmental potential and lower cumulative pregnancy rate in men with multiple morphological abnormalities of the sperm flagella.

Objective: Multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by abnormal flagellar phenotypes, which is a particular kind of asthenoteratozoospermia. Previous studies have reported a comparable intracytoplasmic sperm injection (ICSI) outcome in terms of fertilization rate and clinical pregnancy rate in patients with MMAF compared with those with no MMAF; however, others have conflicting opinions. Assisted reproductive technology (ART) outcomes in individuals with MMAF are still controversial and open to debate. Methods: A total of 38 patients with MMAF treated at an academic reproductive center between January 2014 and July 2022 were evaluated in the current retrospective cohort study and followed up until January 2023. Propensity score matching was used to adjust for the baseline clinical characteristics of the patients and to create a comparable control group. The genetic pathogenesis of MMAF was confirmed by whole exome sequencing. The main outcomes were the embryo developmental potential, the cumulative pregnancy rate (CLPR), and the cumulative live birth rate (CLBR). Results: Pathogenic variants in known genes of DNAH1, DNAH11, CFAP43, FSIP2, and SPEF2 were identified in patients with MMAF. Laboratory outcomes, including the fertilization rate, 2PN cleavage rate, blastocyst formation rate, and available blastocyst rate, followed a trend of decline in the MMAF group (p < 0.05). Moreover, according to the embryo transfer times and complete cycles, the CLPR in the cohort of MMAF was lower compared with the oligoasthenospermia pool (p = 0.033 and p = 0.020, respectively), while no statistical differences were observed in the neonatal outcomes. Conclusion: The current study presented decreased embryo developmental potential and compromised clinical outcomes in the MMAF cohort. These findings may provide clinicians with evidence to support genetic counseling and clinical guidance in specific patients with MMAF.

Identification of hub genes and biological mechanisms underlying the pathogenesis of asthenozoospermia and chronic epididymitis.

Objective: Asthenozoospermia (AZS) is one of the most common causes of male fertility, affecting family wellbeing and population growth. Chronic epididymitis (CE) is a common and lingering inflammatory disease in the scrotum. Inflammation in the epididymis has a severe impact on sperm motility. This study aimed to explore the genetic profile and critical pathways involved in the pathological mechanisms of AZS and CE, and discover potential biomarkers. Methods: Genomic datasets of AZS and CE were obtained from the Gene Expression Omnibus (GEO) database, and relevant differentially expressed genes (DEGs) were identified. GO and pathway enrichment analyses, construction of a protein-protein interaction network, and receiver operator characteristic curve analysis were conducted. The expression profile of hub genes was validated in immunohistochemical data and testicular cell data. Immune infiltration, miRNA-hub gene interactions, and gene-disease interactions were explored. The mRNA levels of hub genes were further measured by qRT-PCR. Results: A total of 109 DEGs were identified between the AZS/CE and healthy control groups. Pathways of the immune system, neutrophil degranulation, and interleukin-4 and interleukin-13 signaling were enriched in AZS and CE. Five hub genes (CD300LB, CMKLR1, CCR4, B3GALT5, and CTSK) were selected, and their diagnostic values were validated in AZS, CE, and independent validation sets (area under the curve >0.7). Furthermore, the five-hub gene signature was well characterized in testicular immunohistochemical staining and testicular cells from healthy controls. Immune infiltration analysis showed that infiltration of CD8+ cells and T helper cells was significantly related to the expression level of five hub genes. In addition, a miRNA-hub gene network and interaction of other diseases were displayed. The mRNA levels of hub genes (CD300LB, CMKLR1, CCR4, and B3GALT5) were significantly elevated in the patient group. The mRNA level of CTSK also showed a similar trend. Conclusion: Our study uncovered the genetic profile involved in AZS and CE, and elucidated enriched pathways and molecular associations between hub genes and immune infiltration. This finding provides novel insight into the common pathogenesis of both diseases as well as the potential biomarkers for CE-associated AZS.

Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in patients with psychogenic erectile dysfunction.

Background: Psychological stress and its two stress response systems, the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), are closely related to psychogenic erectile dysfunction (pED). However, the analyses of perceived stress and stress systems in pED patients need to be more in-depth, especially the interactions between them. Methods: Our study included 75 patients with pEDs and 75 healthy men. The International Index of Erectile Function-5 (IIEF-5) and the 10-item Perceived Stress Scale (PSS-10) were used for assessing the severity of ED and perceived stress. All participants collected saliva samples on three consecutive days at eight specific times with strict reference to the time of morning awakening for measuring cortisol parameters and wore electrocardiography for 24 h to derive heart rate variability (HRV). Results: The PSS-10 scores of pED patients were significantly higher than the control group (p<0.001). Although PSS-10 and IIEF-5 scores were negatively correlated in pED patients, there was no statistical significance between them (r=-0.049, p=0.677). Compared with the control group, the HRV parameters of pED patients were significantly increased in LF/HF ratio (p=0.014) but significantly decreased in LF, HF, and pNN50 (p<0.001). However, the two groups had no statistically significant differences in cortisol variables (all p>0.05). The interaction between sympathovagal modulation (HF, rMSSD) and cortisol awakening response (CAR AUCi) explained significantly greater variance in perceived stress than either stress system alone. Higher parasympathetic activity combined with a higher cortisol awakening response was associated with greater perceived stress. Conclusion: Our results suggested that the interrelation between ANS and HPA axis activity might enhance our comprehension of how stress affected the physical and mental health of pED patients.

