Thomas H. Scheike

Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners

BACKGROUND Semen analysis is part of the routine assessment of infertile couples. WHO defines a sperm concentration above 20x10(6) per mL seminal fluid as normal. We studied the association between semen quality and the probability of conception in a single menstrual cycle in Danish couples with no previous reproductive experience. METHODS In 1992-94, we invited 52,255 trades-union members aged 20-35 years, who lived with a partner and had no children to take part in the study; 430 couples agreed. The couples discontinued use of contraception, and were followed up for six menstrual cycles or until a pregnancy was verified within this period. Each man was asked to provide a semen sample at enrolment (which was analysed without freezing). Women kept a daily record of vaginal bleeding and sexual activity. The association between semen quality and likelihood of pregnancy was assessed by logistic regression, adjusted for sexual activity and female factors associated with low fertility. RESULTS There were 256 (59.5%) pregnancies among the 430 couples: 165 (65.0%) among those with a sperm concentration of 40x10(6)/mL or more and 84 (51.2%) among those with lower sperm concentrations. The probability of conception increased with increasing sperm concentration up to 40x10(6)/mL, but any higher sperm density was not associated with additional likelihood of pregnancy. The proportion of sperm with normal morphology was strongly related to likelihood of pregnancy independently of sperm concentration. Semen volume and motility were of limited value in pregnancy prediction. INTERPRETATION Our study suggests that the current WHO guidelines for normal semen quality should be used with caution. Some men with sperm counts above the lower limit of the normal range defined by WHO may in fact be subfertile.

Low Serum Insulin-Like Growth Factor I Is Associated With Increased Risk of Ischemic Heart Disease: A Population-Based Case-Control Study

Background—Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD). Methods and Results—We conducted a nested case-control study within a large prospective study on cardiovascular epidemiology (DAN-MONICA). We measured IGF-I and IGFBP-3 in serum from 231 individuals who had a diagnosis of IHD 7.63 years after blood sampling and among 374 control subjects matched for age, sex, and calendar time. At baseline when all individuals were free of disease, subjects in the low IGF-I quartile had significantly higher risk of IHD during the 15-year follow-up period, with a relative risk (RR) of 1.94 (95% CI, 1.03 to 3.66) of IHD compared with the high IGF-I quartile group, when IGFBP-3, body mass index, smoking, menopause, diabetes, and use of antihypertensives were controlled for. Conversely, individuals in the high IGFBP-3 quartile group had an adjusted RR of 2.16 (95% CI, 1.18 to 3.95) of having IHD. Identification of a high-risk population with low IGF-I and high IGFBP-3 levels resulted in markedly higher risk of IHD (RR 4.07; 95% CI, 1.48 to 11.22) compared with the index group. Conclusions—Individuals without IHD but with low circulating IGF-I levels and high IGFBP-3 levels have significantly increased risk of developing IHD during a 15-year follow-up period. Our findings suggest that IGF-I may be involved in the pathogenesis of IHD.

Does moderate alcohol consumption affect fertility? Follow up study among couples planning first pregnancy

Abstract Objective : To examine the effect of alcohol consumption on the probability of conception. Design : A follow up study over six menstrual cycles or until a clinically recognised pregnancy occurred after discontinuation of contraception. Subjects : 430 Danish couples aged 20-35 years trying to conceive for the first time. Main outcome measures : Clinically recognised pregnancy. Fecundability odds ratio: odds of conception among exposed couples divided by odds among those not exposed. Results : In the six cycles of follow up 64% (179) of women with a weekly alcohol intake of less than five drinks and 55% (75) of women with a higher intake conceived. After adjustment for cycle number, smoking in either partner or smoking exposure in utero, centre of enrolment, diseases in female reproductive organs, womans body mass index, sperm concentration, and duration of menstrual cycle, the odds ratio decreased with increasing alcohol intake from 0.61 (95% confidence interval 0.40 to 0.93) among women consuming 1-5 drinks a week to 0.34 (0.22 to 0.52) among women consuming more than 10 drinks a week (P=0.03 for trend) compared with women with no alcohol intake. Among men no dose-response association was found after control for confounders including womens alcohol intake. Conclusion : A womans alcohol intake is associated with decreased fecundability even among women with a weekly alcohol intake corresponding to five or fewer drinks. This finding needs further corroboration, but it seems reasonable to encourage women to avoid intake of alcohol when they are trying to become pregnant.

