Reproductive effects of male psychologic stress

OBJECTIVES: Male psychologic stress can affect semen quality and couple fecundability. METHODS: We conducted a prospective study of 430 Danish couples who were trying to become pregnant for the first time. In each menstrual cycle, both partners filled out a 12-item version of the General Health Questionnaire (GHQ-12), an assessment of psychologic stress. A blood sample was drawn from both partners. The men collected a semen sample at enrollment and each month during follow up. RESULTS: Semen quality was not related to the man's GHQ score in either within-subject analyses or between-subject analyses. There were no consistent associations between stress and serum concentration of luteinizing hormone, follicle-stimulating hormone, inhibin B, testosterone, or estradiol. The pregnancy rate was 14% in cycles with an absolute GHQ-12 score in the highest quartile, compared with 18% in low-stress cycles. Odds of pregnancy decreased moderately with increasing score. The effect was confined to 77 men with a sperm density below 20 million/mL (adjusted odds ratio = 0.06; 95% confidence interval = 1.01-0.58 for highest distressed quartile vs. lowest distressed quartile in this low sperm density group). In within-subject analyses, cycle-specific changes in male stress did not change the odds of pregnancy. High absolute score was associated with a lower frequency of sexual intercourse, but adjustment for frequency had little effect. CONCLUSION: The effect of a man's daily life psychologic stress on his semen quality is small or nonexistent. Our results indicate an effect of stress only on fecundability, and this only among men with low sperm concentration.     

How would a decline in sperm concentration over time influence the probability of pregnancy?

BACKGROUND: Reports have suggested a decline in sperm concentration during the second half of the 20th century. The effect of this decline on fecundability (the monthly probability of pregnancy) could be detected in principle by a study of time to pregnancy. In practice, the amplitude of this expected effect is not well known and the statistical power of time-to-pregnancy studies to detect it has not been explored. METHODS: We developed a nonparametric model to describe a temporal decline in sperm concentration using data on French semen donors. We then applied this model to 419 Danish couples planning a first pregnancy in 1992, to predict their time to pregnancy as if the pregnancy attempt had begun during earlier decades with higher sperm concentrations. Finally, we used bootstrap simulations to estimate the statistical power of prospective or retrospective studies that compared fecundability (estimated from time to pregnancy) across these time periods. We express the change in fecundability over time as a fecundability ratio (FR), with values less than 1 indicating decreased fecundability. RESULTS: We estimate that the median sperm concentration decreased by 21% from 1977 to 1992 and by 47% from 1947 to 1992. The estimated decline in fecundability with those semen changes was 7% from 1977 to 1992 (FR = 0.93, adjusted) and 15% from 1947 to 1992 (FR = 0.85, adjusted). The total numbers of couples that would be needed in prospective studies of time to pregnancy to detect these changes in fecundability (with a power of 80%) were 12,000 when comparing 1977 to 1992, and 2000 when comparing 1947 to 1992. Retrospective studies of the same size that excluded childless couples had much lower statistical power and were biased toward the null. CONCLUSION: The effect of realistic declines in sperm concentration on time to pregnancy may be observed only with studies that include several thousand couples.     

Predictors of serum dioxin levels among adolescent boys in Chapaevsk,Russia: A cross-sectional pilot study

Background

Persistent organochlorine pollutants (POPs) may interfere with reproductive function but direct evidence in humans is very limited.

Methods

Fertility was examined in four regions with contrasting blood levels of POPs. Pregnant women and their partners in Warsaw (Poland), Kharkiv (Ukraine) and Greenland were consecutively enrolled during antenatal visits. Swedish fishermen and their spouses were recruited separately and independently of current pregnancy. Lipid adjusted serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (DDE) were available for both partners. Time to pregnancy interviews were obtained among 2269 women and 798 men provided a semen sample.

