@article {610359, title = {Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology}, journal = {JAMA Intern Med}, volume = {178}, number = {1}, year = {2018}, month = {2018 Jan 01}, pages = {17-26}, abstract = {Importance: Animal experiments suggest that ingestion of pesticide mixtures at environmentally relevant concentrations decreases the number of live-born offspring. Whether the same is true in humans is unknown. Objective: To examine the association of preconception intake of pesticide residues in fruits and vegetables (FVs) with outcomes of infertility treatment with assisted reproductive technologies (ART). Design, Setting, and Participants: This analysis included 325 women who completed a diet assessment and subsequently underwent 541 ART cycles in the Environment and Reproductive Health (EARTH) prospective cohort study (2007-2016) at a fertility center at a teaching hospital. We categorized FVs as having high or low pesticide residues using a validated method based on surveillance data from the US Department of Agriculture. Cluster-weighted generalized estimating equations were used to analyze associations of high- and low-pesticide residue FV intake with ART outcomes. Main Outcomes and Measures: Adjusted probabilities of clinical pregnancy and live birth per treatment cycle. Results: In the 325 participants (mean [SD] age, 35.1 [4.0] y; body mass index, 24.1 [4.3]), mean (SD) intakes of high- and low-pesticide residue FVs were 1.7 (1.0) and 2.8 (1.6) servings/d, respectively. Greater intake of high-pesticide residue FVs was associated with a lower probability of clinical pregnancy and live birth. Compared with women in the lowest quartile of high-pesticide FV intake (, issn = {2168-6114}, doi = {10.1001/jamainternmed.2017.5038}, author = {Chiu, Yu-Han and Williams, Paige L and Matthew W. Gillman and Gaskins, Audrey J and M{\'\i}nguez-Alarc{\'o}n, Lidia and Irene Souter and Thomas L Toth and Ford, Jennifer B and Hauser, Russ and Chavarro, Jorge E} } @article {626397, title = {Caffeine, alcohol, smoking, and reproductive outcomes among couples undergoing assisted reproductive technology treatments}, journal = {Fertil Steril}, volume = {110}, number = {4}, year = {2018}, month = {2018 Sep}, pages = {587-592}, abstract = {During the past decade, as the use of assisted reproductive technologies (ART) has continued to increase worldwide, research investigating whether modifiable lifestyle factors, such as alcohol, caffeine, and smoking, may affect ART outcomes has grown. Despite the vast literature, there is still uncertainty regarding the effects of some of these exposures on ART outcomes. The objective of this review is to summarize the epidemiologic literature on intakes of caffeine and alcohol, smoking, and reproductive outcomes among women undergoing ART. Of the five epidemiologic studies on caffeine intake and ART outcomes, only one found a significant negative effect of caffeine intake on live birth following ART. There have been six epidemiologic studies exploring whether alcohol intake is associated with fertility outcomes among women undergoing ART. Three studies assessed current alcohol consumption and observed a negative effect on outcomes such as fertilization, embryo quality, and implantation. When alcohol intake in the year before treatment was assessed, no relationships were observed with clinical outcomes following ART. Finally, numerous epidemiologic studies and a handful of meta-analyses have confirmed that female current smokers have worse ART outcomes compared with nonsmokers. Although former smokers tend to have better ART outcomes than current smokers, very few individual studies have investigated the influence of smoking cessation on ART outcomes. Literature on male smoking, drinking, and caffeine habits in relation to ART outcomes is even sparser and inconsistent, making it difficult to draw strong conclusions on that topic. In summary, there is little evidence supporting a detrimental effect of moderate caffeine intake on ART outcomes. Current consumption of alcohol may have a negative effect on ART outcomes, but at present the evidence is limited. Women who currently smoke cigarettes have been consistently found to have poorer ART outcomes, including reduced live birth rates, but a quantification of the benefits of smoking cessation is lacking.}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2018.05.026}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Chavarro, Jorge E and Gaskins, Audrey J} } @article {610356, title = {Deciphering the complex relationship between systemic inflammation and fecundity in eumenorrheic women}, journal = {Fertil Steril}, volume = {109}, number = {2}, year = {2018}, month = {2018 02}, pages = {240-241}, keywords = {Amenorrhea, Female, Fertility, Humans, Inflammation, Luteinizing Hormone}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2017.11.038}, author = {Gaskins, Audrey J} } @article {610366, title = {Diet and fertility: a review}, journal = {Am J Obstet Gynecol}, volume = {218}, number = {4}, year = {2018}, month = {2018 04}, pages = {379-389}, abstract = {The literature on the relationship between diet and human fertility has greatly expanded over the last decade, resulting in the identification of a few clear patterns. Intake of supplemental folic acid, particularly at doses higher than those recommended for the prevention of neural tube defects, has been consistently related to lower frequency of infertility, lower risk of pregnancy loss, and greater success in infertility treatment. On the other hand and despite promising evidence from animal models, vitamin D does not appear to exert an important role in human fertility in the absence of deficiency. Antioxidant supplementation does not appear to offer any benefits to women undergoing infertility treatment, but it appears to be beneficial when it is the male partner who is supplemented. However, the available evidence does not allow discerning which specific antioxidants, or at which doses, are responsible for this benefit. Long-chain omega-3 fatty acids appear to improve female fertility, although it remains unclear to what extent contamination of shared food sources, such as fish with high levels of environmental toxicants, can dampen this benefit. Lastly, adherence to healthy diets favoring seafood, poultry, whole grains, fruits, and vegetables are related to better fertility in women and better semen quality in men. The cumulative evidence has also piled against popular hypotheses. Dairy and soy, once proposed as reproductive toxicants, have not been consistently related to poor fertility. In fact, soy and soy supplements appear to exert a beneficial effect among women undergoing infertility treatment. Similarly, because data from large, high-quality studies continue to accumulate, the evidence of a potentially deleterious effect of moderate alcohol and caffeine intake on the ability to become pregnant seems less solid than it once did. While a complete picture of the role of nutrition on fertility is far from complete, much progress has been made. The most salient gaps in the current evidence include jointly considering female and male diets and testing the most consistent findings in randomized trials.}, issn = {1097-6868}, doi = {10.1016/j.ajog.2017.08.010}, author = {Gaskins, Audrey J and Chavarro, Jorge E} } @article {626399, title = {The Environment and Reproductive Health (EARTH) Study: A Prospective Preconception Cohort}, journal = {Hum Reprod Open}, volume = {2018}, number = {2}, year = {2018}, month = {2018 Feb}, abstract = {Background: The Environment and Reproductive Health (EARTH) Study is an ongoing prospective preconception cohort designed to investigate the impact of environmental, nutritional, and lifestyle factors among both women and men on fertility and pregnancy outcomes. Methods: The EARTH Study recruits women 18 to 45 years and men 18 to 55 years seeking fertility evaluation and treatment at the Massachusetts General Hospital (MGH) Fertility Center, Boston, USA. Women and men are eligible to join either independently or as a couple. Participants are followed from study entry throughout each fertility treatment cycle, once per trimester of pregnancy (for those achieving pregnancy), and up to labor and delivery, or until they discontinue treatment or withdraw from the study. The study collects biological samples, self-reported questionnaire data (including a food frequency questionnaire) and clinically abstracted information. Results: As of June 2017, the study cohort included 799 women and 487 men (447 couples; 40 men joined without female partners). Women were on average 34.7 years old at time of enrolment and predominantly Caucasian (81\%), educated (49\% have a graduate degree), and nulliparous (83\%). Men were on average 36.6 years at baseline and mostly Caucasian (86\%) and never-smokers (67\%). Conclusions: The EARTH Study is one of the few cohorts designed to examine multiple potentially critical windows of vulnerability, including the paternal and maternal preconception windows and the periconception and prenatal windows in pregnancy. It is also one of the few human studies that has assessed potential interactions between environmental exposures and dietary factors.}, issn = {2399-3529}, doi = {10.1093/hropen/hoy001}, author = {Carmen Messerlian and Williams, Paige L and Ford, Jennifer B and Chavarro, Jorge E and M{\'\i}nguez-Alarc{\'o}n, Lidia and Dadd, Ramace and Braun, Joseph M and Gaskins, Audrey J and John D Meeker and James-Todd, Tamarra and Chiu, Yu-Han and Nassan, Feiby L and Irene Souter and John Petrozza and Myra Keller and Thomas L Toth and Calafat, Antonia M and Hauser, Russ} } @article {610353, title = {Evaluating pre-pregnancy dietary diversity vs. dietary quality scores as predictors of gestational diabetes and hypertensive disorders of pregnancy}, journal = {PLoS One}, volume = {13}, number = {4}, year = {2018}, month = {2018}, pages = {e0195103}, abstract = {BACKGROUND: Dietary diversity scores (DDS) are considered as metrics for monitoring the implementation of the UN{\textquoteright}s Sustainable Development Goals, but they need to be rigorously evaluated. OBJECTIVE: To examine two DDS, the Food Groups Index (FGI), and the Minimum Dietary Diversity-Women (MDD-W), alongside two dietary quality scores, the Alternate Healthy Eating Index (AHEI-2010) and the Prime Diet Quality Score (PDQS), with risks of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDPs). DESIGN: The analysis included 21,312 (GDM) and 19,917 (HDPs) singleton births reported in the Nurses{\textquoteright} Health Study II cohort (1991-2001), among women without major chronic disease or GDM/HDPs. Scores were derived using prepregnancy diet collected by a comprehensive food frequency questionnaire. Multivariable models were utilized to calculate relative risks (RR) and confidence intervals (95\%CIs). RESULTS: Incident GDM (n = 916) and HDPs (n = 1,421) were reported. The MDD-W and FGI were not associated with risk of GDM or HDPs, but the AHEI-2010 and PDQS were associated with a lower risk of GDM and marginally lower risk of HDP. The RR{\textquoteright}s of GDM comparing the highest vs. lowest quintiles were 1.00 (95\%CI: 0.79, 1.27; p-trend = 0.82) for MDD-W, 0.96 (95\%CI: 0.76, 1.22; p-trend = 0.88) for FGI, 0.63 (95\%CI: 0.50, 0.81; p-trend , keywords = {Adult, Diabetes, Gestational, Diet, Disease Susceptibility, Female, Food Quality, Humans, Hypertension, Pregnancy-Induced, Nurses, Pregnancy, Young Adult}, issn = {1932-6203}, doi = {10.1371/journal.pone.0195103}, author = {Gicevic, Selma and Gaskins, Audrey J and Fung, Teresa T and Rosner, Bernard and Tobias, Deirdre K and Isanaka, Sheila and Willett, Walter C} } @article {626396, title = {Importance of studying infertility from a life course perspective}, journal = {Fertil Steril}, volume = {110}, number = {4}, year = {2018}, month = {2018 Sep}, pages = {628}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2018.06.022}, author = {Gaskins, Audrey J} } @article {626393, title = {Intake of protein-rich foods in relation to outcomes of infertility treatment with assisted reproductive technologies}, journal = {Am J Clin Nutr}, volume = {108}, number = {5}, year = {2018}, month = {2018 Nov 01}, pages = {1104-1112}, abstract = {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 multivariable-adjusted 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.}, issn = {1938-3207}, doi = {10.1093/ajcn/nqy185}, author = {Nassan, Feiby L and Chiu, Yu-Han and Vanegas, Jose C and Gaskins, Audrey J and Williams, Paige L and Ford, Jennifer B and Attaman, Jill and Hauser, Russ and Chavarro, Jorge E} } @article {610352, title = {Moving the science forward on dietary patterns and male fertility}, journal = {Fertil Steril}, volume = {109}, number = {5}, year = {2018}, month = {2018 May}, pages = {783}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2018.03.001}, author = {Gaskins, Audrey J} } @article {610355, title = {Predictors of Sexual Intercourse Frequency Among Couples Trying to Conceive}, journal = {J Sex Med}, volume = {15}, number = {4}, year = {2018}, month = {2018 Apr}, pages = {519-528}, abstract = {BACKGROUND: Little is known about the predictors of sexual intercourse frequency (SIF) among couples trying to conceive despite the well-established link between SIF and fecundity. AIM: To evaluate men{\textquoteright}s and women{\textquoteright}s demographic, occupational, and lifestyle predictors of SIF among couples. METHODS: 469 Couples without a history of infertility participating in the Longitudinal Investigation of Fertility and the Environment Study (2005-2009) were followed up for <=1 year while trying to conceive. At enrollment, both partners were interviewed about demographic, occupational, lifestyle, and psychological characteristics using standardized questionnaires. Multivariable generalized linear mixed models with Poisson distribution were used to estimate the adjusted percent difference in SIF across exposure categories. OUTCOMES: SIF was recorded in daily journals and summarized as average SIF/mo. RESULTS: The median (interquartile range) SIF during follow-up was 6 (4-9) acts/mo. For every year increase in age for women and men, SIF decreased by -0.8\% (95\% CI -2.5 to 1.0\%) and -1.7\% (95\% CI -3.1 to -0.3\%). Women with high school education or less and those of non-white race had 34.4\% and 16.0\% higher SIF, respectively. A similar trend was seen for men{\textquoteright}s education and race. Only couples where both partners (but not just 1 partner) worked rotating shifts had -39.1\% (95\% CI -61.0 to -5.0\%) lower SIF compared to couples where neither partner worked rotating shifts. Men{\textquoteright}s (but not women{\textquoteright}s) exercise was associated with 13.2\% (95\% CI 1.7-26.0\%) higher SIF. Diagnosis of a mood or anxiety disorder in men (but not women) was associated with a 26.0\% (95\% CI -42.7 to -4.4\%) lower SIF. Household income, smoking status, body mass index, night work, alcohol intake, and psychosocial stress were not associated with SIF. CLINICAL TRANSLATION: Even among couples trying to conceive, there was substantial variation in SIF. Both partners{\textquoteright} age, education, race, and rotating shift work as well as men{\textquoteright}s exercise and mental health play an important role in determining SIF. CONCLUSIONS: As this was a secondary analysis of an existing study, we lacked information on many pertinent psychological and relationship quality variables and the hormonal status of participants, which could have affected SIF. The unique population-based couple design, however, captured both partners{\textquoteright} demographics, occupational characteristics, and lifestyle behaviors in advance of their daily, prospective reporting of SIF, which was a major strength. Important predictors of SIF among couples attempting to conceive include men{\textquoteright}s exercise and mental health and both partners{\textquoteright} age, education, race, and rotating shift work. Gaskins AJ, Sundaram R, Buck Louis GM, et~al. Predictors of Sexual Intercourse Frequency Among Couples Trying to Conceive. J Sex Med 2018;15:519-528.}, issn = {1743-6109}, doi = {10.1016/j.jsxm.2018.02.005}, author = {Gaskins, Audrey J and Sundaram, Rajeshwari and Buck Louis, Germaine M and Chavarro, Jorge E} } @article {610380, title = {Pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion}, journal = {Eur J Nutr}, volume = {57}, number = {1}, year = {2018}, month = {2018 Feb}, pages = {107-117}, abstract = {PURPOSE: To investigate the relation between pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion (SAB). METHODS: Our prospective cohort study included 15,590 pregnancies from 11,072 women with no history of SAB in the Nurses{\textquoteright} Health Study II (1991-2009). Beverage intake was assessed every 4~years using a validated questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously at 400~mg/day had 1.11 (95~\% CI 0.98, 1.25) times the risk of SAB compared to women consuming , keywords = {Abortion, Spontaneous, Adult, Beverages, Body Mass Index, Caffeine, Carbonated Beverages, Coffee, Diet, Female, Gestational Age, Humans, Preconception Care, Pregnancy, Prospective Studies, Risk Factors, Surveys and Questionnaires, Tea}, issn = {1436-6215}, doi = {10.1007/s00394-016-1301-2}, author = {Gaskins, Audrey J and Rich-Edwards, Janet W and Williams, Paige L and Thomas L Toth and Missmer, Stacey A and Chavarro, Jorge E} } @article {626394, title = {Recent advances in understanding the relationship between long- and short-term weight change and fertility}, journal = {F1000Res}, volume = {7}, year = {2018}, month = {2018}, abstract = {The impact of excess body weight on fertility is well recognized among both women attempting to conceive spontaneously and those attempting to conceive with medical assistance. Although many leading societies of reproductive medicine have proposed weight loss as a means to counteract the negative consequences of obesity on fertility, there is limited research on this topic. In this review, we provide a brief overview of the recent advances in the literature focused on how long- and short-term weight change affects fertility among women. Overall, despite initial hope that weight loss may be beneficial for fertility, two large well-conducted randomized controlled trials have consistently shown that short-term weight loss among overweight and obese women undergoing infertility treatment does not improve a woman{\textquoteright}s probability of live birth. The observational evidence among women attempting to conceive without medical assistance also suggests limited benefits of weight loss on fecundity or pregnancy loss. In contrast, substantial weight gain between consecutive pregnancies, in the year prior to pregnancy attempt, and throughout adulthood appears to be harmful for not only time to pregnancy but also pregnancy maintenance. Future research focused on efforts to prevent weight gain during adulthood is needed to better understand whether these types of interventions may have beneficial effects on fertility.}, issn = {2046-1402}, doi = {10.12688/f1000research.15278.1}, author = {Gaskins, Audrey J} } @article {626400, title = {Residential distance to major roadways and semen quality, sperm DNA integrity, chromosomal disomy, and serum reproductive hormones among men attending a fertility clinic}, journal = {Int J Hyg Environ Health}, volume = {221}, number = {5}, year = {2018}, month = {2018 Jun}, pages = {830-837}, abstract = {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/m. 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.