Constructing a seventeen-gene signature model for non-obstructive azoospermia based on integrated transcriptome analyses and WGCNA.

BACKGROUND: Non-obstructive azoospermia (NOA) affects approximately 1% of the male population worldwide. The underlying mechanism and gene transcription remain unclear. This study aims to explore the potential pathogenesis for the detection and management of NOA. METHODS: Based on four microarray datasets from the Gene Expression Omnibus database, integrated analysis and weighted correlation network analysis (WGCNA) were used to obtain the intersected common differentially expressed genes (DESs). Differential signaling pathways were identified via GO and GSVA-KEGG analyses. We constructed a seventeen-gene signature model using least absolute shrinkage and selection operation (LASSO) regression, and validated its efficacy in another two GEO datasets. Three patients with NOA and three patients with obstructive azoospermia were recruited. The mRNA levels of seven key genes were measured in testicular samples, and the gene expression profile was evaluated in the Human Protein Atlas (HPA) database. RESULTS: In total, 388 upregulated and 795 downregulated common DEGs were identified between the NOA and control groups. ATPase activity, tubulin binding, microtubule binding, and metabolism- and immune-associated signaling pathways were significantly enriched. A seventeen-gene signature predictive model was constructed, and receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) values were 1.000 (training group), 0.901 (testing group), and 0.940 (validation set). The AUCs of seven key genes (REC8, CPS1, DHX57, RRS1, GSTA4, SI, and COX7B) were all > 0.8 in both the testing group and the validation set. The qRT-PCR results showed that consistent with the sequencing data, the mRNA levels of RRS1, GSTA4, and COX7B were upregulated, while CPS1, DHX57, and SI were downregulated in NOA. Four genes (CPS1, DHX57, RRS1, and SI) showed significant differences. Expression data from the HPA database showed the localization characteristics and trajectories of seven key genes in spermatogenic cells, Sertoli cells, and Leydig cells. CONCLUSIONS: Our findings suggest a novel seventeen-gene signature model with a favorable predictive power, and identify seven key genes with potential as NOA-associated marker genes. Our study provides a new perspective for exploring the underlying pathological mechanism in male infertility.

Evaluation of psychological stress, cortisol awakening response, and heart rate variability in patients with chronic prostatitis/chronic pelvic pain syndrome complicated by lower urinary tract symptoms and erectile dysfunction.

Background: Mental stress and imbalance of its two neural stress systems, the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis, are associated with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED). However, the comprehensive analyses of psychological stress and stress systems are under-investigated, particularly in CP/CPPS patients complicated by lower urinary tract symptoms (LUTS) and ED. Materials and methods: Participants were 95 patients in CP/CPPS+ED group, 290 patients in CP/CPPS group, 124 patients in ED group and 52 healthy men in control group. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function-5 (IIEF-5) and the International Prostate Symptom Score (IPSS) were used for assessing the disease severity of CP/CPPS, LUTS and ED. Psychometric self-report questionnaires including the Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS), Type A Personality Test (TAPT) and Symptom Checklist 90 (SCL-90) were completed for distress from physical symptoms. Twenty-five subjects per group were randomly selected for further investigating the changes of the HPA axis and ANS. Saliva samples were taken on 3 consecutive days at 8 specific times with strict reference to time of morning awakening for evaluation of free cortisol. Heart rate variability (HRV) as marker of the ANS was measured using 24 h electrocardiography, and time-and frequency-domain variables were analyzed. Results: The BAI and SCL-90 scores were significantly higher in the CP/CPPS+ED, CP/CPPS and ED groups compared with the control group (p < 0.01). The PSS scores of both groups with ED were significantly higher than the control group (p < 0.01). Compared with the CP/CPPS group, the differences of PSS, SCL-90 and TAPT scores were statistically significant in CP/CPPS+ED patients (p < 0.01). The IPSS scores were shown to have significantly positive correlations with BAI (r = 0.32, p < 0.0001), PSS (r = 0.18, p < 0.01) and SCL-90 (r = 0.19, p < 0.01) in the CP/CPPS patients. However, in all subjects, the IIEF-5 scores were shown to have significantly negative correlations with BAI (r = -0.17，p < 0.001), PSS (r = -0.25，p < 0.0001), SCL-90 (r = -0.20，p < 0.001) and quality of life score in NIH-CPSI (r = -0.14，p = 0.0075). Cortisol awakening response (CAR) parameters and diurnal cortisol levels did not significantly vary between the four groups. Time-dependent parameters of HRV also did not differ significantly across groups. In the frequency domain analysis, low frequency (LF) was significantly lower in ED patients when compared with CP/CPPS+ED patients (p = 0.044) and healthy controls (p = 0.005), high frequency (HF) power was significantly higher in healthy controls compared to patients with ED (p < 0.001), CP/CPPS (p < 0.001) and CP/CPPS+ED (p < 0.001), and the CP/CPPS+ED group had significantly higher LF/HF ratio than the control group (p = 0.001). Conclusion: CP/CPPS and ED patients score exceedingly high on most psychosocial variables. The symptom scores of LUTS and ED positively correlate with the severity of psychological stress. Our findings also suggest that the ANS sympathovagal imbalance is associated with ED and LUTS in CP/CPPS, whereas HPA axis activity is not.