Results

Inuits had high levels of both POP markers, Swedish fishermen were high in CB-153 but low in DDE, men from Kharkiv were high in DDE and low in CB-153 while men from Warsaw were low in CB-153 and had intermediate DDE levels. Compared to Warsaw couples, fecundability was reduced among couples from Kharkiv [adjusted fecundability ratio (FR) 0.64 (95% CI 0.5–0.8)] and elevated in Swedish fishermen families [FR 1.26 (95% CI 1.0–1.6)]. Adjusted geometric means of sperm counts and morphology did not differ between regions while sperm motility was higher in men living in Warsaw.

Conclusion

We observed regional differences in time to pregnancy and sperm motility that may be related to regional differences in POP blood levels, but other interpretations are also plausible. In particular, differences in access to safe contraception and in the prevalence of contraceptive failures are most likely to bias comparisons of time to pregnancy.     

Geographic variations in probability of pregnancy in four cities of France

BACKGROUND: Several studies have described geographic variations in human fecundability, but this phenomenon has almost exclusively been studied at an international level rather than within a given country. Our aim was to describe geographic variations in fecundability, the monthly probability of pregnancy, between four cities of France. METHODS: We conducted a cross-sectional study in four French maternity units from Toulouse, Rennes, Lyons and Paris, among partners of pregnant women. Women were asked about the time to pregnancy (TTP) of their current pregnancy. TTP was analysed with a discrete Cox model allowing to estimate fecundability ratios (FR). RESULTS: Time to pregnancy was defined for 894 couples. There was no strong evidence of heterogeneity in fecundability between the four compared cities (p=0.05 without adjustment and p=0.25 after adjustment for behavioural and medical factors). The highest fecundability was observed in Rennes and the lowest in Toulouse (fecundability ratio (FR)=1.28, 95% CI: 1.01-1.63). Differences in fecundability were smaller between the other cities. CONCLUSION: We highlighted a possibly slightly higher fecundability in Rennes compared to Toulouse. Possible explanations for this finding are discussed. We note that the finding is consistent with previous observations indicating a higher sperm concentration among semen donors in Rennes than in Toulouse.     

Job strain and male fertility

BACKGROUND: Job strain, defined as high job demands and low job control, has not previously been explored as a possible determinant of male fertility. We collected prospective data on job strain among men, and describe the associations with semen quality and probability of conceiving a clinical pregnancy during a menstrual cycle. METHODS: Danish couples (N = 399) who were trying to become pregnant for the first time were followed for up to 6 menstrual periods. All men collected semen samples, and a blood sample was drawn from both partners. Job demand and job control were measured by a self-administered questionnaire at entry, and in each cycle the participants recorded changes in job control or job demand during the previous 30 days. RESULTS: In adjusted analyses, no associations were found between any semen characteristic or sexual hormones and any job strain variable. The odds for pregnancy were not associated with job strain. CONCLUSIONS: Psychologic job strain encountered in normal jobs in Denmark does not seem to affect male reproductive function.     

Use of time to pregnancy to study environmental exposures

There is need in reproductive epidemiology for sensitive and convenient screening tools that can be used to study environmental and occupational exposures. The measurement of fecundability (the probability of pregnancy in each cycle) by ascertaining how long it takes couples to conceive, may be useful for this purpose. Theoretically, exposures that interfere with any of the biologic processes involved in achieving pregnancy could lower fecundability among exposed men or women. To evaluate problems with collecting data on time to pregnancy, telephone interviews were conducted with nearly 700 pregnant women who reported having planned their pregnancies. Power curves were developed based on the distribution of time to pregnancy in the interviewed population. These curves indicate that relatively small sample sizes are sufficient for investigating an exposure. For example, the authors estimate that to detect a given 50% drop in mean fecundability with 80% power would require data from 55 exposed and 55 unexposed women who are pregnant. Disadvantages of using time to pregnancy as a reproductive endpoint include susceptibility to selection bias and need for data on several potential confounding variables. The next step in evaluating time to pregnancy as a reproductive endpoint is to apply it in studies of environmental or occupational exposures.     

