José J. López-Espín

Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study

BackgroundAnimal studies have shown the reproductive toxicity of a number of heavy metals. Very few human observational studies have analyzed the relationship between male reproductive function and heavy metal concentrations in diverse biological fluids.MethodsThe current study assessed the associations between seminal and hormonal parameters and the concentration of the 3 most frequent heavy metal toxicants (lead, cadmium and mercury) in three different body fluids. Sixty one men attending infertility clinics that participated in a case-control study to explore the role of environmental toxins and lifestyles on male infertility were analyzed. Concentration of lead, cadmium and mercury were measured in blood and seminal plasma and whole blood using anodic stripping voltammetry and atomic absorption spectrophotometry. Serum samples were analyzed for follicle-stimulating hormone, luteinizing hormone and testosterone. Semen analyses were performed according to World Health Organization criteria. Mann-Whitney test and Spearmans rank correlations were used for unadjusted analyses. Multiple linear regression models were performed controlling for age, body mass index and number of cigarettes per day.ResultsThere were no significant differences between cases and controls in the concentrations of heavy metals in any of the three body fluids. In multivariate analyses using all subjects no significant associations were found between serum hormone levels and metal concentrations. However there was a significant positive association between the percentage of immotile sperms and seminal plasma levels of lead and cadmium.ConclusionsOur results suggest that the presence of lead and cadmium in the reproductive tract of men may be related to a moderate alteration of their seminal parameters.

Anogenital distance is related to ovarian follicular number in young Spanish women: a cross-sectional study.

BackgroundIn animals, anogenital distance (AGD) at birth reflects androgen levels during pregnancy and predicts adult AGD. Little is known about AGD in relation to female reproductive characteristics in humans, a question this study was designed to explore.MethodsWe used multiple linear and logistic regression analyses to model the relationships between adult female reproductive system characteristics (e.g. ovarian morphology, menstrual cycle) and two measures of AGD [anus-fourchette (AGDAF) and anus-clitoris (AGDAC)] in 100 college-age volunteers in Spain. Ovarian morphology was classified as having < 6 or ≥ 6 follicles per ovary.ResultsBoth AGD measures were positively associated with ovarian follicle number, with AGDAF being more strongly associated. Women in the upper tertile of the AGDAF and AGDAC distributions were more likely to have ≥ 6 ovarian follicles [OR: 6.0 (95% CI 2.0, 17.6) and 3.0 (95% CI 1.1, 8.6), respectively] compared to women in the lowest tertile.ConclusionsIncreased follicular recruitment has been related to excess androgen exposure in utero in toxicological studies. Our results suggest that the androgenic environment during early fetal life may influence reproductive system development, including AGD, in human females.

Sperm counts may have declined in young university students in Southern Spain

Several studies have investigated temporal trends in semen quality in Northern Europe, but none has examined this question in Southern Europe. A prior study conducted in Almeria Province (Southern Spain) reported higher sperm count and concentration among Spanish young men recruited from 2001 to 2002 compared with young men from Northern Europe. The aim of this new study was to examine whether semen quality has changed among Spanish young men in the last decade. In this cross‐sectional study, questionnaires and semen samples were collected from 215 healthy young university students from Murcia Region between 2010 and 2011. The 273 men from the Almeria study previously studied were included in a trend analysis of the two populations from Southern Spain. Descriptive statistics were calculated for the Murcia study population and these and semen variables for the Murcia and Almeria study populations were compared. Study methods and population characteristics were similar across the two studies. Therefore, we used multiple linear regression analyses on the combined population (controlling for study centre, age, ejaculation abstinence time, season, smoking, medication during the last 3 months, Body mass index (BMI), presence of varicocoele and prenatal exposure to tobacco) to look for a birth‐cohort effect over the combined study period (2001–2011). Sperm concentration and total sperm count declined significantly with year of birth in the pooled analysis (β = −0.04 and β = −0.06, respectively, both p < 0.01). Sperm counts were significantly lower in Murcia study subjects than in the Almeria participants; sperm concentration median (5th–95th) = 44.0 (8.9–129) million/mL vs. 51.0 (5.0–206) million/mL; p < 0.01 and total sperm count = 121 (17.8–400) million vs. 149 (8.0–599) million; p < 0.01. Other semen variables did not differ significantly between the two studies. Our study suggests that total sperm count and sperm concentration may have declined in young Spanish men over the last decade.

