Associations between exposure to pesticides mixture and semen quality among the non-occupationally exposed males: Four statistical models.

Most epidemiological studies on the associations between pesticides exposure and semen quality have been based on a single pesticide, with inconsistent major results. In contrast, there was limited human evidence on the potential effect of pesticides mixture on semen quality. Our study aimed to investigate the relationship of pesticide profiles with semen quality parameters among 299 non-occupationally exposed males aged 25-50 without any clinical abnormalities. Serum concentrations of 21 pesticides were quantified by gas chromatography-tandem mass spectrometry (GC-MS/MS). Semen quality parameters were abstracted from medical records. Generalized linear regression models (GLMs) and three mixture approaches, including weighted quantile sum regression (WQS), elastic net regression (ENR) and Bayesian kernel machine regression (BKMR), were applied to explore the single and mixed effects of pesticide exposure on semen quality. In GLMs, as the serum levels of Bendiocarb, ß-BHC, Clomazone, Dicrotophos, Dimethenamid, Paclobutrazole, Pentachloroaniline and Pyrimethanil increased, the straight-line velocity (VSL), linearity (LIN) and straightness (STR) decreased. This negative association also occurred between the concentration of ß-BHC, Pentachloroaniline, Pyrimethanil and progressive motility, total motility. In the WQS models, pesticides mixture was negatively associated with total motility and several sperm motility parameters (ß: -3.07∼-1.02 per decile, FDR-P<0.05). After screening the important pesticides derived from the mixture by ENR model, the BKMR models showed that the decreased qualities for VSL, LIN, and STR were also observed when pesticide mixtures were at ≥ 70th percentiles. Clomazone, Dimethenamid, and Pyrimethanil (Posterior inclusion probability, PIP: 0.2850-0.8900) were identified as relatively important contributors. The study provides evidence that exposure to single or mixed pesticide was associated with impaired semen quality.

Trends in sperm quality by computer-assisted sperm analysis of 49,189 men during 2015-2021 in a fertility center from China.

Background: Sperm quality, including semen volume, sperm count, concentration, and total and progressive motility (collectively, "semen parameters"), has declined in the recent decades. Computer-assisted sperm analysis (CASA) provides sperm kinematic parameters, and the temporal trends of which remain unclear. Our objective is to examine the temporal trend of both semen parameters and kinematic parameters in Shanghai, China, in the recent years. Methods: This retrospective study analyzed semen parameters and kinematic parameters of 49,819 men attending our reproductive center by using CASA during 2015-2021. The total sample was divided into two groups: samples that surpassed the WHO guideline (2010) low reference limits ("above reference limit" group, ARL; n = 24,575) and samples that did not ("below reference limit" group, BRL; n = 24,614). One-way analysis of variance, Kruskal-Wallis test, independent samples t-test, and covariance analysis were used to assess the differences among groups. Year, age, and abstinence time were included in the multiple linear regression model of the ARL group to adjust the confounders and depict the trends in sperm quality. Results: Among all the total sample and the ARL and BRL groups, the age of subjects increased in recent years. Semen volume and sperm count showed declined tendency with years in the total sample, the ARL and BRL groups, and the subgroup of age or abstinence time, whereas sperm velocities showed increased tendency with years on the contrary. The multiple linear regression model of the ARL group, adjusting for age and abstinence time, confirmed these trends. Semen volume (ß1= -0.162; CI: -0.172, -0.152), sperm count (ß1= -9.97; CI: -10.813, -9.128), sperm concentration (ß1 = -0.535; CI: -0.772, -0.299), motility (ß1 = -1.751; CI: -1.830, -1.672), and progressive motility (ß1 = -1.12; CI: -0.201, -0.145) decreased with year, whereas curvilinear line velocity (VCL) (ß1 = 3.058; CI: 2.912, 3.203), straight line velocity (VSL) (ß1 = 2.075; CI: 1.990, 2.161), and average path velocity (VAP) (ß1 = 2.305; CI: 2.224, 2.386) increased over time (all p < 0.001). In addition, VCL, VSL, and VAP significantly declined with age and abstinence time. Conclusion: The semen parameters declined, whereas the kinematic parameters increased over the recent years. We propose that, although sperm count and motility declined over time, sperm motion velocity increased, suggesting a possible compensatory mechanism of male fertility.

