Search

Objective: Human choriogonadotrophin (hCG) treatment of gonadotrophin-deficient infertile men uses hCG of urinary (uhCG) or recombinant (rhCG) origin, but these treatments have not been compared nor are there studies defining rhCG dosing in men., Design: hCG products were studied in randomized cross-over single-dose studies of standard (Study 1, 1500 IU and 62.5 µg, respectively) or high (Study 2, 5000 IU and 250 µg) dose and a multi-dose population pharmacology study of hCG use., Participants: Eight (Study 1) and seven (Study 2) volunteers in cross-over and 52 gonadotrophin-deficient men in the multi-dose study MEASUREMENTS: In cross-over studies, serum testosterone (T), dihydrotestosterone (DHT) and estradiol by liquid chromatography-mass spectrometry (LCMS) and serum hCG, LH, FSH, SHBG and T (observational study) by immunoassays., Results: After standard and high-dose injection, serum hCG and testosterone responses had similar timing and peak concentrations except for a mildly lower early (<48 h) serum testosterone with uhCG. In the multi-dosing study, both hCGs had similar pharmacokinetics (pooled half-life 5.8 days, p < .001), while serum testosterone concentrations were stable after injection and did not differ between hCG products. Bench testing verified that 20% of pens from 4/10 individuals were used inappropriately., Conclusions: Although hCG pharmacokinetics are not formally bioequivalent, the similar pharmacodynamic effects on serum testosterone indicate that at the doses tested both hCGs provide comparable clinical effects. The starting dose of rhCG for treating gonadotrophin-deficient men should be 62.5 µg (6 clicks) of the rhCG pen., (© 2024 Commonwealth of Australia. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Objective: To explore the taxonomic and predicted functional relationship between the urine microbiome and alterations of semen analysis (SA) parameters., Design: Cross-sectional study., Setting: Academic medical center., Patient(s): Men presenting for fertility evaluation or men presenting for vasectomy consultation with proven biological paternity were recruited and stratified on the basis of alterations, or lack thereof, in SA parameters., Main Outcome Measure: Changes in the functional and taxonomic urine microbiome profiles of participants with or without alterations in SA parameters., Results: Seventy-three participants were included in our study. Men with abnormal sperm motility (N = 27) showed a nearly 50-fold higher abundance of Dialister micraerophilus compared with those with normal sperm motility (N = 46). This relationship persisted on canonical correlational analysis (r = 0.439). Men with abnormal sperm concentration (N = 20) showed a lower abundance of Enterococcus faecalis and Staphylococcus aureus, compared with those with normal sperm concentration (N = 53). The urine of participants with impaired sperm motility demonstrated dramatic differences in predictive functional profiles in pathways involved in oxidation-reduction balance and cell longevity., Conclusions: Our findings underscore differences in the urinary microbiome and abnormalities in semen parameters, especially sperm motility. By incorporating predictive functional profiling, we also highlight possible mechanisms that may drive the observed differences in sperm parameters., Competing Interests: Declaration of Interests V.O. has nothing to disclose. A.B. has nothing to disclose. R.K. has nothing to disclose. J.T.S. has nothing to disclose. T.P.F. has nothing to disclose. J.S.A. has nothing to disclose. T.K. has nothing to disclose. S.F.M. has nothing to disclose. C.D.T. has nothing to disclose. T.-C.M.H. has nothing to disclose. J.N.M. is a consultant for Halozyme Pharma, Boston Scientific, and Endo Pharmaceuticals. S.V.E. has nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Bisphenol S (BPS) was introduced in the market as a potentially safer alternative to bisphenol A (BPA). However, there are limited studies on health effects of BPS and no epidemiologic studies on its relationship with male reproductive health outcomes, specifically semen quality., Objective: To investigate predictors of urinary BPS concentrations and its association with semen parameters among men attending a fertility center., Methods: This cross-sectional analysis included 158 men of couples seeking fertility treatment (2011-2017) contributing 338 paired semen and urine samples. At the time of sample collection, men completed a questionnaire on self-reported use of household products and food intake within the previous 24 h. Urinary concentrations of BPA, BPS and bisphenol F were quantified using isotope-dilution tandem mass spectrometry. Semen samples were analyzed following WHO guidelines. Multivariable mixed models were used to investigate predictors of urinary BPS concentrations and to evaluate associations between urinary BPS concentrations and semen parameters, using random intercept to account for correlation in outcomes across multiple observations per man and adjusting for abstinence time, specific gravity, age, body mass index (BMI), year of sample collection and BPA concentrations. Analyses were also stratified by BMI (≥25 vs <25 kg/m 2 )., Results: Median (IQR) urinary BPS concentration was 0.30 (0.20, 0.90) μg/L, and 76% of samples had detectable (>0.1 μg/L) concentrations. Self-reported fabric softener and paint/solvent use as well as intake of beef and cheese within 24 h before urine collection were positively associated with BPS concentrations. Men with higher BPS concentrations also had significantly higher BMI. Lower semen parameters were found among men with detectable BPS concentrations, compared to men with non-detectable BPS [2.66 vs. 2.91 mL for volume (p = 0.03), 30.7 vs. 38.3 mil/mL for concentration (p = 0.03), 76.8 vs. 90.0 mil for total count (p = 0.09), 43.7 vs. 47.0% for motility (p = 0.06), and 5.42 vs. 6.77% for morphologically normal sperm (p = 0.24)]. Some associations of BPS with lower semen parameters were only found among men with a BMI ≥ 25 kg/m 2 ., Conclusions: We identified dietary and lifestyle factors associated with BPS exposure, suggesting potential avenues for reducing exposures. We also observed negative associations between BPS and semen parameters, especially among overweight and obese men., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study, the presence of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma urealyticum and Ureaplasma parvumDNA were investigated using real-time multiplex PCR detection kit in the urine samples of 50 patients who presented to the infertility polyclinic. Patients were classified into two groups in accordance with the WHO leucocytospermia criteria as over 1 × 10 6 /ml (n = 25) and below 1 × 10 6 /ml (controls; n = 25). In addition, the semen sample results of the patients were evaluated. The mean leucocyte count in the leucocytospermia group was detected as 3.4 × 10 6 /ml. Agent positivity was found in 12 of 25 patients in the leucocytospermia group (U. parvum 10, U. urealyticum 3, M. hominis 3) and 9 of 25 patients in the control group (U. parvum 7, U. urealyticum 2, M. hominis 1). A chi-square test evaluation revealed no statistically significant difference between groups. (p = 0.390). The statistical evaluation using the Mann-Whitney U and chi-square tests revealed no statistically significant negative effect of agent positivity on semen analysis parameters in either group (p > 0.05). Although no significant difference was detected between the groups, this study provides data about the prevalence of asymptomatic sexually transmitted diseases in patients presenting to the infertility polyclinic., (© 2018 Blackwell Verlag GmbH.)

Bisphenol A (BPA) is an endocrine disruptor that is widely produced as a by-product in the plastics industry. The aim of the current study was to identify any association between urinary BPA levels and infertility related factors in patients who presented to the andrology clinic of a university hospital in Upper Egypt. In this case-control study, urinary BPA levels in 50 infertile patients and 50 matched controls were measured by high-performance liquid chromatography. Semen quality (sperm concentration, morphology, and motility) and oxidative stress (total antioxidant activity and malondialdehyde levels) were determined along with sperm DNA damage via alkaline comet assays. BPA concentrations were similarly high in urine samples from all infertile patients and fertile controls, with median values of 24.2 μg/l and 20.9 μg/l, respectively. Total BPA levels were negatively associated with semen quality and antioxidant levels, and positively correlated with DNA damage, especially with multiple semen profile defects, alongside seminal-plasma lipid peroxidation., (Copyright © 2018. Published by Elsevier Inc.)

