Breastfeeding duration and subsequent risk of mortality among US women: A prospective cohort study.

Background: Breastfeeding has been associated with a reduced maternal long-term risk of chronic diseases, but its association with mortality is poorly known. Methods: We included 166,708 female United States (US) nurses from the Nurses' Health Study (1986-2016) and the Nurses' Health Study II (1989-2019) who experienced at least one pregnancy lasting at least six months across their reproductive lifespan. Hazard ratios and 95% confidence intervals (CI) for mortality according to lifetime breastfeeding duration were estimated with time-dependent Cox proportional hazards regression models. Findings: During 4,705,160 person-years of follow-up, 36,634 deaths were documented in both cohorts, including 9880 from cancer and 7709 from cardiovascular disease (CVD). Lifetime total breastfeeding duration was associated with a lower subsequent risk of all-cause mortality in a non-linear manner (p-value for non-linearity=0.0007). The pooled multivariable-adjusted hazard ratios of all-cause mortality were 0.95 (95% CI: 0.92 to 0.98), 0.94 (95% CI: 0.91 to 0.98), 0.93 (95% CI: 0.90 to 0.97), and 0.93 (95% CI: 0.89 to 0.97), respectively, for women reporting lifetime total breastfeeding duration of 4-6, 7-11, 12-23, and ≥24 months, compared to women who breastfed for ≤3 months over their reproductive lifespan. Cause-specific analysis showed a similar pattern of non-linear inverse associations between lifetime total breastfeeding duration and CVD and cancer mortality (both p-values for non-linearity <0.01). There was no evidence of interactions between breastfeeding duration and pre-pregnancy lifestyle factors on mortality risk. Interpretation: Parous women with longer lifetime breastfeeding duration had a modestly lower risk of mortality. Funding: The National Institutes of Health grants.

Sugar- and artificially-sweetened soda consumption and subclinical atherosclerosis among Mexican women.

BACKGROUND AND AIMS: Sugar-sweetened soda consumption is associated with most cardiometabolic risk factors. The role of artificially-sweetened beverages in cardiovascular disease (CVD) is inconclusive, but their consumption correlates with health impairment. Little is known about the contribution of soda consumption in subclinical stages of atherosclerosis. Therefore, we evaluated the relation between sugar- and artificially-sweetened soda consumption and carotid intima-media thickness (IMT) among Mexican women. METHODS AND RESULTS: We cross-sectionally evaluated 1093 women enrolled in the Mexican Teachers' Cohort who were free of CVD, diabetes or cancer. Sugar- and artificially-sweetened soda consumption was estimated from a validated 140-item food frequency questionnaire in 2008 and all women underwent a carotid ultrasound assessment three years later. Participants were categorized into tertiles of soda consumption in servings/week. Subclinical atherosclerosis was defined as a mean left and/or right IMT ≥0.8 mm or the presence of plaque on either common carotid artery. In multivariable regression models, women in the highest tertile of sugar-sweetened soda consumption had 2.6% (95%CI: 0.8, 4.5) mean increased IMT, and had 2-fold the risk of carotid atherosclerosis (PR: 2.0, 95%CI: 1.3, 3.2) compared to those in the lowest tertile. In stratified analyses, older and postmenopausal women who consumed sugar-sweetened soda had an increased IMT and atherosclerosis risk. Artificially-sweetened soda consumption was not associated with IMT or carotid atherosclerosis. CONCLUSIONS: Sugar-sweetened soda consumption was associated with subclinical atherosclerosis among disease-free Mexican women. Public health strategies to decrease CVD should consider the impact of sugar-sweetened soda consumption, particularly in older women.

Women's and men's intake of omega-3 fatty acids and their food sources and assisted reproductive technology outcomes.

