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The article provides an update on the Project Viva study. The study was a pre-birth cohort that began in 1999-2002 in Massachusetts and aimed to examine the long-term health outcomes of women and their offspring. The study collected data on various aspects of women's health, behavior, and environment through questionnaires, in-person measurements, blood tests, and genetic analysis. The study produced numerous publications and was recently focused on analyzing data from the Mid-Life Visit, Year 19 questionnaire, and annual survey. The study's strengths include the collection of exposure and outcome measures using research standard procedures, but limitations include loss to follow-up and limited generalizability. [Extracted from the article]

Background Male obesity has been related to poor semen quality and may also have a negative effect on assisted reproductive technologies (ART) outcomes. Whether male waist circumference (WC), as a measure of central obesity, impacts a couple's fertility independently of BMI is unclear. Objectives To examine the associations of male WC with semen quality and couples' outcomes of infertility treatment with ART. Methods Couples presenting to the Massachusetts General Hospital Fertility Center were invited to participate in the study. Between 2009 and 2019, 269 males provided 671 semen samples and 176 couples underwent 317 ART cycles. Height, weight, and WC were measured on site. We analyzed the association of male WC with semen quality and pregnancy outcomes using cluster-weighted regression models to account for repeated observations while adjusting for potential confounders. Models were also stratified by male BMI (<25 kg/m2 compared with ≥25 kg/m2). Results The median male age, WC, and BMI were 36.1 years, 96.0 cm, and 26.8 kg/m2, respectively. A 5-cm increase in WC was associated with a 6.3% (95% CI, 2.1–10.5%) lower sperm concentration after adjustment for potential confounders, including BMI. Male WC was also inversely related to the probability of achieving a live birth. For each 5-cm increase in male WC, the odds of a live birth per initiated cycle decreased by 9.0% (95% CI, 1.1%–16.4%) after accounting for several anthropometric and demographic characteristics of both partners. These associations were stronger among males in the normal BMI category (<25 kg/m2) than among overweight or obese males. Conclusions A higher male WC may be an additional risk factor for poor outcomes of infertility treatment, even after accounting for male and female partner BMIs, particularly in couples where the male partner has a normal BMI. [ABSTRACT FROM AUTHOR]

Traffic-related air pollution has been linked to higher risks of infertility and miscarriage. We evaluated whether folate intake modified the relationship between air pollution and livebirth among women using assisted reproductive technology (ART). Our study included 304 women (513 cycles) presenting to a fertility center in Boston, Massachusetts (2005–2015). Diet and supplements were assessed by food frequency questionnaire. Spatiotemporal models estimated residence-based daily nitrogen dioxide (NO2), ozone, fine particulate, and black carbon concentrations in the 3 months before ART. We used generalized linear mixed models with interaction terms to evaluate whether the associations between air pollutants and livebirth were modified by folate intake, adjusting for age, body mass index, race, smoking, education, infertility diagnosis, and ART cycle year. Supplemental folate intake significantly modified the association of NO2 exposure and livebirth (P = 0.01). Among women with supplemental folate intakes of <800 μg/day, the odds of livebirth were 24% (95% confidence interval: 2, 42) lower for every 20-parts-per-billion increase in NO2 exposure. There was no association among women with intakes of ≥800 μg/day. There was no effect modification of folate on the associations between other air pollutants and livebirth. High supplemental folate intake might protect against the adverse reproductive consequences of traffic-related air pollution. [ABSTRACT FROM AUTHOR]

