Ejaculate volume is seriously underestimated when semen is pipetted or decanted into cylinders from the collection vessel.
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Ejaculation↗
Biomedical subjects
Shanna H Swan
Publications and source records attributed to Shanna H Swan.
Does our environment affect our fertility? Some examples to help reframe the question.
The burden of unwanted infertility appears to be increasing, but links to environmental causes have, until recently, been difficult to establish. A large body of data suggests that sperm counts have been declining in Europe and the United States, but interpretation of these statistical trends remains controversial, and the role of the environment uncertain. We were able to show that some currently used pesticides are significantly associated with reduced sperm concentration by linking pesticide concentration in men's urine to results of their semen analysis. In a follow-up study, we showed that prenatal phthalate exposure was linked to subtle differences in genital development of male offspring that could impact the child's future fertility. Researchers are increasingly able to measure levels of environmental chemicals in human samples, and are using these to identify agents that impair fertility. These methods, rather than trend analyses, may lead more directly--and more persuasively--to identifying the role of environment in human fertility.
Animals↗
Semen quality in fertile US men in relation to geographical area and pesticide exposure.
We conducted the first US study to compare semen quality among study centres using standardized methods and strict quality control. We present data on semen quality in partners of 493 pregnant women recruited through prenatal clinics in four US cities during 1999-2001. Sperm concentration, semen volume and motility were determined at the centres and morphology was assessed at a central laboratory. While between-centre differences in sperm morphology and sample volume were small, sperm concentration and motility were significantly reduced in Columbia, MO (MO) relative to men in New York, NY, Minneapolis, MN and Los Angeles, CA; total number of motile sperm was 113 x 10(6) in MO and 162, 201 and 196 x 10(6) in CA, MN and NY respectively. Differences among centres remained significant in multivariate models that controlled for abstinence time, semen analysis time, age, race, smoking, history of sexually transmitted disease and recent fever (all p-values <0.01). We hypothesized that poorer sperm concentration and motility in MO men relative to other centres might be related to agricultural pesticides that are commonly used in the mid-west. We investigated this hypothesis by conducting a nested case-control study within the MO cohort. We selected 25 men in this cohort for whom all semen parameters (concentration, % normal morphology and % motile) were low as cases and an equal number of men for whom all semen parameters were within normal limits as controls. We measured metabolites of eight non-persistent, current-use pesticides in urine samples the men had provided at the time of semen collection. Pesticide metabolite levels were elevated in cases compared with controls for the herbicides alachlor and atrazine, and for the insecticide diazinon (2-isopropoxy-4-methyl-pyrimidinol) (p-values for Wilcoxon rank test = 0.0007, 0.012, and 0.0004 for alachlor, atrazine and diazinon respectively). Men with higher levels of alachlor or diazinon were significantly more likely to be cases than men with low levels [odds ratios (OR) = 30.0, 16.7 for alachlor and diazinon respectively], as were men with atrazine over the limit of detection (OR = 11.3). These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduced semen quality seen in fertile men from mid-Missouri.
Agriculture↗
Prenatal phthalate exposure and anogenital distance in male infants.
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Adult↗
Estimated daily phthalate exposures in a population of mothers of male infants exhibiting reduced anogenital distance.
Phthalate diesters have been shown to be developmental and reproductive toxicants in animal studies. A recent epidemiologic study showed certain phthalates to be significantly associated with reduced anogenital distance in human male infants, the first evidence of subtle developmental effects in human male infants exposed prenatally to phthalates. We used two previously published methods to estimate the daily phthalate exposures for the four phthalates whose urinary metabolites were statistically significantly associated with developmental effects in the 214 mother-infant pairs [di-n-butyl phthalate (DnBP) , diethyl phthalate (DEP) , butylbenzyl phthalate (BBzP) , diisobutyl phthalate (DiBP) ] and for another important phthalate [di-2-ethylhexyl phthalate (DEHP) ]. We estimated the median and 95th percentile of daily exposures to DBP to be 0.99 and 2.68 microg/kg/day, respectively ; for DEP, 6.64 and 112.3 microg/kg/day ; for BBzP, 0.50 and 2.47 microg/kg/day ; and for DEHP, 1.32 and 9.32 microg/kg/day. The U.S. Environmental Protection Agency (EPA) reference doses for these chemicals are 100 (DBP) , 800 (DEP) , 200 (BBzP) , and 20 (DEHP) microg/kg/day. The median and 95th percentile exposure estimates for the phthalates associated with reduced anogenital distance in the study population are substantially lower than current U.S. EPA reference doses for these chemicals and could be informative to any updates of the hazard assessments and risk assessments for these chemicals.
