Determinants of organophosphorus pesticide urinary metabolite levels in pregnant women from the CHAMACOS cohort.

Organophosphosphorus pesticides (OPs) are widely used as insecticides in agriculture. Human exposure to OPs has been linked to adverse effects including poorer child neurodevelopment, reduced birth weight, altered serum hormone levels, and reduced semen quality. We measured six OP dialkyl phosphate (DAP) metabolites [three dimethyl alkylphosphates (DMs) and three diethyl alkylphosphates (DEs)] in urine samples collected two times during pregnancy (~13 and ~26 weeks gestation) from 594 women participating in the CHAMACOS birth cohort study and resided in an agricultural community in the United States (U.S.) between 1999 and 2000. Previous studies have shown these women have higher OP exposures compared with the general U.S. population. We examined bivariate associations between prenatal DAP metabolite levels and exposure determinants such as age, season, years living in the US, housing characteristics, fruit and vegetable consumption, occupation and residential proximity to agricultural fields. Final multivariable models indicated that season of urine collection was significantly associated (p < 0.01) with specific gravity-adjusted DM, DE and total DAP metabolites; samples collected in fall and winter had higher concentrations than those collected in spring-summer. Specific gravity-adjusted levels of DM and total DAP metabolites were significantly higher in women who had resided in the U.S. for 5 years or less (p < 0.05). Levels of DM metabolites also increased with daily fruit and vegetable servings (p < 0.01), and levels of DE metabolites were higher in residences with poorer housekeeping quality (p < 0.01) and in mothers that worked in agriculture (p < 0.05). These findings suggest that there are multiple determinants of OP exposure in pregnant women.

Prenatal phthalate exposure and 8-isoprostane among Mexican-American children with high prevalence of obesity.

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

Dichlorodiphenyltrichloroethane exposure and anogenital distance in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) birth cohort study, South Africa.

Dichlorodiphenyltrichloroethane (DDT) is used for malaria control by 10 countries, nine of which are in Africa. Technical DDT contains various isomers with 65-80% insecticidal p,p'-DDT and 15-21% o,p'-DDT, an estrogenic chemical, while the persistent metabolite of p,p'-DDT, dichlorodiphenyldichloroethylene (p,p'-DDE), is an antiandrogen. In utero antiandrogenic exposure reduces anogenital distance in animal models and the anal position index in a single study. This study examined the associations between mother's serum DDT and DDE levels at delivery and anogenital distance in their children at birth and age 1 year. Data were collected as part of the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE), a birth cohort study located in rural South Africa. DDT and DDE concentrations were measured in blood samples collected from 752 mothers at delivery. Anogenital distance measurements, taken at birth (n = 671) and age 1 year (n = 674), included anofourchette and anoclitoral distances in girls, and anoscrotal and anopenile lengths in boys. We also measured anococcygeal and coccyx-fourchette distances in girls, while in boys, we measured anococcygeal and coccyx-scrotal distances as well as penile length and penile width. The anal position index is calculated for both sexes as anoscrotal/coccyx-scrotal in boys and anofourchette/coccyx-fourchette in girls. We found no associations between p,p'-DDT/-DDE or o,p'-DDT and anogenital distance measurements at birth in either boys or girls. At 1 year, o,p'-DDE was negatively associated with anofourchette in girls (ß =-1.32 mm, 95% confidence interval (CI) = -2.27, -0.38) and positively associated with penile width in boys (ß = 0.30 mm, 95% CI = 0.00, 0.60). The results do not suggest an overt antiandrogenic or estrogenic effect on anogenital distance after long-term DDT exposure. These weak associations may be due to chance.

An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso.