Background: Randomized trials of supplementation with antioxidant mixtures during infertility treatment show no benefit on pregnancy or live birth rate. However, the roles of individual antioxidants are poorly understood. We examined the association of baseline intake of vitamins A, C, E, and carotenoids with outcomes of assisted reproductive technologies (ARTs).Methods: We followed 349 women undergoing a total of 588 ART cycles for infertility treatment at the Massachusetts General Hospital. We assessed antioxidant intakes from food and supplements before treatment using a validated food frequency questionnaire. We used generalized linear mixed models to account for multiple ART cycles per woman while adjusting for confounding.Results: Mean (SD) age and body mass index were 35.1 years (4.0 years) and 24.1 kg/m (4.3 kg/m), respectively. Total intake of vitamins A, C, and E was not associated with the probability of live birth. Women in the highest intake category of β-carotene from foods had a lower probability of live birth than women in the lowest intake quartile (50% vs. 22%; P trend = 0.03); for lutein and zeaxanthin, the probability for the highest intake group was 44% vs. 28% for the lowest. Intake of β-carotene from supplements and intakes of retinol and all other carotenoids were unrelated to live birth rates.Conclusions: We found unexpected inverse associations of β-carotene intake from foods and of lutein and zeaxanthin intake with live birth rates. Within the observed intake ranges, total consumption of vitamins A, C, and E before starting infertility treatment with ART was not associated with live birth rates. [ABSTRACT FROM AUTHOR]

Background: Some dietary factors have been linked to outcomes of infertility treatment with assisted reproductive technology (ART), but the role of intake of meats and other protein-rich foods remains unclear. Objective: The aim of this manuscript was to study the relation between preconception intake of meat and other protein-rich foods and outcomes of infertility treatment with ART. Design: A total of 351 women enrolled in a prospective cohort at the Massachusetts General Hospital Fertility Center and underwent 598 ART cycles for infertility treatment. Meat intake was assessed with a validated food-frequency questionnaire, and ART outcomes were abstracted from electronic medical records. We estimated the associations between intake of protein-rich foods (meats, eggs, beans, nuts, and soy) and the outcome of live birth per initiated cycle using generalized linear mixed models. Results: The average total meat intake was 1.2 servings/d, with most coming from poultry (35%), fish (25%), processed meat (22%), and red meat (17%). Fish intake was positively related to the proportion of cycles resulting in live birth. The multivariableadjusted probabilities of live birth for women in increasing quartiles of fish intake were 34.2% (95% CI: 26.5%, 42.9%), 38.4% (95% CI: 30.3%, 47.3%), 44.7% (95% CI: 36.3%, 53.4%), and 47.7% (95% CI: 38.3%, 57.3%), respectively (P-trend = 0.04). In the estimated substitution analyses, the ORs of live birth associated with increasing fish intake by 2 servings/wk were 1.54 (95% CI: 1.14, 2.07) when fish replaced any other meat, 1.50 (95% CI: 1.13, 1.98) when fish replaced any other protein-rich food, and 1.64 (95% CI: 1.14, 2.35) when fish replaced processed meat. Conclusions: Fish consumption is related to a higher probability of live birth following infertility treatment with ART. This trial was registered at clinicaltrials.gov as NCT00011713. [ABSTRACT FROM AUTHOR]

Objective: We examined associations of residential distance to major roadways, as a proxy for traffic-related air pollution exposures, with sperm characteristics and male reproductive hormones.Design: The cohort included 797 men recruited from Massachusetts General Hospital Fertility Center between 2000 and 2015 to participate in fertility research studies.Materials and Methods: Men reported their residential addresses at enrollment and provided 1-6 semen samples and a blood sample during follow-up. We estimated the Euclidean distance to major roadways (e.g. interstates and highways: limited access highways, multi-lane highways (not limited access), other numbered routes, and major roads) using information from the Massachusetts Department of Geographic Information Systems. Semen parameters (1238 semen samples), sperm DNA integrity (389 semen samples), chromosomal disomy (101 semen samples), and serum reproductive hormones (405 serum samples) were assessed following standard procedures.Results: Men in this cohort were primarily Caucasian (86%), not current smokers (92%), with a college or higher education (88%), and had an average age of 36 years and BMI of 27.7 kg/m2. The median (interquartile range) residential distance to a major roadway was 111 (37, 248) meters. Residential proximity to major roadways was not associated with semen parameters, sperm DNA integrity, chromosomal disomy, or serum reproductive hormone concentrations. The adjusted