BACKGROUND: Long-chain omega-3 fatty acids and their food sources have garnered interest as a potential nutrient with wide-range health benefits, including fertility. OBJECTIVE: This study aimed to investigate the association of women's and men's intake of omega-3 fatty acids and omega-3 rich-foods with semen quality and outcomes of infertility treatment with assisted reproductive technologies. STUDY DESIGN: Couples presenting to the Massachusetts General Hospital were invited to enroll in a prospective cohort study (2007-2020). Male and female diets were assessed using a validated 131-item food frequency questionnaire. The primary outcomes were implantation, clinical pregnancy, and live birth probabilities. The secondary outcomes included total and clinical pregnancy loss and conventional semen parameters, for males only. We estimated the relationship between intakes of omega-3 fatty acids, nuts, and fish and the probability (95% confidence interval) of study outcomes using generalized linear mixed models to account for repeated treatment cycles per participant while simultaneously adjusting for age, body mass index, smoking status, education, dietary patterns, total energy intake, and male partner diet. RESULTS: A total of 229 couples and 410 assisted reproductive technology cycles were analyzed for primary and secondary outcomes. Of note, 343 men contributing 896 semen samples were included in analyses for semen quality measures. Women's docosahexaenoic acid + eicosapentaenoic acid intake was positively associated with live birth. The multivariable-adjusted probabilities of live birth for women in the bottom and top quartiles of eicosapentaenoic acid + docosahexaenoic acid intake were 0.36 (95% confidence interval, 0.26-0.48) and 0.54 (95% confidence interval, 0.42-0.66) (P trend=.02). Eicosapentaenoic acid + docosahexaenoic acid intake was inversely related to the risk of pregnancy loss, which was 0.53 among women in the lowest quartile of eicosapentaenoic acid + docosahexaenoic acid intake and 0.05 among women in the highest quartile (P trend=.01). Men's intake of total omega-3 fatty acids was positively related to sperm count, concentration, and motility, but unrelated to any assisted reproductive technology outcomes. Similar associations were observed when evaluating the intake of primary food sources of these fatty acids. CONCLUSION: Women's consumption of omega-3 fatty acids and omega-3-rich foods may improve the probability of conception by decreasing the risk of pregnancy loss. In addition, men's intake of omega-3 fatty acids may influence semen quality.

Associations between patterns of modifiable risk factors in mid-life to late life and longevity: 36 year prospective cohort study.

Objective: To examine the associations between patterns of mid-life to late life modifiable risk factors and longevity. Design: Prospective cohort study. Setting: Data collected from the Nurses' Health Study starting in 1984 and the Health Professionals Follow-up Study starting in 1986. Participants: 85 346 participants from the Nurses' Health Study and the Health Professionals Follow-up Study. Main outcome measures: Death from any cause by 31 October 2020 for the Nurses' Health Study and Health Professionals Follow-up Study. Risk factors investigated were body mass index, physical activity, alcohol intake, smoking status, and quality of diet. Trajectories of each risk factor and trajectories of changes in the risk factor were identified from baseline with smoothing mixture models, and the joint group memberships of participants was used to most efficiently capture patterns of the factor over time. For each risk factor, three trajectories (patterns with high, medium, and low values) and three trajectories of change in the risk factor (patterns with increase, no change, and decrease in the factor from baseline) were assumed, giving nine joint patterns: high-stable, high-increase, high-decrease, medium-stable, medium-increase, medium-decrease, low-stable, low-increase, and low-decrease. Associations between patterns of modifiable risk factors and longevity (age at death ≥85 years) and life expectancy were examined with logistic regression and accelerated failure time models, respectively. Results: The analysis included 85 346 participants, with 46 042 participants achieving longevity and 25 322 participants achieving healthy longevity (those who did not have a diagnosis of cardiovascular disease, type 2 diabetes, or cancer). Mean age at baseline was 56 years (standard deviation 5 years). Maximum longevity was achieved in participants with a low-stable pattern for body mass index (compared with a medium-stable pattern, odds ratio of longevity of 1.05, 95% confidence interval 1.00 to 1.10); those with a medium-increase pattern for physical activity (compared with a medium-stable pattern, odds ratio 1.08, 1.01 to 1.15); those with a medium-stable pattern for alcohol intake (high-increase v medium-stable pattern, odds ratio 0.83, 0.74 to 0.93); those who never smoked (low-stable v medium-stable pattern, odds ratio 3.09, 2.84 to 3.37); and those who with a high-increase pattern for quality of diet (compared with a medium-stable pattern, odds ratio 1.09, 1.01 to 1.18). The associations between each factor and life expectancy and healthy longevity (no diagnosis of cardiovascular disease, type 2 diabetes, or cancer) were similar to those for longevity. Conclusions: During mid-life and late life, maximum longevity was achieved in participants who maintained a normal body mass index, never smoked, ate a healthy diet, and had physical activity levels and alcohol consumption that met public health recommendations.

