Abstract
STUDY QUESTION
Is there a temporal relationship between endometriosis and infertility?
SUMMARY ANSWER
Endometriosis is associated with a higher risk of subsequent infertility, but only among ...women age <35 years.
WHAT IS KNOWN ALREADY
Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown.
STUDY DESIGN, SIZE, DURATION
This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses' Health Study II prospective cohort.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis.
MAIN RESULTS AND THE ROLE OF CHANCE
We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76–2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46–2.14; multivariate HR 35–39 years = 1.20, 95% CI = 0.94–1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years.
LIMITATIONS, REASONS FOR CAUTION
We did not have information on participants' intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosis will be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates.
WIDER IMPLICATIONS OF THE FINDINGS
This study supports a temporal association between endometriosis and infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses.
STUDY FUNDING/COMPETING INTERESTS
This work was supported by the National Institutes of Health (grant numbers: UM1 CA176726, HD52473, HD57210, T32DK007703, T32HD060454, K01DK103720). We have no competing interests to declare.
BACKGROUND
The objective of this study was to examine the relation between dietary fats and semen quality parameters.
METHODS
Data from 99 men with complete dietary and semen quality data were ...analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders.
RESULTS
Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62–14%) lower total sperm count and 38% (95% CI: 58–10%) lower sperm concentration than men in the lowest third (Ptrend = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= −0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4–3.5%) higher normal morphology than men in the lowest third (Ptrend = 0.02).
CONCLUSIONS
In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.
The etiology of endometriosis is poorly understood, and few modifiable risk factors have been identified. Dairy foods and some nutrients can modulate inflammatory and immune factors, which are ...altered in women with endometriosis. We investigated whether intake of dairy foods, nutrients concentrated in dairy foods, and predicted plasma 25-hydroxyvitamin D (25(OH)D) levels were associated with incident laparoscopically confirmed endometriosis among 70,556 US women in Nurses' Health Study II. Diet was assessed via food frequency questionnaire. A score for predicted 25(OH)D level was calculated for each participant. During 737,712 person-years of follow-up over a 14-year period (1991-2005), 1,385 cases of incident laparoscopically confirmed endometriosis were reported. Intakes of total and low-fat dairy foods were associated with a lower risk of endometriosis. Women consuming more than 3 servings of total dairy foods per day were 18% less likely to be diagnosed with endometriosis than those reporting 2 servings per day (rate ratio = 0.82, 95% confidence interval: 0.71, 0.95; P(trend) = 0.03). In addition, predicted plasma 25(OH)D level was inversely associated with endometriosis. Women in the highest quintile of predicted vitamin D level had a 24% lower risk of endometriosis than women in the lowest quintile (rate ratio = 0.76, 95% confidence interval: 0.60, 0.97; P(trend) = 0.004). Our findings suggest that greater predicted plasma 25(OH)D levels and higher intake of dairy foods are associated with a decreased risk of endometriosis.
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.
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.
Objective: To evaluate whether the amount or quality of carbohydrate in diet is associated with ovulatory infertility. Subjects and Methods: In total, 18 555 married, premenopausal women without a ...history of infertility were followed as they attempted a pregnancy or became pregnant during an 8-year period. Diet was assessed two times during follow-up using a validated food-frequency questionnaire and prospectively related to the incidence of infertility due ovulatory disorder. Results: During follow-up, 438 women reported ovulatory infertility. Total carbohydrate intake and dietary glycemic load were positively related to ovulatory infertility in analyses adjusted for age, body mass index, smoking, parity, physical activity, recency of contraception, total energy intake, protein intake and other dietary variables. The multivariable-adjusted risk ratio (RR) (95% confidence interval (CI)) of ovulatory infertility comparing the highest-to-lowest quintile of total carbohydrate intake was 1.91 (1.27-3.02). The corresponding RR (95% CI) for dietary glycemic load was 1.92 (1.26-2.92). Dietary glycemic index was positively related to ovulatory infertility only among nulliparous women. Intakes of fiber from different sources were unrelated to ovulatory infertility risk. Conclusions: The amount and quality of carbohydrate in diet may be important determinants of ovulation and fertility in healthy women.
STUDY QUESTION
Is consumption of fruits and vegetables with high levels of pesticide residues associated with lower semen quality?
SUMMARY ANSWER
Consumption of fruits and vegetables with high levels ...of pesticide residues was associated with a lower total sperm count and a lower percentage of morphologically normal sperm among men presenting to a fertility clinic.
WHAT IS KNOWN ALREADY
Occupational and environmental exposure to pesticides is associated with lower semen quality. Whether the same is true for exposure through diet is unknown.
STUDY DESIGN, SIZE, DURATION
Men enrolled in the Environment and Reproductive Health (EARTH) Study, an ongoing prospective cohort at an academic medical fertility center. Male partners (n = 155) in subfertile couples provided 338 semen samples during 2007–2012.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Semen samples were collected over an 18-month period following diet assessment. Sperm concentration and motility were evaluated by computer-aided semen analysis (CASA). Fruits and vegetables were categorized as containing high or low-to-moderate pesticide residues based on data from the annual United States Department of Agriculture Pesticide Data Program. Linear mixed models were used to analyze the association of fruit and vegetable intake with sperm parameters accounting for within-person correlations across repeat samples while adjusting for potential confounders.
