Niels Henrik Hjollund

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.

Register-based follow-up of social benefits and other transfer payments: Accuracy and degree of completeness in a Danish interdepartmental administrative database compared with a population-based survey

Background: Social consequences of disease may be subject to register based follow-up. A Danish database, DREAM, allows weekly follow-up of any public transfer payment. This study aimed to evaluate the feasibility of the register for use in public health research. Material and methods: The DREAM database includes information on all public transfer payments administered by Danish ministries, municipalities, and Statistics Denmark for all Danish citizens on a weekly basis since 1991. The DREAM database was compared with self-reported information on sources of income in a population survey from 2001 with about 5,000 participants. Results: According to DREAM, 80.2% of respondents had received some kind of transfer income since 1991. For the week they filled in the questionnaire, 9.0% had a record of labour-market-related benefit (unemployment benefit, social assistance, wage subsidy), 6.4% a health-related benefit (sickness benefit, vocational rehabilitation allowance, salary from subsidized jobs for persons with limited work capacity, anticipatory pension), 10.1% a voluntary retirement pension, while 74.4% had no record of transfer payment for that week. The predictive value of DREAM was 74.8% for health-related transfer payment and 98.2% for self-support. Among persons with a record of sickness benefit, 52.4% reported no transfer payment. Conclusion: The DREAM database is feasible for follow-up of social and economic consequences of disease. Respondents may be unaware of payments transferred by the public authorities to the employer, and in such cases DREAM may be the best source of information. The database is useful for public health research, but may also be useful for socioeconomic analyses of selection bias and dropout from other studies.

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.

Assessment of fatigue in chronic disease: a bibliographic study of fatigue measurement scales.

A large number of fatigue scales exist and there is no consensus on which fatigue measuring scales that are most appropriate for use in assessment of fatigue in different diseases. We aimed to describe the use of fatigue scales in studies of disease-related fatigue during the last three decades. We searched databases from 1975 to 2004 for original studies reporting on disease-related fatigue and extracted information on method used to assess fatigue, diseases under study and year of publication. A total of 2285 papers reported measures of fatigue in chronic non-acute diseases of which 80% were published during the last decade. We identified 252 different ways to measure fatigue, of which 150 were use only once. Multi-symptom scales (n = 156) were used in 670 studies, while 71 scales specifically designed to measure fatigue were applied in 416 studies. The majority of these studies used scales with a multidimensional approach to fatigue, and most studies used scales that were disease-specific or only applied to few different diseases. Research in disease-related fatigue has increased exponentially during the last three decades, even if we adjust for the general increase in publishing activity. The number of scales has also increased and the majority of scales were developed for specific diseases. There is need for measure instruments with different sizes and dimensionality, and due to ceiling and floor effects, the same scale may not be useful for patients with different severity of fatigue. However, since fatigue is an unspecific symptom there should not be need for adopting disease specific fatigue scales for each individual disease. There may be differences in characteristics of fatigue between diseases and generic measurement instruments may facilitate documentation of such differences, which may be of clinical importance.

Low concentration of circulating antimüllerian hormone is not predictive of reduced fecundability in young healthy women: a prospective cohort study.

OBJECTIVE To evaluate whether circulating levels of antimüllerian hormone (AMH) predict fecundability in young healthy women. DESIGN Prospective cohort study. SETTING General community. PATIENT(S) A total of 186 couples who intended to discontinue contraception to become pregnant were followed until pregnancy or for six menstrual cycles. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Fecundability was evaluated by the monthly probability of conceiving (i.e., fecundability ratio [FR]). In addition, circulating levels of LH, FSH, T, and sex hormone-binding globulin (SHBG) were evaluated in 158 of 186 women. RESULT(S) Fifty-nine percent of couples conceived during the study period. Compared to the reference group of women with medium AMH (AMH quintiles 2-4), fecundability did not differ significantly in women with low AMH (AMH quintile 1) (FR 0.81; 95% confidence interval [CI] 0.44-1.40). In contrast, women with high AMH (AMH quintile 5) had reduced fecundability (FR 0.62; 95% CI 0.39-0.99) after adjustment for covariates (womans age, body mass index [BMI], smoking, diseases affecting fecundability, and oligozoospermia). Irregular menstrual cycles were more prevalent in women with high AMH compared with women with low or medium AMH levels, and they had higher levels of LH (geometric mean: 8.4 vs. 5.3 IU/L) and LH:FSH ratio (2.4 vs. 1.8). After exclusion of women with irregular cycles, women with high AMH still had reduced fecundability (FR 0.48; 95% CI 0.27-0.85) and elevated LH:FSH ratio (2.4 vs. 1.7). CONCLUSION(S) Low AMH in healthy women in their mid-20s did not predict reduced fecundability. Even after exclusion of women with irregular cycles, the probability of conceiving was reduced in women with high AMH.

Shift work, job stress, and late fetal loss: The National Birth Cohort in Denmark.