Background: The use of PFRs has steadily increased as brominated compounds have been or are being phased out. Human exposure is widespread and animal studies have shown adverse impacts on male reproduction, but human data are lacking., Objective: To study the associations between urinary concentrations of phosphorous-containing flame retardant (PFR) metabolites and semen parameters., Methods: A subset of 220 men from an existing longitudinal cohort of couples were recruited from Massachusetts General Hospital fertility clinic between 2005 and 2015. Semen parameters included sperm count, concentration, motility, and morphology; some men had samples measured from multiple clinic visits (up to five visits; n = 269 semen samples). Metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] were measured in urine samples (between one and five urine samples per participant; n = 355 urine samples). Semen parameters were evaluated continuously and dichotomized for models. Metabolites were assessed for associations with semen parameters as continuous and categorized into quartiles using multivariable generalized mixed models, adjusted for specific gravity, age, BMI, smoking, and abstinence period., Results: Metabolites BDCIPP, DPHP, and ip-PPP were detected in a high proportion of urine samples (85%, 86%, and 65% respectively). Concentrations varied by season of collection, particularly for BDCIPP where samples collected in the summer were approximately 2-fold higher than concentrations of other seasons (p < 0.0001). The odds of having a sperm count less than 39 mil/ejaculate decreased by 20% for increasing BDCIPP concentrations (p = 0.04). When regressing semen parameters on PFR metabolite quartiles, some negative associations were observed for individual quartiles among sample volume and morphology, but overall associations were weak and inconsistent., Conclusion: Detection rates were high for BDCIPP, DPHP, and ip-PPP. We did not observe consistent associations between PFR metabolites and semen parameters. Due to the high prevalence of exposure, further investigation of other potential health effects should be conducted., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

In biomedical research, multiple endpoints are commonly analyzed in "omics" fields like genomics, proteomics and metabolomics. Traditional methods designed for low-dimensional data either perform poorly or are not applicable when analyzing high-dimensional data whose dimension is generally similar to, or even much larger than, the number of subjects. The complex biochemical interplay between hundreds (or thousands) of endpoints is reflected by complex dependence relations. The aim of the paper is to propose tests that are very suitable for analyzing omics data because they do not require the normality assumption, are powerful also for small sample sizes, in the presence of complex dependence relations among endpoints, and when the number of endpoints is much larger than the number of subjects. Unbiasedness and consistency of the tests are proved and their size and power are assessed numerically. It is shown that the proposed approach based on the nonparametric combination of dependent interpoint distance tests is very effective. Applications to genomics and metabolomics are discussed.

Background: Polycyclic aromatic hydrocarbons (PAHs) are a group of ubiquitous environmental pollutants. In vivo and in vitro studies have demonstrated that PAHs can alter endocrine function, yet evidence from human studies is limited., Objectives: The objective of this study was to investigate whether environmental exposure to PAHs was associated with altered reproductive hormone levels, using repeated measures of urinary OH-PAHs as biomarkers., Methods: We measured 10 monohydroxylated PAHs (OH-PAHs) in repeated urine samples from 371 men in an infertility clinic in Wuhan, China. Multivariable linear regression models were used to estimate the associations between average urinary OH-PAH levels and serum reproductive hormones, and restricted cubic spline models were further used to examine the shapes of dose-response relationships., Results: We observed dose-response associations of urinary 2-hydroxynaphthalene (2-OHNa) with decreased serum free testosterone (fT) and urinary 1-hydroxypyrene (1-OHP), 9-hydroxyphenanthrene (9-OHPh), and 9-hydroxyfluorene (9-OHFlu) with decreased serum estradiol (all P for trends <0.05). These associations were linear and significant when these four OH-PAHs were modeled as continuous variables in restricted cubic spline models. Furthermore, a U-shaped association was observed across urinary 4-OHPh levels, with lower levels of serum sex hormone-binding globulin (SHBG) at median concentrations compared with 5th and 95th percentile concentrations., Conclusion: Environmental levels of PAH exposure in our study are associated with altered reproductive hormones. However, further research is needed to confirm our findings., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Objective: The aim of this study was to evaluate the association between environmental exposure to parabens and semen quality parameters [main semen parameters, computer-aided semen analysis (CASA parameters], sperm chromatin structure, and the level of reproductive hormones in men [follicle-stimulating hormone (FSH), testosterone, estradiol]., Methods: Urine samples collected from 315 men who attended the infertility clinic for diagnostic purposes with normal semen concentration of 15 to 300 mln/mL were analyzed for five parabens concentrations using a validated gas chromatography ion-tap mass spectrometry method. Participants were interviewed and also provided a semen, saliva, and blood samples., Results: Urinary parabens concentrations were significantly associated with an increase in the percentage of sperm with abnormal morphology, in sperm with high DNA stainability and a decrease in the percentage of motility and testosterone level., Conclusions: This is one of the first study on this topic, so the observation of the relationship between parabens and semen quality warrants further investigation.

Certain genetic background (mainly Y chromosome haplogroups, Y-hg) may modify the susceptibility of certain environmental exposure to some diseases. Compared with respective main effects of genetic background or environmental exposure, interactions between them reflect more realistic combined effects on the susceptibility to a disease. To identify the interactions on spermatogenic impairment, we performed Y chromosome haplotyping and measurement of 9 urinary phenols concentrations in 774 infertile males and 520 healthy controls in a Han Chinese population, and likelihood ratio tests were used to examine the interactions between Y-hgs and phenols. Originally, we observed that Y-hg C and Y-hg F * might modify the susceptibility to male infertility with urinary 4-n-octylphenol (4-n-OP) level (P inter = 0.005 and 0.019, respectively). Subsequently, based on our results, two panels were tested to identify the possible protective sub-branches of Y-hg F * to 4-n-OP exposure, and Y-hg O3 * was uncovered to interact with 4-n-OP (P inter = 0.019). In conclusion, while 4-n-OP shows an adverse effect on spermatogenesis, Y-hg O3 * makes individuals more adaptive to such an effect for maintaining basic reproductive capacity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The role that adequate iodine intake could have on the male reproductive function is not entirely known. The aim of this study is to determine whether there is a relation between male infertility and urinary and semen iodine levels in 96 couples who underwent consultation for infertility. The median of semen iodine was higher in men who consumed iodized salt than in those who consumed non-iodized salt (p=0.019). Men with a higher semen iodine level had more morphological alterations in spermatozoa (p=0.032). Men with a higher urinary iodine level had a lower motile sperm count according to the "direct swim-up" technique (p=0.044). Men >3years without successfully achieving pregnancy had a higher urinary iodine level than those with ≤ 3years (p=0.035). In conclusion, iodine may play a role in the quality of semen: an increase in semen iodine levels is associated with different variables related to male infertility., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Inconsistent results between polycyclic aromatic hydrocarbons (PAHs) exposure and adverse male reproductive health have been reported in humans. To assess whether PAH exposure is associated with declined sperm function. Ten monohydroxylated PAHs (OH-PAHs) metabolites were analyzed in repeated urine samples from an infertility clinic. We used multivariable linear models to estimate the associations of urinary OH-PAH metabolites with sperm DNA damage (n=405) and spermatozoa apoptosis (n=366). The shapes of dose-dependent associations of exposure measurements with outcomes were further evaluated by restricted cubic splines. Multiple comparisons were adjusted by false discovery rate (FDR). We found that urinary 9-hydroxyfluorene (9-OHFlu) was associated with increased tail length and comet length (p for trend=0.05 and 0.01, respectively), and that urinary 9-hydroxyphenanthrene (9-OHPh) was associated with decreased percentage of Annexin V - /PI - spermatozoa (p for trend=0.04). Also, suggestive associations of urinary 9-OHPh and ∑OHFlu with increased comet length, and urinary 9-OHFlu and 2-OHPh with decreased percentage of Annexin V - /PI - spermatozoa were observed (all p for trends <0.10). Further, these dose-dependent associations were confirmed in restricted cubic splines. Our results suggest that environmental exposure to fluorene and phenanthrene are associated with declined sperm function., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In non-azoospermic patients with low semen volume (LSV), looking for partial retrograde ejaculation (PRE) by searching sperm in the postejaculatory urine (PEU) is required. The use of a retro-ejaculatory index (R-ratio) was suggested to define PRE, but none of the studies indicated a specific threshold above which PRE must be considered. Our objective was to propose a threshold value for the R-ratio as indicative of PRE in patients with LSV selected to be devoid of any known causes or risk factors for retrograde ejaculation or LSV. Among our data base (2000-2009) including 632 patients with PEU, 245 male patients from infertile couples who had had a first semen analysis with LSV (< 2mL) and a second semen analysis associated with PEU, were selected on the previous criteria. A prospective control group was randomly constituted (2007-2008) of 162 first consulting male patients from infertile couples, with a normal semen volume (≥ 2mL) on a first semen analysis and who accepted to collect PEU with their usual second semen analysis, selected on the previous criteria. To define an R-ratio threshold indicative of PRE, we used a ROC curve analysis and a regression tree based on a classification and regression tree (CART) algorithm. Of the 245 LSV patients, 146 still presented low semen volume (< 2 mL) on the second semen analysis. From the use of the CART algorithm, two low (1.5% and 2.8%) and two high R-values (7.1% and 8.3%) were defined, according to the lower reference limit for semen volume of 2.0 mL (WHO 1999) or 1.5 mL (WHO 2010) respectively. As only one or no patient with normal semen volume was observed above the two high R-values, we suggest an R-value higher than the range of [7.1-8.3]% as indicative of PRE until confirmation by a prospective multicenter study., Competing Interests: The authors have declared that no competing interests exist.