[Effect of Shanhaidan Granules combined with tadalafil on erectile dysfunction: A multi-center clinical trial].

OBJECTIVE: To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED. METHODS: In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients. RESULTS: After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators. CONCLUSIONS: Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.

Association of homocysteine with IVF/ICSI outcomes stratified by MTHFR C677T polymorphisms: a prospective cohort study.

RESEARCH QUESTION: What is the association between homocysteine (Hcy) and IVF/intracytoplasmic sperm injection (ICSI) outcomes, stratified by methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms? DESIGN: This prospective cohort study recruited 1011 infertile women undergoing IVF/ICSI treatment for the first time at the International Peace Maternity and Child Health Hospital between June 2015 and March 2018. RESULTS: The concentration of total serum Hcy was significantly negatively associated with clinical pregnancy and implantation rate. When adjusted for maternal and paternal age and educational level, maternal body mass index, and FSH and oestradiol concentrations, logistic regression analysis showed that women with higher Hcy had a higher risk of unsuccessful pregnancy. After stratification by MTHFR C677T polymorphisms and adjustment for confounding factors, a higher risk of unsuccessful pregnancy and a significantly lower implantation rate only existed in women with higher Hcy concentration in the MTHFR C677T TT genotype. There was no significant association between Hcy concentrations and other ovarian stimulation outcomes (oocytes retrieved, metaphase II stage oocytes, fertilization rate, cleavage rate, high-quality embryo rate) or neonatal outcomes (preterm birth, gestational age at delivery, Caesarean section, birthweight, small for gestational age, large for gestational age or birth defects). CONCLUSIONS: Hcy is highly negatively associated with clinical pregnancy and implantation rate during the first IVF/ICSI cycle, especially in women carrying the MTHFR C677T TT genotype. Other factors with impacts on reproductive outcomes, such as stage of embryo transferred, other factors involved in folate metabolism, preimplantation genetic testing, etc., should be taken into account in further research.

Melatonin rescues impaired penetration ability of human spermatozoa induced by mitochondrial dysfunction.

Fertilization failure often occurs during in vitro fertilization (IVF) cycles despite apparently normal sperm and oocytes. Accumulating evidence suggests that mitochondria play crucial roles in the regulation of sperm function and male fertility. 3-Nitrophthalic acid (3-NPA) can induce oxidative stress in mitochondria, and melatonin, as an antioxidant, can improve mitochondrial function by reducing mitochondrial oxidative stress. The role of sperm mitochondrial dysfunction in fertilization failure during IVF is unclear. The present study revealed that spermatozoa with low, or poor, fertilization rates had swollen mitochondria, increased mitochondria-derived ROS, and attenuated mitochondrial respiratory capacity. 3-NPA treatment enhanced mitochondrial dysfunction in sperm. Spermatozoa with poor fertilization rates, and spermatozoa treated with 3-NPA, had reduced penetration ability. The concentration of melatonin was decreased in semen samples with low and poor fertilization rates. Melatonin, not only decreased excessive mitochondria-derived ROS, but also 'rescued' the reduced penetration capacity of spermatozoa treated with 3-NPA. Taken together, the study suggested that mitochondria-derived ROS and mitochondrial respiratory capacity are independent bio-markers for sperm dysfunction, and melatonin may be useful in improving sperm quality and overall male fertility.

Correlation between methylenetetrahydrofolate reductase gene polymorphism and oligoasthenospermia and the effects of folic acid supplementation on semen quality.