percent change (95% CI) in semen quality parameters associated with a 500 m increase in residential distance to a major roadway was -1.0% (-6.3, 4.5) for semen volume, 4.3% (-5.8, 15.7) for sperm concentration, 3.1% (-7.2, 14.5) for sperm count, 1.1% (-1.2, 3.4) for % total motile sperm, and 0.1% (-0.3, 0.5) for % morphologically normal sperm. Results were consistent when we modeled the semen parameters dichotomized according to WHO 2010 reference values.Conclusion: Residential distance to major roadways, as a proxy for traffic-related air pollution exposure, was not related to sperm characteristics or serum reproductive hormones among men attending a fertility clinic in Massachusetts. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests potential links between some dietary fatty acids and improved fertility, because specific fatty acids may affect prostaglandin synthesis and steroidogenesis. Objective: The objective of this exploratory study was to evaluate associations between total and specific types of dietary fat intake and 1) hormone concentrations and 2) the risk of sporadic anovulation in a cohort of 259 regularly menstruating women in the Bio-Cycle Study. Design: Endogenous reproductive hormones were measured up to 8 times/cycle for up to 2 cycles, with visits scheduled with the use of fertility monitors. Dietary intake was assessed with up to four 24-h recalls/cycle. Linear mixed models and generalized linear models were used to evaluate the associations between dietary fatty acids and both reproductive hormone concentrations and ovulatory status. All models were adjusted for total energy intake, age, body mass index, and race. Results: Relative to the lowest levels of percentage of energy from total fat, the highest tertile was associated with increased total and free testosterone concentrations (total: percentage change of 4.0%; 95% CI: 0.7%, 7.3%; free: percentage change of 4.1%; 95% CI: 0.5%, 7.7%). In particular, the percentage of energy from polyunsaturated fatty acids (PUFAs) in the highest tertile was associated with increases in total and free testosterone (total: percentage change of 3.7%; 95% CI: 0.6%, 6.8%; free: percentage change of 4.0%; 95% CI: 0.5%, 7.5%). The PUFA docosapentaenoic acid (22:5n-3) was not significantly associated with testosterone concentrations (P-trend = 0.86 in energy substitution models) but was associated with increased progesterone and a reduced risk of anovulation (highest tertile compared with the lowest tertile: RR: 0.42; 95% CI: 0.18, 0.95). Fat intakes were not associated with other reproductive hormone concentrations. Conclusions: These results indicate that total fat intake, and PUFA intake in particular, is associated with very small increases in testosterone concentrations in healthy women and that increased docosapentaenoic acid was associated with a lower risk of anovulation. [ABSTRACT FROM AUTHOR]

Background: Preconceptional folate and vitamin B-12 have been linked to beneficial reproductive outcomes in both natural pregnancies and those after assisted reproductive technology (ART) treatment. Objective: The objective of the study was to evaluate the associations of serum folate and vitamin B-12 with ART outcomes. Design: This analysis included a random sample of 100 women (154 ART cycles) participating in a prospective cohort study [Environment and Reproductive Health (EARTH)] at the Massachusetts General Hospital Fertility Center (2007-2013). Serum folate and vitamin B-12 were measured in blood samples collected between days 3 and 9 of treatment. Generalized estimating equations with adjustment for age, BMI, and race were used to evaluate the association of serum folate and vitamin B-12 with ART outcomes. Results: Women in the highest quartile of serum folate (.26.3 ng/mL) had 1.62 (95% CI: 0.99, 2.65) times the probability of live birth compared with women in the lowest quartile (,16.6 ng/mL).Women in the highest quartile of serum vitamin B-12 (.701 pg/mL) had 2.04 (95% CI: 1.14, 3.62) times the probability of live birth compared with women in the lowest quartile (,439 pg/mL). Suggestive evidence of an interaction was observed; women with serum folate and vitamin B-12 concentrations greater than the median had 1.92 (95% CI: 1.12, 3.29) times the probability of live birth compared with women with folate and vitamin B-12 concentrations less than or equal to the median. This translated into an adjusted difference in live birth rates of 26% (95% CI: 10%, 48%; P = 0.02). Conclusion: Higher serum concentrations of folate and vitamin B-12 before ART treatment were associated with higher live birth rates among a population exposed to folic acid fortification. This trial was registered at clinicaltrials.gov as NCT00011713. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Polycystic Ovary Syndrome (PCOS) is common among females, with significantmetabolic and reproductive comorbidities.We describe PCOS development in a pediatric population. METHODS: We assessed cardiometabolic biomarkers and adiposity at the midchildhood (mean 7.9 y), early teen (mean 13.1 y), and midteen (mean 17.8 y) visits among 417 females in the prospective Project Viva cohort. We defined PCOS via self-reported diagnosis or ovulatory dysfunction with hyperandrogenism in midlate adolescence. We used multivariable logistic regression to assess associations of metabolic and adiposity markers at each visit with PCOS. RESULTS: Adolescents with PCOS (n = 56, 13%) versus without had higher mean (SD) BMI z-score and truncal fat mass at the midchildhood (0.66 [0.99] vs 0.30 [1.04]; 3.5 kg [2.6] vs 2.7 [1.5]), early teen (0.88 [1.01] vs 0.25 [1.08]; 9.4 kg [6.7] vs 6.1 [3.4]), and midteen (0.78 [1.03] vs 0.33 [0.97]; 11.6 kg [7.2] vs 9.1 [4.9]) visits as well as lower adiponectin to leptin ratio at the early (0.65 [0.69] vs 1.04 [0.97]) and midteen (0.33 [0.26] vs 0.75 [1.21]) visits. In models adjusted for maternal PCOS, education and child race and ethnicity (social factors), we found higher odds of PCOS per 1-SD increase in truncal fat at midchildhood (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.03-1.95) and early teen visits (OR 1.61; 95% CI 1.14-2.28) and lower odds per 1-SD increase in adiponectin/leptin ratio at the midteen visit (OR 0.14; 95% CI 0.03-0.58). CONCLUSIONS: Childhood excess adiposity and adipose tissue dysfunction may be a first signs of later PCOS risk. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between dietary folate intake and antral follicle count (AFC) among women seeing treatment for infertility.Design: Cohort study.Setting: Academic fertility center.Patients: A total of 552 women attending the Massachusetts General Hospital Fertility Center (2007-2019) who participated in the Environment and Reproductive Health Study.Interventions: None. Folate intake was measured with a validated food frequency questionnaire at study entry. Multivariable Poisson regression models with robust standard errors were used to estimate the association of folate intake with AFC adjusting for calorie intake, age, body mass index, physical activity, education, smoking status, year of AFC, and intakes of vitamin B12, iron, and vitamin D. Nonlinearity was assessed with restricted cubic splines.Main Outcome Measure: AFC as measured by transvaginal ultrasonography as part of routine care.Results: Among the 552 women (median age, 35.0 years; median folate intake, 1,005 μg/d), total and supplemental folate intake had a significant nonlinear relationship with AFC. There was a positive linear association with AFC up to approximately 1,200 μg/d for total folate intake and up to 800 μg/d for supplemental folate intake; however, there was no additional benefit of higher folate intakes. The magnitude of the association was modest; for example, the predicted adjusted difference in AFC between a woman consuming 400 vs. 800 μg/d of supplemental folate was approximately 1.5 follicles.Conclusion: Higher intake of folate, particularly from supplements, was associated with modestly higher ovarian reserve as measured by AFC among women attending a fertility center.Clinical Trial Registration Number: This trial was registered at clinicaltrials.gov as NCT00011713. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between ambient temperature and antral follicle count (AFC), a standard measure of ovarian reserve.Design: Prospective cohort study.Setting: Fertility center at an academic hospital in the northeastern United States.Patient(s): 631 women attending the Massachusetts General Hospital Fertility Center (2005-2015) who participated in the Environment and Reproductive Health Study.Intervention(s): Daily temperature at the women's residential address was estimated for the 90 days before their antral follicle scan using a spatially refined gridded climate data set. We evaluated the associations between temperature and AFC using Poisson regression with robust standard errors, adjusting for relative humidity, fine particulate matter exposure, age, education, smoking status, year and month of AFC, and diagnosis of diminished ovarian reserve and ovulation disorders.Main Outcome Measure(s): Antral follicle count as measured with transvaginal