Physical activity before pregnancy and the risk of hypertensive disorders of pregnancy.

BACKGROUND: It is unclear whether prepregnancy physical activity influences the risk of hypertensive disorders of pregnancy and whether any impact is similar for preeclampsia and gestational hypertension. OBJECTIVE: To evaluate the relation of prepregnancy physical activity with hypertensive disorders of pregnancy and its alignment with the current recommendations for physical activity for the general population. STUDY DESIGN: We studied 28,147 singleton pregnancies from 18,283 women without chronic hypertension, cardiovascular disease, or cancer, participating in the Nurses' Health Study-II between 1989 and 2010. The women self-reported their physical activity before pregnancy and pregnancy complications, including preeclampsia and gestational hypertension. Logistic regression models using generalized estimating equations to account for within-woman correlations across pregnancies were used to estimate the relative risk (95% confidence interval) of preeclampsia and gestational hypertension across quartiles of prepregnancy physical activity, adjusting for age at pregnancy, parity, smoking, multivitamin use, infertility history, marital status, race, year of pregnancy, and history of preeclampsia. RESULTS: We identified 842 (3.0%) pregnancies with preeclampsia and 905 (3.2%) pregnancies with gestational hypertension. Physical activity before pregnancy was related to a lower risk of hypertensive disorders of pregnancy (relative risk, 0.75 [95% confidence interval, 0.65-0.87] for women in the highest quartile compared with the lowest quartile). This relation was driven by a 39% lower risk of gestational hypertension (relative risk, 0.61; 95% confidence interval, 0.50-0.76) comparing women in the highest quartile of physical activity (≥30.6 metabolic equivalents of task-hours/week) vs women in the lowest quartile (<6.0 metabolic equivalents of task-hours/week). Women whose moderate physical activity levels exceeded those recommended in the Physical Activity Guidelines for Americans (>5 hours/week) had a 50% lower (relative risk, 0.50; 95% confidence interval, 0.36-0.69) risk of gestational hypertension than women who did not meet this recommendation (<2.5 hours/week). For vigorous physical activity, the risk of gestational hypertension was lower among the women who met (1.25-2.5 hours/week; relative risk, 0.77; 95% confidence interval, 0.64-0.93) or exceeded (>2.5 hours/week; relative risk, 0.76; 95% confidence interval, 0.62-0.92) the recommendations than women whose activity levels were below those recommended. Physical activity was not related to the risk of preeclampsia (relative risk, 0.93; 95% confidence interval, 0.76-1.14). CONCLUSION: Physical activity before pregnancy may lower the risk of developing gestational hypertension but not preeclampsia.

Variation in diet quality across sexual orientation in a cohort of U.S. women.

PURPOSE: Extensive prior research has shown that sexual minority women are more likely to have a number of cancer risk factors, thereby putting them at higher risk for cancer than heterosexual women. However, there has been little research evaluating the association between sexual orientation and diet quality. METHOD: Data come from participants (aged 24-54 years) enrolled in Nurses' Health Study 3, an ongoing, U.S.-based cohort study (N = 15,941). We measured diet using recommendations from the Dietary Approach to Stop Hypertension (DASH) and American Health Association (AHA) 2020 Strategic Impact Goals. RESULTS: We found limited evidence of differences across diet quality by sexual orientation. When examining predicted DASH scores, mostly heterosexual [predicted mean score (95% confidence interval), 24.0 (23.8, 24.3)] and lesbian [24.3 (23.8, 24.9)] women had healthier predicted DASH scores than the reference group of completely heterosexual women with no same-sex partners [23.6 (23.5, 23.7)]. Even though certain sexual minority women had overall healthier predict DASH scores, their consumption of certain food groups-low-fat dairy and fruit-was lower than completely heterosexual women with no same-sex partners. When measuring AHA scores, most sexual minority groups (completely heterosexual women with same-sex partners, mostly heterosexual women, and lesbian women) had higher diet quality compared to the reference group of completely heterosexual women with no same-sex partners. CONCLUSION: Sexual minority women, particularly mostly heterosexual women and lesbian women, had healthier diet quality than completely heterosexual women with no same-sex partners. These data suggest that cancer risk factors (e.g., smoking, drinking, and inactivity) other than diet would drive higher cancer rates among sexual minority compared to heterosexual women. Nonetheless, it is critical for all women to improve their diet quality since diet quality was poor among participants of all sexual orientations.