}, issn = {1618-131X}, doi = {10.1016/j.ijheh.2018.05.007}, author = {Nassan, Feiby L and Chavarro, Jorge E and M{\'\i}nguez-Alarc{\'o}n, Lidia and Williams, Paige L and Tanrikut, Cigdem and Ford, Jennifer B and Dadd, Ramace and Perry, Melissa J and Hauser, Russ and Gaskins, Audrey J} } @article {610354, title = {Residential proximity to major roadways and traffic in relation to outcomes of in vitro fertilization}, journal = {Environ Int}, volume = {115}, year = {2018}, month = {2018 06}, pages = {239-246}, abstract = {BACKGROUND: Emerging data from animal and human studies suggest that traffic-related air pollution adversely affects early pregnancy outcomes; however evidence is limited. OBJECTIVE: We examined whether residential proximity to major roadways and traffic, as proxies for traffic-related air pollution, are associated with in vitro fertilization (IVF) outcomes. METHODS: This analysis included 423 women enrolled in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 726 IVF cycles (2004-2017). Using geocoded residential addresses collected at study entry, we calculated the distance to nearest major roadway and the traffic density within a 100 m radius. IVF outcomes were abstracted from electronic medical records. We used multivariable generalized linear mixed models to evaluate the associations between residential proximity to major roadways and traffic density and IVF outcomes adjusting for maternal age, body mass index, race, education level, smoking status, and census tract median income. RESULTS: Closer residential proximity to major roadways was statistically significantly associated with lower probability of implantation and live birth following IVF. The adjusted percentage of IVF cycles resulting in live birth for women living >=400 m from a major roadway was 46\% (95\% CI 36, 56\%) compared to 33\% (95\% CI 26, 40\%) for women living , issn = {1873-6750}, doi = {10.1016/j.envint.2018.03.029}, author = {Gaskins, Audrey J and Hart, Jaime E and M{\'\i}nguez-Alarc{\'o}n, Lidia and Chavarro, Jorge E and Laden, Francine and Brent A Coull and Ford, Jennifer B and Irene Souter and Hauser, Russ} } @article {626401, title = {Seafood Intake, Sexual Activity, and Time to Pregnancy}, journal = {J Clin Endocrinol Metab}, volume = {103}, number = {7}, year = {2018}, month = {2018 Jul 01}, pages = {2680-2688}, abstract = {Context: Marine long-chain omega-3 fatty acids have been positively related to markers of fecundity in both men and women. However, seafood, their primary food source, can also be a source of toxicants, which could counteract the reproductive benefits. Objective: To examine the relationship of male and female seafood intake with time to pregnancy (TTP). Design: Our prospective cohort study included 501 couples planning pregnancy, who participated in the Longitudinal Investigation of Fertility and the Environment study (2005 to 2009) and were followed up for <=1 year or until pregnancy was detected. Seafood intake was collected daily during follow-up in journals. Setting: Couples residing in Michigan and Texas were recruited using population-based sampling frameworks. Main Outcome Measures: The primary outcome was the TTP, determined using an in-home pregnancy test. A secondary outcome was sexual intercourse frequency (SIF) as recorded in the daily journals. Results: Couples with male and female partners who consumed eight or more seafood servings per cycle had 47\% (95\% CI, 7\% to 103\%) and 60\% (95\% CI, 15\% to 122\%) greater fecundity (shorter TTP) than couples with male and female partners who consumed one or fewer seafood servings per cycle. Couples with both partners consuming eight or more seafood servings per cycle had 61\% (95\% CI, 17\% to 122\%) greater fecundity than couples consuming less. Male and female partners with the highest seafood intake (eight or more servings per cycle) also had 22\% greater SIF. Conclusions: Greater male and female seafood intake was associated with a higher SIF and fecundity among a large prospective cohort of couples attempting pregnancy.}, issn = {1945-7197}, doi = {10.1210/jc.2018-00385}, author = {Gaskins, Audrey J and Sundaram, Rajeshwari and Buck Louis, Germaine M and Chavarro, Jorge E} } @article {626395, title = {Secular trends in semen parameters among men attending a fertility center between 2000 and 2017: Identifying potential predictors}, journal = {Environ Int}, year = {2018}, month = {2018 Oct 30}, abstract = {BACKGROUND: Multiple meta-analyses have shown sperm count declines in Western countries spanning eight decades. Secular trends in other parameters remain unclear, as are potential predictors of these trends. OBJECTIVE: To analyze secular trends in semen quality and to evaluate whether factors previously found to be related to semen quality were responsible for these patterns. METHODS: This is a prospective study including 936 men of couples seeking infertility treatment who provided 1618 semen samples at a single center (2000-2017). Self-reported demographic, nutritional and reproductive characteristics were collected using standardized questionnaires. Urinary concentrations of bisphenol A, parabens and phthalates were quantified by isotope-dilution tandem mass spectrometry. Semen samples were analyzed for volume, sperm concentration, count, motility and morphology following WHO guidelines. We estimated the differences in semen parameters over time by fitting generalized linear mixed models with random intercepts to account for repeated samples while adjusting for abstinence time. We also adjusted for demographic, nutritional and environmental factors to investigate these as potential predictors of time trends. RESULTS: Sperm concentration and count declined by 2.62\% per year (95\% CI -3.84, -1.38) and 3.12\% per year (95\% CI: -4.42, -1.80), corresponding to an overall decline of 37\% and 42\%, respectively, between 2000 and 2017. Decreasing trends were also observed for total motility (per year: -0.44 percentage units, 95\% CI -0.71, -0.17) and morphologically normal sperm (per year: -0.069 percentage units, 95\% CI -0.116, -0.023). These decreases reflected relative percentage declines of 15\% and 16\% over the 17 year study period, respectively. When reproductive factors were included in the model, the downward trends in sperm concentration and sperm count were attenuated by 29\% and 26\%, respectively, while the trends in motility and morphology were attenuated by 54\% and 53\%, respectively. Also, the downward trends in both sperm concentration and sperm morphology over time were attenuated by 19\% when including the DEHP and non-DEHP metabolites, respectively. CONCLUSIONS: Sperm concentration, total count, motility and morphology significantly declined between 2000 and 2017 among subfertile men. These negative trends were attenuated when considering simultaneous changes in reproductive characteristics and urinary phthalates during the course of the study.}, issn = {1873-6750}, doi = {10.1016/j.envint.2018.10.052}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Williams, Paige L and Chiu, Yu-Han and Gaskins, Audrey J and Nassan, Feiby L and Dadd, Ramace and John Petrozza and Hauser, Russ and Chavarro, Jorge E} } @article {610358, title = {Serum omega-3 fatty acids and treatment outcomes among women undergoing assisted reproduction}, journal = {Hum Reprod}, volume = {33}, number = {1}, year = {2018}, month = {2018 01 01}, pages = {156-165}, abstract = {STUDY QUESTION: Are serum polyunsaturated fatty acids (PUFA) concentrations, including omega-3 (ω3-PUFA) and omega-6 (ω6-PUFA), related to ART outcomes? SUMMARY ANSWER: Serum levels of long-chain ω3-PUFA were positively associated with probability of live birth among women undergoing ART. WHAT IS KNOWN ALREADY: Intake of ω3-PUFA improves oocyte and embryo quality in animal and human studies. However, a recent cohort study found no relation between circulating ω3-PUFA levels and pregnancy rates after ART. STUDY DESIGN SIZE, AND DURATION: This analysis included a random sample of 100 women from a prospective cohort study (EARTH) at the Massachusetts General Hospital Fertility Center who underwent 136 ART cycles within one year of blood collection. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum fatty acids (expressed as percentage of total fatty acids) were measured by gas chromatography in samples taken between Days 3 and 9 of a stimulated cycle. Primary outcomes included the probability of implantation, clinical pregnancy and live birth per initiated cycle. Cluster-weighted generalized estimating equation (GEE) models were used to analyze the association of total and specific PUFAs with ART outcomes adjusting for age, body mass index, smoking status, physical activity, use of multivitamins and history of live birth. MAIN RESULTS AND ROLE OF CHANCE: The median [25th, 75th percentile] serum level of ω3-PUFA was 4.7\% [3.8\%, 5.8\%] of total fatty acids. Higher levels of serum long-chain ω3-PUFA were associated with higher probability of clinical pregnancy and live birth. Specifically, after multivariable adjustment, the probability of clinical pregnancy and live birth increased by 8\% (4\%, 11\%) and 8\% (95\% CI: 1\%, 16\%), respectively, for every 1\% increase in serum long-chain ω3-PUFA levels. Intake of long-chain ω3-PUFA was also associated with a higher probability of life birth in these women, with RR of 2.37 (95\% CI: 1.02, 5.51) when replacing 1\% energy of long-chain ω3-PUFA for 1\% energy of saturated fatty acids. Serum ω6-PUFA, ratios of ω6 and ω3-PUFA, and total PUFA were not associated with ART outcomes. LIMITATIONS REASONS FOR CAUTION: The generalizability of the findings to populations not undergoing infertility treatment may be limited. The use of a single measurement of serum fatty acids to characterize exposure may lead to potential misclassification during follow up. WIDER IMPLICATIONS OF THE FINDINGS: Serum ω3-PUFA are considered biomarkers of dietary intake. The association of higher serum long chain ω3-PUFA levels with improved ART outcomes suggests that increased intake of these fats be may be beneficial for women undergoing infertility treatment with ART. STUDY FUNDING/COMPETING INTERESTS: 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.}, issn = {1460-2350}, doi = {10.1093/humrep/dex335}, author = {Chiu, Y-H and Karmon, A E and Gaskins, A J and Arvizu, M and Williams, P L and Souter, I and Rueda, B R and Hauser, R and Chavarro, J E} } @article {626398, title = {Type of underwear worn and markers of testicular function among men attending a fertility center}, journal = {Hum Reprod}, volume = {33}, number = {9}, year = {2018}, month = {2018 Sep 01}, pages = {1749-1756}, abstract = {STUDY QUESTION: Is self-reported type of underwear worn associated with markers of testicular function among men at a fertility center? SUMMARY ANSWER: Men who reported most frequently wearing boxers had higher sperm concentration and total count, and lower FSH levels, compared to men who did not. WHAT IS KNOWN ALREADY: Elevated scrotal temperatures are known to adversely affect testicular function. However, the epidemiologic literature on type of underwear, as a proxy of scrotal temperature, and male testicular function is inconsistent. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study including 656 male partners of couples seeking infertility treatment at a fertility center (2000-2017). PARTICIPANTS/MATERIALS, SETTING, METHODS: Self-reported information on type of underwear worn was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone levels and neutral comet assays for sperm DNA damage. We fit linear regression models to evaluate the association between underwear type and testicular function, adjusting for covariates and accounting for multiple semen samples. MAIN RESULTS AND THE ROLE OF CHANCE: Men had a median (interquartile range) age of 35.5 (32.0, 39.3) years and BMI of 26.3 (24.4, 29.9) kg/m2. About half of the men (53\%; n = 345) reported usually wearing boxers. Men who reported primarily wearing boxers had a 25\% higher sperm concentration (95\% CI = 7, 31\%), 17\% higher total count (95\% CI = 0, 28\%) and 14\% lower serum FSH levels (95\% CI = -27, -1\%) than men who reported not primarily wearing boxers. Sperm concentration and total count were inversely related to serum FSH. Furthermore, the differences in sperm concentration and total count according to type of underwear were attenuated after adjustment for serum FSH. No associations with other measured reproductive outcomes were observed. LIMITATIONS, REASONS FOR CAUTION: Our results may not be generalizable to men from the general population. Underwear use was self-reported in a questionnaire and there may be misclassification of the exposure. The cross-sectional design limits causal inference, and residual confounding is still possible owing to lack of information on other modifiable life styles that can also modify scrotal heat (e.g. type of trousers worn, textile fabric of the underwear). Blood sampling was not limited to the morning and, as a result, we may have missed associations with testosterone or other hormones with significant circadian variation despite statistical adjustment for time of blood draw. WIDER IMPLICATIONS OF THE FINDINGS: Certain styles of male underwear may impair spermatogenesis and this may result in a compensatory increase in gonadotrophin secretion, as reflected by higher serum FSH levels among men who reported most frequently wearing tight underwear. Confirmation of these findings, and in particular the findings on FSH levels suggesting a compensatory mechanism, is warranted. STUDY FUNDING/COMPETING INTEREST(S): The project was financed by Grants (R01ES022955, R01ES009718, P30ES000002, and K99ES026648) from the National Institutes of Health. None of the authors has any conflicts of interest to declare.}, issn = {1460-2350}, doi = {10.1093/humrep/dey259}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Gaskins, Audrey J and Chiu, Yu-Han and Carmen Messerlian and Williams, Paige L and Ford, Jennifer B and Irene Souter and Hauser, Russ and Chavarro, Jorge E} } @article {610357, title = {Urinary concentrations of biomarkers of phthalates and phthalate alternatives and IVF outcomes}, journal = {Environ Int}, volume = {111}, year = {2018}, month = {2018 02}, pages = {23-31}, abstract = {Phthalates are a class of chemicals found in a large variety of consumer products. Available experimental and limited human data show adverse effects of some phthalates on ovarian function, which has raised concerns regarding potential effects on fertility. The aim of the current study was to determine whether urinary concentrations of metabolites of phthalates and phthalate alternatives are associated with intermediate and clinical in vitro fertilization (IVF) outcomes. We enrolled 136 women undergoing IVF in a Tertiary University Affiliated Hospital. Participants provided one to two urine samples per cycle during ovarian stimulation and before oocyte retrieval. IVF outcomes were abstracted from medical records. Concentrations of 17 phthalate metabolites and two metabolites of the phthalate alternative di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) were measured. Multivariable Poisson regression models with log link were used to analyze associations between tertiles of specific gravity adjusted phthalate or DINCH metabolites and number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Multivariable logistic regression models were applied to evaluate the association between tertiles of specific gravity adjusted phthalate or DINCH metabolites and probability of live birth. Urinary concentrations of the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP) and the individual metabolites mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5-oxohexyl phthalate, and mono-2-ethyl-5-carboxypentyl phthalate were negatively associated with the number of total oocytes, mature oocytes, fertilized oocytes, and top quality embryos. Of the low molecular weight phthalates, higher monoethyl phthalate and mono-n-butyl phthalate concentrations were associated with significantly fewer total, mature, and fertilized oocytes. None of the urinary phthalate metabolite concentrations were associated with a reduced probability implantation, clinical pregnancy or live birth. Metabolites of DINCH were not associated with intermediate or clinical IVF outcomes. Our results suggest that DEHP may impair early IVF outcomes, specifically oocyte parameters. Additional research is needed to elucidate the potential effect of DEHP on female fertility in the general population.}, keywords = {Adult, Biomarkers, Environmental Monitoring, Environmental Pollutants, Female, Fertility, Fertilization in Vitro, Humans, Phthalic Acids, Pregnancy, Pregnancy Outcome, Young Adult}, issn = {1873-6750}, doi = {10.1016/j.envint.2017.11.011}, author = {Machtinger, Ronit and Gaskins, Audrey J and Racowsky, Catherine and Mansur, Abdallah and Adir, Michal and Andrea A Baccarelli and Calafat, Antonia M and Hauser, Russ} } @article {610360, title = {Weight change and pregnancy loss: what can be concluded?}, journal = {BJOG}, volume = {125}, number = {6}, year = {2018}, month = {2018 May}, pages = {685}, issn = {1471-0528}, doi = {10.1111/1471-0528.14858}, author = {Gaskins, A J} } @article {610362, title = {Association between preconception maternal beverage intake and in~vitro fertilization outcomes}, journal = {Fertil Steril}, volume = {108}, number = {6}, year = {2017}, month = {2017 12}, pages = {1026-1033}, abstract = {OBJECTIVE: To study whether maternal intake of beverage type affects IVF outcomes. DESIGN: A prospective study. SETTING: Tertiary, university-affiliated center. PATIENT(S): Three hundred forty women undergoing IVF from 2014 through 2016 for infertility as well as for pregenetic diagnosis for autosomal recessive diseases were enrolled during ovarian stimulation and completed a questionnaire describing their usual beverage consumption. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): IVF outcomes were abstracted from medical records. Total caffeine intake was estimated by summing the caffeine content for specific beverages multiplied by frequency of intake. Associations between specific types of beverages and IVF outcomes were analyzed using Poisson and logistic regression models adjusting for possible confounders. RESULT(S): Higher intake of sugared soda was associated with lower total, mature, and fertilized oocytes and top-quality embryos after ovarian stimulation. Women who consumed sugared soda had, on average, 1.1 fewer oocytes retrieved, 1.2 fewer mature oocytes retrieved, 0.6 fewer fertilized oocytes, and 0.6 fewer top-quality embryos compared with women who did not consume sugared soda. Furthermore, compared with women who did not drink sugared soda, the adjusted difference in percent of cycles resulting in live birth for women consuming 0.1-1 cups/day and >1 cup/day were -12\% and -16\%, respectively. No associations were found between consumption of coffee, caffeine, or diet sodas and IVF outcome. CONCLUSION(S): Sugared beverages, independent of their caffeine content, may be a bigger threat to reproductive success than caffeine and caffeinated beverages without added sugar.}, keywords = {Adult, Blastocyst, Caffeine, Carbonated Beverages, Chi-Square Distribution, Coffee, Female, Fertility, Fertilization in Vitro, Habits, Humans, In Vitro Oocyte Maturation Techniques, Infertility, Logistic Models, Maternal Nutritional Physiological Phenomena, Multivariate Analysis, Oocyte Retrieval, Pregnancy, Pregnancy Rate, Prospective Studies, Risk Assessment, Risk Factors, Surveys and Questionnaires, Treatment Outcome}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2017.09.007}, author = {Machtinger, Ronit and Gaskins, Audrey J and Mansur, Abdallah and Adir, Michal and Racowsky, Catherine and Andrea A Baccarelli and Hauser, Russ and Chavarro, Jorge E} } @article {610364, title = {The association between pre-treatment maternal alcohol and caffeine intake and outcomes of assisted reproduction in a prospectively followed cohort}, journal = {Hum Reprod}, volume = {32}, number = {9}, year = {2017}, month = {2017 Sep 01}, pages = {1846-1854}, abstract = {STUDY QUESTION: Is pre-treatment alcohol and caffeine intake associated with infertility treatment outcomes among women undergoing ART? SUMMARY ANSWER: Low to moderate alcohol and caffeine intakes in the year prior to infertility treatment were not related to ART outcomes. WHAT IS KNOWN ALREADY: Alcohol and caffeine intake have been found to be associated with infertility in some studies. Nevertheless, data on their relation with outcomes of infertility treatments are scarce and inconsistent. STUDY DESIGN, SIZE, DURATION: We included 300 women (493 ART cycles) from the Environment and Reproductive Health Study, an ongoing cohort study (2006-2016). PARTICIPANTS/MATERIALS, SETTING, METHODS: Pre-treatment intakes of alcohol and caffeine were assessed retrospectively using a validated food frequency questionnaire. Intermediate and clinical endpoints of ART were abstracted from electronic medical records. Generalized linear mixed models with random intercepts to account for multiple ART cycles per woman were used to evaluate the association with ART outcomes adjusting for age, BMI, smoking status, infertility diagnosis, protocol type, race, dietary patterns, and calories, vitamin B12 and folate intake. MAIN RESULTS AND THE ROLE OF CHANCE: Median (range) pre-treatment alcohol and caffeine intakes were 5.6 (0.0-85.8) g/day and 124.9 (0.3-642.2) mg/day, respectively. The adjusted percentage of initiated cycles resulting in live birth (95\% CI) for women in increasing categories of pre-treatment alcohol intake was 34\% (20, 52\%) for non-consumers, 46\% (36, 57\%) for 0.1-6 g/day, 41\% (29, 53\%) for 6.1-12 g/day, 42\% (31, 55\%) for 12.1-24 g/day, and 41\% (22, 63\%) for >24 g/day (P, trend = 0.87). The adjusted percentage of cycles resulting in live birth (95\% CI) for women in increasing categories of caffeine intake was 46\% (36-57\%) for 300 mg/day (P, trend = 0.34). When specific types of alcoholic and caffeinated beverages were evaluated, no relations with ART treatment outcomes were observed. LIMITATIONS, REASONS FOR CAUTION: Residual confounding by other diet and lifestyle factors cannot be ruled out owing to the observational nature of this study. It is also unclear how generalizable these results are to women who are conceiving without the assistance of ART. WIDER IMPLICATIONS OF THE FINDINGS: Our results provide reassurance that low to moderate intakes of alcohol (e.g. <=12 g/day) and caffeine (e.g. , issn = {1460-2350}, doi = {10.1093/humrep/dex237}, author = {Abadia, L and Chiu, Y-H and Williams, P L and Toth, T L and Souter, I and Hauser, R and Chavarro, J E and Gaskins, A J} } @article {610377, title = {Coenzyme Q10 Intake From Food and Semen Parameters in a Subfertile Population}, journal = {Urology}, volume = {102}, year = {2017}, month = {2017 04}, pages = {100-105}, abstract = {OBJECTIVE: To assess the association between coenzyme Q10 (CoQ10) intake from food sources and semen quality. We assessed this association in a prospective cohort of men attending a fertility clinic. CoQ10 supplementation has been associated with improvements in semen parameters. However, the impact of CoQ10 intake from food sources on semen quality has not been investigated. MATERIALS AND METHODS: Subfertile couples seeking fertility evaluation at the Massachusetts General Hospital Fertility Center were invited to participate in an ongoing study of environmental factors and fertility. In total, 211 male participants completed a validated food frequency questionnaire and provided 476 semen samples. Multivariable linear mixed models were used to examine the relation between CoQ10 intake from food and semen parameters while adjusting for potential confounders and accounting for within-person correlations. RESULTS: Mean dietary CoQ10 intake was 19.2 mg/day (2.4-247.2 mg/day). No subjects were taking CoQ10 supplements. There were no associations between dietary CoQ10 intake from food and conventional semen parameters. The adjusted mean difference (95\% confidence interval) comparing men in the top and bottom quartiles of CoQ10 intake from food were -3.1 mil/mL (95\% confidence interval -29.5, 38.8 mil/mL) for sperm concentration, -4.5\% (-15.1\%, 6.0\%) for total motility, -1.3\% for progressive motility (-8.4\%, 5.7\%), and 0.3\% (-1.4\%, 2.0\%) for sperm morphology. CONCLUSION: CoQ10 intake from food was not related to semen parameters among subfertile men. Mean dietary intake of CoQ10 in this study was 10-fold lower than the supplemental dose used in clinical trials showing improved sperm motility. CoQ10 intake from food alone may be insufficient to optimize semen parameters.