Previous studies have given conflicting results about the effect of generally infection and Chlamydia trachomatis on seminal ILs and semen parameters. The aim of this study was to investigate the relationship between semen quality and the level of seminal interleukins (ILs) in infertile couples with C. trachomatis. Blood, first void urine (FVU) and semen were obtained from 250 infertile men who had failed to conceive after 12 months of trying. Serological analysis for specific IgA, IgM and IgG antibodies to C. trachomatis in serum, the presence of C. trachomatis in FVU and semen sample and semen analysis were carried out. The main results are as follows: (i) elevated IL-6 and IL-8 are observed in C. trachomatis-positive men, but this is not significant and it varies by diagnostic method; and (ii) IL-6 and IL-8 levels were correlated with each other and the concentration of leucocytes, but IL-8 was correlated with semen volume and patient's age. This study showed that men with such an infection in FVU samples (PCR positive) had only lower semen volume compared with men without infection., (© 2015 Blackwell Verlag GmbH.)

This study aimed to examine associations between urinary metal concentrations and sperm DNA damage. Thirteen metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] were detected in urine samples of 207 infertile men from an infertility clinic using inductively coupled plasma mass spectrometry, and also, sperm DNA damage (tail length, percent DNA tail, and tail distributed moment) were assessed using neutral comet assay. We found that urinary Hg and Ni were associated with increasing trends for tail length (both p for trend<0.05), and that urinary Mn was associated with increasing trend for tail distributed moment (p for trend=0.02). These associations did persist even when considering multiple metals. Our results suggest that environmental exposure to Hg, Mn, and Ni may be associated with increased sperm DNA damage., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Study Question: Do phthalates create a male reproductive hormone imbalance by down-regulating the secretion of testosterone and insulin-like factor 3 (INSL3)?, Summary Answer: Our study suggests that exposure to phthalates is related to a reduction in the secretion of testosterone and INSL3 in adult males., What Is Known Already: There is evidence that exposure to phthalates, an abundant group of industrial plasticizers, negatively affects testosterone biosynthesis, but little is known about the mechanism in men. The hypothesis that exposure to phthalates reduces the levels of testosterone and INSL3, a marker of Leydig cell function, is underexplored., Study Design, Size, Duration: This case-control study of 176 men ran from 2010 to 2012. Infertile men were recruited through infertility clinics in Taiwan, fertile men were recruited from childbirth preparation classes and all were categorized based on the World Health Organization definition of infertility and by the diagnoses of obstetricians., Participants/materials, Setting, Methods: Urinary concentrations of 11 phthalate metabolites were measured, along with serum levels of FSH, LH, total testosterone (TT), estradiol, sex hormone-binding globulin and Inhibin B. Androgen status indices including free testosterone (fT) and the free androgen index (FAI) were calculated. The circulating INSL3 level was evaluated using a radioimmunoassay. Non-parametric analyses, trend tests and linear regression models were used., Main Results and the Role of Chance: Urinary mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate (MEHP) and mono-2-ethyl-5-carboxypentyl phthalate were significantly higher in infertile than in fertile men. Serum Inhibin B, the Inhibin B : FSH ratio, the TT : LH ratio and INSL3 were significantly lower in infertile men. In multiple regression models controlled for potential confounders, there is an inverse association between urinary levels of mono-methyl phthalate (MMP), mono-iso-butyl phthalate (MiBP), MEHP, MEHP% and serum TT (P = 0.001, 0.007, 0.042 and 0.012, respectively). The inverse associations were also found between urinary levels of MiBP, monobenzyl phthalate (MBzP), MEHP, MEHP% and serum fT (P = 0.028, 0.017, 0.045 and 0.027, respectively); between urinary levels of MMP, MEHP, MEHP% and the TT : LH ratio (P = 0.004, 0.029 and 0.039, respectively); between urinary levels of MMP, MiBP, MnBP, MBzP, MEHP and the FAI (P = 0.002, 0.008, 0.037, 0.028, 0.042 and 0.016, respectively). Urinary MBzP and MEHP% were negatively associated with a decrease in serum INSL3 (P = 0.049 and <0.001). We also observed a strong inverse relationship between MEHP% quartiles and serum TT, fT, the TT : LH ratio and INSL3 (Ptrend = 0.003, 0.080, 0.002 and 0.012, respectively). Serum INSL3, TT, fT and the TT : LH ratio were lower for men in the highest MEHP% quartile than in the reference group (P = 0.007, 0.002, 0.090 and 0.001, respectively)., Limitations, Reasons for Caution: A potential limitation is using a single urine and blood sample to predict urinary phthalate metabolites and reproductive hormone status over long periods. However, there is evidence that a single measure provides a reliable result in population studies., Wider Implications of the Findings: Non-occupational exposure to phthalates, including di-2-ethylhexyl phthalate, might lead to adverse effects on testicular/Leydig cell function and be of concern owing to the ubiquitous multisource exposure to phthalates among the general population. Although our findings are in agreement with recent experimental data, more studies are required to draw firm conclusions on the relation of INSL3 to phthalate exposure or testicular/Leydig cell function., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: Study microflora of urine, ejaculate, urethra scrape in normal state and infertility., Materials and Methods: 2 groups of men were examined: I (28)--control, conditionally healthy men (20 - 25 years of age), II (26)--infertile patients (25 - 35 years of age). Middle portion of morning urine, ejaculate, urethra scrape were studied in group I, in II--ejaculate. Bacteriologic study of urine and ejaculate was carried out in an extended kit of nutrient media (HiMedia) for facultative- anaerobic (FAB) and non-clostridia anaerobic bacteria (NAB). Urethra scrape and ejaculate were studied by PCR in group I., Results: In urethra scrape and ejaculate a wide spectrum of FAB and NAB was detected in group I. Corynebacterium spp. and coagulase-negative staphylococci (67.9% each) were the dominant cluster of FAB. Eubacterium spp.--in NAB. Bacteriologic study of ejaculate corresponded in PCR with similar results of dominating bacteria. Among FAB the same clusters dominated during bacteriologic study of ejaculate from group II patients, among NAB--Propionibacterium spp., Peptococcus spp. and Peptostreptococcus spp. Quantitative characteristics of ejaculate of group I and II differed insignificantly., Conclusion: The frequency of detection of certain genera of FAB and NAB was significantly higher in patients with infertility than in conditionally healthy men, however quantitative parameters of the isolated microorganisms practically did not differ between groups.