Hypertensive Disorders of Pregnancy and Subsequent Risk of Premature Mortality.

BACKGROUND: Hypertensive disorders of pregnancy (HDPs) are leading causes of maternal and perinatal morbidity and mortality. However, it is uncertain whether HDPs are associated with long-term risk of premature mortality (before age 70 years). OBJECTIVES: The objective of this study was to evaluate whether HDPs were associated with premature mortality. METHODS: Between 1989 and 2017, the authors followed 88,395 parous female nurses participating in the Nurses' Health Study II. The study focused on gestational hypertension and pre-eclampsia within the term HDPs. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between HDPs and premature mortality were estimated by using Cox proportional hazards models, with adjustment for relevant confounders. RESULTS: The authors documented that 2,387 women died before age 70 years, including 1,141 cancer deaths and 212 CVD deaths. The occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an HR of 1.31 (95% CI: 1.18 to 1.46) for premature death during follow-up. When specific causes of death were examined, these relations were strongest for CVD-related mortality (HR: 2.26; 95% CI: 1.67 to 3.07). The association between HDPs and all-cause premature death persisted, regardless of the subsequent development of chronic hypertension (HR: 1.20 [95% CI: 1.02 to 1.40] for HDPs only and HR: 2.02 [95% CI: 1.75 to 2.33] for both HDPs and subsequent chronic hypertension). CONCLUSIONS: An occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an increased risk of premature mortality, particularly CVD mortality, even in the absence of chronic hypertension.

Substantial Weight Gain in Adulthood Is Associated with Lower Probability of Live Birth Following Assisted Reproduction.

BACKGROUND: Overweight and obesity among women have been associated with lower success of assisted reproduction technologies (ARTs). However, the relation of adolescent body weight and adult weight change to ART outcomes is not well understood. OBJECTIVE: Our objective was to evaluate the associations of female BMI (in kg/m2) at 18 y and weight change from 18 y to current age with ART outcomes. METHODS: We included 486 women in a prospective cohort at the Massachusetts General Hospital Fertility Center (2004-2018) who underwent 863 ART cycles. At study entry, height and weight were measured by research personnel. Women recalled their weight at 18 y. Restricted cubic splines were used to evaluate the associations between BMI at 18 y and weight change since 18 y and ART outcomes adjusting for age, race, education, smoking, and height and accounting for the correlated cycles within women. RESULTS: Women had a median (range) BMI of 20.6 (14.8 to 36.4) at 18 y and 23.3 (16.1 to 45.8) at study entry. The median (range) weight change since 18 y was 7.4 kg (-12.1 to 60.1 kg). There was no association between BMI at 18 y and clinical ART outcomes. Long-term weight change had a nonlinear association with live birth such that higher weight gain since 18 y (particularly ≥15 kg) and weight loss were both associated with lower odds of live birth. The negative association between weight change and live birth was stronger in women ≥22.5 kg/m2 at 18 y such that each 10-kg increase was associated with a 30% (6%, 48%) lower odds of live birth. CONCLUSIONS: Weight gain in adulthood is negatively associated with ART success, particularly among women who were heavier at 18 y. These results add to the growing literature supporting the benefits of preventing weight gain in adulthood on female fertility.

Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study.