A new hemizygous missense mutation, c.454T＞C (p.S152P), in AKAP4 gene is associated with asthenozoospermia.

Asthenozoospermia (ASZ) is a condition characterized by reduced forward motility of spermatozoa affecting approximately 19% of infertile men. A kinase anchor protein 4 (AKAP4) is an X-linked testis-specific gene and plays a major role in sperm motility and flagella formation. However, few studies have reported its association with ASZ. Here, we sequenced for exonic mutations of human AKAP4 gene by high-fidelity PCR/Sanger sequencing in peripheral blood samples from 150 ASZ patients and 150 fertile men. We reported the identification of three novel hemizygous mutations unique to four ASZ patients, including one patient carrying missense mutation c.454T>C (p.S152P), two patient carrying synonymous mutation c.1173T>C (p.H391H), and one patient carrying synonymous mutation c.2007 A>G (p.R669R). The p.S152P mutation was located in a precursor pro-polypeptide domain of AKAP4 protein, which was predicted to be damaging by SIFT and PolyPhen-2 and could cause the protein accumulation in the cytoplasm of COS-7 cells. The mature protein of AKAP4 was absent in spermatozoa of ASZ patient harboring AKAP4 p.S152P mutation. Further in vitro cellular assays showed that reactive oxygen species (ROS), malondialdehyde (MDA), myeloperoxidase (MPO) levels, and apoptotic cells were increased in GC2-spd cells by AKAP4 p.S152P mutant protein, whereas superoxide dismutase (SOD) level was decreased. AKAP4 p.H391H and p.R669R mutant proteins were coimmunoprecipitated with ribonuclease T2 (RNASET2) protein in GC2-spd cells, whereas no interaction between the AKAP4 p.S152P mutant protein and RNASET2 protein was observed. In addition, AKAP4 p.S152P mutant protein could decrease the activity of PKA/PI3K signaling. Overall, our study identifies a novel AKAP4 p.S152P mutation is associated with ASZ probably through affecting oxidative stress and cell apoptosis by regulating the interaction with RNASET2 and the activity of the PKA/PI3K signaling pathway.

Intra-abdominal robot-assisted vasovasostomy of obstructive azoospermia in an Asian population following multiple bilateral inguinal herniorrhaphy in childhood: a case report and literature review.

Iatrogenic injury to the vas deferens is an indication for vasovasostomy (VV). Various surgical approaches, including pure microsurgical VV (MVV), pelviscrotal laparoscopic-assisted VV (LAVV), and intra-abdominal robot-assisted VV (RAVV), have been reported to restore vasal patency. MVV is often faced a formidable challenge to provide tension-free VV due to an inadequate vas deferens length. Alternatively, pelviscrotal LAVV is much more effective for the identification and retrieval of the pelvic vas deferens prior to performing MVV. However, vasal laparoscopic mobilization could still be limited by insufficient vasal length for extracorporeal transfer in some cases. The addition of robotic assistance, on the other hand, allows the performance of "in-situ" vasal anastomoses and offers unique features compared with pure MVV/LAVV. However, few such approaches have been described in the literature. This study presents the initial results and validation of robot-assisted VV in an Asian population who had undergone triple herniorrhaphy. Briefly, Intra-operative findings demonstrated a large defect of the vas deferens, and a two-layer bilateral tension-free RAVV was performed to pursue the possibility of naturally achieved pregnancy. With our promising results, intra-abdominal RAVV may be described as a practical approach for cases with iatrogenic large defects of the vas deferens within the inguinal canal.

[Expressions of Th1/Th2 cytokines and autoantibodies in the serum of males with idiopathic oligoasthenozoospermia and their significance].