Parental consumption of contaminated sport fish from Lake Ontario and predicted fecundability

Wildlife studies suggest that consumption of contaminated fish from the Great Lakes may expose humans to polychlorinated biphenyls and persistent chlorinated pesticides. To assess whether time to pregnancy or fecundability is affected, we conducted a telephone survey in 1993 with female members of the New York State Angler Cohort Study who were considering pregnancy between 1991 and 1994 (N = 2,445). Among the 1,234 (50%) women who became pregnant, 895 (73%) had a known time to pregnancy. Upon enrollment into the cohort in 1991, both partners reported duration and frequency of Lake Ontario sport fish consumption. We estimated lifetime exposure to polychlorinated biphenyls from recent consumption and used a discrete-time analog of Cox proportional hazards analysis to estimate conditional fecundability ratios and 95% confidence intervals (CIs) for fish consumption among couples with complete exposure data who discontinued birth control to become pregnant (N = 575). Maternal consumption of fish for 3-6 years was associated with reduced fecundability (fecundability ratio = 0.75; 95% CI = 0.59-0.91), as was more than a monthly fish meal in 1991 (fecundability ratio = 0.73; 95% CI = 0.54-0.98). Our findings suggest that maternal but not paternal consumption of contaminated fish may reduce fecundability among couples attempting pregnancy.     

Indirect fertility analysis in painters exposed to ethylene glycol ethers: sensitivity and specificity

Semen analysis has proven useful in the clinical diagnosis of infertility and is the most widely used method of monitoring the effects of occupational exposure on male fertility. Collection and analysis of semen samples in a field setting, however, require a highly motivated population and excellent technical resources, limiting the widespread application of the method. Techniques of monitoring male worker fertility using questionnaires to avoid some of the difficulties of semen analysis have been developed. These methods compare the rate of observed births for wives of workers with expected birth rates derived either from U.S. fertility tables or from unexposed workers. The present study compares the sensitivity of this questionnaire method with that of semen analysis in an evaluation of reproductive function in men exposed to ethylene glycol ethers. The reproductive function of 74 married painters exposed to ethylene glycol ethers was compared with that of 51 married controls employed at a shipyard. The groups differed in sperm count, but the questionnaire method showed no effect of exposure on fertility. This analysis suggests that the questionnaire assessment of fertility is less sensitive than semen analysis as a screening tool for male reproductive function.     

Serum Vitamin D Concentrations,Time to Pregnancy,and Pregnancy Outcomes among Preconception Couples: A Cohort Study in Shanghai,China

Background: The role of vitamin D in reproductive health is still unclear. This study aimed to assess the effect of serum 25-hydroxyvitamin D (25(OH)D), among preconception couples, on fecundity, and the associations between 25(OH)D concentrations before and during pregnancy, and pregnancy outcomes. Methods: 200 preconception couples attempting to conceive were recruited and were followed-up until childbirth. Time to pregnancy was collected via telephone every two months or obtained via a questionnaire during pregnancy. Blood samples were collected to measure serum 25(OH)D levels from both partners at enrollment and from women during the second and third trimester of pregnancy. Results: Couples had higher conception rates within six months (adjusted odds ratio (aOR): 3.72, 95% CI: 1.16, 11.9) and reduced time to pregnancy (adjusted fecundability ratio (aFR): 1.50, 95% CI: 1.01, 2.23) if male partners had sufficient 25(OH)D compared with insufficient 25(OH)D. Compared to pregnant women with insufficient 25(OH)D in the third trimester of pregnancy, sufficient 25(OH)D was associated with reduced odds of anemia (OR: 0.22, 95% CI: 0.06, 0.82), longer gestational age (β: 0.53, 95% CI: 0.04, 1.01) and newborns’ higher ponderal index (β: 0.10, 95% CI: 0.01, 0.19). Conclusions: Sufficient serum 25(OH)D levels among preconception men or during pregnancy were associated with better reproductive health.     

Time to pregnancy and occupational exposure to pesticides in fruit growers in The Netherlands.