}, keywords = {Adult, Dietary Supplements, Food, Humans, Infertility, Male, Male, Prospective Studies, Semen Analysis, Ubiquinone, Vitamins}, issn = {1527-9995}, doi = {10.1016/j.urology.2016.11.022}, author = {Tiseo, Bruno C and Gaskins, Audrey J and Hauser, Russ and Chavarro, Jorge E and Tanrikut, Cigdem} } @article {610373, title = {Dairy intake in relation to breast and pubertal development in Chilean girls}, journal = {Am J Clin Nutr}, volume = {105}, number = {5}, year = {2017}, month = {2017 May}, pages = {1166-1175}, abstract = { Frequent dairy consumption in childhood has been related to higher growth-hormone concentrations that may affect mammary gland and pubertal development. We evaluated the relation of dairy intake to breast composition at Tanner stage 4 and age at menarche. A total of 515 Chilean girls are included in the Growth and Obesity Cohort Study. The subjects have been followed longitudinally since they were 3-4 y old (from 2006 to the present). Starting in 2013, diet was assessed every 6 mo via a 24-h recall. The breast fibroglandular volume (FGV) was measured with the use of dual-energy X-ray absorptiometry at Tanner stage 4. The date of menarche was reported every 6 mo. Our analysis included 290 girls with data on prospective diet and breast composition and 324 girls with data on prospective diet and age at menarche. The mean {\textpm} SD breast FGV and percentage of fibroglandular volume (\%FGV) (i.e., FGV divided by total breast volume times 100) at Tanner stage 4 was 81.7 {\textpm} 32.2 cm and 42.0\% {\textpm} 16.7\%, respectively. Only sweetened, artificially flavored milk-based drinks were associated with the \%FGV with girls who consumed >125 g/d having a \%FGV that was 4.5\% (95\% CI: 0.9\%, 8.1\%) higher than that of girls who consumed none (-trend = 0.007). Yogurt intake was associated with a lower FGV. Specifically, girls who consumed >125 g yogurt/d had -10.2 cm (95\% CI: -20.2, -0.3 cm) less FGV than did girls who consumed no yogurt (-trend = 0.03). The majority (90.7\%) of girls in our cohort attained menarche before the data analyses with a mean {\textpm} SD age at menarche of 11.9 {\textpm} 0.7 y. In multivariable models, low-fat dairy, low-fat milk, and yogurt intakes were associated with a later age at menarche. In particular, girls who consumed >125 g yogurt/d had menarche, on average, 4.6 mo (95\% CI: 1.9, 7.4 mo) later than girls who consumed no yogurt (-trend = 0.01). More-frequent consumption of sweetened, artificially-flavored milk-based drinks is associated with a higher \%FGV, whereas higher yogurt intake is associated with a lower FGV and delayed age at menarche in Chilean girls.}, keywords = {Absorptiometry, Photon, Age Factors, Animals, Breast, Child, Chile, Dairy Products, Diet, Diet Records, Dietary Sucrose, Energy Intake, Feeding Behavior, Female, Humans, Longitudinal Studies, Mammary Glands, Human, Menarche, Mental Recall, Milk, Prospective Studies, Puberty, Precocious, Sexual Maturation, Yogurt}, issn = {1938-3207}, doi = {10.3945/ajcn.116.150359}, author = {Gaskins, Audrey J and Pereira, Ana and Quintiliano, Daiana and Shepherd, John A and Uauy, Ricardo and Corval{\'a}n, Camila and Michels, Karin B} } @article {610371, title = {Discrete survival model analysis of a couple{\textquoteright}s smoking pattern and outcomes of assisted reproduction}, journal = {Fertil Res Pract}, volume = {3}, year = {2017}, month = {2017}, abstract = {BACKGROUND: Cigarette smoking has been associated with worse infertility treatment outcomes, yet some studies have found null or inconsistent results. METHODS: We followed 225 couples who underwent 354 fresh non-donor assisted reproductive technology (ART) cycles between 2006 and 2014. Smoking history was self-reported at study entry. We evaluated the associations between smoking patterns and ART success using multivariable discrete time Cox proportional hazards models with six time periods: cycle initiation to egg retrieval, retrieval to fertilization, fertilization to embryo transfer (ET), ET to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth to estimate hazard ratios (HR) and 95\% CIs. Time-dependent interactions between smoking intensity and ART time period were used to identify vulnerable periods. RESULTS: Overall, 26\% of women and 32\% of men reported ever smoking. The HR of failing in the ART cycle without attaining live birth for male and female ever smokers was elevated, but non-significant, compared to never smokers regardless of intensity (HR = 1.02 and 1.30, respectively). Female ever smokers were more likely to fail prior to oocyte retrieval (HR: 3.37; 95\% CI: 1.00, 12.73). Every one cigarette/day increase in smoking intensity for females was associated with a HR of 1.02 of failing ART (95\% CI: 0.97, 1.08), regardless of duration or current smoking status. Women with higher smoking intensities were most likely to fail a cycle prior to oocyte retrieval (HR: 1.07; 95\% CI: 1.00, 1.16). Among past smokers, every additional year since a man had quit smoking reduced the risk of failing ART by 4\% (HR: 0.96; 95\% CI: 0.91, 1.00) particularly between clinical pregnancy and live birth (HR: 0.86; 95\% CI: 0.76, 0.96). CONCLUSIONS: Female smoking intensity, regardless of current smoking status, is positively associated with the risk of failing ART cycles between initiation and oocyte retrieval. In men who ever smoked, smoking cessation may reduce the probability of failing ART, particularly between clinical pregnancy and live birth. TRIAL REGISTRATION: NCT00011713. Registered: 27 February 2001.}, issn = {2054-7099}, doi = {10.1186/s40738-017-0032-2}, author = {Vanegas, Jose C and Chavarro, Jorge E and Williams, Paige L and Ford, Jennifer B and Thomas L Toth and Hauser, Russ and Gaskins, Audrey J} } @article {610361, title = {Epidemiologic Approaches for Studying Assisted Reproductive Technologies: Design, Methods, Analysis and Interpretation}, journal = {Curr Epidemiol Rep}, volume = {4}, number = {2}, year = {2017}, month = {2017 Jun}, pages = {124-132}, abstract = {PURPOSE: While considerable progress has been made since the advent of assisted reproductive technology (ART), the field remains a complex and challenging one for clinicians and researchers alike. This review discusses some of the most salient issues pertaining to the study of ART and whenever possible suggestions on how to address them. RECENT FINDINGS: More than 5 million babies have been born through ART to date, representing up to 4\% of all births worldwide. While technologies continue to evolve and demand for treatment grows, it is more important than ever to conduct rigorous and timely research to help guide clinical practice that is safe and effective, and that minimizes potential short- and long-term adverse outcomes to mother and child. SUMMARY: ART research will require exceedingly more sophisticated research methods, designs, and analyses that are rooted in a reproductive epidemiological framework in order to improve future research and ultimately promote better outcomes for all subfertile couples and their children.}, issn = {2196-2995}, doi = {10.1007/s40471-017-0105-0}, author = {Carmen Messerlian and Gaskins, Audrey J} } @article {610369, title = {Female exposure to endocrine disrupting chemicals and fecundity: a review}, journal = {Curr Opin Obstet Gynecol}, volume = {29}, number = {4}, year = {2017}, month = {2017 Aug}, pages = {202-211}, abstract = {PURPOSE OF REVIEW: Endocrine disrupting chemicals (EDCs) have been known for their ability to interfere with aspects of hormone action resulting in adverse health consequences among animals and humans; however, the effects of EDCs on human fecundity have shown inconsistent findings. This review summarizes the most recent epidemiologic literature from humans on the potential effects of female exposure to nonpersistent EDCs, specifically bisphenol A (BPA), phthalates, parabens, and triclosan, on fecundity, measured by markers of reproductive hormones, markers of ovulation or ovarian reserve, IVF outcomes, and time-to-pregnancy. RECENT FINDINGS: Although the epidemiologic literature on this topic is growing, the evidence supporting an association between female urinary concentrations of BPA, phthalates, parabens and triclosan, and fecundity remains unclear. The heterogeneous results could be due to methodological differences in recruitment populations (fertile vs. subfertile), study designs (prospective vs. retrospective), assessment of exposure (including differences in the number and timing of urine samples and differences in the analytical methods used to assess the urinary concentrations), residual confounding due to diet or other lifestyle factors, and coexposures to other chemicals. SUMMARY: At present, there is limited evidence to conclude that female exposure to nonpersistent EDCs affect fecundity in humans. Further studies focusing on exposure to mixtures of EDCs are needed.}, keywords = {Animals, Benzhydryl Compounds, Endocrine Disruptors, Environmental Exposure, Female, Fertility, Fertilization in Vitro, Hormones, Humans, Parabens, Phenols, Phthalic Acids, Triclosan}, issn = {1473-656X}, doi = {10.1097/GCO.0000000000000373}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Gaskins, Audrey J} } @article {610365, title = {Folate, homocysteine and the ovarian cycle among healthy regularly menstruating women}, journal = {Hum Reprod}, volume = {32}, number = {8}, year = {2017}, month = {2017 Aug 01}, pages = {1743-1750}, abstract = {STUDY QUESTION: How are concentrations of plasma homocysteine and serum folate associated with reproductive hormones and anovulation in regularly menstruating women? SUMMARY ANSWER: Higher homocysteine was associated with sporadic anovulation and hormonal changes that may be indicative of impaired ovulatory function, but higher serum folate was associated only with higher luteal phase progesterone. WHAT IS KNOWN ALREADY: Higher folate levels as well as some variants in genes relevant to one-carbon metabolism, are associated with improved reproductive outcomes and responses to fertility treatment, but only a few small studies have explored the relationship between markers of one-carbon metabolism and menstrual cycle characteristics. STUDY DESIGN, SIZE, DURATION: The BioCycle Study (2005-2007) is a prospective, longitudinal cohort of 259 regularly menstruating women not using hormonal contraceptives or dietary supplements who were followed for up to two menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Serum folate and reproductive hormones were measured up to eight times per cycle and plasma homocysteine up to three times. Linear mixed models were used to estimate associations between serum folate or plasma homocysteine and log-transformed reproductive hormone levels while accounting for multiple observations and cycles per woman. Generalized estimating equations were used to examine risk of sporadic anovulation. All models were adjusted for age, race, body mass index, cigarette and alcohol use, and energy and fiber intake. MAIN RESULTS AND THE ROLE OF CHANCE: Higher plasma homocysteine concentrations were associated with lower total estradiol across the cycle (adjusted percent change per unit increase in homocysteine [aPC] -2.3\%, 95\% CI: -4.2, -0.03), higher follicle stimulating hormone around the time of expected ovulation (aPC 2.4\%, 95\% CI: 0.2, 4.7) and lower luteal phase progesterone (aPC -6.5\%, 95\% CI: -11.1, -1.8). Higher serum folate concentrations were associated with higher luteal phase progesterone (aPC per unit increase in folate 1.0\%, 95\% CI: 0.4, 1.6). Higher homocysteine concentrations at expected ovulation were associated with a 33\% increased risk of sporadic anovulation. We observed no risk associated with decreased folate concentrations, but a higher ratio of folate to homocysteine at ovulation was associated with a 10\% decreased risk of anovulation. LIMITATIONS, REASONS FOR CAUTION: Our results are generalizable to healthy women with adequate serum folate levels. The independent influence of homocysteine should be confirmed in larger cohorts and among women with folate deficiency or increased risks of anovulation. WIDER IMPLICATIONS OF THE FINDINGS: If these findings are confirmed, it is possible that lowering homocysteine with B-vitamins through diet or supplementation could improve ovulatory function in some women. Study FUNDING/COMPETING INTEREST(S): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (Contract numbers: HHSN275200403394C, HHSN275201100002I and Task one HHSN27500001). None of the authors has any conflicts of interest to disclose.}, issn = {1460-2350}, doi = {10.1093/humrep/dex233}, author = {Michels, Kara A and Wactawski-Wende, Jean and Mills, James L and Schliep, Karen C and Gaskins, Audrey J and Yeung, Edwina H and Kim, Keewan and Plowden, Torie C and Sjaarda, Lindsey A and Chaljub, Ellen N and Mumford, Sunni L} } @article {610374, title = {Male caffeine and alcohol intake in relation to semen parameters and in~vitro fertilization outcomes among fertility patients}, journal = {Andrology}, volume = {5}, number = {2}, year = {2017}, month = {2017 03}, pages = {354-361}, abstract = {Much of the literature on the impact of male caffeine and alcohol intake on reproductive outcomes has utilized semen quality as a proxy for male fertility, although semen parameters have a limited predictive value for spontaneous pregnancy. The objective of this study was to investigate whether male caffeine and alcohol intakes are associated with semen parameters and assisted reproductive technology outcome. The Environment and Reproductive Health Study, an ongoing prospective cohort study, enrolls subfertile couples presenting for treatment at an academic fertility center (2007-2012). A total of 171 men with 338 semen analyses and 205 assisted reproductive technology cycles were included in this analysis. Diet was assessed using a 131-item food frequency questionnaire. Mixed models adjusting for potential confounders were used to evaluate the relationships of male caffeine and alcohol intakes with semen parameters and assisted reproductive technology outcomes. There was no association between male caffeine and alcohol intake and semen quality. Male caffeine intake was negatively related to live birth after assisted reproductive technologies (p-trend~, keywords = {Adult, Alcohol Drinking, Caffeine, Female, Fertility, Fertilization in Vitro, Humans, Infertility, Male, Pregnancy, Pregnancy Rate, Prospective Studies, Semen Analysis, Sperm Count, Sperm Motility}, issn = {2047-2927}, doi = {10.1111/andr.12310}, author = {Karmon, A E and Toth, T L and Chiu, Y-H and Gaskins, A J and Tanrikut, C and Wright, D L and Hauser, R and Chavarro, J E} } @article {610372, title = {Obesity and Cesarean Section-Reply}, journal = {JAMA Pediatr}, volume = {171}, number = {6}, year = {2017}, month = {2017 Jun 01}, pages = {598-599}, issn = {2168-6211}, doi = {10.1001/jamapediatrics.2017.0391}, author = {Chavarro, Jorge E and Yuan, Changzheng and Gaskins, Audrey J} } @article {610375, title = {Occupational factors and markers of ovarian reserve and response among women at a fertility centre}, journal = {Occup Environ Med}, volume = {74}, number = {6}, year = {2017}, month = {2017 Jun}, pages = {426-431}, abstract = {OBJECTIVES: To explore whether work schedules and physically demanding work were associated with markers of ovarian reserve and response. METHODS: This analysis included women (n=473 and n=313 for ovarian reserve and ovarian response analysis, respectively) enrolled in a prospective cohort study of couples presenting to an academic fertility centre (2004-2015). Information on occupational factors was collected on a take-home questionnaire, and reproductive outcomes were abstracted from electronic medical records. Generalised linear models and generalised linear mixed models were used to evaluate the associations. RESULTS: Women who reported lifting or moving heavy objects at work had 1.0 fewer total oocytes (p=0.08), 1.4 fewer mature oocytes (p=0.007) and 0.7 fewer antral follicles (p=0.06) compared with women who reported never lifting or moving heavy objects at work. The inverse association between heavy lifting and oocyte yield was stronger in women >37 years and with a Body Mass Index >=25 kg/m. Women who worked evening/night/rotating shifts had 2.3 (p, keywords = {Academic Medical Centers, Adolescent, Adult, Ambulatory Care Facilities, Body Mass Index, Female, Fertility, Follicle Stimulating Hormone, Humans, Infertility, Female, Lifting, Linear Models, Massachusetts, Medical Records, Middle Aged, Occupational Diseases, Occupational Exposure, Ovarian Reserve, Prospective Studies, Risk Factors, Surveys and Questionnaires, Ultrasonography, Work Schedule Tolerance, Workload, Young Adult}, issn = {1470-7926}, doi = {10.1136/oemed-2016-103953}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Irene Souter and Williams, Paige L and Ford, Jennifer B and Hauser, Russ and Chavarro, Jorge E and Gaskins, Audrey J} } @article {610376, title = {Occupational use of high-level disinfectants and fecundity among nurses}, journal = {Scand J Work Environ Health}, volume = {43}, number = {2}, year = {2017}, month = {2017 03 01}, pages = {171-180}, abstract = {Objective This study aimed to examine the relationship between occupational use of high-level disinfectants (HLD) and fecundity among female nurses. Methods Women currently employed outside the home and trying to get pregnant (N=1739) in the Nurses{\textquoteright} Health Study 3 cohort (2010-2014) were included in this analysis. Occupational exposure to HLD used to disinfect medical instruments and use of protective equipment (PE) was self-reported on the baseline questionnaire. Every six months thereafter women reported the duration of their ongoing pregnancy attempt. Multivariable accelerated failure time models were used to estimate time ratios (TR) and 95\% confidence intervals (95\% CI). Results Nurses exposed to HLD prior to and at baseline had a 26\% (95\% CI 8-47\%) and 12\% (95\% CI -2-28\%) longer median duration of pregnancy attempt compared to nurses who were never exposed. Among nurses exposed at baseline to HLD, use of PE attenuated associations with fecundity impairments. Specifically, women using 0, 1, and >=2 types of PE had 18\% (95\% CI -7-49\%), 16\% (95\% -3-39\%), and 0\% (95\% -22-28\%) longer median durations of pregnancy attempt compared to women who were never exposed. While the use of PE varied greatly by type (9\% for respiratory protection to 69\% for protective gloves), use of each PE appeared to attenuate the associations of HLD exposure with reduced fecundity. Conclusion Occupational use of HLD is associated with reduced fecundity among nurses, but use of PE appears to attenuate this risk.