MAIN RESULTS AND THE ROLE OF CHANCE
Total fruit and vegetable intake was unrelated to semen quality parameters. High pesticide residue fruit and vegetable intake, however, was associated with poorer semen quality. On average, men in highest quartile of high pesticide residue fruit and vegetable intake (≥1.5 servings/day) had 49% (95% confidence interval (CI): 31%, 63%) lower total sperm count and 32% (95% CI: 7%, 58%) lower percentage of morphologically normal sperm than men in the lowest quartile of intake (<0.5 servings/day) (P, trend = 0.003 and 0.02, respectively). Low-to-moderate pesticide residue fruit and vegetable intake was associated with a higher percentage of morphologically normal sperm (P, trend = 0.04).
LIMITATIONS, REASONS FOR CAUTION
Surveillance data, rather than individual pesticide assessment, was used to assess the pesticide residue status of fruits and vegetables. CASA is a useful method for clinical evaluation but may be considered less favorable for accurate semen analysis in the research setting. Owing to the observational nature of the study, confirmation is required by interventional studies as well.
WIDER IMPLICATIONS OF THE FINDINGS
To our knowledge, this is the first report on the consumption of fruits and vegetables with high levels of pesticide residue in relation to semen quality. Further confirmation of these findings is warranted.
STUDY FUNDING/COMPETING INTEREST(S)
Supported by National Institutes of Health grants ES009718, ES022955, ES000002, P30 DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16. None of the authors has any conflicts of interest to declare.
The relationship between job strain and weight gain has been unclear, especially for women. Using data from over 52,000 working women, we compare the association between change in job strain and ...change in body mass index (BMI) across different levels of baseline BMI.
We used data from participants in the Nurses' Health Study II (n=52,656, mean age=38.4 years), an ongoing prospective cohort study. Using linear regression, we modeled the change in BMI over 4 years as a function of the change in job strain, baseline BMI and the interaction between the two. Change in job strain was characterized in four categories combining baseline and follow-up levels as follows: consistently low strain (low at both points), decreased strain (high strain at baseline only), increased strain (high strain at follow-up only) and consistently high strain (high at both points). Age, race/ethnicity, pregnancy history, job types and health behaviors at baseline were controlled for in the model.
In adjusted models, women who reported high job strain at least once during the 4-year period had a greater increase in BMI (ΔBMI=0.06-0.12, P<0.05) compared with those who never reported high job strain. The association between the change in job strain exposure and the change in BMI depended on the baseline BMI level (P=0.015 for the interaction): the greater the baseline BMI, the greater the BMI gain associated with consistently high job strain. The BMI gain associated with increased or decreased job strain was uniform across the range of baseline BMI.
Women with higher BMI may be more vulnerable to BMI gain when exposed to constant work stress. Future research focusing on mediating mechanisms between job strain and BMI change should explore the possibility of differential responses to job strain by initial BMI.
Among adults, the Mediterranean dietary pattern (MDP) is inversely related to body mass index (BMI). Data are lacking on adherence to the MDP among youth in the United States and whether the MDP is ...related to weight change in that group.
To assess whether adherence to the MDP was associated with BMI change among adolescents. To examine temporality, we studied the association between baseline and 2-3-year changes in adherence to the MDP with concurrent changes in BMI, as well as subsequent changes in BMI over a 7-year period.
We prospectively followed 6002 females and 4916 males in the Growing Up Today Study II, aged 8-15 years in 2004, living across United States. Data were collected by questionnaire in 2004, 2006, 2008 and 2011. Dietary intake was assessed by the Youth/Adolescent Questionnaire. The KidMed Index was derived to measure the adherence to the MDP. We used generalized estimating equations with repeated measures within subjects to assess the association between MDP and BMI change.
A two-point increment in the KidMed Index was independently associated with a lower gain in BMI (-0.04 kg m(-2); P=0.001). A greater increase in adherence to the KidMed Index was independently related to a lower gain in BMI in both the concurrent (P-for-trend<0.001) and the subsequent period (P-for-trend=0.002).
Adherence to MDP was inversely associated with change in BMI among adolescents. Two-year improvement in adherence to MDP was independently associated with less steep gain in the BMI in both the concurrent and the subsequent period.
BACKGROUND Endometriosis is a prevalent but enigmatic gynecologic disorder for which few modifiable risk factors have been identified. Fish oil consumption has been associated with symptom ...improvement in studies of women with primary dysmenorrhea and with decreased endometriosis risk in autotransplantation animal studies. METHODS To investigate the relation between dietary fat intake and the risk of endometriosis, we analyzed 12 years of prospective data from the Nurses' Health Study II that began in 1989. Dietary fat was assessed via food frequency questionnaire in 1991, 1995 and 1999. We used Cox proportional hazards models adjusted for total energy intake, parity, race and body mass index at age 18, and assessed cumulatively averaged fat intake across the three diet questionnaires. RESULTS During the 586 153 person-years of follow-up, 1199 cases of laparoscopically confirmed endometriosis were reported. Although total fat consumption was not associated with endometriosis risk, those women in the highest fifth of long-chain omega-3 fatty acid consumption were 22% less likely to be diagnosed with endometriosis compared with those with the lowest fifth of intake 95% confidence interval (CI) = 0.62–0.99; P-value, test for linear trend (Pt) = 0.03. In addition, those in the highest quintile of trans-unsaturated fat intake were 48% more likely to be diagnosed with endometriosis (95% CI = 1.17–1.88; Pt = 0.001). CONCLUSION These data suggest that specific types of dietary fat are associated with the incidence of laparoscopically confirmed endometriosis, and that these relations may indicate modifiable risk. This evidence additionally provides another disease association that supports efforts to remove trans fat from hydrogenated oils from the food supply.