OBJECTIVE: To investigate the expressions of Th1/Th2 cytokines and autoantibodies in the serum of the patients with idiopathic oligoasthenozoospermia (IO) and their significance. METHODS: From November 2017 to April 2020, we examined the levels of Th1/Th2 cytokines (IL-2, IL-4, IL-10, IL-21, TNF-α, IFN-γ) and the expressions of AhCGAb, AsAb and AcAb in the serum of 48 infertile men with mild or moderate IO, 48 with severe IO and another 72 males with normal semen parameters by ELISA. We compared the results of detection among the three groups and analyzed them with the logistic regression model. RESULTS: Compared with the normal controls, the patients with mild or moderate IO showed significant increases in the levels of IL-10, IL-21 and IFN-γ and the expressions of AhCGAb, AsAb and AcAb (P < 0.05), and so were those of the severe IO group in the levels of all the six cytokines and the expressions of the three autoantibodies (P < 0.05). The levels of IL-2, IL-4, IL-21 and TNF-α and the expressions of AhCGAb and AsAb were even higher in the patients with severe IO than in those with mild or moderate IO (P < 0.05). Multivariate logistic regression analysis showed that the increased levels of IL-21/IL-10 (OR = 1.694, 95% CI: 0.319－4.035, P < 0.05) and positive expressions of AhCGAb (OR = 4.357, 95% CI: 1.204－9.426, P < 0.05) and AsAb (OR = 2.135, 95% CI: 1.902－5.429, P < 0.05) were the risk factors for IO. CONCLUSIONS: The levels of the cytokines IL-2, IL-4, IL-10, IL-21, TNF-α and IFN-γ and the expressions of the autoantibodies AhCGAb, AsAb and AoAb are significantly higher in IO patients than in normal healthy males. Quantitative analysis of cytokines and autoantibodies in the serum of IO patients may provide some valuable information for studies of the pathogenesis of male infertility.

Prediction model for clinical pregnancy for ICSI after surgical sperm retrieval in different types of azoospermia.

STUDY QUESTION: Can a counselling tool be developed for couples with different types of azoospermia to predict the probability of clinical pregnancy in ICSI after surgical sperm retrieval? SUMMARY ANSWER: A prediction model for clinical pregnancy in ICSI after surgical sperm retrieval in different types of azoospermia was created and clinical type of azoospermia, testicular size, male FSH, male LH, male testosterone, female age, female antral follicle count (AFC) and female anti-Müllerian hormone (AMH) were used as predictors. WHAT IS KNOWN ALREADY: Prediction models are used frequently to predict treatment success in reproductive medicine; however, there are few prediction models only for azoospermia couples who intend to conceive through surgical sperm retrieval and ICSI. Furthermore, no specific clinical types of azoospermia have been reported as predictors. STUDY DESIGN, SIZE, DURATION: A cohort study of 453 couples undergoing ICSI was conducted between 2016 and 2019 in an academic teaching hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples undergoing ICSI with surgically retrieved sperm were included, with 302 couples included in the development set and 151 couples included in the validation set. We constructed a prediction model using multivariable logistic regression analysis. The internal validation was based on discrimination and calibration. MAIN RESULTS AND THE ROLE OF CHANCE: We found that for male patients involved in our model, different clinical types of azoospermia are associated with different clinical pregnancy outcomes after ICSI. Considering the clinical type of azoospermia, larger testicular volume and higher levels of FSH, LH and testosterone in the body are associated with higher clinical pregnancy success rates. For women involved in our model, younger age and higher AFC and AMH levels are associated with higher clinical pregnancy success rates. In the development set, the AUC was 0.891 (95% CI 0.849-0.934), indicating that the model had good discrimination. The slope of the calibration plot was 1.020 (95% CI 0.899-1.142) and the intercept of the calibration plot was -0.015 (95% CI -0.112 to 0.082), indicating that the model was well-calibrated. From the validation set, the model had good discriminative capacity (AUC 0.866, 95% CI 0.808-0.924) and calibrated well, with a slope of 1.015 (95% CI 0.790-1.239) and an intercept of -0.014 (95% CI -0.180 to 0.152) in the calibration plot. LIMITATIONS, REASONS FOR CAUTION: We found that BMI was not an effective indicator for predicting clinical pregnancy, which was inconsistent with some other studies. We lacked data about the predictors that reflected sperm characteristics, therefore, we included the clinical type of azoospermia instead as a predictor because it is related to sperm quality. We found that almost all patients did not have regular alcohol consumption, so we did not use alcohol consumption as a possible predictor, because of insufficient data on drinking habits. We acknowledge that our development set might not be a perfect representation of the population, although this is a common limitation that researchers often encounter when developing prediction models. The number of non-obstructive azoospermia patients that we could include in the analysis was limited due to the success rate of surgical sperm retrieval, although this did not affect the establishment and validation of our model. Finally, this prediction model was developed in a single centre. Although our model was validated in an independent dataset from our centre, validation for different clinical populations belonging to other centres is required before it can be exported. WIDER IMPLICATIONS OF THE FINDINGS: This model enables the differentiation between couples with a low or high chance of reaching a clinical pregnancy through ICSI after surgical sperm retrieval. As such it can provide couples dealing with azoospermia a new approach to help them choose between surgical sperm retrieval with ICSI and the use of donor sperm. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the National Natural Science Foundations of China (81501246 and 81501020 and 81671443). The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.