}, keywords = {Adult, Disinfectants, Employment, Epidemiologic Studies, Female, Fertility, Humans, Nursing Staff, Hospital, Occupational Exposure, Pregnancy, Protective Clothing, Respiratory Protective Devices, Surveys and Questionnaires}, issn = {1795-990X}, doi = {10.5271/sjweh.3623}, author = {Gaskins, Audrey J and Chavarro, Jorge E and Rich-Edwards, Janet W and Missmer, Stacey A and Laden, Francine and Henn, Scott A and Lawson, Christina C} } @article {610363, title = {Personal Care Product Use in Men and Urinary Concentrations of Select Phthalate Metabolites and Parabens: Results from the Environment And Reproductive Health (EARTH) Study}, journal = {Environ Health Perspect}, volume = {125}, number = {8}, year = {2017}, month = {2017 08 18}, pages = {087012}, abstract = {BACKGROUND: Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men{\textquoteright}s exposure is understudied. OBJECTIVES: We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men. METHODS: In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004-2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for each PCP in a weighted binary score regression and modeled the resulting composite weighted PCP use. RESULTS: Four hundred men contributed 1,037 urine samples (mean of 3/man). The largest percent increase in monoethyl phthalate (MEP) was associated with use of cologne/perfume (83\%, -value, keywords = {Adult, Cosmetics, Environmental Exposure, Hazardous Substances, Humans, Male, Parabens, Phthalic Acids}, issn = {1552-9924}, doi = {10.1289/EHP1374}, author = {Nassan, Feiby L and Brent A Coull and Gaskins, Audrey J and Michelle A. Williams and Skakkebaek, Niels E and Ford, Jennifer B and Ye, Xiaoyun and Calafat, Antonia M and Braun, Joseph M and Hauser, Russ} } @article {610367, title = {Reply to AT Wijayabahu}, journal = {Am J Clin Nutr}, volume = {106}, number = {2}, year = {2017}, month = {2017 Aug}, pages = {707}, issn = {1938-3207}, doi = {10.3945/ajcn.117.160176}, author = {Gaskins, Audrey J and Corval{\'a}n, Camila and Michels, Karin B} } @article {610368, title = {Smoking during pregnancy in relation to grandchild birth weight and BMI trajectories}, journal = {PLoS One}, volume = {12}, number = {7}, year = {2017}, month = {2017}, pages = {e0179368}, abstract = {BACKGROUND: Maternal smoking has been linked to lower birth weight and higher risk of childhood obesity. However, it is unknown whether grand-maternal smoking during pregnancy is associated with grandchildren birth weight and body mass index (BMI) trajectories. METHODS: We investigated associations of smoking during pregnancy with birth weight, risks of overweight and BMI trajectories among 46,858 mother-child dyads and 6,583 grandmother-mother-child triads of three cohort studies of related individuals. Smoking during pregnancy was reported by mothers, and anthropometric data were provided by participants in each cohort. RESULTS: Compared to grandchildren of non-smoking women, grandchildren of women who smoked more than 14 cigarettes per day throughout pregnancy were 70 g (95\% CI: 12, 129 g; P for trend = 0.01) heavier at birth, and 18\% (95\% CI: 4\%, 34\%; P for trend = 0.01) more likely to become overweight. The mean BMI of grandchildren of women who smoked during pregnancy was 0.45 kg/m2 (95\% CI: 0.14, 0.75 kg/m2; P for trend = 0.006) higher through adolescence and young adulthood than that of grandchildren of non-smoking mothers. CONCLUSIONS: Grandmothers{\textquoteright} smoking during pregnancy was associated with higher birth weight, higher risk of overweight, and higher BMI through adolescence and young adulthood.}, keywords = {Adolescent, Adult, Birth Weight, Body Mass Index, Child, Female, Grandparents, Humans, Male, Overweight, Pregnancy, Prenatal Exposure Delayed Effects, Smoking}, issn = {1932-6203}, doi = {10.1371/journal.pone.0179368}, author = {Ding, Ming and Yuan, Changzheng and Gaskins, Audrey J and Field, Alison E and Missmer, Stacey A and Michels, Karin B and Hu, Frank and Zhang, Cuilin and Matthew W. Gillman and Chavarro, Jorge} } @article {610370, title = {What Does a Single Semen Sample Tell You? Implications for Male Factor Infertility Research}, journal = {Am J Epidemiol}, volume = {186}, number = {8}, year = {2017}, month = {2017 Oct 15}, pages = {918-926}, abstract = {Semen parameters are variable within individuals, but it is unclear whether 1 semen sample could represent a man{\textquoteright}s long-term average values in epidemiologic studies. Between 2005 and 2014, a total of 329 men from a fertility clinic in Boston, Massachusetts, provided 768 semen samples as part of the Environment and Reproductive Health (EARTH) Study. Total sperm count, sperm concentration, morphology, motility, and ejaculate volume were assessed. We used linear mixed models to compare values from men{\textquoteright}s first semen samples with their long-term averages and to calculate intraclass correlation coefficients for each parameter. We calculated positive predictive values (PPVs) and negative predictive values (NPVs) by comparing agreement in classification according to World Health Organization reference limits. There were no differences in mean semen parameters between men{\textquoteright}s first samples and the remaining replicates. Intraclass correlation coefficients ranged from 0.61 for morphology to 0.75 for concentration, indicating consistently greater between-man variability than within-man variability. Nevertheless, using 1 sample alone resulted in high NPVs but low PPVs (range, 43\%-91\%). The average of 2 samples was needed to achieve high PPVs (range, 86\%-100\%) and NPVs (range, 91\%-100\%). We conclude that 1 semen sample may suffice for studies aimed at identifying average differences in semen quality between individuals. Studies aimed at classifying men based on World Health Organization reference limits may benefit from collection of 2 or more samples.}, keywords = {Adult, Humans, Infertility, Male, Linear Models, Male, Semen Analysis}, issn = {1476-6256}, doi = {10.1093/aje/kwx169}, author = {Chiu, Yu-Han and Edifor, Regina and Rosner, Bernard A and Nassan, Feiby L and Gaskins, Audrey J and M{\'\i}nguez-Alarc{\'o}n, Lidia and Williams, Paige L and Tanrikut, Cigdem and Hauser, Russ and Chavarro, Jorge E} } @article {610379, title = {Association Between Cesarean Birth and Risk of Obesity in Offspring in Childhood, Adolescence, and Early Adulthood}, journal = {JAMA Pediatr}, volume = {170}, number = {11}, year = {2016}, month = {2016 Nov 07}, pages = {e162385}, abstract = {Importance: Cesarean birth has been associated with higher risk of obesity in offspring, but previous studies have focused primarily on childhood obesity and have been hampered by limited control for confounders. Objective: To investigate the association between cesarean birth and risk of obesity in offspring. Design, Setting, and Participants: A prospective cohort study was conducted from September 1, 1996, to December 31, 2012, among participants of the Growing Up Today Study, including 22 068 offspring born to 15 271 women, followed up via questionnaire from ages 9 to 14 through ages 20 to 28 years. Data analysis was conducted from October 10, 2015, to June 14, 2016. Exposure: Birth by cesarean delivery. Main Outcomes and Measures: Risk of obesity based on International Obesity Task Force or World Health Organization body mass index cutoffs, depending on age. Secondary outcomes included risks of obesity associated with changes in mode of delivery and differences in risk between siblings whose modes of birth were discordant. Results: Of the 22 068 offspring (20 950 white; 9359 male and 12 709 female), 4921 individuals (22.3\%) were born by cesarean delivery. The cumulative risk of obesity through the end of follow-up was 13\% among all participants. The adjusted risk ratio for obesity among offspring delivered via cesarean birth vs those delivered via vaginal birth was 1.15 (95\% CI, 1.06-1.26; P = .002). This association was stronger among women without known indications for cesarean delivery (adjusted risk ratio, 1.30; 95\% CI, 1.09-1.54; P = .004). Offspring delivered via vaginal birth among women who had undergone a previous cesarean delivery had a 31\% (95\% CI, 17\%-47\%) lower risk of obesity compared with those born to women with repeated cesarean deliveries. In within-family analysis, individuals born by cesarean delivery had 64\% (8\%-148\%) higher odds of obesity than did their siblings born via vaginal delivery. Conclusions and Relevance: Cesarean birth was associated with offspring obesity after accounting for major confounding factors. Although additional research is needed to clarify the mechanisms underlying this association, clinicians and patients should weigh this risk when considering cesarean delivery in the absence of a clear indication.}, keywords = {Adolescent, Adult, Body Mass Index, Cesarean Section, Child, Cohort Studies, Delivery, Obstetric, Female, Follow-Up Studies, Humans, Male, Obesity, Pediatric Obesity, Prospective Studies, Risk Factors, Time Factors, Young Adult}, issn = {2168-6211}, doi = {10.1001/jamapediatrics.2016.2385}, author = {Yuan, Changzheng and Gaskins, Audrey J and Blaine, Arianna I and Zhang, Cuilin and Matthew W. Gillman and Missmer, Stacey A and Field, Alison E and Chavarro, Jorge E} } @article {610384, title = {Contributions of the Nurses{\textquoteright} Health Studies to Reproductive Health Research}, journal = {Am J Public Health}, volume = {106}, number = {9}, year = {2016}, month = {2016 Sep}, pages = {1669-76}, abstract = {OBJECTIVES: To review the Nurses{\textquoteright} Health Study{\textquoteright}s (NHS{\textquoteright}s) contribution to identifying risk factors and long-term health consequences of reproductive events. METHODS: We performed a narrative review of the NHS I, NHS II, NHS3, and Growing Up Today Study (GUTS) publications between 1976 and 2016. RESULTS: Collection of detailed reproductive history to identify breast cancer risk factors allowed the NHS to document an association between menstrual irregularities, a proxy for polycystic ovary syndrome (PCOS), and increased risk of diabetes and cardiovascular disease. The NHS II found that infertility associated with ovulation problems and gestational diabetes are largely preventable through diet and lifestyle modification. It also identified developmental and nutritional risk factors for pregnancy loss, endometriosis, and uterine leiomyomata. As women in NHS II age, it has become possible to address questions regarding long-term health consequences of pregnancy complications and benign gynecologic conditions on chronic disease risk. Furthermore, the NHS3 and GUTS are allowing new lines of research into human fertility, PCOS, and transgenerational effects of environmental exposures. CONCLUSIONS: The multigenerational resources of the NHSs and GUTS, including linkages of related individuals across cohorts, can improve women{\textquoteright}s health from preconception through late adulthood and onto the next generation.}, keywords = {Adult, Diet, Epidemiologic Studies, Female, Genital Diseases, Female, Humans, Life Style, Longitudinal Studies, Middle Aged, Nurses, Pregnancy, Pregnancy Complications, Prospective Studies, Reproductive Health, Risk Factors, United States, Women{\textquoteright}s Health}, issn = {1541-0048}, doi = {10.2105/AJPH.2016.303350}, author = {Chavarro, Jorge E and Rich-Edwards, Janet W and Gaskins, Audrey J and Farland, Leslie V and Terry, Kathryn L and Zhang, Cuilin and Missmer, Stacey A} } @article {610391, title = {Dairy intake in relation to in vitro fertilization outcomes among women from a fertility clinic}, journal = {Hum Reprod}, volume = {31}, number = {3}, year = {2016}, month = {2016 Mar}, pages = {563-71}, abstract = {STUDY QUESTION: Is dairy food consumption associated with live birth among women undergoing infertility treatment? SUMMARY ANSWER: There was a positive association between total dairy food consumption and live birth among women >=35 years of age. WHAT IS KNOWN ALREADY: Dairy food intake has been previously related to infertility risk and measures of fertility potential but its relation to infertility treatment outcomes are unknown. STUDY DESIGN, SIZE, DURATION: Our study population comprised a total of 232 women undergoing 353 in vitro fertilization (IVF) treatment cycles between February 2007 and May 2013, from the Environment and Reproductive Health study, an ongoing prospective cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diet was assessed before assisted reproductive technology (ART) treatment using a validated food frequency questionnaire. Study outcomes included ovarian stimulation outcomes (endometrial thickness, estradiol levels and oocyte yield), fertilization rates, embryo quality measures and clinical outcomes (implantation, clinical pregnancy and live birth rates). We used generalized linear mixed models with random intercepts to account for multiple ART cycles per woman while simultaneously adjusting for age, caloric intake, BMI, race, smoking status, infertility diagnosis, protocol type, alcohol intake and dietary patterns. MAIN RESULTS AND THE ROLE OF CHANCE: The age- and calorie-adjusted difference in live birth between women in the highest (>3.0 servings/day) and lowest (, keywords = {Adult, Dairy Products, Diet, Eating, Female, Fertilization in Vitro, Humans, Infertility, Linear Models, Pregnancy, Pregnancy Rate, Risk Factors, Treatment Outcome}, issn = {1460-2350}, doi = {10.1093/humrep/dev344}, author = {Afeiche, M C and Chiu, Y-H and Gaskins, A J and Williams, P L and Souter, I and Wright, D L and Hauser, R and Chavarro, J E} } @article {610385, title = {Dietary folate intake and modification of the association of urinary bisphenol A concentrations with in vitro fertilization outcomes among women from a fertility clinic}, journal = {Reprod Toxicol}, volume = {65}, year = {2016}, month = {2016 10}, pages = {104-112}, abstract = {Experimental data in rodents suggest that the effects of bisphenol A (BPA) on oocyte development may be modified by dietary methyl donors. Whether the same interaction exists in humans is unknown. We evaluated whether intake of methyl donors modified the associations between urinary BPA concentrations and treatment outcomes among 178 women who underwent 248 IVF cycles at a fertility center in Boston between 2007 and 2012. Participants completed a validated food frequency questionnaire and provided up to two urine samples per treatment cycle. High urinary BPA concentrations were associated with a 66\% lower probability of implantation (p=0.007) among women who consumed , keywords = {Adult, Benzhydryl Compounds, Diet, Embryo Implantation, Environmental Pollutants, Female, Fertilization in Vitro, Folic Acid, Humans, Live Birth, Phenols, Pregnancy}, issn = {1873-1708}, doi = {10.1016/j.reprotox.2016.07.012}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Gaskins, Audrey J and Chiu, Yu-Han and Irene Souter and Williams, Paige L and Calafat, Antonia M and Hauser, Russ and Chavarro, Jorge E} } @article {610381, title = {Effects of bisphenol A on male and couple reproductive health: a review}, journal = {Fertil Steril}, volume = {106}, number = {4}, year = {2016}, month = {2016 09 15}, pages = {864-70}, abstract = {Bisphenol A (BPA) is a ubiquitous environmental toxicant with endocrine-disrupting properties and is suspected to affect human reproduction. The objective of this review was to summarize the potential effects of male exposure to BPA on markers of testicular function and couple reproductive outcomes. Five epidemiologic studies on BPA and reproductive hormones all found significant associations with at least one reproductive hormone; however, no consistent relationships were observed across studies. Six epidemiologic studies evaluated the relation between BPA and semen parameters, and although the majority reported negative associations with various parameters, there were few consistent trends across studies. Finally, three epidemiologic studies examined BPA and couple reproductive outcomes, and only one found an association. Overall, the evidence supporting an association between BPA exposure and adverse male reproductive health outcomes in humans remains limited and inconclusive. Reasons for the discrepancies in results could include, but are not limited to, differences in study populations (e.g., fertile vs. subfertile men), BPA urinary concentrations (occupationally vs. nonoccupationally exposed), misclassification of BPA exposure (e.g., using one urine sample to characterize exposure vs. multiple samples), sample sizes, study design (e.g., cross-sectional vs. prospective), and residual confounding (e.g., due to diet and lifestyle factors). It is also possible that some of the statistically significant findings were due to chance alone. Clearly, further studies are needed to further clarify the role of this ubiquitous endocrine-disrupting chemical on male reproductive health.}, keywords = {Endocrine Disruptors, Environmental Exposure, Environmental Pollutants, Female, Fertility, Gonadal Steroid Hormones, Gonadotropins, Humans, Infertility, Male, Male, Pregnancy, Reproduction, Reproductive Health, Risk Assessment, Risk Factors, Spermatozoa}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2016.07.1118}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Hauser, Russ and Gaskins, Audrey J} } @article {610378, title = {Genome-wide analysis identifies 12 loci influencing human reproductive behavior}, journal = {Nat Genet}, volume = {48}, number = {12}, year = {2016}, month = {2016 12}, pages = {1462-1472}, abstract = {The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.}, keywords = {Birth Order, Female, Fertility, Genome-Wide Association Study, Humans, Maternal Age, Parity, Phenotype, Polymorphism, Single Nucleotide, Pregnancy, Quantitative Trait Loci, Reproduction, Reproductive Behavior}, issn = {1546-1718}, doi = {10.1038/ng.3698}, author = {Barban, Nicola and Jansen, Rick and de Vlaming, Ronald and Vaez, Ahmad and Mandemakers, Jornt J and Tropf, Felix C and Shen, Xia and Wilson, James F and Chasman, Daniel I and Nolte, Ilja M and Tragante, Vinicius and van der Laan, Sander W and Perry, John R B and Kong, Augustine and Ahluwalia, Tarunveer S and Albrecht, Eva and Yerges-Armstrong, Laura and Atzmon, Gil and Auro, Kirsi and Ayers, Kristin and Bakshi, Andrew and Ben-Avraham, Danny and Berger, Klaus and Bergman, Aviv and Bertram, Lars and Bielak, Lawrence F and Bjornsdottir, Gyda and Bonder, Marc Jan and Broer, Linda and Bui, Minh and Barbieri, Caterina and Cavadino, Alana and Chavarro, Jorge E and Turman, Constance and Concas, Maria Pina and Cordell, Heather J and Davies, Gail and Eibich, Peter and Nicholas Eriksson and Esko, T{\~o}nu and Eriksson, Joel and Falahi, Fahimeh and Felix, Janine F and Mark Alan Fontana and Franke, Lude and Gandin, Ilaria and Gaskins, Audrey J and Gieger, Christian and Gunderson, Erica P and Guo, Xiuqing and Hayward, Caroline and He, Chunyan and Hofer, Edith and Huang, Hongyan and Joshi, Peter K and Kanoni, Stavroula and Karlsson, Robert and Kiechl, Stefan and Kifley, Annette and Kluttig, Alexander and Kraft, Peter and Lagou, Vasiliki and Lecoeur, Cecile and Lahti, Jari and Li-Gao, Ruifang and Lind, Penelope A and Liu, Tian and Makalic, Enes and Mamasoula, Crysovalanto and Matteson, Lindsay and Mbarek, Hamdi and McArdle, Patrick F and McMahon, George and Meddens, S Fleur W and Mihailov, Evelin and Miller, Mike and Missmer, Stacey A and Monnereau, Claire and van der Most, Peter J and Myhre, Ronny and Nalls, Mike A and Nutile, Teresa and Kalafati, Ioanna Panagiota and Porcu, Eleonora and Prokopenko, Inga and Rajan, Kumar B and Janet Rich-Edwards and Cornelius A. Rietveld and Robino, Antonietta and Rose, Lynda M and Rueedi, Rico and Ryan, Kathleen A and Saba, Yasaman and Schmidt, Daniel and Smith, Jennifer A and Stolk, Lisette and Streeten, Elizabeth and T{\"o}njes, Anke and Thorleifsson, Gudmar and Ulivi, Sheila and Wedenoja, Juho and Wellmann, Juergen and Willeit, Peter and Yao, Jie and Yengo, Loic and Zhao, Jing Hua and Wei Zhao and Zhernakova, Daria V and Amin, Najaf and Andrews, Howard and Balkau, Beverley and Barzilai, Nir and Bergmann, Sven and Biino, Ginevra and Bisgaard, Hans and B{\o}nnelykke, Klaus and Boomsma, Dorret I and Buring, Julie E and Campbell, Harry and Cappellani, Stefania and Ciullo, Marina and Cox, Simon R and Cucca, Francesco and Toniolo, Daniela and George Davey-Smith and Deary, Ian J and Dedoussis, George and Deloukas, Panos and van Duijn, Cornelia M and de Geus, Eco J C and Eriksson, Johan G and Evans, Denis A and Faul, Jessica D and Sala, Cinzia Felicita and Froguel, Philippe and Gasparini, Paolo and Girotto, Giorgia and Grabe, Hans-J{\"o}rgen and Greiser, Karin Halina and Patrick J.F. Groenen and de Haan, Hugoline G and Haerting, Johannes and Tamara B. Harris and Heath, Andrew C and Heikkil{\"a}, Kauko and Hofman, Albert and Homuth, Georg and Holliday, Elizabeth G and Hopper, John and Hypp{\"o}nen, Elina and Jacobsson, Bo and Jaddoe, Vincent W V and Magnus Johannesson and Jugessur, Astanand and K{\"a}h{\"o}nen, Mika and Kajantie, Eero and Kardia, Sharon L R and Keavney, Bernard and Kolcic, Ivana and Koponen, P{\"a}ivikki and Kovacs, Peter and Kronenberg, Florian and Kutalik, Zoltan and La Bianca, Martina and Lachance, Genevieve and Iacono, William G and Lai, Sandra and Lehtim{\"a}ki, Terho and Liewald, David C and Lindgren, Cecilia M and Liu, Yongmei and Luben, Robert and Lucht, Michael and Luoto, Riitta and Magnus, Per and Patrik K.E. Magnusson and Martin, Nicholas G and McGue, Matt and McQuillan, Ruth and