Charlene Brazil

Alcohol and male reproductive health: a cross-sectional study of 8344 healthy men from Europe and the USA

STUDY QUESTION Is there an association between alcohol intake and semen quality and serum reproductive hormones among healthy men from the USA and Europe? SUMMARY ANSWER Moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels. WHAT IS KNOWN ALREADY High alcohol intake has been associated with a wide range of diseases. However, few studies have examined the correlation between alcohol and reproductive function and most have been conducted in selected populations of infertile men or have a small sample size and the results have been contradictory. STUDY DESIGN, SIZE, DURATION A coordinated international cross-sectional study among 8344 healthy men. A total of 1872 fertile men aged 18-45 years (with pregnant partners) from four European cities and four US states, and 6472 young men (most with unknown fertility) aged 18-28 years from the general population in six European countries were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS The men were recruited using standardized protocols. A semen analysis was performed and men completed a questionnaire on health and lifestyle, including their intake of beer, wine and liquor during the week prior to their visit. Semen quality (semen volume, sperm concentration, percentage motile and morphologically normal sperm) and serum reproductive hormones (FSH, LH, testosterone, sex hormone-binding globulin, and inhibin B and free testosterone) were examined. MAIN RESULTS AND THE ROLE OF CHANCE The participation rate for our populations was 20-30%. We found no consistent association between any semen variable and alcohol consumption, which was low/moderate in this group (median weekly intake 8 units), either for total consumption or consumption by type of alcohol. However, we found a linear association between total alcohol consumption and total or free testosterone in both groups of men. Young and fertile men who consumed >20 units of alcohol per week had, respectively, 24.6 pmol/l (95% confidence interval 16.3-32.9) and 19.7 pmol/l (7.1-32.2) higher free testosterone than men with a weekly intake between 1 and 10 units. Alcohol intake was not significantly associated with serum inhibin B, FSH or LH levels in either group of men. The study is the largest of its kind and has sufficient power to detect changes in semen quality and reproductive hormones. LIMITATIONS, REASONS FOR CAUTION The participation rate was low, but higher than in most previous semen quality studies. In addition, the study was cross-sectional and the men were asked to recall their alcohol intake in the previous week, which was used as a marker of intake up to 3 months before. If consumption in that week differed from the typical weekly intake and the intake 3 months earlier, misclassification of exposure may have occurred. However, the men were unaware of their semen quality when they responded to the questions about alcohol intake. Furthermore, we cannot exclude that our findings are due to unmeasured confounders, including diet, exercise, stress, occupation and risk-taking behavior. WIDER IMPLICATIONS OF THE FINDINGS Our study suggests that moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels which may be due to a changed metabolism of testosterone in the liver. Healthy men may therefore be advised that occasional moderate alcohol intake may not harm their reproductive health; we cannot address the risk of high alcohol consumption of longer duration or binge drinking on semen quality and male reproductive hormones. STUDY FUNDING/COMPETING INTERESTS All funding sources were non-profitable and sponsors of this study played no role in the study design, in data collection, analysis, or interpretation, or in the writing of the article. The authors have no conflicts of interest.

Effects of antibodies to sperm surface fertilization antigen-1 on human sperm-zona pellucida interaction.

OBJECTIVE To investigate the effects of antibodies to well-defined sperm surface antigens (the fertilization antigen [FA-1] and germ-cell antigen [GA-1]) and nuclear antigen (protamine) on human sperm-zona interaction. DESIGN Number of total and acrosome-reacted human sperm bound to the human zona pellucida and the sperm movement characteristics assessed by computer-aided sperm analysis were evaluated after incubation of sperm with the antibodies. SETTING Academic research environment approved by the Institute Review Board. PATIENTS Human oocytes were obtained from ovaries removed at surgery. Semen from fertile donors was used in all assays. INTERVENTIONS Human oocytes were stored in salt solution at -80 degrees C until used. Spermatozoa were treated with the antibodies to various sperm antigens. MAIN OUTCOME MEASURES Total and acrosome-reacted sperm bound to zona pellucida and sperm movement characteristics were evaluated after 3 to 5 hours of incubation of the antibodies with human sperm. RESULTS Anti-FA-1 antibodies significantly reduced human sperm fusion with zona-free hamster oocytes and sperm binding to the human zona pellucida but did not affect binding of acrosome-reacted sperm and sperm movement characteristics. Anti-GA-1 and antiprotamine antibodies did not affect sperm-oocyte interaction, acrosomal reaction, or sperm motility. CONCLUSIONS Antibodies to FA-1 but not to GA-1 and protamine inhibit human sperm-zona interaction.