OBJECTIVES--Although pesticides are regularly used in agriculture, relatively little is known about possible adverse health effects, especially reproductive effects, due to occupational exposure. This explorative study investigates the relation between exposure of the fruit grower to pesticides and fecundability (probability of pregnancy) in a population of fruit growers. METHODS--The analysis is based on self reported data and includes 91 pregnancies during 1978-1990 of 43 couples. Cox' proportional hazards model was used to analyse time to pregnancy after correction for gravidity and consultation with a physician for fertility problems. RESULTS AND CONCLUSIONS--Application of pesticides solely by the owner was associated with a long time to pregnancy, resulting in a fecundability ratio of 0.46 (95% confidence interval (95% CI) 0.28-0.77). Similarly a low spraying velocity (< or = 1.5 hectares/h) resulted in a fecundability ratio of 0.47 (95% CI 0.29-0.76) and is associated with the use of older spraying techniques and tractors without a cabin. These factors were assumed to cause high exposure, which was confirmed by exposure measurements in the field. The effect of high exposure was mainly apparent if the couple had intended to become pregnant in the period from March-November (fecundability ratio 0.42, 95% CI 0.20-0.92). This is the period in which pesticides are applied. Out of the spraying season the effect of a high exposure was absent (fecundability ratio 0.82, 95% CI 0.33-2.02). In the high exposure group 28% of the pregnancies had been preceded by consulting a physician because of fertility problems, compared with 8% in the low exposure group. These findings indicate that an adverse effect of exposure to pesticides on fecundability is likely.     

Reduced fecundability in women with prenatal exposure to cigarette smoking

Animal studies have suggested that fertility may be impaired by transplacental exposures, but little is known about human prenatal exposures and subsequent adult reproduction. A possible relation between prenatal exposure to cigarette smoking and adult fecundability in women was explored, with the use of data from a prospective study of 221 North Carolina couples. These couples were recruited during 1983-1985, at the time they stopped using birth control in order to become pregnant. The relative fecundability of exposed compared with unexposed women was estimated by applying a discrete-time proportional probabilities model to the cycle-by-cycle conception rates. Women with prenatal exposure to their mother's cigarette smoking had reduced fecundability. The fecundability ratio associated with prenatal exposure to mother's smoking, adjusted for age, frequency of intercourse, current smoking status, age at menarche, and childhood exposure to cigarette smoking, was 0.5 (95% confidence interval 0.4-0.8). This association was not changed by further adjustment for other possible confounding variables, including educational level, reproductive history, body weight, and consumption of alcohol and caffeine. Thus, women whose mothers smoked while pregnant with them may be on average substantially less fecund than women whose mothers did not smoke during pregnancy.     

Extremely low frequency magnetic fields and fertility: a follow up study of couples planning first pregnancies. The Danish First Pregnancy Planner Study Team

OBJECTIVES: To evaluate the impact of extremely low frequency (ELF) magnetic fields on markers of human fertility. METHODS: A follow up study of time to pregnancy, semen quality, and reproductive hormones was conducted among couples planning first pregnancies (36 males were welders and 21 were non-welders). The male and the female partner were monitored for exposure to ELF magnetic field by personal exposure meters. As summary measures of exposure the median value was calculated together with the 75 percentile value and the proportion of measurements exceeding 0.2 and 1.0 microT, respectively. Each summary measure was divided in three categories: low, medium, and high. RESULTS: Couples in which the man had a medium or a high proportion of measurements > 1.0 microT had a reduced probability of conception per menstrual cycle compared with the men with low exposure, but the result was only significant for the men with medium exposure. This finding was partly attributable to a high probability of conception per menstrual cycle among the men with low exposure compared with non-welders in the original cohort of 430 couples. Other summary measures were not related to probability of conception or other markers of fertility. A possible negative association was found between high probability of conception and female exposure measures based on the median, the 75 percentile, and the proportion of measurements > 0.2 microT, but no association was found with the proportion of measurements > 1.0 microT. CONCLUSIONS: The findings provide no consistent support for a hypothesis of a deleterious effect of low level ELF magnetic fields on markers of human fertility. However, due to the relatively small size of the studied population only large associations would be detected.