BACKGROUND: The present study investigated the correlation between 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and oligoasthenospermia, as well as the effects of folic acid supplementation on semen quality. METHODS: The present study was a case control study. The PCR-chip assay was applied to analyze the distribution characteristics of the frequencies and genotypes of the MTHFR C677T allele in 167 Han Chinese patients with idiopathic male infertility (including 86 patients with oligospermia and 81 patients with asthenospermia) and in 78 males with normal semen parameters. Moreover, homocysteine (Hcy) levels were assessed for the different groups. Semen quality was measured following three months of folic acid supplementation for the oligospermia and asthenospermia groups. RESULTS: The cytosine-thymine (CT) genotype (50% vs. 39.5%) and the thymine-thymine (TT) genotype (51.2% vs. 7.7%) carriers in the oligospermia group exhibited significantly higher percentages compared with those of the control group. The percentage of the CT genotype carriers in the asthenospermia group was significantly higher compared with that of the control group (59.3% vs. 50%), while the frequency of the TT genotype was significantly increased (22.2% vs. 7.7%). Furthermore, serum Hcy levels in the oligospermia and asthenospermia groups were significantly higher compared with those of the control group. The data also demonstrated that sperm density increased significantly following three months of folic acid supplementation to patients with oligospermia or asthenospermia. In these patients, the highest increase was noted for the subjects carrying the TT genotype. CONCLUSIONS: The MTHFR C677T mutation and the elevated Hcy levels are important risk factors for the development of oligoasthenospermia. Folic acid supplementation can significantly improve sperm density.

An adapted carrier for the cryopreservation of human testicular spermatozoa.

RESEARCH QUESTION: Does the adapted carrier Cryoplus improve the quality of cryopreserved spermatozoa compared with the use of conventional containers, and what is the effect of the adapted carrier on clinical outcomes? DESIGN: Semen samples from 27 cases of oligozoospermia were used to investigate whether the adapted carrier improved cryopreserved sperm quality compared with the use of 0.25-ml straws and 2-ml cryogenic vials. Thirty testicular sperm samples were used to study the quality of testicular spermatozoa cryopreserved in the adapted carrier. The retrospective study included a further 104 men with azoospermia to investigate the clinical outcomes of testicular spermatozoa cryopreserved with the adapted carriers. Men with mostly obstructive azoospermia were included in this study. RESULTS: The adapted carrier improved cryopreserved spermatozoa motility of semen samples compared with 2-ml cryogenic vials but not compared with 0.25-ml straws. No differences were found in cryopreserved sperm DNA fragmentation among the three carriers. Fertilization and good-quality embryo rates were similar in ICSI cycles using fresh or cryopreserved testicular spermatozoa. Additionally, no difference was evident between frozen-thawed embryo transfer cycles using fresh or cryopreserved testicular spermatozoa in clinical pregnancy, implantation, miscarriage, live birth rates or birth weight. CONCLUSIONS: The adapted carrier improved the cryopreserved sperm motility compared with the effects of 2-ml cryogenic vials. The outcomes of intracytoplasmic sperm injection and frozen-thawed embryo transfer outcomes indicate that testicular spermatozoa cryopreserved using the adapted carrier is not inferior to fresh testicular spermatozoa. The use of the adapted carrier for cryopreserving human testicular spermatozoa especially from obstructive azoospermia is simple and effective.

Effects of vitamin C on the outcome of in vitro fertilization-embryo transfer in endometriosis: A randomized controlled study.

OBJECTIVE: This study was performed to investigate the effect of vitamin C (VitC) supplementation on the outcomes of in vitro fertilization-embryo transfer (IVF-ET) in patients with endometriosis (EMs). METHODS: A total of 280 patients with EMs underwent IVF-ET (VitC treatment group, n=160; VitC non-treatment group, n=120). An additional 150 patients who did not have EMs but underwent IVF-ET (control group) were also enrolled in this study. Superoxide dismutase (SOD), total antioxidant capacity (TAC), malondialdehyde (MDA) and reactive oxygen species (ROS) were measured to determine the role of VitC on oxidative stress markers in serum and follicular fluid (FF). RESULTS: In total, 245 patients with EMs and 132 patients without EMs underwent successful IVF-ET and follow-up. The serum or FF levels of VitC, SOD, and TAC were lower in the EMs than control group; however, the MDA and ROS levels in serum or FF were higher in the EMs than control group. After 2 months of VitC treatment, the serum VitC levels in serum and FF were significantly increased, while oxidative stress markers were unaffected. CONCLUSION: Treatment with VitC oral formulation improved the serum and FF levels of VitC but did not affect oxidative stress markers in patients with EMs.

Effects of fulvic acids on goat sperm.