Background/aim: Studies suggest that trace elements may have an adverse impact on male reproduction, even at low levels. We tried to investigate the relationships between these metals and semen quality in various body fluids among men with infertility., Materials and Methods: A total of 255 samples of blood, semen, and urine were collected from 85 men suffering from infertility. Inductively coupled plasma-optical emission spectrometry was used for the determination of 22 trace elements. We compared the results of the semen parameters with the results of the element determinations., Results: Because of the high proportion of samples with values lower than the limit of detection for a number of the elements, only 8 of a total 22 trace elements were determined in the samples. When the concentrations of sperm were classified according to the World Health Organization's guidelines for normospermia, oligospermia, and azoospermia, statistically significant differences were found among Zn, Ca, Al, Cu, Mg, Se, and Sr concentrations in various serum, sperm, and urine samples (P < 0.05)., Conclusion: In the present study, we found significant correlations between concentrations of Zn, Ca, Al, Cu, Mg, Se, and Sr and semen parameters in various body fluids.

Retrograde ejaculation, sometimes called dry orgasm, refers to the medical condition when semen enters the urinary bladder (retrograde) instead of emerging through the penis after orgasm (antegrade). In some instances, a very minute quantity of antegrade semen appears in the ejaculate and may or may not be devoid of spermatozoa. Complete retrograde ejaculation causes male infertility. Intracytoplasmic sperm injection (ICSI) has been employed to achieve fertilization in some cases of male subfertility, e.g., severe oligoasthenoteratozoospermia. Assisted reproductive techniques to aid conception in cases of retrograde ejaculation have been described extensively elsewhere but there is paucity of knowledge on the occurrence and treatment in Africa. This case report describes the identification and successful treatment of a couple where the male partner suffered from retrograde ejaculation.

Objective: To detect Mycoplasma genitalium in urine samples of infertile men and men without any signs of infection in order to investigate whether M. genitalium and other genital mycoplasmas (Mycoplasma hominis and Ureaplasma spp) are found more often in urine samples of infertile men than in asymptomatic controls and to determine resistance to macrolides., Methods: The study included first void urine samples taken from 145 infertile men and 49 men with no symptoms of urethritis. M. genitalium, Chlamydia trachomatis and Neisseria gonorrhoeae were detected by commercial PCR. Trichomonas vaginalis was detected by microscopy and culture. M. hominis and Ureaplasma spp were detected by culture. M. genitalium was detected by in-house conventional and real-time PCR., Results: Two M. genitalium positive samples were found among samples obtained from infertile men. All asymptomatic men were M. genitalium negative. Macrolide resistance was not found in either of the two positive samples., Conclusions: In comparison with reported data, an unusually low prevalence of M. genitalium was found in infertile men. The reasons for this unexpected result are not known; possibly, local demographic and social characteristics of the population influenced the result. Further studies to investigate M. genitalium in infertile and other groups of patients are needed., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Phytoestrogens are plant-derived compounds that may interact with estrogen receptors and mimic estrogenic effects. It remains unclear whether the individual variability in metabolizing phytoestrogens contributes to phytoestrogens-induced beneficial or detrimental effects. Our aim was to determine whether there is any interaction between metabolic rates (MR) of phytoestrogens and genetic polymorphisms in related xenobiotic metabolizing enzyme genes. MR was used to assess phytoestrogen exposure and individual metabolic ability. The amount of phytoestrogens in urine was measured by ultra-high performance liquid chromatography-tandem mass spectrometry in 600 idiopathic infertile male patients and 401 controls. Polymorphisms were genotyped using the SNPstream platform combined with the Taqman method. Prototypes and metabolites of secoisolariciresinol (SEC) have inverse effects on male reproduction. It was found that low MR of SEC increased the risk of male infertility (OR 2.49, 95 % CI 1.78, 3.48, P trend = 8.00 × 10(-8)). Novel interactions were also observed between the MR of SEC and rs1042389 in CYP2B6, rs1048943 in CYP1A1, and rs1799931 in NAT2 on male infertility (P inter = 1.06 × 10(-4), 1.14 × 10(-3), 3.55 × 10(-3), respectively). By analyzing the relationships between urinary phytoestrogen concentrations, their metabolites and male infertility, we found that individual variability in metabolizing SEC contributed to the interpersonal differences in SEC's effects on male reproduction.

Normozoospermic infertility has become a common and important health problem worldwide. We designed this metabolomic case-control study to investigate the possible mechanism and urinary biomarkers of normozoospermic infertility. Normozoospermic infertile cases (n = 71) and fertile controls (n = 47) were recruited. A urinary metabolome pattern could discriminate normozoospermic infertile cases from fertile controls. A total of 37 potential biomarkers were identified; these have functionally important roles in energy production, antioxidation, and hormone regulation in spermatogenesis. This gave rise to a combined biomarker pattern of leukotriene E4, 3-hydroxypalmitoylcarnitine, aspartate, xanthosine, and methoxytryptophan pointing to a diagnostic capability (AUC = 0.901, sensitivity = 85.7%, and specificity = 86.8%) in a ROC model; these markers may highlight keynote events of normozoospermic infertility. Stalled medium- and long-chain fatty acid metabolism with improved ketone body metabolism, plus decreased levels of malate and aspartate could result in citrate cycle alterations via a malate-aspartate shuttle in ATP generation in spermatogenesis. Inhibitory alterations in the normal hormone-secreting activity in spermatogenesis were suggested in normozoospermic infertility. Folate deficiency and oxidative stress may jointly impact infertile patients. The disruption of eicosanoid metabolism and xanthine oxidase system, which were tightly associated with energy metabolism and oxidative stress, was also a potential underlying mechanism. In addition, depression might be associated with normozoospermic infertility via neural activity-related metabolites. This study suggests that the urinary metabolome can be used to differentiate normozoospermic infertile men from fertile individuals. Potential metabolic biomarkers derived from these analyses might be used to diagnose what remains a somewhat idiopathic condition and provide functional insights into its pathogenesis.