 

     

A prospective study of influenza vaccination and time to pregnancy

BackgroundAlthough pregnancy planners are a priority group for influenza vaccination in the United States, little is known about the extent to which influenza vaccination affects fecundability.MethodsWe analyzed data from Pregnancy Study Online (PRESTO), an ongoing preconception cohort study of North American pregnancy planners. During June 2013 to August 2019, 8654 female participants and 2137 of their male partners completed a baseline questionnaire and were followed until reported pregnancy, fertility treatment initiation, loss to follow-up, or 12 menstrual cycles of attempt time, whichever came first. At baseline, male and female participants reported whether they received an influenza vaccination in the past year and the date of vaccination. We used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) comparing those who did and did not report influenza vaccination, adjusting for demographics, anthropometrics, behavioral factors, and medical history.ResultsInfluenza vaccination in the past year was more common among female participants than male participants (47% vs. 37%). FRs were 1.04 (95% CI: 0.98–1.10) for female vaccination and 1.03 (95% CI: 0.93–1.14) for male vaccination. Among the 2137 couples with complete data on both partners, for 40% neither partner was vaccinated, 23% had female-only vaccination, 9% had male-only vaccination, and in 28% both partners were vaccinated. Compared with couples in which neither participant was vaccinated, FRs were 1.13 for female-only vaccination (95% CI: 0.99–1.29), 0.94 for male-only vaccination (95% CI: 0.78–1.12), and 1.07 when both partners were vaccinated (95% CI: 0.94–1.21). When restricted to recent vaccination before peak influenza season, results were similar.ConclusionsOur data indicate no adverse effect of influenza vaccination on fecundability.     

FROM ZERO TO ONE HUNDRED MILLION IN SIX MONTHS: THE TREATMENT OF AZOOSPERMIA IN CONGENITAL ADRENAL HYPERPLASIA

In the majority of the 25% of couples in which a male factor is responsible for their infertility, no identifiable pathology is found. It is unusual to be faced with an etiology that is readily amenable to successful treatment without the eventual dependence on assisted reproductive techniques for pregnancy. The diagnosis of congenital adrenal hyperplasia has variable implications on fertility. A case is presented of azoospermia in a man diagnosed with classical non-salt-losing congenital adrenal hyperplasia. Within 9 months of treatment with dexamethasone, his sperm count had risen to above 100 million per milliliter, enough to overcome very poor morphology and a naturally conceived pregnancy ensued. The pregnancy is ongoing. Although an increase in sperm count has been shown in such cases, the degree of improvement in semen parameters is unique, especially in an azoospermic patient.     

Has human fertility declined over time?: why we may never know

BACKGROUND: Reports of decreased semen quality over time have raised concerns about possible reductions in human fertility. Studies of couple fertility have produced conflicting results. We evaluate how changes in the availability and use of effective contraception and induced abortion might bias the direct study of time trends in couple fertility. METHODS: We assess the potential for bias in the context of 2 common study designs: (1) a study of time-to-pregnancy that estimates fecundability (excluding unintended pregnancies) and (2) a study of infertility rates that categorizes couples as fertile or infertile (including couples with unintended pregnancies as fertile). RESULTS: In time-to-pregnancy studies, bias alone could produce more than a 2-fold apparent increase in fecundability over recent decades. In studies of infertility rates, the bias works in the opposite direction: a 30% underestimation of infertility during earlier decades could produce an apparent decrease in fertility over time. CONCLUSIONS: Over the past 5 decades, changes in social factors that affect the rate and fate of unintended pregnancies could substantially bias time trends in fertility. These biases may explain the conflicting reports in the literature. Except in rare settings in which the factors affecting reproductive choices have not changed, it is probably impossible to identify biologic changes in fertility over recent decades.     