ultrasonography.Result(s): A 1°C increase in average maximum temperature during the 90 days before ovarian reserve testing was associated with a -1.6% (95% confidence interval [CI], -2.8, -0.4) lower AFC. Associations remained negative, but were attenuated, for average maximum temperature exposure in the 30 days (-0.9%, 95% CI, -1.8, 0.1) and 14 days (-0.8%, 95% CI, -1.6, 0.0) before AFC. The negative association between average maximum temperature and AFC was stronger in November through June than during the summer months, suggesting that timing of heat exposure and acclimatization to heat may be important factors to consider in future research.Conclusion(s): Exposure to higher temperatures was associated with lower ovarian reserve. These results raise concern that rising ambient temperatures worldwide may result in accelerated reproductive aging among women. [ABSTRACT FROM AUTHOR]

Importance: Although the literature on the association between birth by cesarean delivery and children's anthropometry has continued to increase, only a few studies have examined the association of cesarean delivery with measures of body composition assessed using dual-energy x-ray absorptiometry (DXA), which allows the differentiation of fat and lean mass overall and in specific regions of the body., Objective: To investigate whether differences exist in DXA-measured body composition between children and adolescents born by cesarean delivery and those born by vaginal delivery., Design, Setting, and Participants: This prospective cohort study included singleton children of mothers enrolled between April 1999 and July 2002 in Project Viva, a longitudinal prebirth cohort of mother-child pairs in Massachusetts. The children had at least 1 DXA scan at a follow-up visit during middle childhood (2007-2010) and/or early adolescence (2013-2016). Data analysis was performed from October 16, 2020, to May 9, 2021., Exposures: Mode of delivery (cesarean vs vaginal)., Main Outcomes and Measures: Total lean mass index, total and truncal fat mass indexes, visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue, and total abdominal adipose tissue (TAAT) were estimated using DXA. Multivariable linear regression models were used to estimate the association between mode of delivery and DXA-derived outcomes with adjustment for confounders. Stabilized inverse probability weights were used to control for potential selection bias owing to loss to follow-up., Results: A total of 975 mother-child pairs were included in the study. The mean (SD) maternal age at study entry was 32.0 (5.5) years, and the mean (SD) self-reported prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was 25.0 (5.4). Of the children included in the study, 491 (50%) were female; 212 (22%) were born by cesarean delivery and 763 (78%) by vaginal delivery. Body composition in middle childhood as measured by DXA did not differ by mode of delivery. In early adolescence, participants born by cesarean delivery had a significantly greater total lean mass index (β, 0.4; 95% CI, 0.0-0.7), total fat mass index (β, 0.6; 95% CI, 0.1-1.1), truncal fat mass index (β, 0.3; 95% CI, 0.0-0.5), VAT area (β, 4.7; 95% CI, 0.9-8.6), and TAAT area (β, 23.8; 95% CI, 0.8-46.8) in a model adjusted for child sex and age at the time of DXA measurements; maternal age, educational level, race and ethnicity, total gestational weight gain, and smoking status during pregnancy; birth-weight-per-gestational-age z score; and paternal BMI. Associations between mode of delivery and measures of adiposity were found for cesarean deliveries performed in the absence of labor (total fat mass index: β, 1.3; 95% CI, 0.3-2.3; truncal fat mass index: β, 0.6; 95% CI, 0.1-1.0; VAT area: β, 10.7; 95% CI, 3.1-18.3; TAAT area: β, 47.3; 95% CI, 2.3-92.2). There were no associations after adjustment for maternal self-reported prepregnancy BMI (total lean mass index: β, 0.2; 95% CI, -0.1 to 0.6; total fat mass index: β, 0.4; 95% CI, -0.1 to 0.9; truncal fat mass index: β, 0.2; 95% CI, -0.1 to 0.4; VAT area: β, 3.0; 95% CI, -0.6 to 6.7; TAAT area: β, 13.6; 95% CI, -8.2 to 35.3)., Conclusions and Relevance: In this cohort study, adolescents born by cesarean delivery had significantly higher measures of lean mass, fat mass, and central adiposity compared with those born by vaginal delivery, but associations did not remain after adjustment for the mothers' self-reported prepregnancy BMI. The findings suggest that the association between birth by cesarean delivery and adolescent adiposity may partly be explained by maternal self-reported prepregnancy BMI.

