Background.-There is growing acceptance that nutrition may be related to fertility, and specifically to ART success in women; however, there is still no specific dietary guidance. Objective.-To evaluate the relationship between pre-treatment adherence to various dietary patterns and outcomes of assisted reproductive technologies (ART). Study Design.-We followed 357 women enrolled in the prospective Environment and Reproductive Health (EARTH) Study, who underwent 608 ART cycles (2007-2017). Using a validated food frequency questionnaire completed prior to treatment, we assessed adherence to the Mediterranean Diet (MedDiet), the alternate Healthy Eating Index 2010 (aHEI2010), the Fertility Diet (FD) (developed based on risk factors for anovulatory infertility), and a "pro-fertility" diet we developed based on factors previously related to ART outcomes (higher intake of supplemental

ObjectiveTo evaluate whether irregular or long menstrual cycles throughout the life course are associated with all cause and cause specific premature mortality (age <70 years).DesignProspective cohort study.SettingNurses’ Health Study II (1993-2017).Participants79 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 measuresHazard 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.ResultsDuring 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.ConclusionsIrregular 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.

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...

NIH grants R01-ES009718 from the National Institute of Environmental Health Sciences, P30-DK046200 and T32-DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases, and L50-HD085359 from the National Institute of Child Health and Human Development, and the Early Life Nutrition Fund from Danone Nutricia US. Dr Rueda is involved in a patent 9,295,662, methods for enhancing, improving, or increasing fertility or reproductive function (http://patents.com/us-9295662.html). This patent, however, does not lead to financial gain for Dr Rueda, or for Massachusetts General Hospital. Dr Rueda does not own any part of the company nor does he have any equity in any fertility related company. As Dr Rueda is not a physician, he does not evaluate patients or prescribe medications. All other coauthors have no conflicts of interest to declare.

No abstract

Key Points Question Are irregular or long menstrual cycles and unhealthy lifestyle factors jointly associated with type 2 diabetes? Findings In this prospective cohort study of 75 546 women, irregular and long menstrual cycles across the reproductive life span were associated with a greater risk of type 2 diabetes. These associations were stronger among women with overweight or obesity, low-quality diet, and low levels of physical activity. Meaning These findings suggest that menstrual cycle characteristics may serve as an early sign of the long-term risk of developing type 2 diabetes and that lifestyle interventions may be a useful strategy to reduce the risk of type 2 diabetes among women with menstrual cycle dysfunction.

IMPORTANCE Cesarean delivery is associated with an increased risk of childhood obesity in offspring. However, whether this increased risk also includes obesity-associated conditions remains unclear. OBJECTIVE To evaluate the association of birth by cesarean delivery with offspring's risks of obesity and type 2 diabetes in adulthood. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study compared the incidence of obesity and type 2 diabetes between birth by cesarean delivery and vaginal delivery among 33 226 women participating in the Nurses' Health Study II who were born between 1946 and 1964, with follow-up through the end of the 2013-2015 follow-up cycle. Participants' mothers provided information on mode of delivery and pregnancy characteristics. Participants provided information every 2 years on weight and diagnosis of type 2 diabetes. Relative risks of obesity and type 2 diabetes were estimated using log-binomial and proportional hazards regression accounting for maternal body mass index and other confounding factors. Statistical analysis was performed from June 2017 to December 2019. EXPOSURE Birth by cesarean delivery compared with birth by vaginal delivery. MAIN OUTCOMES AND MEASURES Risk of obesity and incidence of type 2 diabetes. RESULTS At baseline, the participants' mean (SD) age was 33.8 (4.6) years (range, 24.0-44.0 years). A total of 1089 of the 33 226 participants (3.3%) were born by cesarean delivery. After 1 913 978 person-years of follow-up, 12 156 (36.6%) women were obese and 2014 (6.1%) had received a diagnosis of type 2 diabetes. Women born by cesarean delivery were more likely to be classified as obese and to have received a diagnosis of type 2 diabetes during follow-up. The multivariableadjusted relative risk of obesity among women born by cesarean vs vaginal delivery was 1.11 (95% CI, 1.03-1.19). The multivariable-adjusted hazard ratio for type 2 diabetes among women born by cesarean vs vaginal delivery was 1.46 (95% CI, 1.18-1.81); this association remained significant after additional adjustment for participant's own body mass index (relative risk, 1.34 [95% CI, 1.08-1.67]). These associations persisted when analyses were restricted to women at low risk of cesarean delivery based on maternal characteristics. CONCLUSIONS AND RELEVANCE This study suggests that women born by cesarean delivery may have a higher risk than women born by vaginal delivery of being obese and developing type 2 diabetes during adult life.

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.