Serum inhibin-b in fertile men is strongly correlated with low but not high sperm counts: a coordinated study of 1,797 European and US men

OBJECTIVE To describe associations between serum inhibin-b and sperm counts, adjusted for effect of time of blood sampling, in larger cohorts than have been previously reported. DESIGN Cross-sectional studies of spermatogenesis markers. SETTING Four European and four US centers. PATIENT(S) Fertile men (1,797) were included and examined from October 1996-February 2005. INTERVENTION(S) The study was observational and therefore without any intervention. MAIN OUTCOME MEASURE(S) Associations between inhibin-b and semen variables controlled for time of blood sampling and other covariates. RESULT(S) Inhibin-b decreased about 2.00% per hour from 8 am-12 pm and then about 3.25% per hour from 12 pm-4 pm. There was a strong positive association between inhibin-b levels less than 150 pg/mL and both sperm concentration and total sperm count (slopes of the regression lines were β=0.011 and β=0.013 for natural logarithm-transformed sperm concentration and total sperm count, respectively). For inhibin-b levels of 150-300 pg/mL the associations were not as steep (β=0.002), but still significant. For inhibin-b levels more than 300 pg/mL there was little association to the sperm counts. Neither sperm motility nor morphology was significantly related to inhibin-b level in any group. CONCLUSION(S) Serum inhibin-b levels decrease nonlinearly during the daytime, and are positively correlated with sperm counts, but the predictive power is best when inhibin-b is low.

Semen parameters in fertile US men: the Study for Future Families.

Establishing reference norms for semen parameters in fertile men is important for accurate assessment, counselling and treatment of men with male factor infertility. Identifying temporal or geographic variability in semen quality also requires accurate measurement of semen parameters in well‐characterized, defined populations of men. The Study for Future Families (SFF) recruited men who were partners of pregnant women attending prenatal clinics in Los Angeles CA, Minneapolis MN, Columbia MO, New York City NY and Iowa City IA. Semen samples were collected on site from 763 men (73% White, 15% Hispanic/Latino, 7% Black and 5% Asian or other ethnic group) using strict quality control and well‐defined protocols. Semen volume (by weight), sperm concentration (hemacytometer) and sperm motility were measured at each centre. Sperm morphology (both WHO, 1999 strict and WHO, 1987) was determined at a central laboratory. Mean abstinence was 3.2 days. Mean (median; 5th–95th percentile) values were: semen volume, 3.9 (3.7; 1.5–6.8) mL; sperm concentration, 60 (67; 12–192) × 106/mL; total sperm count 209 (240; 32–763) × 106; % motile, 51 (52; 28–67) %; and total motile sperm count, 104 (128; 14–395) × 106 respectively. Values for sperm morphology were 11 (10; 3–20) % and 57 (59; 38–72) % normal forms for WHO (1999) (strict) and WHO (1987) criteria respectively. Black men had significantly lower semen volume, sperm concentration and total motile sperm counts than White and Hispanic/Latino men. Semen parameters were marginally higher in men who achieved pregnancy more quickly but differences were small and not statistically significant. The SFF provides robust estimates of semen parameters in fertile men living in five different geographic locations in the US. Fertile men display wide variation in all of the semen parameters traditionally used to assess fertility potential.

Human sperm function in the ejaculate following vasectomy.

Semen specimens were obtained for analysis from nine men immediately before vasectomy and 3 days following the vasectomy procedure. After vasectomy there was a significant decrease in seminal sperm concentration, percentage of sperm motility, and mean swimming speed. In seven of nine cases the spermatozoa did not survive overnight incubation in capacitation media, and in no case was penetration of zonafree hamster oocytes observed 3 days after vasectomy.

Sperm-immunobead binding decreases with in vitro incubation *

OBJECTIVE To characterize the stability of the sperm-immunobead association over time. DESIGN Prospective evaluation of sperm-immunobead binding, using direct and indirect assays. SETTING Male Infertility Clinic, University of California, Davis, Davis, California. PATIENTS Eleven men with sperm surface antibodies and 25 men with serum antisperm antibodies volunteered. MAIN OUTCOME MEASURES Repeated assessment of sperm-immunobead binding over time. RESULTS Serum immunoglobulin (Ig)G decreased a mean of 42.6% over 30 minutes, and serum IgA decreased a mean of 22.7% over 30 minutes. Semen-derived IgG binding fell a mean of 59.9% and semen-derived IgA fell a mean of 27.0% over 25 to 40 minutes. CONCLUSIONS Sperm-immunobead coincubation results in a decrease in the number of sperm bound to immunobeads.