Dietary intake of antioxidant nutrients is associated with semen quality in young university students

STUDY QUESTION What are the associations between the dietary intake of antioxidant nutrients and semen parameters in young men? SUMMARY ANSWER Our study suggests that some sperm parameters are sensitive to dietary intake of antioxidant nutrients. WHAT IS KNOWN ALREADY A few reports have suggested that some dietary factors might be related to semen quality. However, the relationship between the intake of antioxidant nutrients and semen quality in young men remains unexplored. STUDY DESIGN, SIZE, DURATION In this cross-sectional study, 215 young men were included between October 2010 and November 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS Healthy university students with complete dietary and semen quality data were analyzed. Dietary intake was recorded using a validated food frequency questionnaire. The associations between the energy-adjusted nutrient intake of antioxidants in quartiles and the semen volume, sperm concentration, sperm motility, sperm morphology, total sperm count and total motile sperm count were assessed using multivariate linear regression. MAIN RESULTS AND THE ROLE OF CHANCE Out of 240 students who contacted us, 223 (92.9%) were eligible to participate in this study, and 215 attended the clinical appointment. In the multivariate adjusted linear regression models, there was a positive association between dietary intakes of cryptoxanthin (P(trend) = 0.03), vitamin C (P(trend) = 0.04), lycopene (P(trend) = 0.03) and β-carotene (P(trend) = 0.04) and total motile sperm count. The semen volume increased with higher intakes of vitamin C (P(trend) = 0.04). LIMITATIONS, REASONS FOR CAUTION Only one sample of semen was taken for each subject. However, there are indications that one semen sample may be sufficient to characterize the semen quality of the individuals in epidemiological studies. Bias due to measurement errors may also occur since there is no perfect method to assess diet. However, any bias due to measurement error would be non-differential and would reduce, not increase, the strength of the associations. Although selection bias in cross-sectional studies might not always be ruled out, our subjects were university student volunteers who were rewarded for their participation and the study was not advertised as a fertility study. WIDER IMPLICATIONS OF THE FINDINGS Previous articles in this area have focused mainly on men attending fertility clinics, thus our study brings generalizability to young men of the general population with unknown or untested fertility. Some of our results are in agreement with the previously reported papers.

Trans fatty acid intake is inversely related to total sperm count in young healthy men

STUDY QUESTION Is intake of fatty acids related to semen quality among young men? SUMMARY ANSWER The intake of trans fatty acids is inversely related to total sperm count in healthy young men. WHAT IS KNOWN ALREADY Spain has seen an increase in the proportion of calories consumed as fat over the same period that a downward trend in semen quality has been observed. In addition, rodent models suggest that trans fat intake may severely affect testicular function. STUDY DESIGN, SIZE, DURATION Cross-sectional study of 209 men recruited between October 2010 and November 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS A group of 209 healthy young university students 18-23 years of age provided a semen sample and completed a previously validated food frequency questionnaire. The association between intake of fatty acids with semen quality parameters (sperm concentration, motility, morphology and total count) was assessed using multivariate linear regression. MAIN RESULTS AND THE ROLE OF THE CHANCE Trans fatty acid intake was inversely related to total sperm count after adjusting for potential confounders (P, trend = 0.03). The multivariate adjusted mean (95% confidence interval) total sperm count in increasing quartiles of trans fat intake was 144 (110-190), 113 (87-148), 100 (18-130) and 89 (69-117). There also was an inverse association between cholesterol intake and ejaculate volume (P, trend = 0.04). No other statistically significant relations were observed. LIMITATIONS, REASONS FOR CAUTION The cross-sectional design of the study limits causal inference, we cannot exclude the possibility of unmeasured confounding and there was insufficient statistical power to identify modest associations. WIDER IMPLICATIONS OF THE FINDINGS The results of this study, together with previous experimental work in rodents and biomarker studies among infertility patients, suggest that intake of trans fatty acids may be related to lower semen quality. Although the data provide further evidence that diet is a modifiable factor that could impact male fertility, it is not known whether the observed differences in sperm count translate into differences in fertility. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by The Seneca Foundation, Regional Agency of Science and Technology, grant no 00694/PI/04, Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (FIS), grant no PI10/00985, and grant P30 DK46200 from the National Institutes of Health. The authors have no competing interests to declare.