Cohort Studies↗
Influence of paternal age on the risk of spontaneous abortion.
The frequency of chromosomal anomalies in spermatozoa appears to increase with male age. Because these anomalies play a role in the etiology of spontaneous abortion, an influence of paternal age on risk of spontaneous abortion is plausible but not established. The aim was to characterize this influence in a prospective study among 5,121 California women, who as members of a prepaid health plan were interviewed in 1990 or 1991 when they were less than 13 weeks' pregnant and who were followed until the end of pregnancy. The risk of spontaneous abortion between weeks 6 and 20 of pregnancy was studied using a Cox model adjusted for maternal age. The adjusted hazard ratio of spontaneous abortion associated with paternal age of 35 years or more, compared with less than 35 years, was 1.27 (95% confidence interval: 1.00, 1.61), with no modification by maternal age. Among women aged less than 30 years, the hazard ratio of spontaneous abortion associated with paternal age of 35 years or more was 1.56 for first trimester spontaneous abortion and 0.87 for early second trimester spontaneous abortion (test of interaction, p = 0.25). In conclusion, the risk of spontaneous abortion increased with increasing paternal age, with a suggestion that the association is stronger for first trimester losses.
Abortion, Spontaneous↗
Longitudinal changes in semen parameters in young Danish men from the Copenhagen area.
BACKGROUND: Several recent studies have reported low sperm concentration in young men recruited from the general population, but it is unknown whether the semen quality of these young men reflects that of more mature men or is reduced due to relative immaturity. We conducted a longitudinal follow-up study to address this question. METHODS: We followed 158 young men (median age = 19.1 years at entry) for up to 4 years and requested quarterly semen samples (total 1838 semen samples) and yearly genital examinations. We examined longitudinal changes in sperm concentration, semen volume, percentage of immotile sperm and percentage of morphologically normal sperm. We used general linear models in which each man served as his own control which also controlled for age, smoking, urogenital infections or disorders, fever and abstinence time. RESULTS: We found no evidence that sperm concentration, total sperm count or percentage of morphologically normal sperm changed appreciably during the 4 years of follow-up. Semen volume appeared to increase slightly with age, perhaps due to greater acceptance of the study protocol by participants. Sperm motility also improved somewhat, although this may, at least in part, reflect a trend in motility measurement. CONCLUSIONS: In this analysis of 1838 semen samples from 158 young men from the Copenhagen area, sperm concentration, total sperm count and sperm morphology did not change significantly during 4 years of follow-up, suggesting that previously reported low sperm concentration and poor sperm morphology among young Danish men are unlikely to be the result of immaturity.
Adolescent↗
Decrease in anogenital distance among male infants with prenatal phthalate exposure.
Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2-36 months of age. AGD was significantly correlated with penile volume (R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent (R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples (n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p-values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p-values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score (p-value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.
Child, Preschool↗
Trihalomethane levels in home tap water and semen quality.
BACKGROUND: Trihalomethanes (THMs) are byproducts of drinking water chlorination whose effects on semen quality have not been previously studied in humans. METHODS: We examined the relationship of THMs to semen quality in 157 healthy men from couples without known risk factors for infertility. Total THM (TTHM) levels were assigned based on water utility measurements taken during the 90 days preceding semen collection. We analyzed continuous semen parameters in relation to total and individual THMs, adjusting for potential confounders by using repeated measures analyses. RESULTS: TTHM level was not associated with decrements in semen quality. Percent normal morphology decreased and percent head defects increased at higher levels of an ingestion metric (TTHM multiplied by cold home tap water consumption). At the highest level of the ingestion metric (>160 mug/L x glasses/day, which is equivalent to >2 glasses/day of water containing 80 mug/L) we observed a difference of -7.1 (95% confidence interval = -12.7 to -1.6) for percent morphologically normal sperm compared with the lowest level (</= 40 mug/L x glasses/day). Of the individual THMs, bromodichloromethane exposure was inversely related to linearity (a motility parameter); we observed a small decrease (beta = -0.09, SE 0.04) for every unit increase in bromodichloromethane. CONCLUSION: Although our study had a limited exposure assessment and a selective sample, our results suggest the need for further study of the effects of THMs on semen quality.