On July 10, 1976, an explosion at a chemical plant in Seveso, Italy, released up to 30kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-the most potent dioxin congener. Twenty years later, the Seveso Women's Health Study (SWHS) initiated a follow-up assessment of a cohort of female Seveso residents. Researchers collected serial blood, measured for TCDD levels, and recorded information about the women's medical history after the explosion. The study's aims were to: 1) modify the human PBPK model for TCDD (Emond et al. 2004; Emond et al. 2005; NCEA-USEPA, 2010) to include repetitive gestation and lactation; 2) simulate TCDD blood concentrations during different life stages including pregnancy and lactation, under different exposure scenarios; and 3) use this PBPK model to compare the influence of gestation and lactation on elimination of TCDD. After optimization of the model, it was assessed using data from the SWHS cohort. The 23 women in Subcohort A, were 4-39years old and in Subcohort B, the 18 women were 3-17years old when the explosion occurred. The model accurately predicted the blood concentrations during the 20years post-exposure, including periods of pregnancy and lactation. The model was also used to analyze the contribution of gestation and lactation to the mother's elimination of TCDD. The results suggest that gestation and lactation do not significantly impact TCDD blood elimination. Future efforts will focus on using additional data to evaluate the PBPK model and improving the mathematical descriptions of lactation and multiple gestations.

Higher measured moisture in California homes with qualitative evidence of dampness.

Relationships between measured moisture and qualitative dampness indicators (mold odor, visible mold, visible water damage, or peeling paint) were evaluated using data collected from California homes in a prospective birth cohort study when the infants were 6 or 12 months of age (737 home visits). For repeated visits, agreement between observation of the presence/absence of each qualitative indicator at both visits was high (71-87%, P < 0.0001). Among individual indicators, musty odor and visible mold were most strongly correlated with elevated moisture readings. Measured moisture differed significantly between repeated visits in opposite seasons (P < 0.0001), and dampness increased with the number of indicators in a home. Linear mixed-effect models showed that 10-unit increases in maximum measured moisture were associated with the presence of 0.5 additional dampness indicators (P < 0.001). Bedroom (BR) walls were damper than living room (LR) walls in the same homes (P < 0.0001), although both average and maximum readings were positively correlated across room type (r = 0.75 and 0.67, respectively, both P < 0.0001). Exterior walls were significantly damper than interior walls (P < 0.0001 in both LRs and BRs), but no differences were observed between maximum wall readings and measurements at either window corners or sites of suspected dampness.

Determinants of manganese levels in house dust samples from the CHAMACOS cohort.

INTRODUCTION: Manganese (Mn) is an essential nutrient, but at high exposure levels Mn is a neurotoxicant. The fungicides maneb and mancozeb are approximately 21% Mn by weight and more than 150,000 kg are applied each year to crops in the Salinas Valley, California. It is not clear, however, whether agricultural use of these fungicides increases Mn levels in homes. MATERIALS AND METHODS: We collected house dust samples from 378 residences enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study with a second sample collected approximately nine months later from 90 of the residences. House dust samples were analyzed for Mn using inductively coupled plasma optical emission spectroscopy. Information from interviews, home inspections, and pesticide use reports was used to identify potential predictors of Mn dust concentrations and loadings. RESULTS: Mn was detectable in all dust samples. The median Mn concentration was 171 µg/g and median Mn loading was 1,910 µg/m(2) at first visit. In multivariable models, Mn dust concentrations and loadings increased with the number of farmworkers in the home and the amount of agricultural Mn fungicides applied within three kilometers of the residence during the month prior to dust sample collection. Dust concentrations of Mn and other metals (lead, cadmium and chromium) were higher in residences located in the southern Salinas Valley compared those located in other areas of the Salinas Valley. Dust loadings of Mn and other metals were also higher in residences located on Antioch Loam soil than other soil types, and in homes with poor or average housekeeping practices. CONCLUSIONS: Agricultural use of Mn containing fungicides was associated with Mn dust concentrations and loadings in nearby residences and farmworker homes. Housekeeping practices and soil type at residence were also important factors related to dust metal concentrations and loadings.

Next-generation DNA sequencing reveals that low fungal diversity in house dust is associated with childhood asthma development.