Sarah E. Medland and Meisinger, Christa and Mellstr{\"o}m, Dan and Metspalu, Andres and Traglia, Michela and Milani, Lili and Mitchell, Paul and Montgomery, Grant W and Mook-Kanamori, Dennis and de Mutsert, Ren{\'e}e and Nohr, Ellen A and Ohlsson, Claes and Olsen, J{\o}rn and Ong, Ken K and Paternoster, Lavinia and Pattie, Alison and Penninx, Brenda W J H and Perola, Markus and Peyser, Patricia A and Pirastu, Mario and Polasek, Ozren and Power, Chris and Kaprio, Jaakko and Raffel, Leslie J and R{\"a}ikk{\"o}nen, Katri and Raitakari, Olli and Ridker, Paul M and Ring, Susan M and Roll, Kathryn and Rudan, Igor and Ruggiero, Daniela and Rujescu, Dan and Salomaa, Veikko and Schlessinger, David and Schmidt, Helena and Schmidt, Reinhold and Schupf, Nicole and Smit, Johannes and Sorice, Rossella and Spector, Tim D and Starr, John M and St{\"o}ckl, Doris and Strauch, Konstantin and Stumvoll, Michael and Swertz, Morris A and Thorsteinsdottir, Unnur and A. Roy Thurik and Timpson, Nicholas J and Joyce Y. Tung and Uitterlinden, Andr{\'e} G and Vaccargiu, Simona and Viikari, Jorma and Vitart, Veronique and V{\"o}lzke, Henry and Vollenweider, Peter and Vuckovic, Dragana and Waage, Johannes and Wagner, Gert G and Wang, Jie Jin and Wareham, Nicholas J and Weir, David R and Willemsen, Gonneke and Willeit, Johann and Wright, Alan F and Zondervan, Krina T and Stefansson, Kari and Robert F. Krueger and James J. Lee and Daniel J. Benjamin and David Cesarini and Philipp D. Koellinger and den Hoed, Marcel and Snieder, Harold and Mills, Melinda C} } @article {610393, title = {In Reply}, journal = {Obstet Gynecol}, volume = {127}, number = {1}, year = {2016}, month = {2016 Jan}, pages = {162-3}, keywords = {Female, Humans, Time-to-Pregnancy, Weight Gain}, issn = {1873-233X}, doi = {10.1097/AOG.0000000000001221}, author = {Gaskins, Audrey J and Rich-Edwards, Janet W and Missmer, Stacey A and Rosner, Bernard and Chavarro, Jorge E} } @article {610387, title = {Intake of Fruits and Vegetables with Low-to-Moderate Pesticide Residues Is Positively Associated with Semen-Quality Parameters among Young Healthy Men}, journal = {J Nutr}, volume = {146}, number = {5}, year = {2016}, month = {2016 05}, pages = {1084-92}, abstract = {BACKGROUND: Numerous studies have shown that occupational or environmental pesticide exposure can affect male fertility. There is less evidence, however, regarding any potentially adverse effects of pesticide residues in foods on markers of male fertility potential. OBJECTIVES: We examined the relations between fruit and vegetable intake, considering pesticide residue status, and semen quality and serum concentrations of reproductive hormones in healthy young men. METHODS: The Rochester Young Men{\textquoteright}s Study is a cross-sectional study that recruited men aged 18-22 y (n = 189) in Rochester, New York. Participants completed a questionnaire, provided a semen sample, had a blood sample drawn, and underwent a physical examination at enrollment. Semen samples were analyzed for total sperm count, sperm concentration, morphology, motility, ejaculate volume, total motile count, and total normal count. Dietary intake during the previous year was assessed by a validated food-frequency questionnaire. Fruit and vegetables were categorized as having high [Pesticide Residue Burden Score (PRBS) >=4] or low-to-moderate (PRBS , keywords = {Adolescent, Adult, Cross-Sectional Studies, Diet, Diet Surveys, Environmental Exposure, Feeding Behavior, Fruit, Gonadal Steroid Hormones, Humans, Male, new york, Pesticide Residues, Semen, Semen Analysis, Sperm Count, Spermatozoa, Surveys and Questionnaires, Vegetables, Young Adult}, issn = {1541-6100}, doi = {10.3945/jn.115.226563}, author = {Chiu, Yu-Han and Gaskins, Audrey J and Williams, Paige L and Mendiola, Jaime and J{\o}rgensen, Niels and Levine, Hagai and Hauser, Russ and Swan, Shanna H and Chavarro, Jorge E} } @article {610389, title = {Maternal whole grain intake and outcomes of in~vitro fertilization}, journal = {Fertil Steril}, volume = {105}, number = {6}, year = {2016}, month = {2016 06}, pages = {1503-1510.e4}, abstract = {OBJECTIVE: To evaluate the relationship between pretreatment intake of whole grains and outcomes of IVF. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENT(S): A total of 273 women who collectively underwent 438 IVF cycles. INTERVENTION(S): Whole grain intake was assessed with a validated food frequency questionnaire at enrollment. MAIN OUTCOME MEASURE(S): Intermediate and clinical end points of IVF were abstracted from medical records. RESULT(S): Women had a median whole grain intake of 34.2~g per day (\~{}1.2 servings/day). Higher pretreatment whole grain intake was associated with higher probability of implantation and live birth. The adjusted percentage of cycles resulting in live birth for women in the highest quartile of whole grain intake (>52.4~g/day) was 53\% (95\% confidence interval [CI] 41\%, 65\%) compared with 35\% (95\% CI 25\%, 46\%) for women in the lowest quartile (, keywords = {Adult, Cohort Studies, Diet Records, Dietary Carbohydrates, Female, Fertilization in Vitro, Humans, Live Birth, Maternal Nutritional Physiological Phenomena, Pregnancy, Prospective Studies, Surveys and Questionnaires, Whole Grains}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2016.02.015}, author = {Gaskins, Audrey J and Chiu, Yu-Han and Williams, Paige L and Keller, Myra G and Thomas L Toth and Hauser, Russ and Chavarro, Jorge E} } @article {610392, title = {Parental smoking during pregnancy and the risk of gestational diabetes in the daughter}, journal = {Int J Epidemiol}, volume = {45}, number = {1}, year = {2016}, month = {2016 Feb}, pages = {160-9}, abstract = {BACKGROUND: Fetal exposure to parental smoking may have long-term impact on the development of disease in adulthood. We examined the association of parental smoking during pregnancy with risk of gestational diabetes mellitus (GDM) in the daughter. METHODS: We included 15,665 singleton pregnancies from 10,152 women in the Nurses{\textquoteright} Health Study II cohort whose mothers participated in the Nurses{\textquoteright} Mothers{\textquoteright} Cohort Study. Data on maternal and paternal smoking during pregnancy and associated covariates were recalled by the mothers. GDM diagnosis was self-reported by the daughters and was validated by medical record review in a previous study. We used log-binomial models with generalized estimating equations to estimate relative risks (RRs) and 95\% confidence intervals (CIs). RESULTS: We observed a positive association between maternal heavy smoking during pregnancy and risk of GDM in the daughter. The multivariable-adjusted RRs (95\% CIs) of GDM among women whose mothers did not smoke during pregnancy, continued smoking 1-14, 15-24, and >= 25 cigarettes/day were 1.00 (reference), 1.05 (0.81-1.35), 1.27 (0.95-1.70) and 1.98 (1.18-3.30), respectively (P for trend = 0.01). Further adjustment for the women{\textquoteright}s perinatal variables, adult-life characteristics and body mass index during various periods of life modestly attenuated the association. No association was observed between paternal smoking during the pregnancy period and risk of GDM in the daughter. CONCLUSIONS: Maternal heavy smoking (>= 25 cigarettes/day) during pregnancy was associated with higher risk of gestational diabetes in the daughter. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms.}, keywords = {Adult, Diabetes, Gestational, Female, Humans, Mothers, Multivariate Analysis, Pregnancy, Prenatal Exposure Delayed Effects, Prospective Studies, Regression Analysis, Risk Factors, Smoking, Surveys and Questionnaires, Young Adult}, issn = {1464-3685}, doi = {10.1093/ije/dyv334}, author = {Bao, Wei and Michels, Karin B and Tobias, Deirdre K and Li, Shanshan and Chavarro, Jorge E and Gaskins, Audrey J and Vaag, Allan A and Hu, Frank B and Zhang, Cuilin} } @article {610388, title = {Prepregnancy Low to Moderate Alcohol Intake Is Not Associated with Risk of Spontaneous Abortion or Stillbirth}, journal = {J Nutr}, year = {2016}, month = {2016 Mar 09}, abstract = {BACKGROUND: Numerous studies have documented the negative effects of maternal alcohol consumption during pregnancy on risk of pregnancy loss, yet whether prepregnancy alcohol intake affects the risk of spontaneous abortion is still unclear. OBJECTIVE: This study aimed to assess prepregnancy alcohol intake and risk of spontaneous abortion and stillbirth. METHODS: Our prospective cohort study included 27,580 pregnancies reported by 17,929 women in the Nurses{\textquoteright} Health Study II between 1990 and 2009. Alcohol intake was assessed in 1989 and 1991 and every 4 y thereafter with the use of a validated questionnaire. Women were classified into 5 categories of consumption: 0, 0.1-1.9, 2-4.9, 5-9.9, and >=10 g/d (1 serving = \~{}12 g). Pregnancies were self-reported, with case pregnancies lost spontaneously (spontaneous abortion after gestation of , issn = {1541-6100}, doi = {10.3945/jn.115.226423}, author = {Gaskins, Audrey J and Rich-Edwards, Janet W and Williams, Paige L and Thomas L Toth and Missmer, Stacey A and Chavarro, Jorge E} } @article {610386, title = {A prospective cohort study of endometriosis and subsequent risk of infertility}, journal = {Hum Reprod}, volume = {31}, number = {7}, year = {2016}, month = {2016 07}, pages = {1475-82}, 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 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.}, keywords = {Adult, Endometriosis, Female, Humans, Infertility, Female, Proportional Hazards Models, Prospective Studies, Risk Factors}, issn = {1460-2350}, doi = {10.1093/humrep/dew085}, author = {Prescott, J and Farland, L V and Tobias, D K and Gaskins, A J and Spiegelman, D and Chavarro, J E and Rich-Edwards, J W and Barbieri, R L and Missmer, S A} } @article {610383, title = {Serum 25-hydroxyvitamin D concentrations and treatment outcomes of women undergoing assisted reproduction}, journal = {Am J Clin Nutr}, volume = {104}, number = {3}, year = {2016}, month = {2016 Sep}, pages = {729-35}, abstract = {BACKGROUND: Vitamin D deficiency impairs fertility in animal models, but the role of vitamin D in human fertility or treatment of infertility is less clear. OBJECTIVE: We examined the association between circulating 25-hydroxyvitamin D [25(OH)D] concentrations and the outcome in women undergoing assisted reproduction technologies (ARTs). DESIGN: We randomly selected 100 women undergoing infertility treatment with ART enrolled in an ongoing prospective cohort study who underwent 168 treatment cycles. Serum 25(OH)D concentrations were measured in samples collected from women between days 3 and 9 of gonadotropin treatment. Generalized linear mixed models were used to evaluate the association of 25(OH)D concentrations with ART outcomes while adjusting for potential confounders and accounting for repeated treatment cycles per woman. RESULTS: Median (range) serum 25(OH)D concentrations were 86.5 (33.5-155.5) nmol/L. Ninety-one percent of participants consumed multivitamins. Serum 25(OH)D concentrations were positively related to fertilization rate. The adjusted fertilization rate for women in increasing quartiles of serum 25(OH)D were 0.62 (95\% CI: 0.51, 0.72), 0.53 (95\% CI: 0.43, 0.63), 0.67 (95\% CI: 0.56, 0.76), and 0.73 (95\% CI: 0.63, 0.80), respectively (P-trend = 0.03). This association persisted when analyses were restricted to women with serum 25(OH)D between 50 and 125 nmol/L when models were further adjusted for season of blood draw and when analyses were restricted to the first treatment cycle. However, 25(OH)D concentrations were unrelated to probability of pregnancy (P-trend = 0.83) or live birth after ART (P-trend = 0.47). CONCLUSION: Vitamin D may be associated with higher fertilization rates, but this apparent benefit does not translate into higher probability of pregnancy or live birth. This trial was registered at www.clinicaltrials.gov as NCT00011713.}, keywords = {25-Hydroxyvitamin D 2, Adult, Boston, Calcifediol, Cohort Studies, Confounding Factors (Epidemiology), Dietary Supplements, Family Characteristics, Female, Fertilization in Vitro, Humans, Infertility, Female, Infertility, Male, Live Birth, Male, Pregnancy, Pregnancy Rate, Prospective Studies, Sperm Injections, Intracytoplasmic, Sperm-Ovum Interactions, Vitamin D Deficiency, Vitamins}, issn = {1938-3207}, doi = {10.3945/ajcn.115.126359}, author = {Abadia, Laura and Gaskins, Audrey J and Chiu, Yu-Han and Williams, Paige L and Myra Keller and Wright, Diane L and Irene Souter and Hauser, Russ and Chavarro, Jorge E} } @article {610390, title = {Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction}, journal = {J Clin Endocrinol Metab}, volume = {101}, number = {3}, year = {2016}, month = {2016 Mar}, pages = {1082-90}, abstract = {CONTEXT: Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. OBJECTIVE: The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. SETTING: The study was conducted in a fertility center in a teaching hospital. DESIGN: We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. MAIN OUTCOME MEASURE: Live birth rates per initiated treatment cycle were measured. RESULTS: Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54\%, 35\%, 31\%, and 17\% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38\%, 42\%, 47\%, and 49\% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. CONCLUSION: Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations.}, keywords = {Benzhydryl Compounds, Cohort Studies, Diet, Female, Fertilization in Vitro, Humans, Phenols, Phytoestrogens, Pregnancy, Pregnancy Outcome, Pregnancy Rate, Prospective Studies, Reproductive Techniques, Assisted, Soy Foods}, issn = {1945-7197}, doi = {10.1210/jc.2015-3473}, author = {Chavarro, Jorge E and M{\'\i}nguez-Alarc{\'o}n, Lidia and Chiu, Yu-Han and Gaskins, Audrey J and Irene Souter and Williams, Paige L and Calafat, Antonia M and Hauser, Russ} } @article {610395, title = {Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study}, journal = {Environ Health Perspect}, volume = {124}, number = {6}, year = {2016}, month = {2016 06}, pages = {831-9}, abstract = {BACKGROUND: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. OBJECTIVE: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). METHODS: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004-2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. RESULTS: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95\% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were -0.19 (-0.29, -0.08) and -0.19 (-0.28, -0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. CONCLUSIONS: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy, and live birth following ART. CITATION: Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL, for the EARTH Study Team. 2016. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect 124:831-839; http://dx.doi.org/10.1289/ehp.1509760.}, keywords = {Adult, Environmental Pollutants, Female, Fertilization in Vitro, Humans, Maternal Exposure, Phthalic Acids, Pregnancy, Pregnancy Outcome, Reproduction, Reproductive Health}, issn = {1552-9924}, doi = {10.1289/ehp.1509760}, author = {Hauser, Russ and Gaskins, Audrey J and Irene Souter and Smith, Kristen W and Dodge, Laura E and Ehrlich, Shelley and John D Meeker and Calafat, Antonia M and Williams, Paige L} } @article {610394, title = {Urinary phthalate metabolites and ovarian reserve among women seeking infertility care}, journal = {Hum Reprod}, volume = {31}, number = {1}, year = {2016}, month = {2016 Jan}, pages = {75-83}, abstract = {STUDY QUESTION: Are urinary phthalate metabolites associated with reduced antral follicle growth among women in an infertility setting? SUMMARY ANSWER: Higher urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites were associated with significant decreases in antral follicle count (AFC) among women seeking infertility care. WHAT IS KNOWN ALREADY: Experimental animal studies show that DEHP accelerates primordial follicle recruitment and inhibits antral follicle growth. Whether phthalates also reduce the growing antral follicle pool in humans remains unknown. STUDY DESIGN, SIZE, DURATION: We examined the association between urinary phthalate metabolites and AFC using prospective data from 215 females recruited between 2004 and 2012 in the Environment and Reproductive Health (EARTH) study. PARTICIPANTS/MATERIALS, SETTING, METHODS: We quantified the urinary concentrations of 11 phthalate metabolites. We estimated the geometric mean for all urine samples provided prior to unstimulated day 3 AFC assessment for each woman. We evaluated the association of AFC with ∑DEHP (molar sum of four DEHP metabolites) and individual phthalate metabolites using Poisson regression, adjusting for age, BMI and smoking. MAIN RESULTS AND THE ROLE OF CHANCE: We observed significant decreases in mean AFC for all higher quartiles of ∑DEHP as compared with the lowest quartile. Compared with women in the first quartile of ∑DEHP, women in the second, third and fourth quartiles had a -24\% (95\% confidence interval (CI): -32\%, -16\%), -19\% (95\% CI: -27\%, -9\%), and -14\% (95\% CI: -23\%, -5\%) decrease in mean AFC. The absolute mean AFC in the first quartile was 14.2 follicles (95\% CI: 13.2, 15.2) compared with 10.7 follicles (95\% CI: 9.9, 11.6) in the second quartile. We observed similar trends among the four individual DEHP metabolites. There was no consistent change in AFC among the remaining phthalate metabolite concentrations evaluated. LIMITATIONS, REASONS FOR CAUTION: We demonstrated a negative association between DEHP and a well-established marker of ovarian reserve among a subfertile population. However these findings may not be generalizable to women without fertility concerns, and we cannot rule out co-exposure to other chemicals. WIDER IMPLICATIONS OF THE FINDINGS: Environmental chemicals that inhibit the size of the growing antral follicle pool can impair fertility and reduce fecundity. This study suggests evidence in need of further investigation on the impact of phthalates on the human oocyte and follicular development. STUDY FUNDING/COMPETING INTERESTS: Work supported by grants ES009718, ES022955, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32 DK007703-16 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). C.M. was supported by a post-doctoral training award from the Canadian Institutes of Health Research. There are no competing interests to declare.}, keywords = {Adult, Female, Humans, Infertility, Female, Ovarian Follicle, Ovarian Reserve, Phthalic Acids}, issn = {1460-2350}, doi = {10.1093/humrep/dev292}, author = {Carmen Messerlian and Irene Souter and Gaskins, Audrey J and Williams, Paige L and Ford, Jennifer B and Chiu, Yu-Han and Calafat, Antonia M and Hauser, Russ} } @article {610397, title = {Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies}, journal = {Am J Clin Nutr}, volume = {102}, number = {4}, year = {2015}, month = {2015 Oct}, pages = {943-50}, abstract = {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 (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 (, keywords = {Adult, Body Mass Index, Endpoint Determination, Female, Folic Acid, Gonadotropins, Humans, Infertility, Live Birth, Nutrition Assessment, Pregnancy, Prospective Studies, Reproductive Techniques, Assisted, Surveys and Questionnaires, Treatment Outcome, Vitamin B 12}, issn = {1938-3207}, doi = {10.3945/ajcn.115.112185}, author = {Gaskins, Audrey J and Chiu, Yu-Han and Williams, Paige L and Ford, Jennifer B and Thomas L Toth and Hauser, Russ and Chavarro, Jorge E} } @article {610398, title = {Association of Fecundity With Changes in Adult Female Weight}, journal = {Obstet Gynecol}, volume = {126}, number = {4}, year = {2015}, month = {2015 Oct}, pages = {850-8}, abstract = {OBJECTIVE: To evaluate whether weight change since age 18 years, current body mass index (BMI), and BMI at age 18 years are associated with fecundity. METHODS: Our study included 1,950 women in the Nurses{\textquoteright} Health Study 3 (2010-2014), a prospective cohort study, currently attempting pregnancy. Height, current weight, and weight at age 18 years were self-reported on the baseline questionnaire. Every 3-6 months thereafter, women reported the current duration of their pregnancy attempt. Multivariable-accelerated failure time models were used to estimate the time ratios and 95\% confidence intervals (CIs). RESULTS: For every 5-kg increase in body weight from age 18 years, current duration of pregnancy attempt increased by 5\% (95\% CI 3-7\%). Compared with women who maintained weight, the adjusted median current duration was 0.5 months shorter in those who lost weight, 0.3 months longer for those who gained 4-9.9 kg and 10-19.9 kg, and 1.4 months longer for those who gained 20 kg or more (P trend <=.001). The adjusted time ratio (95\% CI) for a 5-kg/m increase in current BMI was 1.08 (1.04-1.12). After multivariable adjustment (including adjustment for current BMI), being underweight at age 18 years (BMI less than 18.5) was associated with a longer current duration of pregnancy attempt compared with normal-weight women (time ratio 1.25, 95\% CI 1.07-1.47); however, being overweight or obese at age 18 years was not associated with fecundity. CONCLUSION: Gaining weight in adulthood, being overweight or obese in adulthood, and being underweight at age 18 years were associated with a modest reduction in fecundity. LEVEL OF EVIDENCE: II.