OBJECTIVE: To evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years). DESIGN: Prospective cohort study. SETTING: Nurses' Health Study II (1993-2017). PARTICIPANTS: 79 505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes and who reported the usual length and regularity of their menstrual cycles at ages 14-17 years, 18-22 years, and 29-46 years. MAIN OUTCOME MEASURES: Hazard ratios and 95% confidence intervals for all cause and cause specific premature mortality (death before age 70 years) were estimated from multivariable Cox proportional hazards models. RESULTS: During 24 years of follow-up, 1975 premature deaths were documented, including 894 from cancer and 172 from cardiovascular disease. Women who reported always having irregular menstrual cycles experienced higher mortality rates during follow-up than women who reported very regular cycles in the same age ranges. The crude mortality rate per 1000 person years of follow-up for women reporting very regular cycles and women reporting always irregular cycles were 1.05 and 1.23 for cycle characteristics at ages 14-17 years, 1.00 and 1.37 for cycle characteristics at ages 18-22 years, and 1.00 and 1.68 for cycle characteristics at ages 29-46 years. The corresponding multivariable adjusted hazard ratios for premature death during follow-up were 1.18 (95% confidence interval 1.02 to 1.37), 1.37 (1.09 to 1.73), and 1.39 (1.14 to 1.70), respectively. Similarly, women who reported that their usual cycle length was 40 days or more at ages 18-22 years and 29-46 years were more likely to die prematurely than women who reported a usual cycle length of 26-31 days in the same age ranges (1.34, 1.06 to 1.69; and 1.40, 1.17 to 1.68, respectively). These relations were strongest for deaths related to cardiovascular disease. The higher mortality associated with long and irregular menstrual cycles was slightly stronger among current smokers. CONCLUSIONS: Irregular and long menstrual cycles in adolescence and adulthood are associated with a greater risk of premature mortality (age <70 years). This relation is slightly stronger among women who smoke.

Marijuana smoking and outcomes of infertility treatment with assisted reproductive technologies.

STUDY QUESTION: What is the association of female and male partner marijuana smoking with infertility treatment outcomes with ART? SUMMARY ANSWER: Women who were marijuana smokers at enrollment had a significantly higher adjusted probability of pregnancy loss during infertility treatment with ART whereas, unexpectedly, there was a suggestion of more favorable treatment outcomes in couples where the man was a marijuana smoker at enrollment. WHAT IS KNOWN ALREADY: Data on the relation of female and male partner marijuana use with outcomes of infertility treatment is scarce despite increased use and legalization worldwide. STUDY DESIGN, SIZE, DURATION: We followed 421 women who underwent 730 ART cycles while participating in a prospective cohort (the Environment and Reproductive Health Study) at a fertility center between 2004 and 2017. Among them, 200 women (368 cycles) were part of a couple in which their male partner also enrolled in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants self-reported marijuana smoking at baseline. Clinical endpoints were abstracted from electronic medical records. We used generalized linear mixed models with empirical standard errors to evaluate the association of baseline marijuana smoking with ART outcomes adjusting for participants' age, race, BMI, tobacco smoking, coffee and alcohol consumption, and cocaine use. We estimated the adjusted probability of implantation, clinical pregnancy, and live birth per ART cycle, as well as the probability of pregnancy loss among those with a positive B-hCG. MAIN RESULTS AND THE ROLE OF CHANCE: The 44% of the women and 61% of the men had ever smoked marijuana; 3% and 12% were marijuana smokers at enrollment, respectively. Among 317 women (395 cycles) with a positive B-hCG, those who were marijuana smokers at enrollment (N = 9, cycles = 16) had more than double the adjusted probability of pregnancy loss than those who were past marijuana smokers or had never smoked marijuana (N = 308, 379 cycles) (54% vs 26%; P = 0.0003). This estimate was based on sparse data. However, couples in which the male partner was a marijuana smoker at enrollment (N = 23, 41 cycles) had a significantly higher adjusted probability of live birth than couples in which the male partner was a past marijuana smoker or had never smoked marijuana (N= 177, 327 cycles) (48% vs 29%; P = 0.04), independently of the women's marijuana smoking status. Treatment outcomes of past marijuana smokers, male and female, did not differ significantly from those who had never smoked marijuana. LIMITATIONS, REASONS FOR CAUTION: Marijuana smoking was self-reported with possible exposure misclassification. Chance findings cannot be excluded due to the small number of exposed cases. The results may not be generalizable to couples from the general population. WIDER IMPLICATIONS OF THE FINDINGS: Even though marijuana smoking has not been found in past studies to impact the ability to become pregnant among pregnancy planners in the general population, it may increase the risk of pregnancy loss among couples undergoing infertility treatment. Marijuana smoking by females and males may have opposing effects on outcomes of infertility treatment with ART. STUDY FUNDING/COMPETING INTEREST(S): The project was financed by grants R01ES009718, P30ES000002, and K99ES026648 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare.