A GC-MS method was successfully applied to measure simultaneously the concentrations of endocrine disrupting compounds (5 dialkyl phthalates, 9 phthalate monoesters, 3 alkylphenols and bisphenol A) in 136 male urine samples. In the present study the method was validated and concentrations of EDCs were determined. The results were compared with results from other studies. Correlations between endocrine disrupting compounds and also correlations of endocrine disrupting compounds with two semen quality parameters are presented and evaluated. Significant positive correlations were found between almost all the endocrine disrupting compounds. The parameter sum of DEHP (SUM DEHP) was positively correlated to all the endocrine disrupting compounds but negatively to two semen quality parameters. Negative correlations between the endocrine disrupting compounds and the semen quality parameters could indicate that endocrine disrupting compounds could cause reproductive problems by decreasing the semen count and quality. This research will have helped to evaluate human exposure to endocrine disrupting compounds.

Phytoestrogens (PEs) are naturally occurring chemical constituents of certain plants. The internal PE exposures, mainly from diet, vary among different populations and in different regions due to various eating habits. To investigate the potential relationship between urinary PE levels and idiopathic male infertility and semen quality in Chinese adult males, 608 idiopathic infertile men and 469 fertile controls were recruited by eligibility screening procedures. Individual exposure to PEs was measured using UPLC-MS/MS as spot urinary concentrations of 6 PEs (daidzein, DAI; equol, EQU; genistein, GEN; naringenin, NAR; coumestrol, COU; and secoisolariciresinol, SEC), which were adjusted with urinary creatinine (CR). Semen quality was assessed by sperm concentration, number per ejaculum and motility. We found that exposures to DAI, GEN and SEC were significantly associated with idiopathic male infertility (P-value for trend=0.036; 0.002; and 0.0001, respectively), while these exposures had stronger association with infertile subjects with at least one abnormal semen parameter than those with all normal semen parameters. Exposures to DAI, GEN and SEC were also related to idiopathic male infertility with abnormal sperm concentration, number per ejaculum and motility (P-value for trend<0.05), while these exposures had stronger association with the infertile men with abnormal sperm number per ejaculum. These findings provide the evidence that PE exposures are related to male reproductive function and raise a public health concern because that exposure to PEs is ubiquitous in China., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Abnormal spermatozoa frequently display typical features of oxidative stress, i.e. excessive level of reactive oxygen species (ROS) and depleted antioxidant capacity. Moreover, it has been found that a high level of oxidatively damaged DNA is associated with abnormal spermatozoa and male infertility. Therefore, the aim of our study was the comparison of oxidative stress/DNA damage in semen and blood of fertile and infertile men. The broad range of parameters which describe oxidative stress and oxidatively damaged DNA and repair were analyzed in the blood plasma and seminal plasma of groups of fertile and infertile subjects. These parameters include: (i) 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanine (8-oxoGua) levels in urine; (ii) 8-oxodG level in DNA isolated from leukocytes and spermatozoa; (iii) antioxidant vitamins (A, C and E) and uric acid. Urinary excretion of 8-oxodG and 8-oxoGua and the level of oxidatively damaged DNA in leukocytes as well as the level of antioxidant vitamins were analyzed using HPLC and HPLC/GC/MS methods. The results of our study demonstrate that 8-oxodG level significantly correlated with every parameter which describe sperm quality: sperm count, motility and morphology. Moreover, the data indicate a higher level of 8-oxodG in sperm DNA compared with DNA of surrogate tissue (leukocytes) in infertile men as well as in healthy control group. For the whole study population the median values of 8-oxodG/10(6) dG were respectively 7.85 and 5.87 (p=0.000000002). Since 8-oxodG level in sperm DNA is inversely correlated with urinary excretion rate of 8-oxoGua, which is the product of OGG1 activity, we hypothesize that integrity of spermatozoa DNA may be highly dependent on OGG1 activity. No relationship between the whole body oxidative stress and that of sperm plasma was found, which suggests that the redox status of semen may be rather independent on this characteristic for other tissues.

Widespread human exposure to phenols has been documented recently, and some phenols which are potential endocrine disruptors have demonstrated adverse effects on male reproduction in animal and in vitro studies. However, implications about exposure to phenols and male infertility are scarce in humans. Case-control study of 877 idiopathic infertile men and 713 fertile controls was conducted. Urinary levels of bisphenol A, benzophenone-3, pentachlorophenol, triclosan, 4-tert-octylphenol (4-t-OP), 4-n-octylphenol (4-n-OP) and 4-n-nonylphenol (4-n-NP) and semen parameters were measured. After multivariate adjustment, we found 4-t-OP, 4-n-OP and 4-n-NP exposure was associated with idiopathic male infertility (p-value for trend: <0.0001, 0.014 and 0.001, respectively). Aside from these associations, 4-t-OP and 4-n-NP exposure was also associated with idiopathic male infertility with abnormal semen parameters. Moreover, we observed significant associations between sum alkylphenols (APs) exposure and idiopathic male infertility. There were no relationships between exposure to other phenols and idiopathic male infertility in the present study. Our study provides the first evidence that exposure to APs (4-t-OP, 4-n-OP and 4-n-NP) is associated with idiopathic male infertility., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Although sperm have been shown to be present in the postejaculate urinalysis (PEU) of both fertile and infertile men, the number of sperm present in the PEU of the general population has never been well defined. The objective of this study was to describe the semen and PEU findings in both the general and infertile population, in order to develop a better appreciation for "normal." Infertile men (n = 77) and control subjects (n = 71) were prospectively recruited. Exclusion criteria included azoospermia and medications known to affect ejaculation. All men underwent a history, physical examination, semen analysis, and PEU. The urine was split into 2 containers: PEU1, the initial voided urine, and PEU2, the remaining voided urine. Parametric statistical methods were applied for data analysis to compare sperm concentrations in each sample of semen and urine between the 2 groups of men. Controls had higher average semen volume (3.3 ± 1.6 vs 2.0 ± 1.4 mL, P < .001) and sperm concentrations (112 million vs 56.2 million, P = .011), compared with infertile men. The presence of sperm in urine was common in both groups, but more prevalent among infertile men (98.7% vs 88.7%, P = .012), in whom it comprised a greater proportion of the total sperm count (46% vs 24%, P = .022). The majority of sperm present in PEU were seen in PEU1 of both controls (69%) and infertile men (88%). An association was noted between severe oligospermia (<5 million/mL) with low semen volume (<0.5 mL), and significant sperm counts in PEU (<5 million). Although infertile men tend to have a higher proportion of their total sperm in the urine compared with control, there is a large degree of overlap between the 2 populations, making it difficult to identify a specific threshold to define a positive test. Interpretation of a PEU should be directed by whether the number of sperm in the urine could affect subsequent management.

The widespread use of phthalates results in human exposure: phthalates are rapidly metabolized to their respective monoesters and other oxidative products, which are glucuronidated and excreted through the urine and feces. Several in vivo studies showed that some phthalates, in particular diethyl-hexyl phthalate (DEHP), diethyl phthalate (DEP), di(n-butyl)phthalate (DnBP) and n-butylbenzylphthalate (BBzP), are able to interact with the human endocrine system, interfering with the reproduction ability. In this study, 56 couples were recruited from a centre of assisted reproduction. Spot urine samples were collected and five urinary metabolites of the above phthalates were determined using an HPLC/MS/MS analytical method with isotopic dilution. The results were compared with those of 56 couples of parents of one or more children and the statistical analysis revealed a significant difference between the two groups in terms of urinary concentrations of phthalates metabolites. A further step will be the correlation of these results with information on the life styles and working conditions collected through a specifically designed questionnaire., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Urinary concentrations of metabolites of the anti-androgenic xenobiotic di-(2-ethylhexyl) phthalate (DEHP) were previously shown to be weakly associated with serum levels of several hormones in 2 disparate US populations: partners of pregnant women participating in the Study for Future Families and partners in infertile couples from Massachusetts General Hospital infertility clinic. The observed associations between phthalate metabolites and reproductive hormones were robust and insensitive to the characteristics of the subpopulation or the laboratory in which the hormones were measured, despite the fact that these 2 populations span a range of fertility, urinary phthalate metabolites, and reproductive hormone levels. We therefore examined associations between urinary metabolites of DEHP and reproductive hormones-follicle-stimulating hormone, luteinizing hormone, testosterone (T), inhibin B, and estradiol (E(2))-and sex hormone-binding globulin (SHBG) in the pooled population. The magnitude of the associations seen were similar to those reported for each population separately, but effect estimates were more precise because of the increased sample size and the greater range of phthalate metabolite concentrations and hormone levels. Urinary concentrations of 3 metabolites of DEHP [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were inversely associated with the free androgen index (FAI = T/SHBG) and calculated free testosterone. Urinary concentrations of MEHHP and MEOHP were positively associated with SHBG, and MEHP was inversely associated with E(2). No other phthalate metabolites were associated with serum hormones, consistent with results in each population. Our results in this diverse population suggest that DEHP exposure is robustly associated with some male sex steroid hormones.