}, keywords = {Adult, Body Mass Index, Female, Humans, Infertility, Female, Obesity, Retrospective Studies, Time-to-Pregnancy, Weight Gain}, issn = {1873-233X}, doi = {10.1097/AOG.0000000000001030}, author = {Gaskins, Audrey J and Rich-Edwards, Janet W and Missmer, Stacey A and Rosner, Bernard and Chavarro, Jorge E} } @article {610399, title = {Dynamic antim{\"u}llerian hormone levels during controlled ovarian hyperstimulation predict in vitro fertilization response and pregnancy outcomes}, journal = {Fertil Steril}, volume = {104}, number = {5}, year = {2015}, month = {2015 Nov}, pages = {1153-61.e1-7}, abstract = {OBJECTIVE: To evaluate the patterns of change in serum antim{\"u}llerian hormone (AMH) during controlled ovarian hyperstimulation (COH) and their relation to concurrent response and in vitro fertilization (IVF) pregnancy outcomes. DESIGN: Prospective cohort study. SETTING: Academic medical center. PATIENT(S): A total of 113 consecutive fresh IVF embryo transfer cycles from September 1, 2012 through January 1, 2013. INTERVENTION(S): Serial serum AMH measurements were analyzed on each day that serum estradiol (E2) was drawn during COH. MAIN OUTCOME MEASURE(S): Relationship between the rate of COH AMH change [Δ ng/mL per day] (stratified into tertiles), and ovarian response, and pregnancy outcomes. RESULT(S): During COH, AMH declined. Age and ovarian reserve testing were associated with the rate of AMH decline (RAD). Women with intermediate and minimal RAD had statistically significantly fewer follicles >= 12 mm, lower peak serum E2, fewer oocytes, and inferior early embryo development compared with women with the greatest RAD. Compared with patients with the lowest RAD, clinical pregnancy was more likely in patients with the greatest RAD in the total population (adjusted odds ratio 3.51; 95\% confidence interval, 1.03, 11.94) and among patients older than 35 years (adjusted odds ratio 6.95; 95\% confidence interval, 1.09, 44.1). CONCLUSION(S): The rate of COH AMH decline was associated with ovarian reserve testing, oocyte yield, embryo progression, and clinical pregnancy rates, particularly in women older than 35 years. These results suggest that dynamic AMH levels may provide a novel intracycle approach to predict response and treatment outcomes after IVF.}, keywords = {Academic Medical Centers, Adult, Anti-Mullerian Hormone, Biomarkers, Chi-Square Distribution, Embryo Transfer, Estradiol, Female, Fertilization in Vitro, Humans, Infertility, Logistic Models, Multivariate Analysis, Odds Ratio, Oocyte Retrieval, Ovarian Reserve, Ovulation Induction, Predictive Value of Tests, Pregnancy, Pregnancy Outcome, Prospective Studies, Risk Factors, Time Factors, Treatment Outcome}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2015.07.1161}, author = {Styer, Aaron K and Gaskins, Audrey J and Brady, Paula C and Sluss, Patrick M and Chavarro, Jorge E and Hauser, Russ B and Thomas L Toth} } @article {610404, title = {Fruit and vegetable intake and their pesticide residues in relation to semen quality among men from a fertility clinic}, journal = {Hum Reprod}, volume = {30}, number = {6}, year = {2015}, month = {2015 Jun}, pages = {1342-51}, abstract = {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 (, keywords = {Adult, Cohort Studies, Diet, Environmental Exposure, Fruit, Humans, Male, Middle Aged, Pesticide Residues, Semen Analysis, Vegetables}, issn = {1460-2350}, doi = {10.1093/humrep/dev064}, author = {Chiu, Y H and Afeiche, M C and Gaskins, A J and Williams, P L and Petrozza, J C and Tanrikut, C and Hauser, R and Chavarro, J E} } @article {610405, title = {History of infertility and risk of type 2 diabetes mellitus: a prospective cohort study}, journal = {Diabetologia}, volume = {58}, number = {4}, year = {2015}, month = {2015 Apr}, pages = {707-15}, abstract = {AIMS/HYPOTHESIS: We sought to evaluate the relationship between delayed conception and type 2 diabetes risk, given that there are plausible underlying mechanisms linking the two, including inflammation and insulin resistance. METHODS: Participants of the Nurses{\textquoteright} Health Study II prospective cohort were included if they were free of chronic disease (cardiovascular disease, type 2 diabetes, cancer) at baseline. Biennial questionnaires updated information on infertility status (>12 months attempted pregnancy), lifestyle characteristics and several health-related outcomes. Self-reported cases of diabetes were confirmed using a follow-up questionnaire. Multivariable Cox proportional hazards models were used to compute the HRs and 95\% CIs. RESULTS: Incident type 2 diabetes occurred in 5,993 of the 112,106 participants over 24 years of follow-up (1989-2013). A history of infertility was reported in 27,774 (24.8\%) women and was associated with a 20\% greater risk of developing diabetes, compared with those never reporting infertility (HR 1.20 [95\% CI 1.14, 1.28]), after adjusting for age, lifestyle factors, marital status, oral contraceptive use, family history of diabetes and BMI. Compared with women without a history of infertility, the causes of infertility associated with a higher diabetes risk were ovulation disorders (HR 1.43 [95\% CI 1.29, 1.58]) and tubal factor (HR 1.34 [95\% CI 1.13, 1.58]). Cervical factor (HR 1.06 [95\% CI 0.81, 1.40]) and endometriosis (HR 1.06 [95\% CI 0.89, 1.27]) were not associated, while male factor infertility was associated with a modestly higher diabetes risk (HR 1.15 [95\% CI 1.00, 1.33]). CONCLUSIONS/INTERPRETATION: These novel findings suggest a history of infertility, particularly that related to ovulation disorders and tubal blockage, is significantly associated with a higher risk of type 2 diabetes.}, keywords = {Adult, Diabetes Mellitus, Type 2, Female, Fertility, Health Surveys, Humans, Incidence, Infertility, Female, Infertility, Male, Longitudinal Studies, Male, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Risk Factors, Surveys and Questionnaires, Time Factors, United States, Young Adult}, issn = {1432-0428}, doi = {10.1007/s00125-015-3493-z}, author = {Tobias, Deirdre K and Gaskins, Audrey J and Missmer, Stacey A and Hu, Frank B and Manson, Joann E and Buck Louis, Germaine M and Zhang, Cuilin and Chavarro, Jorge E} } @article {610402, title = {Men{\textquoteright}s meat intake and treatment outcomes among couples undergoing assisted reproduction}, journal = {Fertil Steril}, volume = {104}, number = {4}, year = {2015}, month = {2015 Oct}, pages = {972-979}, abstract = {OBJECTIVE: To study the relationship between men{\textquoteright}s meat intake and clinical outcomes in couples undergoing infertility treatment with the use of assisted reproductive technology (ART). DESIGN: Prospective cohort study. SETTING: Fertility center. PATIENT(S): A total of 141 men whose female partners underwent 246 ART cycles from 2007 to 2014. INTERVENTION(S): None. Total and specific types of meat intake were estimated from dietary questionnaires. MAIN OUTCOME MEASURE(S): Fertilization, implantation, clinical pregnancy, and live-birth rates per initiated cycle. Mixed-effects models account for multiple IVF cycles per woman. RESULT(S): There was a positive association between poultry intake and fertilization rate, with a 13\% higher fertilization rate among men in the highest quartile of poultry intake compared with those in the lowest quartile (78\% vs. 65\%). Processed meat intake was inversely related to fertilization rate in conventional IVF cycles but not in IVF cycles using intracytoplasmic sperm injection. The adjusted fertilization rates for men in increasing quartiles of processed meat intake were 82\%, 67\%, 70\%, and 54\% in conventional IVF cycles. Men{\textquoteright}s total meat intake, including intake of specific types of meat, was not associated with implantation, clinical pregnancy, or live-birth rates. CONCLUSION(S): Poultry intake was positively associated with fertilization rates, whereas processed meat intake was negatively associated with fertilization rates among couples undergoing conventional IVF. This, however, did not translate into associations with clinical pregnancy or live-birth rates.}, keywords = {Adolescent, Adult, Animals, Diet Surveys, Eating, Family Characteristics, Feeding Behavior, Female, Food Handling, Humans, Infertility, Male, Meat, Middle Aged, Paternal Exposure, Poultry, Pregnancy, Reproductive Techniques, Assisted, Treatment Outcome, Young Adult}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2015.06.037}, author = {Xia, Wei and Chiu, Yu-Han and Williams, Paige L and Gaskins, Audrey J and Thomas L Toth and Tanrikut, Cigdem and Hauser, Russ and Chavarro, Jorge E} } @article {610421, title = {Physical activity and television watching in relation to semen quality in young men}, journal = {Br J Sports Med}, volume = {49}, number = {4}, year = {2015}, month = {2015 Feb}, pages = {265-70}, abstract = {BACKGROUND: Semen quality appears to have declined over the past decades but reasons for this decline are unresolved. The concurrent increase in sedentary behaviour may be a contributing factor. The objective of this study was to evaluate the relationship of physical activity and television (TV) watching with sperm parameters in a population of young, healthy men. METHODS: Men aged 18-22 years (n=189) from the Rochester Young Men{\textquoteright}s Study (2009-2010) participated in this analysis. Physical activity (h/week of moderate and vigorous exercise) and TV watching (h/week of TV, video or DVD watching) over the past 3 months were assessed via questionnaire. Semen quality was assessed by sperm concentration, motility, morphology and total sperm count. RESULTS: Sperm concentration and total sperm count were directly related to physical activity after multivariable adjustment (p-trend=0.01 and 0.04); men in the highest quartile of moderate-to-vigorous activity (>=15 h/week) had 73\% (95\% CI 15\% to 160\%) higher sperm concentration than men in the lowest quartile (20 h/week) had 44\% (95\% CI 15 to 63\%) lower sperm concentration than men in the lowest quartile (0 h/week). These measures of physical and leisure time activities were not significantly associated with sperm motility or morphology. CONCLUSIONS: In this population of healthy men, higher moderate-to-vigorous activity and less TV watching were significantly associated with higher total sperm count and sperm concentration.}, keywords = {Adolescent, Cross-Sectional Studies, Exercise, Humans, Leisure Activities, Male, Sedentary Lifestyle, Semen Analysis, Specimen Handling, Sperm Count, Sperm Motility, Television, Young Adult}, issn = {1473-0480}, doi = {10.1136/bjsports-2012-091644}, author = {Gaskins, Audrey Jane and Mendiola, Jaime and Afeiche, Myriam and J{\o}rgensen, Niels and Swan, Shanna H and Chavarro, Jorge E} } @article {610396, title = {Prepregnancy Nutrition and Early Pregnancy Outcomes}, journal = {Curr Nutr Rep}, volume = {4}, number = {3}, year = {2015}, month = {2015 Sep}, pages = {265-272}, abstract = {Implantation failure and pregnancy loss are estimated to affect up to 75\% of fertilized ova; however as of yet there is limited empirical evidence, particularly at the population level, for understanding the environmental determinants of these losses. The purpose of this review is to summarize the current knowledge on prepregnancy nutrition and early pregnancy outcomes with particular focus on the outcome of spontaneous abortion among pregnancies conceived naturally and early pregnancy end points among pregnancies conceived through fertilization. To date, there is limited evidence to support associations of prepregnancy vitamin D and caffeine intake with pregnancy loss. There is suggestive data supporting a link between a healthy diet and lower risk of pregnancy loss. High folate and minimal to no alcohol intake prior to conception have the most consistent evidence supporting an association with lower risk of pregnancy loss.}, issn = {2161-3311}, doi = {10.1007/s13668-015-0127-5}, author = {Gaskins, Audrey J and Thomas L Toth and Chavarro, Jorge E} } @article {610403, title = {Reply: Pesticide residues and semen quality}, journal = {Hum Reprod}, volume = {30}, number = {9}, year = {2015}, month = {2015 Sep}, pages = {2241-2}, keywords = {Diet, Environmental Exposure, Fruit, Humans, Male, Pesticide Residues, Semen Analysis, Vegetables}, issn = {1460-2350}, doi = {10.1093/humrep/dev165}, author = {Chiu, Y H and Afeiche, M C and Gaskins, A J and Williams, P L and Petrozza, J C and Tanrikut, C and Hauser, R and Chavarro, J E} } @article {610406, title = {Soy food intake and treatment outcomes of women undergoing assisted reproductive technology}, journal = {Fertil Steril}, volume = {103}, number = {3}, year = {2015}, month = {2015 Mar}, pages = {749-55.e2}, abstract = {OBJECTIVE: To study the relation of dietary phytoestrogens intake and clinical outcomes of women undergoing infertility treatment with the use of assisted reproductive technology (ART). DESIGN: Prospective cohort study. SETTING: Fertility center. PATIENT(S): A total of 315 women who collectively underwent 520 ART cycles from 2007 to~2013. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, and live birth rates per initiated cycle. RESULT(S): Soy isoflavones intake was positively related to live birth rates in ART. Compared with women who did not consume soy isoflavones, the multivariable-adjusted odds ratios of live birth (95\% confidence interval) for women in increasing categories of soy isoflavones intake were 1.32 (0.76-2.27) for women consuming 0.54-2.63~mg/d, 1.87 (1.12-3.14) for women consuming 2.64-7.55~mg/d, and 1.77 (1.03-3.03) for women consuming 7.56-27.89~mg/d. CONCLUSION(S): Dietary soy intake was positively related to the probability of having a live birth during infertility treatment with ART.}, keywords = {Adolescent, Adult, Cohort Studies, Eating, Female, Humans, Infertility, Male, Maternal Nutritional Physiological Phenomena, Middle Aged, Pregnancy, Pregnancy Outcome, Reproductive Techniques, Assisted, Soy Foods, Treatment Outcome, Young Adult}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2014.12.104}, author = {Vanegas, Jose C and Afeiche, Myriam C and Gaskins, Audrey J and M{\'\i}nguez-Alarc{\'o}n, Lidia and Williams, Paige L and Wright, Diane L and Thomas L Toth and Hauser, Russ and Chavarro, Jorge E} } @article {610401, title = {Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women from a fertility clinic}, journal = {Hum Reprod}, volume = {30}, number = {9}, year = {2015}, month = {2015 Sep}, pages = {2120-8}, abstract = {STUDY QUESTION: Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center? SUMMARY ANSWER: Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic. WHAT IS KNOWN ALREADY: Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal. STUDY DESIGN, SIZE AND DURATION: This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis. MAIN RESULTS AND THE ROLE OF CHANCE: The specific gravity-adjusted geometric mean of BPA was 1.87 {\textmu}g/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (, keywords = {Adult, Benzhydryl Compounds, Estrogens, Non-Steroidal, Female, Fertilization in Vitro, Humans, Infertility, Female, Phenols, Pregnancy, Pregnancy Outcome, Prospective Studies}, issn = {1460-2350}, doi = {10.1093/humrep/dev183}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Gaskins, Audrey J and Chiu, Yu-Han and Williams, Paige L and Ehrlich, Shelley and Chavarro, Jorge E and Petrozza, John C and Ford, Jennifer B and Calafat, Antonia M and Hauser, Russ} } @article {610400, title = {Work schedule and physical factors in relation to fecundity in nurses}, journal = {Occup Environ Med}, volume = {72}, number = {11}, year = {2015}, month = {2015 Nov}, pages = {777-83}, abstract = {OBJECTIVES: To evaluate the association of work schedule and physical factors with fecundity. METHODS: Women currently employed outside the home and trying to get pregnant (n=1739) in the Nurses{\textquoteright} Health Study 3 cohort (2010-2014) were included in this analysis. Work schedule and physical labour were self-reported on the baseline questionnaire, and every 6 months thereafter the women reported the duration of their ongoing pregnancy attempt. Multivariable accelerated failure time models were used to estimate time ratios (TR) and 95\% CIs. RESULTS: Among the 1739 women (median age=33 years, 93\% Caucasian) the estimated proportions of women not pregnant after 12 and 24 months were 16\% and 5\%, respectively. None of the various shift work patterns were associated with duration of pregnancy attempt (as a surrogate for fecundity). However, women working >40 h/week had a 20\% (95\% CI 7 to 35\%) longer median duration of pregnancy attempt compared to women working 21-40 h/week (p-trend=0.005). Women whose work entailed heavy lifting or moving (ie, 25+ pounds) >15 times/day also had a longer median duration of pregnancy attempt (adjusted TR=1.49; 95\% CI 1.20 to 1.85) compared to women who never lifted or moved heavy loads (p-trend=0.002). The association between heavy moving and lifting and duration of pregnancy attempt was more pronounced among overweight or obese women (body mass index, BMI, keywords = {Adult, Body Mass Index, Female, Fertility, Humans, Infertility, Female, Lifting, Nurses, Obesity, Occupational Exposure, Pregnancy, Surveys and Questionnaires, Work, Work Schedule Tolerance}, issn = {1470-7926}, doi = {10.1136/oemed-2015-103026}, author = {Gaskins, Audrey J and Rich-Edwards, Janet W and Lawson, Christina C and Schernhammer, Eva S and Missmer, Stacey A and Chavarro, Jorge E} } @article {610413, title = {Assessment of anovulation in eumenorrheic women: comparison of ovulation detection algorithms}, journal = {Fertil Steril}, volume = {102}, number = {2}, year = {2014}, month = {2014 Aug}, pages = {511-518.e2}, abstract = {OBJECTIVE: To compare previously used algorithms to identify anovulatory menstrual cycles in women self-reporting regular menses. DESIGN: Prospective cohort study. SETTING: Western New York. PATIENT(S): Two hundred fifty-nine healthy, regularly menstruating women followed for one (n=9) or two (n=250) menstrual cycles (2005-2007). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of sporadic anovulatory cycles identified using 11 previously defined algorithms that use E2, P, and LH concentrations. RESULT(S): Algorithms based on serum LH, E2, and P levels detected a prevalence of anovulation across the study period of 5.5\%-12.8\% (concordant classification for 91.7\%-97.4\% of cycles). The prevalence of anovulatory cycles varied from 3.4\% to 18.6\% using algorithms based on urinary LH alone or with the primary E2 metabolite, estrone-3-glucuronide, levels. CONCLUSION(S): The prevalence of anovulatory cycles among healthy women varied by algorithm. Mid-cycle LH surge urine-based algorithms used in over-the-counter fertility monitors tended to classify a higher proportion of anovulatory cycles compared with luteal-phase P serum-based algorithms. Our study demonstrates that algorithms based on the LH surge, or in conjunction with estrone-3-glucuronide, potentially estimate a higher percentage of anovulatory episodes. Addition of measurements of postovulatory serum P or urine pregnanediol may aid in detecting ovulation.