SummaryThe effects of adding fulvic acids (FAs) to semen extenders on the quality parameters of frozen-thawed goat buck spermatozoa remain undetermined. Buck semen samples collected from six mature goat bucks once a week were diluted with Tris-egg yolk-based extenders. The diluted semen samples were supplemented with FAs (0.2, 0.4 and 0.6%, w/w), cryopreserved, and evaluated for sperm-quality parameters. Addition of FAs to the extender increased progressive motility, acrosome integrity, membrane integrity, and superoxide dismutase and catalase activities and decreased percentage abnormality and sperm malondialdehyde level compared with the control group. However, excessive FA addition (>0.4%, w/w) to semen extenders did not improve the efficiency. The results indicated that FAs could be a promising cryoprotectant for goat buck sperm.

Multicenter study of genetic abnormalities associated with severe oligospermia and non-obstructive azoospermia.

Objective * Chong Xie, Xiangfeng Chen, and Yulin Liu contributed equally to this work. Genetic defects are identified in nearly 20% of infertile males. Determining the frequency and types of major genetic abnormalities in severe male infertility helps inform appropriate genetic counseling before assisted reproductive techniques. Methods Cytogenetic results of 912 patients with non-obstructive azoospermia (NOA) and severe oligozoospermia (SOS) in Eastern China were reviewed in this multicenter study from January 2011 to December 2015. Controls were 215 normozoospermic men with offspring. Results Among all patients, 22.6% (206/912) had genetic abnormalities, including 27.3% (146/534) of NOA patients and 15.9% (60/378) of SOS patients. Chromosomal abnormalities (all autosomal) were detected in only 1.9% (4 /215) of controls. In NOA patients, sex chromosomal abnormalities were identified in 25.8% (138/534), of which 8% (43/534) had a 47,XXY karyotype or its mosaic; higher than the SOS group prevalence (1.1%; 4/378). The incidence of Y chromosome microdeletions was lower in the SOS group (13.2%; 50/378) than in the NOA group (17.8%; 95/534). Conclusions The high prevalence of genetic abnormalities in our study indicates the importance of routine genetic testing in severe male infertility diagnosis. This may help determine the choice of assisted reproductive technique and allow specific pre-implantation genetic testing to minimize the risk of transmitting genetic defects.

Liver receptor homologue-1 and steroidogenic factor-1 expression in cultured granulosa cells from patients with endometriosis: A preliminary study.

AIM: The expression of aromatase (via CYP19 and the CYP19 PII promoter) and the orphan nuclear receptor family members, liver receptor homologue-1 (LRH-1) and steroidogenic factor-1 (SF-1) in cultured luteinized granulosa cells from women with endometriosis were investigated. METHODS: Luteinized granulosa cells from patients undergoing in vitro fertilization (16 patients with endometriosis and 28 controls) were examined for messenger ribonucleic acid (mRNA) expression of CYP19, CYP19 PII, LRH-1 and SF-1, determined by quantitative reverse transcription-polymerase chain reaction. Student's t-test, the Mann-Whitney U test and Spearman's rank correlation were used for statistical analysis. RESULTS: The number of high quality embryos in the endometriosis group was significantly lower than in the control group. The mRNA expression levels of CYP19, CYP19 PII, LRH-1 and SF-1 in granulosa-lutein cells were decreased in women with endometriosis compared to the control group. The simultaneous down-regulation expression of LRH-1, SF-1 and CYP19 PII in endometriotic granulosa cells indicated their positive correlation. CONCLUSION: Our results demonstrate aberrant expressions of SF-1 and LRH-1 in endometriotic granulosa-lutein cells. This finding may be helpful in understanding infertility associated with endometriosis and reduced P450 aromatase activity in endometriotic granulosa cells.

Correlation between body mass index of Chinese males and assisted reproductive technology outcome.

OBJECTIVE: To investigate the relationship between male's body mass index (BMI) and the outcome of assisted reproductive technology (ART). In this retrospective study, we analyzed the data from 729 cycles of female patients aged 38 years or less, with normal BMI and who received IVF treatments between January, 2013 and June, 2014. The patients were divided into normal weight (n = 358), overweight (n = 267), and obese (n = 104) groups according to the BMI of their male partners. Embryonic development and pregnancy outcomes in these three groups were compared. RESULTS: With increasing BMI, fertilization rates decreased proportionately (P < 0.05); but embryonic cleavage rates and effective embryo rates were not significantly affected (P > 0.05). There was no significant difference in implantation rates, pregnancy rates, or early miscarriage rates (P > 0.05) among the three groups. CONCLUSIONS: High male BMI affects fertilization rate with ART; and we recommend that men of reproductive age adjust their lifestyles accordingly and make efforts to control their weight.