Adolescent↗
Geographic differences in semen quality of fertile U.S. males.
Although geographic variation in semen quality has been reported, this is the first study in the United States to compare semen quality among study centers using standardized methods and strict quality control. We evaluated semen specimens from partners of 512 pregnant women recruited through prenatal clinics in four U.S. cities during 1999-2001; 91% of men provided two specimens. Sperm concentration, semen volume, and motility were determined at the centers, and morphology was assessed at a central laboratory. Study protocols were identical across centers, and quality control was rigorously maintained. Sperm concentration was significantly lower in Columbia, Missouri, than in New York, New York; Minneapolis, Minnesota; and Los Angeles, California. Mean counts were 58.7, 102.9, 98.6, and 80.8 X 10(6)/mL (medians 53.5, 88.5, 81.8, and 64.8 X 10(6)/mL) in Missouri, New York, Minnesota, and California, respectively. The total number of motile sperm was also lower in Missouri than in other centers: 113, 196, 201, and 162 X 10(6) in Missouri, New York, Minnesota, and California, respectively. Semen volume and the percent morphologically normal sperm did not differ appreciably among centers. These between-center differences remained significant in multivariate models that controlled for abstinence time, semen analysis time, age, race, smoking, history of sexually transmitted disease, and recent fever (all p-values < 0.01). Confounding factors and differences in study methods are unlikely to account for the lower semen quality seen in this mid-Missouri population. These data suggest that sperm concentration and motility may be reduced in semirural and agricultural areas relative to more urban and less agriculturally exposed areas.
Adult↗
Semen quality in relation to biomarkers of pesticide exposure.
We previously reported reduced sperm concentration and motility in fertile men in a U.S. agrarian area (Columbia, MO) relative to men from U.S. urban centers (Minneapolis, MN; Los Angeles, CA; New York, NY). In the present study we address the hypothesis that pesticides currently used in agriculture in the Midwest contributed to these differences in semen quality. We selected men in whom all semen parameters (concentration, percentage sperm with normal morphology, and percentage motile sperm) were low (cases) and men in whom all semen parameters were within normal limits (controls) within Missouri and Minnesota (sample sizes of 50 and 36, respectively) and measured metabolites of eight current-use pesticides in urine samples provided at the time of semen collection. All pesticide analyses were conducted blind with respect to center and case-control status. Pesticide metabolite levels were elevated in Missouri cases, compared with controls, for the herbicides alachlor and atrazine and for the insecticide diazinon [2-isopropoxy-4-methyl-pyrimidinol (IMPY)]; for Wilcoxon rank test, p = 0.0007, 0.012, and 0.0004 for alachlor, atrazine, and IMPY, respectively. Men from Missouri with high levels of alachlor or IMPY were significantly more likely to be cases than were men with low levels [odds ratios (ORs) = 30.0 and 16.7 for alachlor and IMPY, respectively], as were men with atrazine levels higher than the limit of detection (OR = 11.3). The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and metolachlor were also associated with poor semen quality in some analyses, whereas acetochlor levels were lower in cases than in controls (p = 0.04). No significant associations were seen for any pesticides within Minnesota, where levels of agricultural pesticides were low, or for the insect repellent DEET (N,N-diethyl-m-toluamide) or the malathion metabolite malathion dicarboxylic acid. These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduction in semen quality in fertile men from mid-Missouri we reported previously.
Adult↗
Do environmental agents affect semen quality?
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Environmental Exposure↗
Ovarian hormones in premenopausal women: variation by demographic, reproductive and menstrual cycle characteristics.