The management of missed miscarriage in an outpatient setting: 800 versus 600 μg of vaginal misoprostol.

Background:  Many misoprostol regimens have been used to treat early pregnancy loss as an alternative to surgical evacuation, with differing adverse event and success rates.

Anogenital distance of women in relation to their mother’s gynaecological characteristics before or during pregnancy

Animal models suggest that anogenital distance (AGD) at birth reflects androgen concentrations during in-utero development and predicts adult AGD. Several human observational studies show an association between menstrual cycle irregularities and a hyperandrogenic environment and that may result in a potential alteration of the female reproductive tract during in-utero development. This study examined associations between AGD of young women and their mothers gynaecological characteristics before or during pregnancy. This is cross-sectional study of 100 college-age volunteers in southern Spain. Physical and gynaecological examinations were conducted on the young women and they and their mothers completed epidemiological questionnaires on lifestyles and gynaecological history. Linear regression analysis was used to examine the association between AGD measurements (anus-fourchette (AGDAF) and anus-clitoris (AGDAC)) of women and their mothers gynaecological characteristics. Longer AGDAF was associated with the presence of mothers menstrual cycle irregularities before pregnancy (P=0.03). Longer female AGD has been related to excess androgen exposure in utero in toxicological studies. The current findings may be consistent with studies in which an association between menstrual cycle irregularities and an hyperandrogenic environment has been reported, which therefore may result in a potential modification of the female offsprings reproductive tract during in-utero development, including AGD. Rodent models suggest that perineal length at birth reflects male hormone concentrations (androgens) during in-utero development and predicts adult perineal length. Several human studies show a relationship between menstrual cycle irregularities and an excessive androgen environment. We hypothesize that androgen excess may result in a potential alteration of the female reproductive tract during in-utero development. Our aim was to examine associations between perineal length of young women and their mothers gynaecological characteristics before or during pregnancy. This is a study of 100 college-age volunteers in Southern Spain. Physical and gynaecological examinations were conducted on the young women and they and their mothers completed epidemiological questionnaires on lifestyles and gynaecological history. We used multivariate analyses to assess the association between perineal length of women and their mothers gynaecological characteristics. Longer perineal length was associated with the presence of mothers menstrual cycle irregularities before pregnancy. Longer female perineal length has been related to excess androgen exposure in utero in rodent studies. Our findings may be consistent with previous studies in which an association between menstrual cycle irregularities and an excess of androgen has been reported, which therefore may result in a potential modification of the female offsprings reproductive tract during in-utero development, including perineal length.