}, keywords = {Adult, Algorithms, Anovulation, Biomarkers, Estradiol, Female, Healthy Volunteers, Humans, Luteinizing Hormone, Menstrual Cycle, new york, Ovulation, Ovulation Detection, Predictive Value of Tests, Prevalence, Progesterone, Prospective Studies, Urinalysis, Young Adult}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2014.04.035}, author = {Lynch, Kristine E and Mumford, Sunni L and Schliep, Karen C and Whitcomb, Brian W and Zarek, Shvetha M and Pollack, Anna Z and Bertone-Johnson, Elizabeth R and Danaher, Michelle and Wactawski-Wende, Jean and Gaskins, Audrey J and Schisterman, Enrique F} } @article {610417, title = {Dairy intake and semen quality among men attending a fertility clinic}, journal = {Fertil Steril}, volume = {101}, number = {5}, year = {2014}, month = {2014 May}, pages = {1280-7}, abstract = {OBJECTIVE: To examine the relationship between dairy food intake and semen parameters. DESIGN: Longitudinal study. SETTING: Academic medical center fertility clinic. PATIENT(S): One hundred fifty-five men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Total sperm count, sperm concentration, progressive motility, morphology, and semen volume. RESULT(S): Low-fat dairy intake was positively related to sperm concentration and progressive motility. On average, men in the highest quartile of intake (1.22-3.54 servings/d) had 33\% (95\% confidence interval [CI] 1, 55) higher sperm concentration and 9.3 percentage units (95\% CI 1.4, 17.2) higher sperm motility than men in the lowest quartile of intake (<=0.28 servings/d). These associations were primarily explained by intake of low-fat milk. The corresponding results for low-fat milk were 30\% (95\% CI 1, 51) higher sperm concentration and 8.7 percentage units (95\% CI 3.0, 14.4) higher sperm motility. Cheese intake was associated with lower sperm concentration among ever-smokers. In this group, men in the highest tertile of intake (0.82-2.43 servings/d) had 53.2\% (95\% CI 9.7, 75.7) lower sperm concentration than men in the lowest tertile of cheese intake (, keywords = {Academic Medical Centers, Adult, Dairy Products, Diet, Fat-Restricted, Dietary Fats, Humans, Infertility, Male, Longitudinal Studies, Male, Outpatient Clinics, Hospital, Prospective Studies, Semen Analysis, Sperm Count, Sperm Motility}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2014.02.003}, author = {Afeiche, Myriam C and Bridges, Naima D and Williams, Paige L and Gaskins, Audrey J and Tanrikut, Cigdem and Petrozza, John C and Hauser, Russ and Chavarro, Jorge E} } @article {610409, title = {Dietary folate and reproductive success among women undergoing assisted reproduction}, journal = {Obstet Gynecol}, volume = {124}, number = {4}, year = {2014}, month = {2014 Oct}, pages = {801-9}, abstract = {OBJECTIVE: To prospectively evaluate the associations of folate with assisted reproductive technology outcomes within a population in the United States. METHODS: This analysis included women (n=232) in a prospective cohort study at the Massachusetts General Hospital Fertility Center. Diet was assessed before assisted reproductive technology treatment using a validated food frequency questionnaire. Intermediate and clinical endpoints of assisted reproductive technology were abstracted from medical records. Generalized linear mixed models with random intercepts to account for multiple cycles per woman were used to evaluate the association of folate intake with assisted reproductive technology outcomes adjusting for calorie intake, age, body mass index, race, smoking status, infertility diagnosis, and protocol type. RESULTS: Among the 232 women (median age 35.2 years, median folate intake 1,778 micrograms/day), higher folate intake was associated with higher rates of implantation, clinical pregnancy, and live birth. The adjusted percentage (95\% confidence interval [CI]) of initiated assisted reproductive technology cycles resulting in a live birth for women in increasing quartiles of folate intake were 30\% (95\% CI 21-42\%), 47\% (95\% CI 35-59\%), 42\% (95\% CI 30-35\%) and 56\% (95\% CI 43-67\%) (P for trend=0.01). Live birth rates were 20\% (95\% CI 8-31\%) higher among women in the highest quartile of supplemental folate intake (more than 800 micrograms/day) than among women in the lowest quartile (less than 400 micrograms/day). Higher supplemental folate intake was associated with higher fertilization rates and lower cycle failure rates before embryo transfer (P for trend=0.03 and 0.02). CONCLUSION: Higher intake of supplemental folate was associated with higher live birth rates after assisted reproductive technology treatment. LEVEL OF EVIDENCE: : II.}, keywords = {Adult, Cohort Studies, Confidence Intervals, Dietary Supplements, Dose-Response Relationship, Drug, Drug Administration Schedule, Embryo Transfer, Female, Fertilization in Vitro, Folic Acid, Humans, Linear Models, Live Birth, Pregnancy, Pregnancy Rate, Prospective Studies, Reference Values, Reproductive Techniques, Assisted, Treatment Outcome, United States}, issn = {1873-233X}, doi = {10.1097/AOG.0000000000000477}, author = {Gaskins, Audrey J and Afeiche, Myriam C and Wright, Diane L and Thomas L Toth and Williams, Paige L and Matthew W. Gillman and Hauser, Russ and Chavarro, Jorge E} } @article {610412, title = {Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth}, journal = {Obstet Gynecol}, volume = {124}, number = {1}, year = {2014}, month = {2014 Jul}, pages = {23-31}, abstract = {OBJECTIVE: To evaluate prospectively the relationship between prepregnancy folate intake and risk of spontaneous abortion and stillbirth. METHODS: Women in the Nurses{\textquoteright} Health Study II who self-reported a pregnancy between 1992 and 2009 were included in this analysis. Dietary folate and supplement use was assessed every 4 years, starting in 1991, by a food frequency questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously (spontaneous abortion less than 20 weeks of gestation and stillbirth 20+ weeks of gestation) and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. RESULTS: Among the 11,072 women, 15,950 pregnancies were reported of which 2,756 (17.3\%) ended in spontaneous abortion and 120 (0.8\%) ended in stillbirth. Compared with women in the lowest quintile of prepregnancy folate intake (less than 285 micrograms/d), those in the highest quintile (greater than 851 micrograms/d) had a relative risk of spontaneous abortion of 0.91 (95\% confidence interval [CI] 0.82-1.02) after multivariable adjustment (P trend=.04). This association was primarily attributable to intake of folate from supplements. Compared with women without supplemental folate intake (0 micrograms/d), those in the highest category (greater than 730 micrograms/d) had a relative risk of spontaneous abortion of 0.80 (95\% CI 0.71-0.90) after multivariable adjustment (P trend , keywords = {Abortion, Spontaneous, Adult, Cohort Studies, Diet, Dietary Supplements, Female, Folic Acid, Humans, Maternal Nutritional Physiological Phenomena, Preconception Care, Pregnancy, Prospective Studies, Risk Factors, Stillbirth, Surveys and Questionnaires, United States, Women{\textquoteright}s Health, Young Adult}, issn = {1873-233X}, doi = {10.1097/AOG.0000000000000343}, author = {Gaskins, Audrey J and Rich-Edwards, Janet W and Hauser, Russ and Williams, Paige L and Matthew W. Gillman and Ginsburg, Elizabeth S and Missmer, Stacey A and Chavarro, Jorge E} } @article {610416, title = {Meat intake and reproductive parameters among young men}, journal = {Epidemiology}, volume = {25}, number = {3}, year = {2014}, month = {2014 May}, pages = {323-30}, abstract = {BACKGROUND: In the United States, anabolic sex steroids are administered to cattle for growth promotion. There is concern regarding the reproductive consequences of this practice in men who eat beef. We investigated whether meat consumption was associated with semen quality parameters and reproductive hormone levels in young men. METHODS: Semen samples were obtained from 189 men aged 18-22 years. Diet was assessed with a previously validated food frequency questionnaire. We used linear regression to analyze the cross-sectional associations of meat intake with semen quality parameters and reproductive hormones while adjusting for potential confounders. RESULTS: There was an inverse relation between processed red meat intake and total sperm count. The adjusted relative differences in total sperm counts for men in increasing quartiles of processed meat intake were 0 (ref), -3 (95\% confidence interval = -67 to 37), -14 (-82 to 28), and -78 (-202 to -5) million (test for trend, P = 0.01). This association was strongest among men with abstinence time less than 2 days and was driven by a strong inverse relation between processed red meat intake and ejaculate volume (test for trend, P = 0.003). CONCLUSIONS: In our population of young men, processed meat intake was associated with lower total sperm count. We cannot distinguish whether this association is because of residual confounding by abstinence time or represents a true biological effect.}, keywords = {Adolescent, Analysis of Variance, Androstanes, Animals, Cattle, Confidence Intervals, Cross-Sectional Studies, Feeding Behavior, Humans, Incidence, Infertility, Male, Linear Models, Male, Meat Products, Nutrition Assessment, Reproduction, Risk Assessment, Semen Analysis, Sperm Count, Sperm Motility, Surveys and Questionnaires, Testosterone, United States, Young Adult}, issn = {1531-5487}, doi = {10.1097/EDE.0000000000000092}, author = {Afeiche, Myriam C and Williams, Paige L and Gaskins, Audrey J and Mendiola, Jaime and J{\o}rgensen, Niels and Swan, Shanna H and Chavarro, Jorge E} } @article {610410, title = {Paternal physical and sedentary activities in relation to semen quality and reproductive outcomes among couples from a fertility center}, journal = {Hum Reprod}, volume = {29}, number = {11}, year = {2014}, month = {2014 Nov}, pages = {2575-82}, abstract = {STUDY QUESTION: Is paternal physical activity associated with semen quality parameters and with outcomes of infertility treatment? SUMMARY ANSWER: Among men presenting for infertility treatment, weightlifting and outdoor activities were associated with higher sperm concentrations but not with greater reproductive success. WHAT IS ALREADY KNOWN: Higher physical activity is related to better semen quality but no studies to date have investigated whether it predicts greater reproductive success. STUDY DESIGN, SIZE, DURATION: The Environment and Reproductive Health (EARTH) Study is an on-going prospective cohort study which enrolls subfertile couples presenting at Massachusetts General Hospital (2005-2013). In total, 231 men provided 433 semen samples and 163 couples underwent 421 IVF or intrauterine insemination cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Leisure time spent in physical and sedentary activities over the past year was self-reported using a validated questionnaire. We used mixed models to analyze the association of physical and sedentary activities with semen quality and with clinical pregnancy and live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE: Men in this cohort engaged in a median of 3.2 h/week of moderate-to-vigorous activities. Men in the highest quartile of moderate-to-vigorous activity had 43\% (95\% confidence interval (CI) 9, 87\%) higher sperm concentrations than men in the lowest quartile (P-trend = 0.04). Men in the highest category of outdoor activity (>=1.5 h/week) and weightlifting (>=2 h/week) had 42\% (95\% CI 10, 84\%) and 25\% (95\% CI -10, 74\%) higher sperm concentrations, respectively, compared with men in the lowest category (0 h/week) (P-trend = 0.04 and 0.02). Conversely, men who reported bicycling >=1.5 h/week had 34\% (95\% CI 4, 55\%) lower sperm concentrations compared with men who reported no bicycling (P-trend = 0.05). Paternal physical and sedentary activities were not related to clinical pregnancy or live birth rates following infertility treatment. LIMITATIONS, REASONS FOR CAUTION: The generalizability of the findings on live birth rates to populations not undergoing infertility treatment is limited. WIDER IMPLICATIONS OF THE FINDINGS: Certain types of physical activity, specifically weightlifting and outdoor activities, may improve semen quality but may not lead to improved success of infertility treatments. Further research is needed in other non-clinical populations. STUDY FUNDING/COMPETING INTERESTS: The authors are supported by NIH grants R01-ES009718, ES000002, P30-DK046200, T32-DK007703-16 and ES022955 T32-HD060454. None of the authors has any conflicts of interest to declare.}, keywords = {Adult, Birth Rate, Exercise, Family Characteristics, Fathers, Female, Humans, Male, Pregnancy, Pregnancy Outcome, Prospective Studies, Sedentary Lifestyle, Semen Analysis, Sperm Count, Surveys and Questionnaires}, issn = {1460-2350}, doi = {10.1093/humrep/deu212}, author = {Gaskins, A J and Afeiche, M C and Hauser, R and Williams, P L and Gillman, M W and Tanrikut, C and Petrozza, J C and Chavarro, J E} } @article {610411, title = {Physical activity is not related to semen quality in young healthy men}, journal = {Fertil Steril}, volume = {102}, number = {4}, year = {2014}, month = {2014 Oct}, pages = {1103-9}, abstract = {OBJECTIVE: To study the relationship of physical activity with semen quality among healthy young men from Spain. DESIGN: Cross-sectional study. SETTING: University and college campuses of Murcia Region, Spain. PATIENT(S): Healthy young men with untested fertility (n = 215). INTERVENTION(S): A physical examination, blood and semen samples, and completion of a questionnaire. MAIN OUTCOME MEASURE(S): Semen quality parameters. RESULT(S): Physical activity was not related to semen quality parameters. The adjusted percentage differences (95\% confidence interval) in semen parameters comparing men in the top quartile of moderate-to-vigorous physical activity (>=9.5~h/wk) with men in the bottom quartile (<=3~h/wk) were 4.3\% (-30.2\%, 38.9\%) for total sperm count, 7.2\% (-30.6\%, 45.1\%) for sperm concentration, -2.42\% (-6.53\%, 1.69\%) for sperm motility, and 12.6\% (-12.0\%, 37.2\%) for sperm morphology. CONCLUSION(S): In contrast to previous research among athletes, these data suggest that physical activity is not deleterious to testicular function, as captured by semen quality parameters in this population of healthy young men in Spain.}, keywords = {Adolescent, Cell Shape, Healthy Volunteers, Humans, Male, Motor Activity, Semen Analysis, spain, Sperm Count, Sperm Motility, Spermatozoa, Time Factors, Young Adult}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2014.06.032}, author = {M{\'\i}nguez-Alarc{\'o}n, Lidia and Chavarro, Jorge E and Mendiola, Jaime and Gaskins, Audrey J and Torres-Cantero, Alberto M} } @article {610408, title = {Prepregnancy and early adulthood body mass index and adult weight change in relation to fetal loss}, journal = {Obstet Gynecol}, volume = {124}, number = {4}, year = {2014}, month = {2014 Oct}, pages = {662-9}, abstract = {OBJECTIVE: To examine prospectively the relationships of prepregnancy body mass index (BMI), BMI at age 18 years, and weight change since age 18 years with risk of fetal loss. METHODS: Our prospective cohort study included 25,719 pregnancies reported by 17,027 women in the Nurses{\textquoteright} Health Study II between 1990 and 2009. In 1989, height, current weight, and weight at age 18 years were self-reported. Current weight was updated every 2 years thereafter. Pregnancies were self-reported, with case pregnancies lost spontaneously and comparison pregnancies ending in ectopic pregnancy, induced abortion, or live birth. RESULTS: Incident fetal loss was reported in 4,494 (17.5\%) pregnancies. Compared with those of normal BMI, the multivariate relative risks of fetal loss were 1.07 (95\% CI [confidence interval] 1.00-1.15) for overweight women, 1.10 (95\% CI 0.98-1.23) for class I obese women, and 1.27 (95\% CI 1.11-1.45) for class II and class III obese women (P trend <= .001). Body mass index at age 18 years was not associated with fetal loss (P trend=.59). Compared with women who maintained a stable weight ({\textpm} 4 kg) between age 18 years and before pregnancy, women who lost weight had a 20\% (95\% CI 9-29\%) lower risk of fetal loss. This association was stronger among women who were overweight at age 18 years. CONCLUSION: Being overweight or obese before pregnancy was associated with higher risk of fetal loss. In women overweight or obese at age 18 years, losing 4 kg or more was associated with a lower risk of fetal loss. LEVEL OF EVIDENCE: : II.}, keywords = {Adolescent, Adult, Age Factors, Body Mass Index, Cohort Studies, Confidence Intervals, Female, Fetal Mortality, Humans, Linear Models, Multivariate Analysis, Overweight, Pregnancy, Pregnancy Outcome, Pregnancy Rate, Prospective Studies, Reference Values, Risk Assessment, Surveys and Questionnaires, Weight Gain, Young Adult}, issn = {1873-233X}, doi = {10.1097/AOG.0000000000000478}, author = {Gaskins, Audrey J and Rich-Edwards, Janet W and Colaci, Daniela S and Afeiche, Myriam C and Thomas L Toth and Matthew W. Gillman and Missmer, Stacey A and Chavarro, Jorge E} } @article {610407, title = {Prepregnancy dietary patterns and risk of pregnancy loss}, journal = {Am J Clin Nutr}, volume = {100}, number = {4}, year = {2014}, month = {2014 Oct}, pages = {1166-72}, abstract = {BACKGROUND: Two previous case-control studies observed associations between specific food groups and risk of miscarriage; however, to our knowledge, no previous studies have investigated dietary patterns and risk of pregnancy loss. OBJECTIVE: We aimed to assess prepregnancy adherence to the alternate Healthy Eating Index 2010 (aHEI-2010), alternate Mediterranean diet (aMED), and Fertility Diet (FD) and risk of pregnancy loss. DESIGN: Our prospective cohort study included 15,950 pregnancies reported by 11,072 women in the Nurses{\textquoteright} Health Study II between 1992 and 2009. Diet was assessed every 4 y starting in 1991 by using a validated food-frequency questionnaire. Prepregnancy dietary pattern scores were computed as the sum of a woman{\textquoteright}s score on each pattern{\textquoteright}s predefined components. Multivariable log-binomial regression models with generalized estimating equations were used to estimate RRs and 95\% CIs. RESULTS: Incident spontaneous abortions and stillbirths were reported in 2756 (17.3\%) and 120 (0.8\%) pregnancies, respectively. None of the 3 dietary patterns were associated with risk of pregnancy loss. In the multivariable model, RR of pregnancy loss for a 1-SD increase in score was 1.02 (95\% CI: 0.98, 1.05) for the aMED pattern, 1.01 (95\% CI: 0.98, 1.05) for the aHEI-2010 pattern, and 0.98 (95\% CI: 0.95, 1.01) for the FD pattern. Results were consistent when pregnancy loss was classified as either a spontaneous abortion (loss at , keywords = {Abortion, Spontaneous, Adult, Diet, Diet, Mediterranean, Feeding Behavior, Female, Humans, Life Style, Maternal Nutritional Physiological Phenomena, Multivariate Analysis, Pregnancy, Pregnancy Outcome, Prospective Studies, Risk Factors, Stillbirth, Surveys and Questionnaires, Young Adult}, issn = {1938-3207}, doi = {10.3945/ajcn.114.083634}, author = {Gaskins, Audrey J and Rich-Edwards, Janet W and Hauser, Russ and Williams, Paige L and Matthew W. Gillman and Penzias, Alan and Missmer, Stacey A and Chavarro, Jorge E} } @article {610414, title = {Processed meat intake is unfavorably and fish intake favorably associated with semen quality indicators among men attending a fertility clinic}, journal = {J Nutr}, volume = {144}, number = {7}, year = {2014}, month = {2014 Jul}, pages = {1091-8}, abstract = {Emerging literature suggests that men{\textquoteright}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. }, keywords = {Adult, Animals, Cohort Studies, Diet, Fishes, Functional Food, Humans, Infertility, Male, Longitudinal Studies, Male, Massachusetts, Meat Products, Nutrition Assessment, Prospective Studies, Risk Factors, Seafood, Semen Analysis, Severity of Illness Index, Shellfish, Spermatogenesis, Spermatozoa}, issn = {1541-6100}, doi = {10.3945/jn.113.190173}, author = {Afeiche, Myriam C and Gaskins, Audrey J and Williams, Paige L and Thomas L Toth and Wright, Diane L and Tanrikut, Cigdem and Hauser, Russ and Chavarro, Jorge E} } @article {610415, title = {Sugar-sweetened beverage intake in relation to semen quality and reproductive hormone levels in young men}, journal = {Hum Reprod}, volume = {29}, number = {7}, year = {2014}, month = {2014 Jul}, pages = {1575-84}, abstract = {STUDY QUESTION: Is consumption of sugar-sweetened beverages (SSB) associated with semen quality? SUMMARY ANSWER: Higher consumption of SSB was associated with lower sperm motility among healthy, young men. WHAT IS KNOWN ALREADY: The existing literature on the potential role of SSBs on male reproductive function is scarce and primarily focused on the relation between caffeinated beverages and semen quality. However, a rodent model suggests that SSBs may hamper male fertility. STUDY DESIGN, SIZE, DURATION: The Rochester Young Men{\textquoteright}s Study; a cross-sectional study of 189 healthy young men carried out at the University of Rochester during 2009-2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men aged 18-22 years provided semen and blood samples, underwent a physical examination and completed a previously validated food frequency questionnaire (FFQ). Linear regression was used to analyze the association of SSBs with sperm parameters and reproductive hormone levels while adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: SSB intake was inversely related to progressive sperm motility. Men in the highest quartile of SSB intake (>=1.3 serving/day) had 9.8 (95\% CI: 1.9,17.8) percentage units lower progressive sperm motility than men in the lowest quartile of intake (, keywords = {Adolescent, Beverages, Cross-Sectional Studies, Diet, Healthy Volunteers, Hormones, Humans, Male, new york, Semen, Semen Analysis, Sperm Motility, Sweetening Agents, Young Adult}, issn = {1460-2350}, doi = {10.1093/humrep/deu102}, author = {Chiu, Y H and Afeiche, M C and Gaskins, A J and Williams, P L and Mendiola, J and J{\o}rgensen, N and Swan, S H and Chavarro, J E} } @article {610420, title = {Adherence to the Mediterranean diet and body fat distribution in reproductive aged women}, journal = {Eur J Clin Nutr}, volume = {67}, number = {3}, year = {2013}, month = {2013 Mar}, pages = {289-94}, abstract = {BACKGROUND/OBJECTIVES: Adherence to the Mediterranean diet (MD), high in fruits, vegetables and monounsaturated fats, has been associated with lower body mass index. Associations with measured body fat, including regional adiposity, have not been previously investigated. We examined the associations between the alternate Mediterranean diet score (aMED), anthropometry and measured adiposity by dual-energy x-ray absorptiometry (DXA). SUBJECTS/METHODS: This study included 248 healthy females, aged 18-44 years from the BioCycle Study. Each woman{\textquoteright}s aMED (range 0-9) was calculated from up to eight 24-h dietary recalls over 1-2 menstrual cycles (>97\% had >= 7 recalls). Multiple linear regression was used to determine whether aMED and its specific components were associated with total and regional adiposity after adjusting for age, race, education, physical activity and energy intake. RESULTS: Participants had an average (s.d.) aMED of 4.2 (1.7) and percent body fat of 29.5 (6.0)\%. Significant inverse associations were found between aMED and all the examined adiposity measures except waist-to-hip ratio. Among the DXA measures, a 1-unit increment in aMED was associated with a 0.06 (95\% confidence interval (CI): -0.09, -0.02) lower trunk-to-leg fat ratio (T/L), a measure of upper to lower body fat. In an analysis examining T/L as an outcome with the separate components of the aMED, T/L was lower with increased legume consumption (β=-0.280, 95\% CI: -0.550, -0.010) but was higher with increased consumption of red and processed meat (β=0.060, 95\% CI: 0.002, 0.117). CONCLUSIONS: Adherence to the aMED was associated with lower total and regional adiposity, adding to the mounting evidence of the health benefits of the MD.