Marijuana smoking and markers of testicular function among men from a fertility centre.

STUDY QUESTION: Is marijuana smoking associated with semen quality, sperm DNA integrity or serum concentrations of reproductive hormones among subfertile men? SUMMARY ANSWER: Men who had ever smoked marijuana had higher sperm concentration and count and lower serum FSH concentrations than men who had never smoked marijuana; no differences were observed between current and past marijuana smokers. WHAT IS KNOWN ALREADY: Studies of marijuana abuse in humans and animal models of exposure to marijuana suggest that marijuana smoking adversely impacts spermatogenesis. Data is less clear for moderate consumption levels and multiple studies have found higher serum testosterone concentrations among marijuana consumers. STUDY DESIGN, SIZE, DURATION: This longitudinal study included 662 subfertile men enroled at the Massachusetts General Hospital Fertility Center between 2000 and 2017. The men provided a total of 1143 semen samples; 317 men also provided blood samples in which we measured reproductive hormones. PARTICIPANTS/MATERIALS, SETTING, METHODS: Use of marijuana and other drugs was self-reported at baseline. Standard protocols were followed for measuring semen quality, sex hormones and DNA integrity. We used linear mixed effect models with a random intercept to evaluate the associations of self-reported marijuana smoking at enrolment with semen parameters from subsequently collected samples, and linear regression models for sperm DNA integrity and serum reproductive hormones, while adjusting for confounders including smoking and cocaine use. MAIN RESULTS AND THE ROLE OF CHANCE: Men who had ever smoked marijuana (N = 365) had significantly higher sperm concentration (62.7 (95% confidence interval: 56.0, 70.3) million/mL) than men who had never smoked marijuana (N = 297) (45.4 (38.6, 53.3) million/mL) after adjusting for potential confounders (P = 0.0003). There were no significant differences in sperm concentration between current (N = 74) (59.5 (47.3, 74.8) million/mL) and past marijuana smokers (N = 291) (63.5 (56.1, 72.0) million/mL; P = 0.60). A similar pattern was observed for total sperm count. Furthermore, the adjusted prevalence of sperm concentration and total sperm motility below WHO reference values among marijuana smokers was less than half that of never marijuana smokers. Marijuana smokers had significantly lower follicle stimulating hormone (FSH) concentrations than never marijuana smokers (-16% (-27%, -4%)) and there were no significant differences between current and past marijuana smokers (P = 0.53). Marijuana smoking was not associated with other semen parameters, with markers of sperm DNA integrity or with reproductive hormones other than FSH. Chance findings cannot be excluded due to the multiple comparisons. LIMITATIONS, REASONS FOR CAUTION: Our results may not be generalisable to men from the general population. Marijuana smoking was self-reported and there may be misclassification of the exposure. WIDER IMPLICATIONS OF THE FINDINGS: These findings are not consistent with a deleterious effect of marijuana on testicular function. Whether these findings are reflective of the previously described role of the endocannabinoid system in spermatogenesis or a spurious association requires confirmation in further studies. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by grants R01ES009718 and P30ES000002 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Waist circumference in relation to outcomes of infertility treatment with assisted reproductive technologies.

