[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.

[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.

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.

[Effects of abnormal structure of sperm chromatin on the outcome of in vitro fertilization and embryo transfer].

OBJECTIVE: To explore the effects of sperm chromatin structure abnormalities on the outcome of in vitro fertilization and embryo transfer (IVF-ET). METHODS: Sperm DNA fragmentation and chromatin packaging defects were assessed in 136 couples undergoing IVF-ET because of infertility. The relationship between sperm DNA fragmentation, chromatin packaging defects and fertilization rate and clinical pregnancy was evaluated. RESULTS: Both sperm DNA fragmentation and chromatin packaging defect had a negative correlation with fertilization rate (r=-0.198, P<0.05, and r=-0.389, P<0.01, respectively). Both parameters were higher in couples who failed to achieve pregnancy than those who achieved clinical pregnancy (10.74% vs. 5.40%, P<0.01 and 23.58% vs. 11.83%, P<0.01, respectively). CONCLUSION: Abnormality of sperm chromatin structure is one of the reasons for IVF-ET failure. Examination of sperm chromatin structure is helpful in predicting the risk of IVF-ET failure and optimizing treatment of infertility.

Sperm chromatin anomalies have an adverse effect on the outcome of conventional in vitro fertilization: a study with strictly controlled external factors.

Conflicting conclusions present in earlier studies on the relationship between sperm chromatin anomalies and outcome of conventional in vitro fertilization (IVF) may result from confounding by poorly controlled external factors. We examined the relationship of sperm chromatin parameters and outcome of conventional IVF while strictly controlling external factors.

[Effects of mTR antisense oligodeoxynucleotide on telomerase activity and the expression of telomerase mTR in type A spermatogonia].

OBJECTIVES: To study the inhibitory effects of mouse telomerase RNA (mTR) antisense oligodeoxynucleotide(ASODN) on telomerase activity in rat spermatogonia. METHODS: 9-mer phosphorothioate mTR-ASODN was encapsulated by Lipofect AMINE 2000 (LF 2000) and transfected to type A spermatogonia in Snrague Dawley (SD) rat. Telomerase activity was detected by aid of TRAP-SYBR-Green staining and Bioluminescence technique in type A spermatogonia treated or untreated with ASODN. RESULTS: mTR-ASODN conjugated with LF 2000 could significantly inhibit telomerase activity of spermatogonia(P < 0.01). mTR mRNA level also decreased while the spermatogonia were treated with ASODN for 24 h. No change of telomerase activity and apoptosis were observed when SODN, RODN or single LF 2000 was used. CONCLUSIONS: Antisense oligodeoxynucleotide of mTR conjugated with LF 2000 could significantly inhibit telomerase activity of spermatogonia. mTR-ASODN might inhibit telomerase activity of spermatogonia at transcription level.