Assessment of density gradient centrifugation (DGC) and sperm chromatin dispersion (SCD) measurements in couples with male factor infertility undergoing ICSI.

PURPOSE: To investigate how effectively density gradient centrifugation (DGC) improves sperm nuclear integrity and to determine whether the sperm chromatin dispersion (SCD) test of sperm nuclear integrity in native or DGC-treated semen can predict the outcome of assisted reproductive technology (ART) in couples undergoing intracytoplasmic sperm injection (ICSI). METHODS: The DNA integrity of spermatozoa from 63 male factor infertility patients undergoing ICSI was analyzed by the SCD test before and after DGC. The predictive value of the sperm DNA fragmentation index (DFI) for ART outcomes was assessed in a cohort of 45 patients who were undergoing fresh embryo transfer. For the analysis, they were divided into pregnant and non-pregnant groups and, independently, into high sperm DFI (DFI > 30%) and low sperm DFI (DFI ≤ 30%) groups. Both raw and DGC semen parameters were examined. RESULTS: In the asthenospermia and oligozoospermia groups, DGC decreased the sperm DFI from 31.5 ± 19.7 and 28.5 ± 10.3 to 19.2 ± 18.3 and 16.0 ± 12.8, respectively (P < 0.01). DGC decreased the sperm DFI in the severe oligozoospermia group from 41.4 ± 19.0 to 36.3 ± 20.6 (P > 0.01). The pregnant and non-pregnant groups did not differ in their fertilization rate and sperm DFI in native or DGC semen (P > 0.05). There was also no significant difference between the high sperm DFI (DFI > 30%) and low sperm DFI (DFI ≤ 30 %) groups with regard to fertilization rate, implantation rate, and clinical pregnancy rate for both native and DGC semen (P > 0.05). The patients undergoing ICSI with a high sperm DFI had a higher pregnancy loss rate (defined as spontaneous miscarriage or biochemical pregnancy) compared with patients with a low sperm DFI in both the native and DGC semen groups. CONCLUSIONS: DGC highly significantly reduces sperm DNA fragmentation in the semen of ICSI patients, with the exception of those with severe oligozoospermia. The results of the SCD test of sperm DNA fragmentation in native or DGC semen do not correlate with the fertilization rate, implantation rate, or clinical pregnancy rate in patients undergoing ICSI.

[Short-term medication of L-carnitine before intracytoplasmic sperm injection for infertile men with oligoasthenozoospermia].

OBJECTIVE: To observe the pregnancy promoting effect of L-carnitine combined with intracytoplasmic sperm injection (ICSI) in treating male infertility with oligoasthenozoospermia. METHODS: We assigned 129 patients with oligoasthenozoospermia to receive 2 weeks of oral L-carnitine followed by ICSI (medication group, n = 42) and ICSI alone (control group, n = 87). We compared the sperm concentration and motility, the percentage of grade a + b sperm, and sperm deformity before and after L-carnitine medication, as well as the rates of fertilization, cleavage, available embryo and clinical pregnancy between the two groups. RESULTS: The percentage of grade a + b sperm was significantly increased after L-carnitine medication as compared with the baseline ([13.5 +/- 10.7] % vs [9.6 +/- 7.2] %, P<0.05), and so was the rate of available embryo in the medication group after ICSI in comparison with that of the control group (77.50% vs 69.04%, P<0.05). CONCLUSION: Short-term medication of L-carnitine can improve sperm quality and raise the success rate of ICSI.

[Advances in application of sildenafil to erectile dysfunction].

Since the worldwide introduction of sildenafil in 1998, 23 million patients with ED have been treated with the drug, and the accumulated experiences have proved its safety and efficacy. This article presents a review about the action mechanism and metabolic process of sildenafil, with a particular focus on the application of sildenafil to ED diagnosis, the curative effect of its daily use on ED, the standard treatment, combined therapy and progressive protocol with sildenafil for ED and its complications, along with such safety aspect as its effect on the sight.