Neonatal outcome of children born after ICSI with epididymal or testicular sperm: A 10-year study in China.

Some studies show that children born after ICSI with non-ejaculated sperm are at increased risk of birth defects, other studies hold the opposite view. Does neonatal outcome including congenital malformations in children born after ICSI with percutaneous epididymal sperm aspiration (PESA) and testicular sperm aspiration (TESA) differ from neonatal outcome in children born after ICSI with ejaculated sperm? In this study, we examined the data from our IVF center from 2006 to 2016, to compare neonatal outcomes and rates of congenital malformations in children born after ICSI with different sperm origin. The results showed the clinical pregnancy rate and implantation rate of non-ejaculated sperm group were significantly higher (P < 0.001) than ejaculated sperm group. There were 775 clinical pregnancies from non-ejaculated sperm group and 2,486 clinical pregnancies from ejaculated sperm group. Most of the clinical pregnancy outcomes were comparable between non-ejaculated sperm group and ejaculated sperm group (p > 0.05): the miscarriage rate per transfer, ectopic pregnancy rate per clinical pregnancy, induced abortion rate per clinical pregnancy and fetal deaths per clinical pregnancy. However, the live delivery rate per transfer of non-ejaculated sperm group was significantly higher than that of ejaculated sperm group (45.4% vs 36.7%, P < 0.001). Moreover, the comparison between the epididymal sperm, testicular sperm and ejaculated sperm groups showed there were no difference in the incidence of congenital malformations of babies live birth. Among singleton gestation live births, there were more girls than boys in both non-ejaculated sperm and ejaculated sperm group. In conclusion, the present study clearly showed no statistical increased risk in neonatal outcomes of newborns were found in the ICSI treatment with epididymal or testicular sperm. It may provide information for consultation for ICSI treatment in PESA or TESA patients.

[Predictive factors for clinical pregnancy in patients with nonmosaic Klinefelter's syndrome undergoing microdissection testicular sperm extraction].

OBJECTIVE: To investigate the efficiency of microdissection testicular sperm extraction (micro-TESE) in male patients with nonmosaic Klinefelter's syndrome (NMKS), the outcomes of intracytoplasmic sperm injection (ICSI) in their wives, and the possible predictors of clinical pregnancy. METHODS: Forty-nine males with NMKS underwent micro-TESE in our hospital from July 2016 to November 2018. We compared the age, reproductive hormone levels, and testis volume of the patients between the sperm-positive and -negative groups. We performed ICSI for the wives of the sperm-positive patients, recorded the numbers of pregnancies and births, compared the age, reproductive hormone levels and number of mature oocytes between the successful and failed ICSI groups, and analyzed the possible predictors of the results of micro-TESE and outcomes of ICSI. RESULTS: The 49 patients were aged (28.20 ± 3.52) years, all diagnosed as with 47,XXY nonmosaicism by karyotype analysis, with a testis volume of (2.95 ± 0.84) ml, a serum FSH content of (42.42 ± 14.37) IU/L, a serum LH level of (22.50 ± 8.64) IU/L, and a serum T level of (6.64 ± 4.13) nmol/L. Sperm were obtained from 32 of the patients, with a sperm retrieval rate (SRR) of 65.31%, and the wives (aged ï¼»26.79 ± 2.97ï¼½ years) of 29 of the sperm-positive males underwent ICSI, achieving a fertilization rate of (48.14 ± 27.33)%, an available embryo rate of (63.71 ± 28.90)%, a pregnancy rate of 48.28% (14/29), and a birth rate of 24.14% (7/29) up to the present time, with 7 cases awaiting delivery. The 2 cases failing to achieve pregnancy were waiting for transplantation of the frozen embryos. Logistic regression analysis showed that the preoperative serum T level of the NMKS patients had a significant predictive value for the pregnancy rate (AUC = 0.832, cut-off value = 5.17 nmol/L, P = 0.015), but not the other factors for either the SRR or the pregnancy rate. CONCLUSIONS: Sperm can be retrieved from over 60% of the NMKS patients undergoing micro-TESE, and some of them can achieve pregnancy and have their own children by ICSI. Moreover, those with a preoperative serum T level of >5.17 nmol/L are very likely to achieve clinical pregnancy after successful sperm retrieval.