UNLABELLED: Dampness and visible mold in homes are associated with asthma development, but causal mechanisms remain unclear. The goal of this research was to explore associations among measured dampness, fungal exposure, and childhood asthma development without the bias of culture-based microbial analysis. In the low-income, Latino CHAMACOS birth cohort, house dust was collected at age 12 months, and asthma status was determined at age 7 years.The current analysis included 13 asthma cases and 28 controls. Next-generation DNA sequencing methods quantified fungal taxa and diversity. Lower fungal diversity (number of fungal operational taxonomic units) was significantly associated with increased risk of asthma development: unadjusted odds ratio(OR) 4.80 (95% confidence interval (CI) 1.04­22.1). Control for potential confounders strengthened this relationship. Decreased diversity within the genus Cryptococcus was significantly associated with increased asthma risk (OR 21.0, 95% CI 2.16­204). No fungal taxon (species, genus, class) was significantly positively associated with asthma development, and one was significantly negatively associated. Elevated moisture was associated with increased fungal diversity, and moisture/mold indicators were associated with four fungal taxa. Next-generation DNA sequencing provided comprehensive estimates of fungal identity and diversity, demonstrating significant associations between low fungal diversity and childhood asthma development in this community. PRACTICAL IMPLICATIONS: Early life exposure to low fungal diversity in house dust was associated with increased risk for later asthma developmen tin this low-income, immigrant community. No individual fungal taxon (species, genus, or class) was associated with asthma development, although exposure to low diversity within the genus Cryptococcus was associated with asthma development. Future asthma development studies should incorporate fungal diversity measurements, in addition to measuring individual fungal taxa. These results represent a step toward identifying the aspect(s) of indoor microbial populations that are associated with asthma development and suggest that understanding the factors that control diversity in the indoor environment may lead to public health recommendations for asthma prevention in the future.

A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project.

Impaired fetal growth and preterm birth are the leading causes of neonatal and infant mortality worldwide and there is a growing scientific literature suggesting that environmental exposures during pregnancy may play a causal role in these outcomes. Our purpose was to assess the environmental exposure of the Fetal Growth Longitudinal Study (FGLS) participants in the multinational INTERGROWTH-21(st) Project. First, we developed a tool that could be used internationally to screen pregnant women for such exposures and administered it in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is a study of fetal growth among healthy pregnant women living in relatively affluent areas, at low risk of adverse pregnancy outcomes and environmental exposures. We confirmed that most women were not exposed to major environmental hazards that could affect pregnancy outcomes according to the protocol's entry criteria. However, the instrument was able to identify some women that reported various environmental concerns in their homes such as peeling paint, high residential density (>1 person per room), presence of rodents or cockroaches (hence the use of pesticides), noise pollution and safety concerns. This screening tool was therefore useful for the purposes of the project and can be used to ascertain environmental exposures in studies in which the primary aim is not focused on environmental exposures. The instrument can be used to identify subpopulations for more in-depth assessment, (e.g. environmental and biological laboratory markers) to pinpoint areas requiring education, intervention or policy change.

BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis.

BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.

Sex ratio variations among the offspring of women with diabetes in pregnancy.

AIMS: It has long been hypothesized that natural selection would favour a reproductive strategy biased towards females under adverse circumstances in order to maximize the number of surviving grandchildren. An excess of daughters in women with Type 1 diabetes and a greater likelihood of gestational diabetes in women carrying male fetuses have also been reported. This study aims to compare the sex ratio across categories of maternal glycaemia. METHODS: Among 288,009 mother-infant pairs delivering at Kaiser Permanente Northern California in 1996-2008, sex ratios were calculated for the following categories: pregravid diabetes, gestational diabetes, mild pregnancy hyperglycaemia (defined as an abnormal screening but normal diagnostic test for gestational diabetes) and normoglycaemia. Odds ratios for delivering a male were estimated with logistic regression; normoglycaemic pregnancies comprised the reference. RESULTS: Women with pregravid diabetes delivered the fewest males (ratio male/female = 1.01), followed by women with normoglycaemic pregnancies and those with an abnormal screening only (both sex ratios = 1.05); women with gestational diabetes delivered the most males (sex ratio = 1.07). Odds ratio estimates suggested the same pattern, but none attained statistical significance. CONCLUSIONS: The crude sex ratios in this cohort suggest a possible gradient by category of maternal glycaemia. Women with gestational diabetes, a condition characterized by excessive fuel substrates, appear to deliver more males. Women with pregravid diabetes delivered the fewest males, possibly reflecting the unfavourable state of chronic disease.