In recent years the incidence of male infertility has increased. Many risk factors have been taken into consideration, including viral infections. Investigations into viral agents and male infertility have mainly been focused on human papillomaviruses, while no reports have been published on polyomaviruses and male infertility. The aim of this study was to verify whether JC virus and BK virus are associated with male infertility. Matched semen and urine samples from 106 infertile males and 100 fertile males, as controls, were analyzed. Specific PCR analyses were carried out to detect and quantify large T (Tag) coding sequences of JCV and BKV. DNA sequencing, carried out in Tag JCV-positive samples, was addressed to viral protein 1 (VP1) coding sequences. The prevalence of JCV Tag sequences in semen and urine samples from infertile males was 34% (72/212), whereas the BKV prevalence was 0.94% (2/212). Specifically, JCV Tag sequences were detected in 24.5% (26/106) of semen and 43.4% (46/106) of urine samples from infertile men. In semen and urine samples from controls the prevalence was 11% and 28%, respectively. A statistically significant difference (p<0.05) in JCV prevalence was disclosed in semen and urine samples of cases vs. controls. A higher JC viral DNA load was detected in samples from infertile males than in controls. In samples from infertile males the JC virus type 2 strain, subtype 2b, was more prevalent than ubiquitous type 1. JCV type 2 strain infection has been found to be associated with male infertility. These data suggest that the JC virus should be taken into consideration as an infectious agent which is responsible for male infertility.

Objective: To determine whether urine bisphenol-A (BPA) levels are associated with lower semen quality., Design: Cohort study., Setting: Four regions in China where high exposure to BPA in the workplace existed., Patient(s): 218 men with and without BPA exposure in the workplace., Intervention(s): None., Main Outcome Measure(s): Semen parameters., Result(s): After adjustment for potential confounders using linear regression, increasing urine BPA level was statistically significantly associated with [1] decreased sperm concentration, [2] decreased total sperm count, [3] decreased sperm vitality, and [4] decreased sperm motility. Compared with men who did not have detectable urine BPA levels, those with detectable urine BPA had more than three times the risk of lowered sperm concentration and lower sperm vitality, more than four times the risk of lower sperm count, and more than twice the risk of lower sperm motility. The urine BPA level was not associated with semen volume or abnormal sperm morphology. Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population. Despite a markedly reduced sample size, the inverse correlation between increased urine BPA levels and decreased sperm concentration and total sperm count remained statistically significant., Conclusion(s): These results provide the first epidemiologic evidence of an adverse effect of BPA on semen quality., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Bisphenol A (BPA) impairs spermatogenesis in animals, but human studies are lacking. We measured urinary BPA concentrations, semen quality, and sperm DNA damage (comet assay) in 190 men recruited through an infertility clinic. BPA was detected in 89% of samples, with a median (interquartile range [IQR]) concentration of 1.3 (0.8-2.5) ng/mL. Urinary BPA concentration was associated with slightly elevated, though not statistically significant, odds for below reference sperm concentration, motility, and morphology. When modeled as continuous dependent variables, an IQR increase in urinary BPA concentration was associated with declines in sperm concentration, motility, and morphology of 23% (95%CI -40%, -0.3%), 7.5% (-17%, +1.5%), and 13% (-26%, -0.1%), respectively, along with a 10% (0.03%, 19%) increase in sperm DNA damage measured as the percentage of DNA in comet tail. In conclusion, urinary BPA may be associated with declined semen quality and increased sperm DNA damage, but confirmatory studies are needed., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effects of polycyclic aromatic hydrocarbon (PAH) exposure and four functional genetic polymorphisms in the nucleotide excision repair pathway, alone or combined, on sperm DNA integrity and male fertility., Design: Retrospective case-only and case-control study., Setting: One university and three centers of clinical reproductive medicine in the Jiangsu Province of China., Patient(s): Six hundred twenty infertile men and 273 controls were recruited for the study., Intervention(s): None., Main Outcome Measure(s): Exposure to PAHs was detected as urinary 1-hydroxypyrene level. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism, and sperm DNA damage was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay with use of flow cytometry., Result(s): Increased sperm DNA damage was found to be associated significantly with increased urinary concentrations of 1-hydroxypyrene. We also observed that the xeroderma pigmentosum group A (XPA)-4 G/A polymorphism was associated with sperm DNA damage. Subjects homozygous for XPA-4 AA had significantly more sperm DNA damage compared with subjects for XPA-4 GG. Moreover, on the basis of a case-control study, a significant interaction was found between XPA-4 G/A polymorphism and PAH exposures on the sperm DNA damage risk (odds ratio = 2.86, 95% confidence interval = 1.77-4.61)., Conclusion(s): We provide the first evidence for potential gene-environment interactions between nucleotide excision repair polymorphisms and PAH exposure on the sperm DNA damage and male factor infertility in men with no occupational exposure to PAHs., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Serotonin is a neurotransmitter that modulates a wide range of neuroendocrine functions. However, excessive circulating serotonin levels may induce harmful effects in the male reproductive system. The objective of this study was to evaluate whether the levels of urinary 5-hydroxyindoleacetic acid (5-HIIA), a major serotonin metabolite, correlate with different classical seminal parameters., Methods: Human ejaculates were obtained from 40 men attending infertility counselling and rotating shift workers by masturbation after 4-5 days of abstinence. Urinary 5- HIIA concentration was quantified by using a commercial ELISA kit. Forward motility was assessed by a computer-aided semen analysis (CASA) system. Sperm concentration was determined using the haemocytometer method. Sperm morphology was evaluated after Diff-Quik staining, while sperm vitality was estimated after Eosin-Nigrosin vital staining., Results: Our results show that urinary 5-HIIA levels obtained from a set of 20 volunteers negatively correlated with sperm concentration, forward motility, morphology normal range and sperm vitality. On the other hand, we checked the relationship between male infertility and urinary 5-HIIA levels in 20 night shift workers. Thus, urinary 5-HIIA levels obtained from 10 recently-proven fathers were significantly lower than those found in 10 infertile males. Additionally, samples from recent fathers exhibited higher sperm concentration, as well as better forward motility and normal morphology rate., Conclusions: In the light of our findings, we concluded that high serotonin levels, indirectly measured as urinary 5-HIIA levels, appear to play a role as an infertility determinant in male subjects.