BACKGROUND: Ovarian function influences many areas of concern in women's health, including breast cancer and other chronic diseases. However, ovarian function has been little studied in healthy, premenopausal women, partly because of cyclical variation. METHODS: We measured biomarkers of ovarian function (daily urinary metabolites of estrogen and progesterone) among 411 women age 18-39 years, who were Kaiser Permanente members in Northern California in 1990-1991. We have summarized the hormone metabolite levels of about 1,500 cycles and examined their associations with demographic and menstrual cycle characteristics. RESULTS: Cycles with a short follicular phase showed elevations of 10-13% in both baseline (days 1-5) and average follicular-phase estrogen metabolite levels, as well as some elevations in progesterone metabolites. Progesterone metabolite levels were directly related to the length of the luteal phase. Compared with whites, Hispanics had estrogen metabolite levels that were 7-13% higher in the follicular and luteal phases, whereas nonwhite, non-Hispanic women (primarily Asians) had slightly lower levels. Generally, women with a prior pregnancy or those with a later age at menarche had lower estrogen metabolite levels, whereas women with prior induced abortions had higher levels. Luteal-phase progesterone metabolite levels tended to be lower among women who were overweight, were less educated, were older at their first livebirth, or had an induced abortion. CONCLUSIONS: Some menstrual cycle characteristics provide a crude surrogate of the hormonal milieu, particularly luteal-phase length and progesterone levels. Hormone levels varied by reproductive characteristics, potentially explaining their relevance to breast cancer risk.
Adolescent↗
Standardized methods for semen evaluation in a multicenter research study.
Semen evaluation methodology is complex and difficult to standardize. Rigorously standardized laboratory protocols and strict quality control (QC) are essential for meaningful comparison of data from multiple sites. We describe the methods used for determination of semen volume, sperm concentration, and percent sperm motility in the Study for Future Families, a multicenter study of semen quality in the United States. Each of these 3 semen parameters was assessed using 2 techniques, which provided the opportunity to compare precision and assess suitability for multicenter studies. Detailed protocols were used, and technicians were centrally trained. A total of 509 semen evaluations were performed. Semen volume measured by weight was greater (P <.0001) than that determined by pipetting (3.7 +/- 1.6 mL vs 3.2 +/- 1.6 mL). Sperm concentration determined using hemacytometer chambers was consistently higher (P <.001) than that using disposable MicroCell chambers (81.0 x 10(6)/mL vs 65.9 x 10(6)/mL). Precision was slightly greater for the MicroCell chamber. The percentage of motile sperm was assessed by a simple counting technique as well as by the World Health Organization categorical method that assigns individual motile sperm to "a," "b," and "c" categories on the basis of progression. When these 3 categories were collapsed, the methods provided values that were not statistically different (P >.05), although the collapsed values tended to be higher (58.1% vs 51.6%) and less precise (CV 7.7% vs 4.1%) for the categorical method than for motility determined using the simple method. The data obtained in this study demonstrate the critical need for rigorous standardization of protocols and techniques for multicenter studies.
Fertility↗
Quality control of laboratory methods for semen evaluation in a multicenter research study.
Rigorously standardized laboratory protocols and strict quality control (QC) are essential for meaningful comparisons between semen quality data from multiple sites. We describe our experience with the Study for Future Families (SFF), a multicenter study of semen quality in the United States. Detailed protocols were developed, and technicians from each study site attended a training session at the central laboratory. Technicians received blinded replicates from diluted semen specimens for counting by MicroCell and hemacytometer. Sperm motility was assessed using videotaped recordings for simple percent motility and categorical assessment of individual sperm progression as recommended by the World Health Organization (WHO). The mean intertechnician coefficient of variation for individual specimens was 12.6% for MicroCell counts, 15.2% for hemacytometer counts, and 10.5% for percent motility. Intratechnician coefficients of variation averaged 10.3% for MicroCell counts, 12.5% for hemacytometer counts, and 5.2% for percent motility. The average percent differences between the technicians' values and the central standard for individual specimens were 13.5%, 16.6%, and 11.9% for MicroCell counts, hemacytometer counts, and simple percent motility, respectively. We achieved our goal of maintaining mean intratechnician coefficients of variation and mean percent differences from the standard values of 15% or less for measurements of simple percent motility and sperm concentration by MicroCell. Standardization using the Improved Neubauer hemacytometer chamber proved more difficult. We were not successful in standardizing a method for categorical assessment of individual sperm progression.
Biomedical Research↗
Semen quality in relation to pesticide exposure in Missouri males.
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Environmental Exposure↗