Fungi and pollen exposure in the first months of life and risk of early childhood wheezing.

BACKGROUND: Many studies have found that the risk of childhood asthma varies by month of birth, but few have examined ambient aeroallergens as an explanatory factor. A study was undertaken to examine whether birth during seasons of elevated ambient fungal spore or pollen concentrations is associated with risk of early wheezing or blood levels of Th1 and Th2 type cells at 24 months of age. METHODS: 514 children were enrolled before birth and followed to 24 months of age. Early wheezing was determined from medical records, and Th1 and Th2 type cells were measured in peripheral blood using flow cytometry. Ambient aeroallergen concentrations were measured throughout the study period and discrete seasons of high spore and pollen concentrations were defined. RESULTS: A seasonal pattern was observed, with birth in autumn to winter (the spore season) associated with increased odds of early wheezing (adjusted odds ratio 3.1; 95% confidence interval 1.3 to 7.4). Increasing mean daily concentrations of basidiospores and ascospores in the first 3 months of life were associated with increased odds of wheeze, as were increasing mean daily concentrations of total and specific pollen types. Levels of Th1 cells at age 24 months were positively associated with mean spore concentrations and negatively associated with mean pollen concentrations in the first 3 months of life. CONCLUSIONS: Children with higher exposure to spores and pollen in the first 3 months of life are at increased risk of early wheezing. This association is independent of other seasonal factors including ambient levels of particulate matter of aerodynamic diameter

The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men.

BACKGROUND: Little is known about the effect of paternal nutrition on aneuploidy in sperm. We investigated the association of normal dietary and supplement intake of folate, zinc and antioxidants (vitamin C, vitamin E and beta-carotene) with the frequency of aneuploidy in human sperm. METHODS: Sperm samples from 89 healthy, non-smoking men from a non-clinical setting were analysed for aneuploidy using fluorescent in situ hybridization with probes for chromosomes X, Y and 21. Daily total intake (diet and supplements) for zinc, folate, vitamin C, vitamin E and beta-carotene was derived from a food frequency questionnaire. Potential confounders were obtained from a self-administered questionnaire. RESULTS: After adjusting for covariates, men with high folate intake (>75th percentile) had lower frequencies of sperm with disomies X, 21, sex nullisomy, and a lower aggregate measure of sperm aneuploidy (P

The effects of male age on sperm DNA damage in healthy non-smokers.

BACKGROUND: The trend for men to have children at older age raises concerns that advancing age may increase the production of genetically defective sperm, increasing the risks of transmitting germ-line mutations. METHODS: We investigated the associations between male age and sperm DNA damage and the influence of several lifestyle factors in a healthy non-clinical group of 80 non-smokers (mean age: 46.4 years, range: 22-80 years) with no known fertility problems using the sperm Comet analyses. RESULTS: The average percentage of DNA that migrated out of the sperm nucleus under alkaline electrophoresis increased with age (0.18% per year, P = 0.006), but there was no age association for damage measured under neutral conditions (P = 0.7). Men who consumed >3 cups coffee per day had approximately 20% higher percentage tail DNA under neutral but not alkaline conditions compared with men who consumed no caffeine (P = 0.005). CONCLUSIONS: Our findings indicate that (i) older men have increased sperm DNA damage associated with alkali-labile sites or single-strand DNA breaks and (ii) independent of age, men with substantial daily caffeine consumption have increased sperm DNA damage associated with double-strand DNA breaks. DNA damage in sperm can be converted to chromosomal aberrations and gene mutations after fertilization, increasing the risks of developmental defects and genetic diseases among offspring.

Exogenous shocks to the human sex ratio: the case of September 11, 2001 in New York City.