[Medication of Compound Amino Acid Capsules for obstructive azoospermia patients undergoing percutaneous epididymal sperm aspiration and intracytoplasmic sperm injection].

OBJECTIVE: To investigate the effects of Compound Amino Acid Capsules (CAAC) for obstructive azoospermia (OA) patients undergoing percutaneous epididymal sperm aspiration (PESA) and ICSI. METHODS: We retrospectively studied 134 cycles of PESA-ICSI in OA males, who were divided into a CAAC group (n = 64) and a control group (n = 70), the former, aged (32.1 ± 5.7) years, treated with CAAC for 3 months before PESA-ICSI while the latter, aged (32.3 ± 4.5) years, left untreated. We compared the rates fertilization, cleavage, high-quality embryos and blastocyst formation between the two groups of patients. RESULTS: Compared with the control, the CAAC group achieved significantly higher rates of high-quality embryos (ï¼»67.4 ± 13.8ï¼½% vs ï¼»74.3 ± 12.6ï¼½%, P < 0.05) and blastocyst formation (ï¼»60.3±14.2ï¼½% vs ï¼»66.8±14.6ï¼½%, P < 0.05), but no statistically significant differences were observed between the two groups in the ages of the males and females, number of oocytes retrieved, or the rates of fertilization and cleavage. CONCLUSIONS: Medication of Compound Amino Acid Capsules can effectively improve the rates of high-quality embryos and blastocyst formation in obstructive azoospermia patients undergoing PESA-ICSI.

[Results of micro-TESE and outcomes of ICSI in patients with different etiological types of non-obstructive azoospermia].

OBJECTIVE: To compare the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (micro-TESE) and the outcomes of intracytoplasmic sperm injection (ICSI) among different etiological types of non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data on 155 cases of NOA undergoing micro-TESE in our hospital from September 2016 to December 2017, which were classified into three types according to etiological factors: congenital NOA (n = 49), acquired NOA (n = 15) and idiopathic NOA (n = 91). We compared the age, testis volume, levels of reproductive hormones, ultrasonographic manifestations, and SRR of micro-TESE among the three groups of patients. We also recorded and analyzed the rates of fertilization, available embryos and clinical pregnancy in the spouses of the patients included for successful sperm retrieval in micro-TESE. RESULTS: The testis volume was significantly lower in the congenital than in the acquired and idiopathic NOA groups (ï¼»6.4 ± 5.0ï¼½ vs ï¼»10.2 ± 2.0ï¼½ and ï¼»9.9 ± 3.2ï¼½ ml, P < 0.05), while the LH level was markedly higher in the former group than in the latter two (ï¼»15.2 ± 10.1ï¼½ vs ï¼»9.1 ± 6.5ï¼½ and ï¼»7.8 ± 3.5ï¼½ mIU/ml, P < 0.05), and so was the T level in the idiopathic than in the congenital NOA group (ï¼»11.8 ± 4.8ï¼½ vs ï¼»8.9 ± 4.5ï¼½ nmol /L, P < 0.05). The SRRs of micro-TESE in the congenital, acquired and idiopathic NOA patients were 73.5% (36/49), 100% (15/15), and 24.2% (22/91) respectively, with statistically significant differences among the three groups (P < 0.05). The fertilization rate after ICSI was remarkably higher in the acquired than in the congenital and idiopathic NOA groups (ï¼»73.1±23.3ï¼½% vs ï¼»48.9±21.7ï¼½% and ï¼»52.6±22.7ï¼½%, P < 0.05). There were no statistically significant differences among the three groups in the rates of embryo utilization and clinical pregnancy. CONCLUSIONS: The sperm retrieval rate of micro-TESE and the rates of fertilization, embryo utilization and clinical pregnancy after ICSI were the highest in the acquired NOA but the lowest in the idiopathic NOA patients.

Relationships between seminal plasma metals/metalloids and semen quality, sperm apoptosis and DNA integrity.

This study aimed to investigate the relationships between environmental exposure to metals/metalloids and semen quality, sperm apoptosis and DNA integrity using the metal/metalloids levels in seminal plasma as biomarkers. We determined 18 metals/metalloids in seminal plasma using an inductively coupled plasma-mass spectrometry among 746 men recruited from a reproductive medicine center. Associations of these metals/metalloids with semen quality (n = 746), sperm apoptosis (n = 331) and DNA integrity (n = 404) were evaluated using multivariate linear and logistic regression models. After accounting for multiple comparisons and confounders, seminal plasma arsenic (As) quartiles were negatively associated with progressive and total sperm motility using multivariable linear regression analysis, which were in accordance with the trends for increased odds ratios (ORs) for below-reference semen quality parameters in the logistic models. We also found inverse correlations between cadmium (Cd) quartiles and progressive and total sperm motility, whereas positive correlations between zinc (Zn) quartiles and sperm concentration, between copper (Cu) and As quartiles and the percentage of tail DNA, between As and selenium (Se) quartiles and tail extent and tail distributed moment, and between tin (Sn) categories and the percentage of necrotic spermatozoa (all Ptrend<0.05). These relationships remained after the simultaneous consideration of various elements. Our results indicate that environmental exposure to As, Cd, Cu, Se and Sn may impair male reproductive health, whereas Zn may be beneficial to sperm concentration.