Feasibility of the current-duration approach to studying human fecundity

Approaches for monitoring time trends in couples' fecundity and for studying its sensitivity to environmental factors are needed. Two approaches rely on the inclusion of a cross-sectional sample of couples currently "at risk" of pregnancy either with follow up (prevalent cohort) or without follow up (current-duration design). To illustrate the feasibility of the current-duration design, we contacted a random sample of 1204 French women age 18 to 44 years in 2004 and recruited those who were currently having unprotected sexual intercourse. The current duration since the beginning of unprotected intercourse was defined for 69 women (5.7%). An additional 15 women (1.2%) were planning to start trying to become pregnant within the next 6 months. Parametric methods allowed, based on current duration of unprotected intercourse, estimation of fecundity as if the couples had been followed prospectively. The estimated proportion of couples not pregnant after 12 months of unprotected intercourse was 34% (95% confidence interval [CI] = 15-54%). The accelerated-failure time model allows study of the influence of environmental factors on fecundity. As an illustration, tobacco smoking by the woman was associated with a doubling in the median duration of unprotected intercourse before pregnancy (adjusted time ratio = 2.4; 95% CI = 1.1-5.2). We quantified the influence of time trends in the prevalence of smoking on this estimate. We suggest ways to quantify or avoid other potential bias. In conclusion, it is possible to recruit a sample of couples currently having unprotected intercourse. The current-duration design appears feasible with approximately 5 times as many women eligible for study as for an incident cohort design.     

Time to pregnancy and secondary sex ratio in men exposed prenatally to diethylstilbestrol

Little is known about the influence of prenatal diethylstilbestrol (DES) exposure on time to pregnancy or secondary sex ratio in men. The authors evaluated these associations among men participating in the DES Combined Cohort Follow-up Study for whom exposure status was confirmed by medical record. In 2001, men provided data on their reproductive histories. Demographic, behavioral, and medical data were collected in 1994, 1997, and 2001. Cox's proportional hazards models with frailty were used to estimate fecundability ratios for time to pregnancy in relation to DES. Generalized estimating equations were used to estimate odds ratios for fathering a male birth in relation to DES. Models included potential confounders and accounted for multiple pregnancies contributed by each man. Overall, DES was not associated with a delay in time to pregnancy (fecundability ratio = 0.95, 95% confidence interval: 0.86, 1.06). The odds ratio for fathering a male birth was 0.92 (95% confidence interval: 0.80, 1.04) comparing the exposed with the unexposed. In conclusion, prenatal DES exposure was not associated with a significant decrease in either fecundability or secondary sex ratio.     

Potential for bias in estimating human fecundability parameters: a comparison of statistical models

Fecundability studies, where couples attempting pregnancy subject to 'failure' (conception) one time in each menstrual cycle, present a natural discrete failure-time scenario. Because the biologic capacity to conceive varies among couples in the population, a complication arises in choosing a method of analysis, related to the fact that the maximum follow-up time can vary from study to study, and follow-up time could potentially have different effects on parameters based on different approaches to modelling. Traditional development in fertility studies has been based on an implicit assumption that binary outcomes for different menstrual cycles are mutually independent. We contrast traditional models to a random effects model where cycle viability is modelled as subject-specific. We clarify the interpretations for different parameters from different models. We show that the traditional approach yields some regression parameters that depend on follow-up time, limiting the generalizability of inferences based on this analytic approach. By contrast, the subject-specific model consistently estimates parameters of interest, if the underlying distribution is properly specified. Data from a fecundability study carried out in North Carolina serves to illustrate these points.     

Incidence and implications of altered semen quality on family planning

Alterations in the expression of the human genome, or interference with its products, can be induced in the male reproductive system by chemicals mimicking or antagonizing naturally occurring hormones. Opportunities exist for disruption at the hypothalamus, pituitary and testis levels. Recent concerns generated by the increased incidence of testicular cancer, congenital anomalies of the male genitalia and possible alterations in human semen quality have been linked to the environment.The report by Carlsen in 1992 [1] suggested that semen quality has deteriorated over the past six decades. More recent reports suggest that the decline may be globally non-uniform and regional in nature. The effects of any such declines upon overall pregnancy rates are generally unknown, although some studies have attempted to address them. A preliminary review of the impact of a small decrease in sperm concentrations suggests that a directly measurable reduction in fecundity does not occur, but that future problems could be anticipated. Decrements in semen quality will alter the epidemiological probabilities of pregnancy due to coitus on different cycle days and may thereby change the duration of the fertile time. Current understanding of the implications of altered semen quality on relative fertility is not sufficient to change our current teaching and practice of NFP.