Objective: The Danish National Birth Cohort (DNBC) was used to examine whether shift work or job stress correlate with late fetal loss. Methods: We identified 33,694 pregnancies of daytime workers and 8,075 pregnancies of shift workers in women recruited to the DNBC between 1998 and 2001. Pregnancy outcomes were obtained by linkages to the national registers. Hazard ratios of fetal loss were calculated by using Cox regressions with left truncation. Results: Fixed night work was associated with fetal loss (hazard ratio = 1.85, 95% confidence interval = 1.00–3.42). No high risk of fetal loss was seen for other types of shift work. Job stress, as measured in our study, was not associated with fetal loss. Conclusions: Our results suggest that fixed night work during pregnancy increases the risk of late fetal loss.

Distress and reduced fertility: a follow-up study of first-pregnancy planners

OBJECTIVE To assess the effect of psychological distress on time to first pregnancy. DESIGN A follow-up study of time to pregnancy with prospective data on distress, with controlling for potential confounding variables. SETTING Two university hospitals. PATIENT(S) Danish couples (n = 430) who were planning their first pregnancy and had no previous reproductive experience were followed for six menstrual cycles. Psychological distress was measured in each menstrual cycle by the General Health Questionnaire. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) A clinically recognized pregnancy or a biochemical pregnancy detected in urine samples from each period of vaginal bleeding. RESULT(S) For cycles with the highest distress score (General Health Questionnaire score >80th percentile), the probability of conception per cycle was 12.8%, compared with 16.5% in other cycles (adjusted odds ratio [OR] 0.6; 95% confidence interval [CI] 0.4-1.0). The effect of distress was found almost exclusively among women with long menstrual cycles (OR 0.1; 95% CI 0.01-0.4 and OR 0.9; 95% CI 0.5-1.4 for women with cycles of > or =35 and <35 days, respectively). An increased incidence of early embryonal loss was also found among highly distressed women with long cycles, but was based on a small number of observations. CONCLUSION(S) Psychological distress may be a risk factor for reduced fertility in women with long menstrual cycles.

A follow-up study of environmental and biologic determinants of fertility among 430 Danish first-pregnancy planners: design and methods.

This paper presents design and methods of a follow-up study of fecundability (defined as the probability of conception during one menstrual cycle) in first-pregnancy planners. We recruited 430 couples by postal letter among 52,255 members of four trade unions. Couples without earlier reproductive experience were enrolled when they discontinued contraception and were followed in six complete menstrual cycles or until a pregnancy was recognized. Data included daily recordings of coitus and menstrual bleeding. Blood, semen, and urine specimens were collected to assess endocrine profile, semen quality, occult embryonal loss, and occupational exposures. Information was obtained about 1661 menstrual cycles (94% of expected). The proportion of couples obtaining a clinical pregnancy during 6 months of follow-up was 65%, and the average probability to obtain a pregnancy across all cycles was 16% (95% CI 14-18%). Among all conceptions the proportion of early embryonal loss was 17% (95% CI 12-22%). This study demonstrates the feasibility of a prospective study of fertility and that the established study base can provide useful information on environmental risk to subfertility.

Association between Pregnancy Loss and Urinary Phthalate Levels around the Time of Conception

Background: Animal studies indicate that some phthalate metabolites may harm female reproductive function. Objectives: We assessed the associations between exposure to phthalate metabolites and pregnancy loss. Methods: Using a previously established cohort of couples planning their first pregnancy, we analyzed four primary and two oxidized secondary phthalate metabolites in urine samples collected on day 10 after the first day of the last menstrual period before conception occurred (n = 128) and during the previous cycle (if any, n = 111). Subclinical embryonal loss was identified by repeated measurement of urinary human chorionic gonadotropin, and information on clinical spontaneous abortions was obtained by telephone interview with the mother. Results: Pregnancy loss (n = 48) was increased among women with urinary concentration of monoethylhexyl phthalate (MEHP) in the upper tertile in the conception sample compared with women in the lowest tertile [adjusted odds ratio (OR) = 2.9; 95% confidence interval (CI): 1.1, 7.6]. The corresponding OR for subclinical embryonal loss (n = 32) was 40.7 (95% CI: 4.5, 369.5). Conclusions: The phthalate metabolite MEHP was associated with higher occurrence of pregnancy loss. Because this is the first human study to show this association and the sample size is small, the findings need to be corroborated in independent studies.

Impact of diurnal scrotal temperature on semen quality

A high scrotal temperature is a common finding in infertile patients and experimental studies indicate that specific types of heat exposure reduce semen quality. More and more men have a sedentary work position, which increases scrotal temperature. Semen and blood samples from 99 healthy men were analysed in relation to scrotal skin temperature obtained by a 24-h continuous monitoring protocol. Information on sedentary position at work and during spare time was collected by questionnaires. A negative correlation was found between high scrotal temperature and sperm output. Sperm concentration decreased 40% per 1 degrees C increment of median daytime scrotal temperature (95% CI: 8-71%). Similar results were found for total sperm count, FSH, and inhibin B. Motility, morphology, pH, and testosterone were not significantly associated with temperature. Only weak and inconsistent associations were found between sedentary position and semen quality. We conclude that scrotal temperature and semen quality are closely associated. Sedentary work position encountered in ordinary jobs, although a strong determinant of scrotal temperature, does not seem to have any effect on semen quality.