[Therapeutic effect of Jinghuosu on oligospermia and asthenospermia.]

OBJECTIVE: To investigate the effects of the compound preparation Jinghuosu on oligospermia and asthenospermia. METHODS: This multi-centered clinical study included 120 cases of mild to moderate idiopathic oligospermia or asthenospermia, all treated with oral Jinghuosu once a bag, bid, for 3 successive months. Before and at 1, 2 and 3 months after treatment, we detected sperm concentration, total sperm motility, progressive sperm motility and normal sperm morphology of each ejaculate, and recorded whether the patients had any adverse reactions. RESULTS: After 3 months of treatment, all the patients showed obvious improvement in semen parameters, most significantly in sperm concentration, total sperm motility, and the percentages of progressive motile sperm and morphologically normal sperm (P <0.05). No significant adverse reactions were observed during the 3 months of medication. CONCLUSIONS: Jinghuosu has a significant efficacy and no obvious adverse effect in the treatment of mild to moderate oligospermia and asthenospermia.

Associations of urinary metal levels with serum hormones, spermatozoa apoptosis and sperm DNA damage in a Chinese population.

BACKGROUND: Exposure to metals, including essential and nonessential elements, is widespread and may be associated with male reproductive health. OBJECTIVE: To examine whether environmental exposure to metals contributes to reproductive hormone changes, spermatozoa apoptosis and sperm DNA damage in a Chinese population. METHODS: Eighteen metals (aluminum, arsenic, antimony, chromium, cobalt, copper, cadmium, iron, lead, manganese, molybdenum, nickel, selenium, tin, tungsten, thallium, uranium and zinc) were analyzed in two urine samples collected a few hours apart from male partners of couples attending an infertility clinic. Multivariable linear regression models were used to assess the cross-sectional associations of average urinary metal levels with serum hormones (n=511), spermatozoa apoptosis measures (n=460) and sperm DNA damage parameters (n=516). RESULTS: We found significant inverse dose-dependent trends of urinary tin quartiles with total testosterone (T), and tin, nickel, zinc and molybdenum with the ratio of total T to luteinizing hormone (total T/LH ratio) (all Ptrend<0.05). Additionally, we found significantly dose-dependent trends of increasing urinary manganese quartiles with increasing percentage of Annexin V+/PI- spermatozoa and increasing iron with decreasing percentage of PI+ spermatozoa (both Ptrend<0.05). These dose-dependent trends remained suggestive or significant after controlling for multiple testing and other metals, and they persisted when the metals were modeled as continuous variables in a cubic spline analysis. There were no significant associations between urinary metals and sperm DNA damage after adjustment for multiple testing. CONCLUSION: Environmental exposure to tin, nickel, zinc and molybdenum may be associated decreased total T or total T/LH ratio; manganese may induce spermatozoa apoptosis, while iron may be important for living spermatozoa. However, additional prospective research is needed to corroborate these findings in the general population.

Association of urinary metal levels with human semen quality: A cross-sectional study in China.

BACKGROUND: Exposure to metals, including essential and nonessential elements, has been linked to male reproductive health in animals. However, findings from human studies are inconsistent. OBJECTIVE: To examine the associations between metal exposure at environmental levels and semen quality in a Chinese population by performing repeated measurements of urinary metals to estimate individual-level exposure. METHODS: From March to June 2013, 1052 men seeking semen evaluation were recruited from the Reproductive Center of Tongji Hospital in Wuhan, China. Each man provided one semen sample and two urine sample. Semen quality parameters and urinary levels of 18 metals were determined. Associations between the urinary metal levels and semen quality parameters were assessed using confounder adjusted linear and logistic regressions. Restricted cubic spline analysis was performed to assess dose-response relationships between continuous metal measurements and outcomes. RESULTS: Urinary levels of cadmium were significantly inversely associated with progressive sperm motility and total motility (both P<0.02) based on multivariable linear regression models, consistent with the trends of increased odds ratios for below-reference semen quality parameters observed in the logistic models (both P<0.05). Additionally, we found significant inverse associations of urinary molybdenum and lead with percentages of normal sperm morphology (both P<0.05). These associations remained suggestive or significant after adjustment for multiple testing. They were also robust to the simultaneous consideration of multiple metals, and curves of restricted cubic spline showed clear dose-response relationships. CONCLUSION: Our findings suggest that environmental exposure to cadmium, molybdenum and lead may contribute to a decline in human semen quality.