Mediterranean and western dietary patterns are related to markers of testicular function among healthy men

STUDY QUESTION Are there any associations of dietary patterns with semen quality, reproductive hormone levels, and testicular volume, as markers of testicular function? SUMMARY ANSWER These results suggest that traditional Mediterranean diets may have a positive impact on male reproductive potential. WHAT IS KNOWN ALREADY The Mediterranean diet has been related to lower risk of multiple chronic diseases, but its effects on reproduction potential are unclear. STUDY DESIGN, SIZE, DURATION Cross-sectional sample of 215 male university students recruited from October 2010 to November 2011 in Murcia Region (Spain). PARTICIPANTS/MATERIALS, SETTING, METHODS Two hundred and nine healthy men aged 18-23 years were finally included in this analysis. Diet was assessed using a validated food frequency questionnaire, and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns with semen quality parameters, reproductive hormone levels and testicular volume adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE We identified two dietary patterns: a Mediterranean (characterized by high intakes of vegetables, fruits and seafood) and a Western pattern (characterized by high intakes of processed meats, French fries and snacks). The Mediterranean pattern was positively associated with total sperm count (P, trend = 0.04). The Western pattern was positively related to the percentage of morphologically normal sperm (P, trend = 0.008). We found an inverse association between adherence to the Western pattern and sperm concentration among overweight or obese men (P, trend = 0.04). LIMITATIONS, REASONS FOR CAUTION As with all cross-sectional studies, causal inference is limited. However, participants were blinded to the study outcomes thus reducing the potential influenced their report of diet. Although we adjusted for a large number of known and suspected confounders, we cannot exclude the possibility of residual confounding or chance findings. WIDER IMPLICATIONS OF THE FINDINGS This study was carried out on healthy and young men, so it is difficult to predict whether and how the observed differences in semen quality translate into reproductive success for men in couples trying to conceive. These results suggest that traditional Mediterranean diets may have a positive impact on male reproductive potential.

Correlations between Different Heavy Metals in Diverse Body Fluids: Studies of Human Semen Quality

It has been hypothesized that exposure to heavy metals may impair male reproduction. To measure the effect produced by low doses of heavy metals on semen parameters, it is necessary to clarify in which body fluids those measurements must be performed. Sixty-one men attending infertility clinics participated in our study. Concentrations of lead, cadmium, and mercury were measured in whole blood, blood plasma, and seminal plasma using spectroanalytical and electrochemical methods. Semen analyses were performed according to World Health Organization criteria. For statistical analysis, Spearmans rank correlations, mean comparison tests, and discriminant analysis were calculated. Significant correlations between the measured concentrations of the three heavy metals in the same biological fluids were observed. However, no similar relationship was seen when comparing the concentrations in different body fluids of the same metal. According to our results and previous publications, seminal plasma might be the best body fluid for assessing impairment of human semen parameters.

Anogenital distance and variability in semen parameters

ABSTRACT The purpose of this study was to analyze whether the anogenital distance (AGD) was associated with variability in semen parameters. Semen parameters analyzed following the WHO guidelines and sperm DNA fragmentation were evaluated in 160 semen samples obtained over a period of a year from 16 healthy male volunteers. Two types of AGD measurements from the anus to the rear base of the scrotum (AGDAS) and to the cephalic insertion of the penis (AGDAP) were taken in each individual. The association between AGDs and semen parameters were studied using three statistical tools: a) general coefficient of variation (CV) and intra-individual coefficient of variation (CVi), b) general linear models for repeated measures, and c) mixed model fixed effects panel data. Men with shortened AGDAP have significantly greater intra-individual variability in sperm concentration, total sperm count, and normal sperm morphology. Conversely, greater total sperm motility was observed in men with long AGDAS. Shortened AGDAS was associated with less intra-individual variability of total sperm motility (progressive and non-progressive). AGD measurements were associated with the variability in semen parameters. AGD may be useful to determine intra-individual variability in semen parameters. Abbreviations: AGD: anogenital distance; AGDAP: anogenital distance from the anus to the cephalic insertion of the penis; AGDAS: anogenital distance from the anus to the rear base of the scrotum; AIC: Akaike information criteria; BMI: body mass index; CV: general coefficient of variation; CVi: intra-individual coefficient of variation; GLM: generalized linear model; PR+NP: total sperm motility