Etiologically, chronic prostatitis can result from urogenital latent infections caused by chlamydia, ureaplasma and others. First of all, such patients should be examined for urethritis. We examined 306 patients aged 23-45 years with chronic prostatitis caused by chlamydial and ureaplasmic infection. The samples were taken from the urethra, urine, prostatic secretion, ejaculate and were examined using direct immunofluorescence, polymerase chain reaction, culturing. We found spermatogenetic disorders in 50% patients, 35 (11.4%) patients had a deferent duct obstruction. The patients had also immunointerferon deficiency and alterations in prostatic echostructure. In chronic prostatitis caused by chlamydial-ureaplasmic infection the treatment must combine antibacterial drugs (vilprophen, unidox, solutab) with interferons (lavomax, genferon). Male infertility treatment should be started only after elimination of the bacterial infection.

Human exposure to bisphenol A (BPA) is widespread. Animal studies have demonstrated that BPA can alter endocrine function, but human studies are limited. For the present study, we measured urinary BPA concentrations and serum thyroid and reproductive hormone levels in 167 men recruited through an infertility clinic. BPA was detected in 89% of urine samples with a median (range) of 1.3 (<0.4 - 36.4) ng/mL. In multivariable regression models adjusted for potential confounders, BPA concentrations in urine collected on the same day as a blood sample were inversely associated with serum levels of inhibin B and estradiol:testosterone ratio (E(2):T) and positively associated with follicle-stimulating hormone (FSH) and FSH:inhibin B ratio. Because BPA is metabolized quickly and multiple urine measures may better reflect exposure than a single measure, we also considered among a subset of the men the BPA concentrations in repeated urine samples collected weeks or months following serum sample collection. In these analyses, the effect estimates remained consistent for FSH and E(2):T but were somewhat weakened for inhibin B. In addition, we observed inverse relationships between urinary BPA concentrations and free androgen index (ratio of testosterone to sex hormone binding globulin), estradiol, and thyroid stimulating hormone. Our results suggest that urinary BPA concentrations may be associated with altered hormone levels in men, but these findings need to be substantiated through further research.

Background: Limited studies have suggested that male reproductive function might be associated with exposure to polycyclic aromatic hydrocarbons (PAHs)., Methods: Five hundred and thirteen idiopathic infertile male subjects and 273 fertile males as controls were recruited in this study, through eligibility screening procedures. Individual exposures to PAHs were measured as spot urinary concentrations of four PAH metabolites, including 1-hydroxynaphthalene (1-N), 2-hydroxynaphthalene (2-N), 1-hydroxypyrene (1-OHP) and 2-hydroxyfluorene (2-OHF), which were adjusted by urinary creatinine (CR). Subjects with idiopathic infertility were further divided into 'normal' and 'abnormal' semen quality groups based on their semen volume, sperm concentration, sperm number per ejaculum and sperm motility., Results: The median CR-adjusted urinary concentrations of 1-N, 2-N, 1-OHP, 2-OHF and Sum PAH metabolites (sum of all four metabolites) of control group were lower than those found in case groups. Subjects with higher urinary concentrations of 1-OHP, 2-OHF and Sum PAH metabolites (assessed as tertiles) were more likely to have idiopathic male infertility (P-value for trend = 0.034, 0.022 and 0.022, respectively). Comparing the two groups of idiopathic infertile subjects with different semen quality, a higher idiopathic infertility risk was found in the group with abnormal semen quality., Conclusions: Increased urinary concentrations of 1-OHP, 2-OHF and Sum PAH metabolites were associated with increased male idiopathic infertility risks, while the idiopathic infertile subjects with abnormal semen might be at higher risk.

Objective: To design a new method for oral preparation of urine for sperm retrieval after retrograde ejaculation (RE) and to test the motility of sperm exposed to prepared and unprepared urine., Design: In vitro testing of urine conditions and sperm motility., Setting: Assisted conception unit at a teaching hospital in the United Kingdom., Patient(s): Ten healthy volunteers to provide urine and sperm specimens from men attending the unit for semen analysis., Intervention(s): Various solutions of sodium bicarbonate and sodium chloride were drunk by a single subject until a suitable regimen was achieved. This regimen (called the Liverpool solution) was then tested on 10 volunteers. Samples of sperm were then added to prepared urine, unprepared urine, and culture medium, and the motility was analyzed., Main Outcome Measure(s): Urinary pH and osmolarity, sperm motility., Result(s): Urine produced by the 10 volunteers had a mean pH of 7.47 (range, 7.23-7.79) and a mean osmolarity of 289 mOsmol/L (range, 225-412 mOsmol/L), similar to that of medium. The progressive motility of sperm exposed to the unprepared urine was reduced (42.4% of sperm in medium), whereas that in the prepared urine was similar to that in the control medium., Conclusion(s): Liverpool solution can be used in any unit treating couples with RE, and it is a noninvasive and inexpensive regimen that may optimize urine pH and osmolarity for sperm survival after RE.

The purpose of this study was threefold: to compare semen and first void urine (FVU) specimens from asymptomatic infertile men for the detection of Chlamydia trachomatis, genital ureaplasma, and genital mycoplasma infections using in-house inhibitor-controlled polymerase chain reaction (PCR)-microtiter plate hybridization assay; to determine the prevalence of those organisms in infertile men in Tunisia; and to study the relationship between these bacteria and male infertility. Paired urine and semen specimens from 104 patients were examined by in-house PCR for the presence of DNA of Chlamydia trachomatis, genital ureaplasmas (Ureaplasma urealyticum and Ureaplasma parvum) and genital mycoplasmas (Mycoplasma hominis and Mycoplasma genitalium). Semen analysis was assessed according to the guidelines of the World Health Organization. Nominal scale variables, the Mann-Whitney test, and the Kruskal-Wallis nonparametric analysis of variance test were used for statistical analysis. There was a very high concordance (>95%) and a very good agreement (kappa > 0.9) between the detection of Chlamydia trachomatis, genital ureaplasmas, and Mycoplasma hominis in semen and corresponding FVU specimens. Our findings also show a high concordance (81.1%) and a good agreement (kappa = 0.79) between the detection of Mycoplasma genitalium in both specimens. C trachomatis, genital mycoplasmas, and genital ureaplasmas were found to be widespread among infertile male patients in Tunisia, as shown by their respective prevalences of 43.3%, 18.3%, and 14.4%. The mean values of seminal volume, sperm concentration, sperm viability, sperm motility, sperm morphology, and leukocyte count were not significantly related either to the detection of C trachomatis DNA or to that of genital ureaplasma or mycoplasma DNA in semen specimens. Using our in-house PCR, both semen and FVU were found to be sensitive diagnostic specimens for the detection of C trachomatis, ureaplasmas, and mycoplasmas. The FVU, a less invasive and self-collected specimen, can serve as a marker for the presence of these organisms in the genital tract and can be used as a reliable way of detecting asymptomatic carriers of infection.

Objectives: The purpose of this study was to determine the prevalence of sperm within post-ejaculatory urine in both fertile and infertile men., Methods: Fifteen men of proven fertility and 66 non-azoospermic men being evaluated for infertility were recruited in two academic centers. Laboratory studies included a semen analysis and the examination of post-ejaculate urine for the presence and concentration of sperm., Results: The median total urine sperm count for the fertile group (26.6 million) was not significantly greater than the infertile group (8.3 million, P = 0.63). The median percentage of total sperm (urine plus semen) present in urine for the fertile group (14.8%) was not different from that in the infertile group (15.3%, P = 0.36). Sperm were found in the urine of 73% of fertile and 65% of infertile patients (P = 0.54)., Conclusions: The prevalence of sperm in the post-ejaculatory urine in the fertile population is similar to that in infertile patients, which suggests that a great deal more information is needed to interpret this test in the management of these patients.