BACKGROUND: The human secondary sex ratio reportedly falls in populations subjected to exogenous stressors such as earthquakes or political and social upheavals. Explanations of the association include reduced conception of males and increased fetal deaths among males. The latter explanation has been supported by research reporting that the sex ratio in California fell 3 months, but not 8, 9 or 10 months, after the terrorist attacks of September 11, 2001. California's distance from the attacks raises the questions of whether the results arose from chance and would be found elsewhere. We contribute to the literature by testing the association between the secondary sex ratio and the events of September 11 in New York City. METHODS: We replicate the California tests by applying interrupted time-series methods, which control for secular trends, seasonality and other forms of autocorrelation, to 91 cohorts born in New York City during 28-day periods from January 1996 to June 2002. RESULTS: As hypothesized, the sex ratio in New York City in the period 1 January to 28 January 2002 fell to 1, which was the lowest observed value during the test period and significantly (i.e. P < 0.01, two-tailed test) below the value expected from history. CONCLUSIONS: Our findings support the male fetal loss explanation of the association between exogenous population shocks and the secondary sex ratio.

Quantitative effects of male age on sperm motion.

BACKGROUND: Semen quality is associated with fertility status, but there is little quantitative information on risk factors that affect semen quality, especially in non-clinical populations. Advancing male age has been associated with a decline in semen quality, with the largest effect being on sperm motility. However, there is little quantitative data on the specific components of sperm motion that are affected by male age. METHODS: We performed linear regression analyses of 14 aspects of semen quality measured by computer-assisted semen analysis (CASA) in a non-clinical cohort of 90 non-smoking men, aged 22-80 years, who had no history of infertility or reproductive problems. RESULTS: We found age-associated declines in CASA-determined motility (% motile, 0.8% per year; % progressively motile, 0.9% per year; % rapidly motile, 0.4% per year, P

Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.

This study compares the relative effects of advancing male age on multiple genomic defects in human sperm [DNA fragmentation index (DFI), chromatin integrity, gene mutations, and numerical chromosomal abnormalities], characterizes the relationships among these defects and with semen quality, and estimates the incidence of susceptible individuals for a well characterized nonclinical nonsmoking group of 97 men (22-80 years). Adjusting for confounders, we found major associations between age and the frequencies of sperm with DFI and fibroblast growth factor receptor 3 gene (FGFR3) mutations associated with achondroplasia (P < 0.01) with no evidence for age thresholds. However, we found no associations between age and the frequencies of sperm with immature chromatin, aneuploidies/diploidies, FGFR2 mutations (Apert syndrome), or sex ratio in this cohort. There were also no consistent correlations among genomic and semen-quality endpoints, except between DFI and sperm motility (r = -0.65, P < 0.001). These findings suggest there are multiple spermatogenic targets for genomically defective sperm with substantially variable susceptibilities to age. Our findings predict that as healthy males age, they have decreased pregnancy success with trends beginning in their early reproductive years, increased risk for producing offspring with achondroplasia mutations, and risk of fathering offspring with Apert syndrome that may vary across cohorts, but with no increased risk for fathering aneuploid offspring (Down, Klinefelter, Turner, triple X, and XYY syndromes) or triploid embryos. Our findings also suggest that the burden of genomic damage in sperm cannot be inferred from semen quality, and that a small fraction of men are at increased risk for transmitting multiple genetic and chromosomal defects.

Antioxidant intake is associated with semen quality in healthy men.

BACKGROUND: We seek to determine whether dietary and supplement intake of specific micronutrients (zinc and folate) and antioxidants (vitamins C, E and beta-carotene) is associated with semen quality. METHODS: Ninety-seven healthy, non-smoking men provided semen and were interviewed. Average daily nutrient intake from food and supplements was derived from a self-administered food frequency questionnaire. Intake levels were summarized as low, moderate and high. Semen volume, sperm concentration, total sperm count, motility, progressive motility and total progressively motile sperm count (TPMS) were measured. RESULTS: After controlling for covariates, a high intake of antioxidants was associated with better semen quality but, in almost all cases, there was no clear dose relationship in that moderate intake groups had the poorest semen quality. For example, positive associations were observed between vitamin C intake and sperm number as reflected in the higher mean count (P=0.04), concentration (P=0.05) and TPMS (P = 0.09); between vitamin E intake and progressive motility (P = 0.04) and TPMS (P = 0.05); and between beta-carotene intake and sperm concentration (P = 0.06) and progressive motility (P = 0.06). Folate and zinc intake were not associated with improved semen quality. CONCLUSIONS: In a convenience sample of healthy non-smoking men from a non-clinical setting, higher antioxidant intake was associated with higher sperm numbers and motility.