Background: Biomarkers of cardiovascular and metabolic risk track from adolescence into adulthood, therefore characterising the direction and magnitude of these changes is an important first step to identifying health trajectories that presage future disease risk. Aim: To characterise changes in metabolic biomarkers across early adolescence in a multi-ethnic cohort. Subjects and methods: Among 891 participants in Project Viva we estimated changes in insulin resistance (HOMA-IR), adipokines, lipids, and SBP between ages 6-10 years and 11-16 years. Next, we used multivariable linear regression to examine associations of sex, baseline overweight/obesity, baseline pubertal status and race/ethnicity with change in the biomarkers during follow-up. Results: Boys exhibited a larger decrement in adiponectin (-0.66 [95% CI = -1.14, -0.18)] ng/mL) and a greater increase in SBP (3.20 [2.10, 4.30] mmHg) than girls. Overweight/obese participants experienced larger increases in HOMA-IR, leptin, and triglycerides; and a steeper decrement in HDL. Pubertal youth showed larger decrements in total and LDL cholesterol than their pre-pubertal counterparts. In comparison to White participants, Black youth experienced a larger magnitude of increase in HOMA-IR, and Hispanic youth exhibited larger decrements in adiponectin and HDL. Conclusions: Change in metabolic biomarkers across early adolescence differed by sex, weight status, pubertal status and race/ethnicity. Some of the metabolic changes may reflect normal physiological changes of puberty, while others may presage future disease risk. Future studies are warranted to link metabolic changes during adolescence to long-term health.

Emerging literature suggests that men's diets may affect spermatogenesis as reflected in semen quality indicators, but literature on the relation between meat intake and semen quality is limited. Our objective was to prospectively examine the relation between meat intake and indicators of semen quality. Men in subfertile couples presenting for evaluation at the Massachusetts General Hospital Fertility Center were invited to participate in an ongoing study of environmental factors and fertility. A total of 155 men completed a validated food-frequency questionnaire and subsequently provided 338 semen samples over an 18-mo period from 2007-2012. We used linear mixed regression models to examine the relation between meat intake and semen quality indicators (total sperm count, sperm concentration, progressive motility, morphology, and semen volume) while adjusting for potential confounders and accounting for within-person variability across repeat semen samples. Among the 155 men (median age: 36.1 y; 83% white, non-Hispanic), processed meat intake was inversely related to sperm morphology. Men in the highest quartile of processed meat intake had, on average, 1.7 percentage units (95% CI: -3.3, -0.04) fewer morphologically normal sperm than men in the lowest quartile of intake (P-trend = 0.02). Fish intake was related to higher sperm count and percentage of morphologically normal sperm. The adjusted mean total sperm count increased from 102 million (95% CI: 80, 131) in the lowest quartile to 168 million (95% CI: 136, 207) sperm in the highest quartile of fish intake (P-trend = 0.005). Similarly, the adjusted mean percentages of morphologically normal sperm for men in increasing quartiles of fish intake were 5.9 (95% CI: 5.0, 6.8), 5.3 (95% CI: 4.4, 6.3), 6.3 (95% CI: 5.2, 7.4), and 7.5 (95% CI: 6.5, 8.5) (P-trend = 0.01). Consuming fish may have a positive impact on sperm counts and morphology, particularly when consumed instead of processed red meats., (© 2014 American Society for Nutrition.)