We recently reported associations between urinary 1-naphthol (1N) levels and several intermediate measures of male reproductive health, namely sperm motility, serum testosterone levels, and sperm DNA damage. However, because 1N is a major urinary metabolite of both naphthalene and the insecticide carbaryl, exposure misclassification stemming from differences in exposure source was probable and interpretation of the results was limited. As naphthalene, but not carbaryl, is also metabolized to 2-naphthol (2N), the relationship of urinary 1N to 2N within an individual may give information about source of 1N. Utilizing data from two previous studies that measured both 1N and 2N in urine of men exposed to either carbaryl or naphthalene, the present study employed several methods to differentiate urinary 1N arising from exposures to carbaryl and naphthalene among men in the reproductive health study. When re-evaluating the reproductive health data, techniques for identifying 1N source involved exploring interaction terms, stratifying the data set based on 1N/2N ratios, and performing an exposure calibration using a linear 1N to 2N relationship from a study of workers exposed to naphthalene in jet fuel. Despite some inconsistencies between the methods used to distinguish 1N source, we found that 1N from carbaryl exposure is likely responsible for the previously observed association between 1N and sperm motility, whereas 1N from naphthalene exposure is likely accountable for the association between 1N and sperm DNA damage. We demonstrate that studies of health effects associated with carbaryl should utilize a 1N/2N ratio to identify subgroups in which carbaryl is the primary source of 1N. Conversely, studies of naphthalene-related outcomes may utilize 2N levels to estimate exposure.

Background: Phthalates are multifunctional chemicals used in a variety of consumer, medical, and personal care products. Previously, we reported dose-response associations of decreased semen quality with urinary concentrations of monobutyl phthalate (MBP) and monobenzyl (MBzP) phthalate, which are metabolites of dibutyl phthalate and butylbenzyl phthalate, respectively. The present study extends our work in a larger sample of men and includes measurements of di(2-ethylhexyl) phthalate (DEHP) oxidative metabolites., Methods: Between January 2000 and May 2004, we recruited 463 male partners of subfertile couples who presented for semen analysis to the Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values for sperm concentration (<20 million/mL) and motility (<50% motile) and the Tygerberg Kruger Strict criteria for morphology (<4% normal). The comparison group was men with all 3 semen parameters above the reference values. In a single spot urine sample from each man, phthalate metabolites were measured using solid-phase extraction coupled to high-performance liquid chromatography isotope-dilution tandem mass spectrometry., Results: There were dose-response relationships of MBP with low sperm concentration (odds ratio per quartile adjusted for age, abstinence time, and smoking status = 1.00, 3.1, 2.5, 3.3; P for trend = 0.04) and motility (1.0, 1.5, 1.5, 1.8; P for trend = 0.04). There was suggestive evidence of an association between the highest MBzP quartile and low sperm concentration (1.00, 1.1, 1.1, 1.9; P for trend = 0.13). There were no relationships of monoethyl phthalate, monomethyl phthalate, and the DEHP metabolites with these semen parameters., Conclusion: The present study confirms previous results on the relationship of altered semen quality with exposure to MBP at general population levels. We did not find associations between semen parameters and 3 DEHP metabolites.

Cyclamate and its metabolite cyclohexylamine affect male fertility in high dose animal studies, but this affect has not been investigated in epidemiological studies. This paper reports the first epidemiological study designed to investigate the possibility of a relationship between cyclamate and cyclohexylamine and male fertility in humans, in which 405 cases of clinically defined infertility in men and 379 controls were surveyed. Semen evaluation, urine analysis for cyclamate and cyclohexylamine and dietary questionnaires were compared between cases and controls. No evidence was found of a significant association between cyclamate intake and male infertility; neither high cyclamate nor high cyclohexylamine excretion were associated with elevated risk. The lack of association remained after adjusting by age, area of residence, education, total energy intake and other variables. No significant correlations were observed between cyclamate intake, metabolism or excretion, and sperm count and motility. The results demonstrate no effect of cyclamate or cyclohexylamine on male fertility at the present levels of cyclamate consumption.

Aim: To develop an algorithm for use in population-based studies to assess testicular function by measurements of total urinary follicle stimulating hormone (FSH)., Methods: Total concentrations of urinary FSH were measured in a group of 44 men at the University of California, Davis (UCD) and were compared to FSH measurements in serum. On the basis of these and other published data, a urinary FSH value of >2 ng/mg creatinine (Cr) was selected as the cutoff point to identify men with elevated serum FSH ( > 12 IU/L) or low sperm counts ( < 20 million/mL)., Results: The sensitivity and specificity of this algorithm for detecting elevated serum FSH in a group of 58 agricultural workers in the People' s Republic of China were 100% and 50%, respectively. The sensitivity and specificity of this algorithm for detecting low sperm counts in a population of 105 infertility patients at UCD were 58 % and 76 %, respectively., Conclusion: This test may have particular value in identifying populations with no evidence of testicular toxicity, and in which labor-intensive semen studies may not be feasible.

Urethral swabs, first-catch urine or urine collected at least 2 h after the previous micturition, and semen swabs were collected from 131 asymptomatic men during the routine workup for infertility at the andrology clinic at Ga-Rankuwa Hospital, Medunsa. The urethral and seminal swabs were used for enzyme immunoassay (EIA) (IDEIA III), tissue culture, and direct immunofluorescent antibody (DFA) test (IMAGEN) to detect Chlamydia trachomatis, and similarly the urine was tested by EIA. In 82/131 (62.6%) cases all tests for chlamydiae were negative and in 49/131 (37.4%) cases at least one test was positive. Tissue culture detected 24/131 (18.3%) as positive for C. trachomatis. Urethral swab EIA detected 33/131 (25.2%) and DFA 34/131 (26%) positive patients. Urine EIA was positive in 33/131 cases (25.2%). Semen EIA was positive in 35/131 (26.7%) of cases of whom 7/131 (5.3%) were positive in semen EIA only (all samples were conformed by PCR). It would seem, therefore, that testing for the presence of chlamydia was incomplete if semen samples were not included. The positivity in only semen samples raises the possibility that the organisms are harbored in the epididymis, seminal vesicles, or the prostate.

Retrograde ejaculation was diagnosed in a 32-year-old man. This condition is an uncommon cause of male infertility. In most cases the only possible treatment is recovery of spermatozoa from the urine followed by artificial insemination; the couple underwent this treatment; the women received intrauterine insemination. In order to ensure the best possible survival of the sperm cells the pH (7.2-8.2) and the osmolality (300-380 mosmol/kg) of the urine were adjusted beforehand by administering bicarbonate and water to the man a few hours before ejaculation. A successful pregnancy ensued. When the couple desired another child the semen quality had deteriorated and in-vitro fertilisation with spermatozoa collected from urine was chosen as a treatment. A second successful pregnancy developed.

Retrograde ejaculation is an uncommon cause of male infertility. It should be suspected in any case of azoospermia, and might be congenital, acquired or idiopathic in origin. When pharmacological attempts to restore anterograde ejaculation fail, it is suggested that spermatozoa should be recovered from post-ejaculation urine to be applied in one of the modern techniques of assisted reproduction. The successful recovery of viable spermatozoa from the urine is dependent upon careful regulation of pH and osmolarity of the urine at the time of ejaculation. Careful handling of the retrieved spermatozoa enables isolation of sperm cells with good quality for insemination of ovulated oocytes (in vivo) or retrieved oocytes (in vitro).