BACKGROUND: Many studies have documented a lower likelihood of live birth with increasing body mass index among women undergoing assisted reproductive technology, but few have examined the association with waist circumference, an anthropometric measure that allows assessment of central adiposity. OBJECTIVE: To examine the relation between baseline waist circumference and infertility treatment outcomes among women undergoing treatment with assisted reproductive technology. MATERIALS AND METHODS: We followed up 264 women who underwent 445 assisted reproductive technology cycles for infertility treatment at the Massachusetts General Hospital between 2010 and 2017. Waist circumference was assessed at enrollment. We used cluster-weighted generalized estimating equation models to estimate the probability of live birth by tertiles of waist circumference (<77, 77-86, >86 cm), while accounting for multiple treatment cycles per woman and adjusting for age, race, smoking, infertility diagnosis, day 3 follicle-stimulating hormone, body mass index, and height. RESULTS: Mean (standard deviation) waist circumference and body mass index were 83.6 (12.6) cm and 24.1 (4.3) kg/m2, respectively. Waist circumference and body mass index were positively correlated (r = 0.69, P < .0001). Waist circumference was inversely related to the probability of live birth after adjusting for BMI and other confounders. The multivariable adjusted probability of live birth (95% confidence interval) for women in increasing tertiles of waist circumference were 53% (42-65%), 42% (32-53%), and 38% (28-50%) (P, trend = .04). When women were classified in joint categories of body mass index and waist circumference, women with a body mass index ≥25 kg/m2 and a waist circumference ≥77 cm had the lowest live birth rate (38% [27-50%]), whereas women with a body mass index between 18.5 and 25 kg/m2 and a waist circumference <77 cm had the highest (54% [42-66%]). The results were similar using different waist circumference cut-off values. CONCLUSION: Waist circumference was inversely related to the probability of live birth among women undergoing assisted reproductive technology independently of body mass index.

Dietary patterns and outcomes of assisted reproduction.

BACKGROUND: There is growing acceptance that nutrition may be related to fertility and specifically to assisted reproductive technologies success in women; however, there is still no specific dietary guidance. OBJECTIVE: The objective of the study was to evaluate the relationship between pretreatment adherence to various dietary patterns and outcomes of assisted reproductive technologies. STUDY DESIGN: We followed up 357 women enrolled in the prospective Environment and Reproductive Health (EARTH) study, who underwent 608 assisted reproductive technologies cycles (2007-2017). Using a validated food frequency questionnaire completed prior to treatment, we assessed adherence to the Mediterranean diet, the alternate Healthy Eating Index 2010, the Fertility Diet (developed based on risk factors for anovulatory infertility), and a profertility diet we developed based on factors previously related to assisted reproductive technologies outcomes (higher intake of supplemental folic acid, vitamin B12, vitamin D, low- rather than high-pesticide residue produce, whole grains, dairy, soy foods, and seafood rather than other meats). RESULTS: Higher adherence to the alternate Healthy Eating Index 2010 and Fertility Diet was not related to live birth following assisted reproductive technologies. Women in the second through the fourth quartiles of Mediterranean diet adherence had significantly higher probability of live birth (0.44, 95% confidence interval, 0.39-0.49) compared with women in the first quartile (0.31, 95% confidence interval, 0.25-0.39); however, there was no additional benefit of adherence to the Mediterranean diet above the second quartile. Increased adherence to the profertility diet was linearly associated with assisted reproductive technologies outcomes. The adjusted odds (95% confidence interval) of implantation, clinical pregnancy, and live birth were higher by 47% (21%, 77%), 43% (19%, 72%), and 53% (26%, 85%), respectively, per SD increase. The adjusted difference in the proportion of cycles resulting in live birth for women in the fourth vs first quartile of adherence to the profertility diet was 0.28 (95% confidence interval, 0.16-0.38). While the profertility diet was not related to estradiol levels, oocyte counts, or endometrial thickness, it was inversely associated with clinical pregnancy loss (odds ratio, 0.69, 95% confidence interval, 0.53-0.90 per SD increase). CONCLUSION: Higher pretreatment adherence to the profertility diet was associated with an increased probability of live birth among women undergoing assisted reproductive technologies. Commonly recommended dietary advice such as adhering to the Mediterranean diet may not provide the most appropriate guidance for women undergoing infertility treatment in the United States.

Hair mercury (Hg) levels, fish consumption and semen parameters among men attending a fertility center.