Two different concentrations of oxygen for culturing precompaction stage embryos on human embryo development competence: a prospective randomized sibling-oocyte study.

The study was to investigate the effects of oxygen concentration at different levels for culturing pre-compaction embryos on human embryo development competence. A total of 1254 oocytes from 92 patients treated with conventional in vitro fertilization (IVF) were harvested in this study. Oocytes were randomly assigned to the atmospheric (~20%) or low (~5%) oxygen concentration groups on the retrieval day (day 0). Groups were compared with respect to fertilization rates, embryo development, and reproductive outcome. We failed to detect a significant difference on fertilization rate between two groups. However, the low oxygen group yielded more optimal embryos on day 3 when compared with the atmospheric group (72.4% vs. 64.2%). The low oxygen group had a significantly higher blastocyst formation rate than the atmospheric oxygen group (64.5% vs. 52.9%). It is seemly that the optimal blastocyst and frozen blastocyst rates was higher in the low oxygen group, but the data did not reach a statistical significance. Although the use of low oxygen will not affect the clinical outcome in the fresh cleavage-transfer cycles, but it will result in more favorable clinical outcomes in the subsequent warming blastocyst-transfer cycles, with statistically significantly higher clinical pregnancy rate (CPR) and implantation rate (IR) compared with atmospheric oxygen. In conclusion, a low oxygen concentration may significantly improve the developmental potential of pre-compaction embryos, thus resulting in a positive effect on subsequent blastocyst cultivation and optimizing the treatment cycle.

Baseline blood trihalomethanes, semen parameters and serum total testosterone: a cross-sectional study in China.

Toxicological studies showed that trihalomethanes (THMs), the most abundant classes of disinfection by-products (DBPs) in drinking water, impaired male reproductive health, but epidemiological evidence is limited and inconsistent. This study aimed to examine the associations of baseline blood THMs with semen parameters and serum total testosterone in a Chinese population. We recruited 401 men seeking semen examination from the Reproductive Center of Tongji Hospital in Wuhan, China between April 2011 and May 2012. Baseline blood concentrations of THMs, including chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) were measured using SPME-GC/ECD method. Semen quality and serum total testosterone were analyzed. Multivariable linear regressions were used to assess the associations of baseline blood THM concentrations with semen parameters and serum total testosterone levels. We found that baseline blood THM concentrations were not associated with decrements in sperm motility, sperm straight-line and curvilinear velocity. However, moderate levels of BDCM (ß=-0.13 million; 95% CI: -0.22, -0.03) and DBCM (ß=-4.74%; 95% CI: -8.07, -1.42) were associated with decreased sperm count and declined sperm linearity compared with low levels, respectively. Suggestive dose-response relationships were also observed between elevated blood TCM or ∑ THMs (sum of TCM, BDCM, DBCM and TBM) concentration and decreased sperm concentration (both p for trend=0.07), and between elevated blood DBCM concentration and decreased serum total testosterone (p for trend=0.07). Our results indicate that elevated THM exposure may lead to decreased sperm concentration and serum total testosterone. However, the effects of THM exposure on male reproductive health still warrant further studies in humans.

Analysis of birth defects among children 3 years after conception through assisted reproductive technology in China.

BACKGROUND: Previous studies inconsistently suggest that assisted reproduction technology (ART) may increase the risk of birth defects in children. METHOD(S): Live birth infants, conceived by in vitro fertilization fresh embryo transfer (IVF), intracytoplasmic sperm injection fresh embryo transfer (ICSI), or frozen-thawed embryo transfer (FET) in Reproductive Center of Tongji Hospital (Wuhan, China) between 1997 and 2008, were followed up at birth and after 3 years. Preterm pregnancy, multiple pregnancy, sex ratio (male/female), congenital malformation were compared. RESULT(S): A total of 4,236 children were born after ART (IVF 2,543, ICSI 908, FET 785). Compared with IVF, the rate of preterm pregnancy and sex ratio in ICSI were lower (p < 0.05); the rate of multiple pregnancy in ICSI and FET were all lower than IVF (p < 0.05). Congenital defects were comparable in all groups at birth. In total, 2,908 children participated in the second follow-up from 34 months to 60 months with an average of 40 months, and the cases of birth defects had doubled (3 years: 5.16%, birth: 2.22%). The birth defect rate in boys conceived through ICSI was significantly higher than the IVF group after 3-year follow-up (ICSI boys: 8.62%, IVF boys: 5.21% [p < 0.05]), even though there was no significant difference at birth. CONCLUSION(S): Compared with IVF, FET may not increase risk of birth defects. Children conceived through ICSI, especially males, had higher rates of congenital malformations that were inapparent at birth. So longitudinal monitoring may provide insights into the risks of ART.