Uterine leiomyoma and menstrual cycle characteristics in a population-based cohort study.

BACKGROUND: We examined the association of uterine leiomyoma with menstrual cycle characteristics in a population of non-care-seeking women. METHODS: This cross-sectional study uses data from the Seveso Women's Health Study (SWHS), a population-based cohort in Italy. Participants included 341 premenopausal women, 30-60 years old, who had an intact uterus and were not pregnant, lactating, or using oral contraception or intra-uterine devices. We examined the presence of any ultrasound-detected uterine leiomyoma in relation to self-reported menstrual cycle length, flow length and heaviness of flow. The association of leiomyoma number, volume, tissue layer location and axial position with menstrual cycle characteristics was also examined. RESULTS: Uterine leiomyomata were detected in 73 women (21.4%). After adjustment for covariates, the presence of a leiomyoma was not significantly related to menstrual cycle length, flow length or heaviness of flow [odds ratio (OR) for scanty flow =1.9, 95% confidence interval (CI) 0.8-4.3; OR for heavy flow =1.3, 95% CI 0.7-2.5; relative to moderate flow]. Number, volume, tissue layer location (subserosal or intramural) and axial position (anterior or posterior) of the leiomyoma were also not related to menstrual cycle characteristics. CONCLUSION: In this Italian population of women not seeking gynaecological care, menstrual characteristics are not related to leiomyoma.

The association of age and semen quality in healthy men.

BACKGROUND: Although the effect of maternal age on fertility is well known, it is unclear whether paternal age also affects fertility. This cross-sectional study sought to characterize the association between age and semen quality, a well-known proxy of fertility status. METHODS: A convenience sample of 97 non-smoking men (aged 22-80 years) without known fertility problems was recruited from a national government laboratory. The men provided semen samples and information relating to lifestyle, diet, medical and occupational details. Semen volume (ml), sperm concentration (x10(6)/ml), total sperm count (x10(6)), motility (%), progressive motility (%) and total progressively motile sperm count (x10(6)) were measured. RESULTS: After adjusting for covariates, semen volume decreased by 0.03 ml per year of age (95% CI: -0.05, -0.01); motility decreased by 0.7% per year (95% CI: -0.92, -0.43); progressive motility decreased by 3.1% per year (95% CI: -4.5, -1.6); and total progressively motile sperm count decreased by 4.7% per year (95% CI: -7.2, -2.2). There was a suggested decrease in sperm concentration and count. The proportion of men with abnormal volume, concentration and motility was significantly increased across the age decades. CONCLUSIONS: In a convenience sample of healthy men from a non-clinical setting, semen volume and sperm motility decreased continuously between 22-80 years of age, with no evidence of a threshold.

Sperm aneuploidy in fathers of children with paternally and maternally inherited Klinefelter syndrome.

BACKGROUND: It is unclear whether frequency of sperm aneuploidy is associated with risk of fathering children with trisomy. METHODS: We recruited 36 families with a boy with Klinefelter syndrome (KS), interviewed the fathers about their exposures and medical history, received a semen sample from each father, and collected blood samples from the mother, father and child. We applied a multicolour fluorescent in-situ hybridization assay to compare the frequencies of sperm carrying XY aneuploidy and disomies X, Y and 21 in fathers of maternally and paternally inherited KS cases. RESULTS: Inheritance of the extra X chromosome was paternal in 10 and maternal in 26 families. Fathers of paternal KS cases produced higher frequencies of XY sperm (P = 0.02) than fathers of maternal KS cases. After controlling for age, the major confounding variable, the difference between the two groups was no longer significant (P less-than-or-equal 0.2). Also, there were no significant differences between the parental origin groups for disomy X, Y or 21. CONCLUSIONS: Men who fathered a child with a Klinefelter syndrome produced higher frequencies of XY sperm aneuploidy, which is explained, in part, by both paternal age and parent of origin.