Fecundability in relation to body mass and menstrual cycle patterns

Few studies have investigated the association between body mass index and fecundability, that is, the ability to conceive in a menstrual cycle, among fertile women with normal menstrual cycle pattern. We examined the independent and combined effects of duration and regularity of the menstrual cycle, body mass index, and fecundability from records on pregnant women attending antenatal care at Odense University Hospital, Denmark, between 1972 and 1987. We included only the first birth of each woman who had planned pregnancies and no pre-pregnancy disease (N = 10,903). We estimated the fecundability odds ratio (FR) as the odds of conception in a menstrual cycle. After adjusting for confounders, the fecundability for women with a body mass index >25 kg/m2 was lower than for women with a body mass index of 20-25 kg/m2 [FR = 0.77; 95% confidence interval (CI) = 0.70-0.84]. FR was lower for women with long (>35 days) (FR = 0.74; 95% CI = 0.63-0.87) or irregular cycles (FR = 0.78; 95% CI = 0.70-0.87), even when their body mass index was within the normal range (20-25 kg/m2) and/or their cycles were regular.We examined the association between birth characteristics of offspring and the subsequent maternal risk of breast cancer in a population-based cohort of 998,499 women, 13 to 48 years of age at entry. There were 9,495 incident cases of breast cancer during 12.8 million person-years of follow-up among these women. Compared with mothers of singleton infants, mothers having a multiple birth had an increased risk of breast cancer in the first 5 years after a birth (relative risk (RR) = 1.8; 95% confidence interval (CI) = 1.1-2.8). The risk for mothers having a heavy-weighted child (>3.75 kg), as compared with a child of light weight (< or =3 kg), was also slightly increased (RR = 1.2; 95% CI = 0.9-1.5). This latter effect was primarily due to an increased incidence of tumors larger than 2 cm at diagnosis (RR = 1.4; 95% CI = 0.9-1.9). Our findings are compatible with the hypothesis that the hormonal level during pregnancy influences the risk of breast cancer in the early years after delivery.

Ambient particle source apportionment and daily hospital admissions among children and elderly in Copenhagen.

An association between particulate air pollution and morbidity and mortality is well established. However, little is known about which sources of particulate matter contribute most to the adverse health effects. Identification of responsible sources would merit more efficient control. For a 6-year period (01 January 1999 to 31 December 2004), we examined associations between urban background PM10 in the presence of gaseous pollutants (CO, NO2) and hospital admissions due to cardiovascular and respiratory disease in the elderly (age≥65), and asthma in children (age 5–18) in Copenhagen, Denmark. We further studied associations between fractions of PM10 assigned to six sources (biomass, secondary, oil, crustal, sea salt, and vehicle) and admissions during a 1½ -year campaign. We used Poisson generalized additive time-series model adjusted for season, day of the week, public holidays, influenza epidemics, grass pollen, school holidays, and meteorology, with up to 5 days lagged air pollution exposure. We found positive associations between PM10 and the three health outcomes, with strongest associations for asthma. The PM10 effect remained robust in the presence of CO and NO2. We found different PM10 sources to be variably associated with different outcomes: crustal and secondary sources showed strongest associations with cardiovascular, biomass with respiratory, and vehicle with asthma admissions. These novel results may merit future research of potential mechanism, whereas at present, no single PM10 source can be attributed to all morbidity.

Size distribution and total number concentration of ultrafine and accumulation mode particles and hospital admissions in children and the elderly in Copenhagen, Denmark

Objectives: To study the association between short-term exposure to ultrafine particles and morbidity in Copenhagen, Denmark. Methods: We studied the association between urban background levels of the total number concentration of particles (NCtot, 6–700 nm in diameter) measured at a single site (15 May 2001 to 31 December 2004) and hospital admissions due to cardiovascular (CVD) and respiratory disease (RD) in the elderly (age ⩾65 years), and due to asthma in children (age 5–18 years). We examined these associations in the presence of PM10, PM2.5 (particulate matter <10 and 2.5 µm in diameter, respectively) and ambient gasses. We utilised data on size distribution to calculate NCtot for four modes with median diameters 12, 23, 57 and 212 nm, and NC100 (number concentration of particles <100 nm in diameter) and examined their associations with health outcomes. We used a time series Poisson generalised additive model adjusted for overdispersion, season, day of the week, public holidays, school holidays, influenza, pollen and meteorology, with up to 5 days’ lagged exposure. Results and conclusions: The adverse health effects of particulate matter on CVD and RD hospital admissions in the elderly were mainly mediated by PM10 and accumulation mode particles with lack of effects for NC100. For paediatric asthma, accumulation mode particles, NC100 and nitrogen oxides (mainly from traffic related sources) were relevant, whereas PM10 appeared to have little effect. Our results suggest that particle volume/mass from long-range transported air pollution is relevant for CVD and RD admissions in the elderly, and possibly particle numbers from traffic sources for paediatric asthma.