General population exposure to methylmercury (MeHg), the most common organic mercury compound found in the environment, occurs primarily through the consumption of contaminated fish and shellfish. Due to limited studies and lack of consideration of effect modification by fish consumption, it remains uncertain if exposure to mercury affects semen parameters. Thus, we investigated whether hair Hg levels, a biomarker of mercury exposure, were associated with semen parameters among men attending an academic fertility center, and whether this relationship was modified by intake of fish. This analysis included 129 men contributing 243 semen samples who were enrolled in the Environment and Reproductive Health (EARTH) Study between 2005 and 2013, and had data of hair Hg, intake of fish and semen parameters available. Hair Hg levels were assessed using a direct mercury analyzer. Intake of fish was collected using a validated food frequency questionnaire. Semen parameters were analyzed following WHO 2010 evaluation criteria. Generalized linear mixed models with random intercepts accounting for within-man correlations across semen samples were used to evaluate the association of hair Hg levels and semen parameters adjusting for age, BMI, smoking status, abstinence time and alcohol intake. Effect modification by total fish intake (≤1.68 vs. >1.68 servings/week) was tested. The median hair Hg levels of the men was 0.72ppm and ranged from 0.03 to 8.01ppm; almost 30% of the men had hair Hg levels >1ppm. Hair Hg levels were positively related with sperm concentration, total sperm count, and progressive motility, after adjusting for potential confounders and became attenuated after further adjustment for fish intake. Specifically, men in the highest quartile of hair mercury levels had 50%, 46% and 31% higher sperm concentration, total sperm count and progressive motility, respectively, compared to men in the lowest quartile. These associations were stronger among men whose fish intake was above the study population median. Semen volume and normal morphology were unrelated to hair Hg levels. These results confirmed exposure to MeHg through fish intake and showed the important role of diet when exploring the associations between heavy metals and semen parameters among men of couples seeking fertility care. Further research is needed to clarify the complex relationship between fish intake and Hg, and potential effects on male reproductive health, specifically, semen parameters.

The spectrum of vaccine therapies for patients with glioblastoma multiforme.

OPINION STATEMENT: Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system (CNS) and one of the most lethal cancers in adults and children. Despite aggressive treatment with surgery, radiation, and chemotherapy, median survival is less than 15 months and overall survival is less than 10 % at 5 years. Development of therapeutics for malignant gliomas has been hampered by their natural complexity as well as protective mechanisms unique to the CNS. Better understanding of the pathogenesis of GBM is opening the path to novel, specific-targeted therapies. Recently, multiple immunotherapy approaches have been acquiring substantial indication of therapeutic efficacy with a very safe profile. Examples of the leading clinical approaches for GBM will be discussed in detail in this review.

Secondhand smoke exposure in bars and restaurants in Guatemala City: before and after smoking ban evaluation.

OBJECTIVE: In February 2009, Guatemala implemented a comprehensive smoking ban. We assessed air nicotine levels in bars and restaurants 6 months after the ban (post-ban) and compared them with levels found in 2006 (pre-ban). METHODS: Exposure was estimated by passive sampling of vapor-phase nicotine using samplers (n=50) placed for 7 working days in 10 bars and 11 restaurants in Guatemala City. Air nicotine was measured by gas chromatography, and the time-weighted average concentration in µg/m(3) was estimated. Employees answered a survey about smoke-free workplaces (n = 32) and compared with pre-ban (n = 37) results. RESULTS: Nicotine was detectable in all bars pre- and post-ban. In restaurants, it was detectable in all pre- and 73% post-ban. Median nicotine concentrations in bars significantly decreased from 4.58 µg/m(3) (IQR, 1.71, 6.45) pre-ban to 0.28 µg/m(3) (IQR 0.17, 0.66) post-ban (87% decrease). In restaurants, concentrations significantly decreased from 0.58 µg/m(3) (IQR, 0.44, 0.71) to 0.04 µg/m(3) (IQR 0.01, 0.11) (95% decrease). Employees' support for a smoke-free workplace increased in the post-ban survey (from 32 to 81%, p < 0.001). CONCLUSION: Six months after the implementation of a smoke-free law in Guatemala, nicotine levels were significantly decreased in bars and restaurants and workers' support for the law substantially increased.