Familial Risk and Heritability of Cancer Among Twins in Nordic Countries

IMPORTANCE Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. OBJECTIVE To estimate familial risk and heritability of cancer types in a large twin cohort. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. EXPOSURES Shared environmental and heritable risk factors among pairs of twins. MAIN OUTCOMES AND MEASURES The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twins development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). CONCLUSIONS AND RELEVANCE In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

A discrete survival model with random effects: an application to time to pregnancy.

Time to pregnancy, the number of menstrual cycles it takes a couple to conceive, and various covariates have been collected among couples ultimately achieving conception. To assess the influence of the covariates, we constructed a discrete survival model that allows time-dependent covariates. A random effect was included to account for unobserved heterogeneity. The collected waiting times are obtained through retrospective ascertainment and are analyzed as truncated data. Maximum likelihood estimation was implemented by Fisher scoring through iteratively reweighted least squares.

Is the current decline in malaria burden in sub-Saharan Africa due to a decrease in vector population?

BackgroundIn sub-Saharan Africa (SSA), malaria caused by Plasmodium falciparum has historically been a major contributor to morbidity and mortality. Recent reports indicate a pronounced decline in infection and disease rates which are commonly ascribed to large-scale bed net programmes and improved case management. However, the decline has also occurred in areas with limited or no intervention. The present study assessed temporal changes in Anopheline populations in two highly malaria-endemic communities of NE Tanzania during the period 1998-2009.MethodsBetween 1998 and 2001 (1st period) and between 2003 and 2009 (2nd period), mosquitoes were collected weekly in 50 households using CDC light traps. Data on rainfall were obtained from the nearby climate station and were used to analyze the association between monthly rainfall and malaria mosquito populations.ResultsThe average number of Anopheles gambiae and Anopheles funestus per trap decreased by 76.8% and 55.3%, respectively over the 1st period, and by 99.7% and 99.8% over the 2nd period. During the last year of sampling (2009), the use of 2368 traps produced a total of only 14 Anopheline mosquitoes. With the exception of the decline in An. gambiae during the 1st period, the results did not reveal any statistical association between mean trend in monthly rainfall and declining malaria vector populations.ConclusionA longitudinal decline in the density of malaria mosquito vectors was seen during both study periods despite the absence of organized vector control. Part of the decline could be associated with changes in the pattern of monthly rainfall, but other factors may also contribute to the dramatic downward trend. A similar decline in malaria vector densities could contribute to the decrease in levels of malaria infection reported from many parts of SSA.

Ambient Air Pollution Triggers Wheezing Symptoms in Infants

Background: There is limited evidence for the role of air pollution in the development and triggering of wheezing symptoms in young children. A study was undertaken to examine the effect of exposure to air pollution on wheezing symptoms in children under the age of 3 years with genetic susceptibility to asthma. Methods: Daily recordings of symptoms were obtained for 205 children participating in the birth cohort study Copenhagen Prospective Study on Asthma in Children and living in Copenhagen for the first 3 years of life. Daily air pollution levels for particulate matter <10 μm in diameter (PM10) and the concentrations of ultrafine particles, nitrogen dioxide (NO2), nitrogen oxide (NOx) and carbon monoxide (CO) were available from a central background monitoring station in Copenhagen. The association between incident wheezing symptoms and air pollution on the concurrent and previous 4 days was estimated by a logistic regression model (generalised estimating equation) controlling for temperature, season, gender, age, exposure to smoking and paternal history of asthma. Results: Significant positive associations were found between concentrations of PM10, NO2, NOx, CO and wheezing symptoms in infants (aged 0–1 year) with a delay of 3–4 days. Only the traffic-related gases (NO2, NOx) showed significant effects throughout the 3 years of life, albeit attenuating after the age of 1 year. Conclusions: Air pollution related to traffic is significantly associated with triggering of wheezing symptoms in the first 3 years of life.