}, keywords = {Absorptiometry, Photon, Adipose Tissue, Adolescent, Adult, Body Fat Distribution, Body Mass Index, Cross-Sectional Studies, Diet, Mediterranean, Energy Intake, Female, Humans, Motor Activity, Nutrition Assessment, Patient Compliance, Reproduction, Waist-Hip Ratio, Young Adult}, issn = {1476-5640}, doi = {10.1038/ejcn.2013.4}, author = {Boghossian, N S and Yeung, E H and Mumford, S L and C Zhang and Gaskins, A J and Wactawski-Wende, J and Schisterman, E F} } @article {610419, title = {Dairy food intake in relation to semen quality and reproductive hormone levels among physically active young men}, journal = {Hum Reprod}, volume = {28}, number = {8}, year = {2013}, month = {2013 Aug}, pages = {2265-75}, abstract = {STUDY QUESTION: Is increased consumption of dairy foods associated with lower semen quality? SUMMARY ANSWER: We found that intake of full-fat dairy was inversely related to sperm motility and morphology. These associations were driven primarily by intake of cheese and were independent of overall dietary patterns. WHAT IS KNOWN ALREADY: It has been suggested that environmental estrogens could be responsible for the putative secular decline in sperm counts. Dairy foods contain large amounts of estrogens. While some studies have suggested dairy as a possible contributing factor for decreased semen quality, this finding has not been consistent across studies. STUDY DESIGN, SIZE, DURATION: The Rochester Young Men{\textquoteright}s Study (n = 189) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men aged 18-22 years were included in this analysis. Diet was assessed via food frequency questionnaire. Linear regression was used to analyze the relation between dairy intake and conventional semen quality parameters (total sperm count, sperm concentration, progressive motility, morphology and ejaculate volume) adjusting for age, abstinence time, race, smoking status, body mass index, recruitment period, moderate-to-intense exercise, TV watching and total calorie intake. MAIN RESULTS AND THE ROLE OF CHANCE: Total dairy food intake was inversely related to sperm morphology (P-trend = 0.004). This association was mostly driven by intake of full-fat dairy foods. The adjusted difference (95\% confidence interval) in normal sperm morphology percent was -3.2\% (-4.5 to -1.8) between men in the upper half and those in the lower half of full-fat dairy intake (P < 0.0001), while the equivalent contrast for low-fat dairy intake was less pronounced [-1.3\% (-2.7 to -0.07; P= 0.06)]. Full-fat dairy intake was also associated with significantly lower percent progressively motile sperm (P= 0.05). LIMITATIONS, REASONS FOR CAUTION: As it was a cross-sectional study, causal inference is limited. WIDER IMPLICATIONS OF THE FINDINGS: Further research is needed to prove a causal link between a high consumption of full-fat dairy foods and detrimental effects on semen quality. If verified our findings would mean that intake of full-fat dairy foods should be considered in attempts to explain secular trends in semen quality and that men trying to have children should restrict their intake. STUDY FUNDING/COMPETING INTEREST(S): European Union Seventh Framework Program (Environment), {\textquoteright}Developmental Effects of Environment on Reproductive Health{\textquoteright} (DEER) grant 212844. Grant P30 DK046200 and Ruth L. Kirschstein National Research Service Award T32 DK007703-16 from the National Institutes of Health. None of the authors has any conflicts of interest to declare.}, keywords = {Adolescent, Adult, Cheese, Cross-Sectional Studies, Dairy Products, Diet, Humans, Male, Semen Analysis, Spermatozoa}, issn = {1460-2350}, doi = {10.1093/humrep/det133}, author = {Afeiche, M and Williams, P L and Mendiola, J and Gaskins, A J and J{\o}rgensen, N and Swan, S H and Chavarro, J E} } @article {610418, title = {Semen quality in relation to antioxidant intake in a healthy male population}, journal = {Fertil Steril}, volume = {100}, number = {6}, year = {2013}, month = {2013 Dec}, pages = {1572-9}, abstract = {OBJECTIVE: To assess the relationship between dietary antioxidant intake and semen quality in young healthy males. DESIGN: Cross-sectional study. SETTING: University and college campuses in the Rochester, New York, area. PATIENT(S): One hundred eighty-nine university-aged men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen volume, total sperm count, concentration, motility, total motile count, and morphology. RESULT(S): Progressive motility was 6.5 (95\% confidence interval [CI], 0.6, 12.3) percentage units higher among men in the highest quartile of β-carotene intake compared with men in the lowest quartile. Similar results were observed for lutein intake. Lycopene intake was positively related to sperm morphology. The adjusted percentages (95\% CI) of morphologically normal sperm in increasing quartiles of lycopene intake were 8.0 (6.7, 9.3), 7.7 (6.4, 9.0), 9.2 (7.9, 10.5), and 9.7 (8.4, 11.0). There was a nonlinear relationship between vitamin C intake and sperm concentration, with men in the second quartile of intake having, on average, the highest sperm concentrations and men in the top quartile of intake having the lowest concentrations. CONCLUSION(S): In a population of healthy young men, carotenoid intake was associated with higher sperm motility and, in the case of lycopene, better sperm morphology. Our data suggest that dietary carotenoids may have a positive impact on semen quality.}, keywords = {Administration, Oral, Adult, Antioxidants, Diet, Humans, Male, new york, Reference Values, Reproducibility of Results, Semen, Semen Analysis, Sensitivity and Specificity}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2013.08.032}, author = {Zareba, Piotr and Colaci, Daniela S and Afeiche, Myriam and Gaskins, Audrey J and J{\o}rgensen, Niels and Mendiola, Jaime and Swan, Shanna H and Chavarro, Jorge E} } @article {610423, title = {Dietary patterns and semen quality in young men}, journal = {Hum Reprod}, volume = {27}, number = {10}, year = {2012}, month = {2012 Oct}, pages = {2899-907}, abstract = {STUDY QUESTION: Are different dietary patterns associated with semen parameters in young men? STUDY ANSWER: The consumption of a Prudent dietary pattern was significantly associated with higher progressive sperm motility and unrelated to sperm concentration and morphology. The consumption of a Western dietary pattern was unrelated to conventional semen quality parameters. WHAT IS KNOWN ALREADY: Over the past decades there has been evidence of a concomitant decline in sperm and diet quality. Yet whether diet composition influences semen quality remains largely unexplored. STUDY DESIGN, SIZE, DURATION: The Rochester Young Men{\textquoteright}s Study (n= 188) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester. PARTICIPANTS, SETTING, METHODS: Men aged 18-22 years were included in this analysis. Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns and conventional semen quality parameters (sperm concentration, progressive motility and morphology) adjusting for abstinence time, multivitamin use, race, smoking status, BMI, recruitment period, moderate-to-intense exercise and total calorie intake. RESULTS: Two dietary patterns were identified by factor analysis. The {\textquoteright}Western{\textquoteright} pattern was characterized by high intake of red and processed meat, refined grains, pizza, snacks, high-energy drinks and sweets. The {\textquoteright}Prudent{\textquoteright} pattern was characterized by high intake of fish, chicken, fruit, vegetables, legumes and whole grains. The Prudent pattern was positively associated with percent progressively motile sperm in multivariate models (P-trend = 0.04). Men in the highest quartile of the Prudent diet had 11.3\% (95\% CI 1.3, 21.3) higher \% progressively motile sperm compared with men in the lowest quartile. The Prudent pattern was unrelated to sperm concentration and morphology. The Western pattern was not associated with any semen parameter. LIMITATIONS: This was a cross-sectional and observational study, which limited our ability to determine causality of diet on semen quality parameters. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support the suggestion that a diet rich in fruits, vegetables, chicken, fish and whole grains may be an inexpensive and safe way to improve at least one measure of semen quality. STUDY FUNDING/COMPETING INTERESTS: The authors are supported by NIH grant T32DK007703-16 and P30DK46200 and European Union DEER Grant 212844. The authors have no competing interests to declare.}, keywords = {Adolescent, Adult, Body Mass Index, Cross-Sectional Studies, Diet, Feeding Behavior, Humans, Infertility, Male, Male, Risk Factors, Semen Analysis}, issn = {1460-2350}, doi = {10.1093/humrep/des298}, author = {Gaskins, Audrey J and Colaci, Daniela S and Mendiola, Jaime and Swan, Shanna H and Chavarro, Jorge E} } @article {610427, title = {Effect of daily fiber intake on luteinizing hormone levels in reproductive-aged women}, journal = {Eur J Nutr}, volume = {51}, number = {2}, year = {2012}, month = {2012 Mar}, pages = {249-53}, abstract = {PURPOSE: To evaluate whether the association between fiber intake and LH levels is driven by the association between fiber and estradiol, or whether there is an independent association. METHODS: A prospective cohort of 259 premenopausal women were followed for up to 2 menstrual cycles. Estrogen and LH were measured <=8 times per cycle at visits scheduled using fertility monitors. Diet was assessed <=4 times per cycle by 24-h recall. Linear mixed models on the log scale of hormones were utilized to evaluate the total effects of fiber intake. Inverse probability weights were utilized to estimate the independent effect of fiber on LH levels. RESULTS: In unweighted analyses, we observed a significant, inverse association between fiber intake (in 5~g/day increments) and log LH levels (β, -0.051, 95\% confidence interval (CI), -0.100, -0.002). No association was observed in the weighted analyses, after estradiol levels were taken into account (β, -0.016, 95\% CI, -0.060, 0.027). CONCLUSIONS: The decreased levels of LH associated with high fiber intake were attenuated after taking estradiol levels into account, suggesting that the association between fiber and LH is most likely a consequence of fiber{\textquoteright}s impact on estradiol and not due to an independent mechanism.}, keywords = {Adolescent, Adult, Diet, Dietary Fiber, Estradiol, Female, Fertility, Humans, Luteinizing Hormone, Menstrual Cycle, Premenopause, Prospective Studies, Reproduction, Young Adult}, issn = {1436-6215}, doi = {10.1007/s00394-011-0207-2}, author = {Gaskins, Audrey J and Mumford, Sunni L and Wactawski-Wende, Jean and Schisterman, Enrique F} } @article {610425, title = {Endogenous reproductive hormones and C-reactive protein across the menstrual cycle: the BioCycle Study}, journal = {Am J Epidemiol}, volume = {175}, number = {5}, year = {2012}, month = {2012 Mar 01}, pages = {423-31}, abstract = {C-reactive protein (CRP) is one of the most commonly used markers of acute phase reaction in clinical settings and predictors of cardiovascular risk in healthy women; however, data on its physiologic regulation in premenopausal women are sparse. The objective of this study was to evaluate the association between endogenous reproductive hormones and CRP in the BioCycle Study (2005-2007). Women aged 18-44 years from western New York were followed prospectively for up to 2 menstrual cycles (n = 259). Serum levels of CRP, estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured up to 8 times per cycle, timed by fertility monitors. CRP levels varied significantly across the cycle (P < 0.001). More women were classified as being at elevated risk of cardiovascular disease (CRP, >3 mg/L) during menses compared with other phases (12.3\% vs. 7.4\%; P < 0.001). A 10-fold increase in estradiol was associated with a 24.3\% decrease in CRP (95\% confidence interval: 19.3, 29.0). A 10-fold increase in luteal progesterone was associated with a 19.4\% increase in CRP (95\% confidence interval: 8.4, 31.5). These results support the hypothesis that endogenous estradiol might have antiinflammatory effects and highlight the need for standardization of CRP measurement to menstrual cycle phase in reproductive-aged women.}, keywords = {Adolescent, Adult, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Estradiol, Female, Follicle Stimulating Hormone, Humans, Inflammation, Linear Models, Luteinizing Hormone, Menstrual Cycle, Progesterone, Prospective Studies, Risk Assessment, Young Adult}, issn = {1476-6256}, doi = {10.1093/aje/kwr343}, author = {Gaskins, Audrey J and Wilchesky, Machelle and Mumford, Sunni L and Whitcomb, Brian W and Browne, Richard W and Wactawski-Wende, Jean and Perkins, Neil J and Schisterman, Enrique F} } @article {610422, title = {The impact of dietary folate intake on reproductive function in premenopausal women: a prospective cohort study}, journal = {PLoS One}, volume = {7}, number = {9}, year = {2012}, month = {2012}, pages = {e46276}, abstract = {BACKGROUND: Folic acid is recommended to reproductive-aged women to prevent birth defects, though little is known about the effects of dietary intake on other reproductive outcomes. Improved pregnancy rates have been documented after folic acid supplement use, suggesting a possible link with ovulation, however research is limited. Our objective was to evaluate the association between dietary folate intake, hormone levels, and sporadic anovulation in healthy, regularly menstruating women. METHODOLOGY/PRINCIPAL FINDINGS: The BioCycle study (2005-2007) prospectively followed 259 healthy women aged 18-44 years from the western New York region for up to 2 menstrual cycles. Total folate and specific sources of folate were assessed up to 4 times per cycle by 24-hour recall. Estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured in serum up to 8 times per cycle, timed using fertility monitors. Anovulation was defined as a cycle with peak progesterone concentration <= 5 ng/mL and no LH peak in the mid/late luteal phase. Higher intake of dietary folate (in dietary equivalents) across tertiles had a marginally significant association with greater luteal progesterone levels (P trend 0.08). Higher intake of synthetic folate was significantly associated with higher luteal progesterone levels (P trend 0.05). Specifically, women in the 3(rd) tertile of synthetic folate intake had, on average, 16.0\% (95\% CI, 0.5-33.8\%) higher luteal progesterone levels compared to women in the 1(st) tertile. Moreover, consumption of synthetic folate was significantly and inversely associated with anovulation such that women in the 3(rd) tertile had a 64\% (95\% CI, 8-86\%) decreased odds of anovulation compared to the women in the 1(st) tertile (P trend 0.03). CONCLUSIONS/SIGNIFICANCE: These findings suggest that a diet high in synthetic folate may be associated with increased progesterone levels and lower risk of sporadic anovulation. Further study of the effect of dietary folate and folic acid supplement use on reproductive health is warranted.}, keywords = {Adolescent, Adult, Anovulation, Dietary Supplements, Female, Folic Acid, Humans, Premenopause, Progesterone, Young Adult}, issn = {1932-6203}, doi = {10.1371/journal.pone.0046276}, author = {Gaskins, Audrey J and Mumford, Sunni L and Chavarro, Jorge E and Zhang, Cuilin and Pollack, Anna Z and Wactawski-Wende, Jean and Perkins, Neil J and Schisterman, Enrique F} } @article {610424, title = {Men{\textquoteright}s body mass index in relation to embryo quality and clinical outcomes in couples undergoing in vitro fertilization}, journal = {Fertil Steril}, volume = {98}, number = {5}, year = {2012}, month = {2012 Nov}, pages = {1193-9.e1}, abstract = {OBJECTIVE: To evaluate the association between men{\textquoteright}s body mass index (BMI), early embryo quality, and clinical outcomes in couples undergoing in vitro fertilization (IVF). DESIGN: Prospective cohort study. SETTING: Fertility clinic in an academic medical center. PATIENT(S): 114 couples who underwent 172 assisted reproduction cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization rate, embryo quality, implantation rate, clinical pregnancy rate, and live birth rate. RESULT(S): The fertilization rate was higher among obese men than among normal weight men in conventional IVF cycles. No statistically significant associations were found between men{\textquoteright}s BMI and the proportion of poor-quality embryos on day 3, slow embryo cleavage rate, or accelerated embryo cleavage rate. Men{\textquoteright}s BMI was unrelated to positive β-human chorionic gonadotropin rate, clinical pregnancy rate, or live-birth rate per embryo transfer. Among couples undergoing intracytoplasmic sperm injection, the odds of live birth in couples with obese male partners was 84\% lower than the odds in couples with men with normal BMI. CONCLUSION(S): Our data suggest a possible deleterious effect of male obesity on the odds of having a live birth among couples undergoing intracytoplasmic sperm injection.}, keywords = {Academic Medical Centers, Adult, Body Mass Index, Boston, Embryo Implantation, Embryo Transfer, Embryo, Mammalian, Female, Fertilization in Vitro, Humans, Infertility, Linear Models, Live Birth, Logistic Models, Male, Obesity, Odds Ratio, Pregnancy, Pregnancy Rate, Prospective Studies, Risk Assessment, Risk Factors, Sex Factors, Sperm Injections, Intracytoplasmic, Treatment Outcome}, issn = {1556-5653}, doi = {10.1016/j.fertnstert.2012.07.1102}, author = {Colaci, Daniela S and Afeiche, Myriam and Gaskins, Audrey J and Wright, Diane L and Thomas L Toth and Tanrikut, Cigdem and Hauser, Russ and Chavarro, Jorge E} } @article {610429, title = {Cholesterol, endocrine and metabolic disturbances in sporadic anovulatory women with regular menstruation}, journal = {Hum Reprod}, volume = {26}, number = {2}, year = {2011}, month = {2011 Feb}, pages = {423-30}, abstract = {BACKGROUND: Sporadic anovulation among regularly menstruating women is not well understood. It is hypothesized that cholesterol abnormalities may lead to hormone imbalances and incident anovulation. The objective was to evaluate the association between lipoprotein cholesterol levels and endocrine and metabolic disturbances and incident anovulation among ovulatory and anovulatory women reporting regular menstruation. METHODS: The BioCycle Study was a prospective cohort study conducted at the University at Buffalo from September 2005 to 2007, which followed 259 self-reported regularly menstruating women aged 18-44 years, for one or two complete menstrual cycles. Sporadic anovulation was assessed across two menstrual cycles. RESULTS: Mean total and low-density lipoprotein cholesterol and triglycerides levels across the menstrual cycles were higher during anovulatory cycles (mean difference: 4.6 (P = 0.01), 3.0 (P = 0.06) and 6.4 (P = 0.0002) mg/dl, respectively, adjusted for age and BMI). When multiple total cholesterol (TC) measures prior to expected ovulation were considered, we observed a slight increased risk of anovulation associated with increased levels of TC (odds ratio per 5 mg/dl increase, 1.07; 95\% confidence interval, 0.99, 1.16). Sporadic anovulation was associated with an increased LH:FSH ratio (P = 0.002), current acne (P = 0.02) and decreased sex hormone-binding globulin levels (P = 0.005). CONCLUSIONS: These results do not support a strong association between lipoprotein cholesterol levels and sporadic anovulation. However, sporadic anovulation among regularly menstruating women is associated with endocrine disturbances which are typically observed in women with polycystic ovary syndrome.}, keywords = {Adolescent, Adult, Anovulation, Cholesterol, Cholesterol, LDL, Cohort Studies, Female, Follicle Stimulating Hormone, Humans, Luteinizing Hormone, Menstruation, Prospective Studies, Triglycerides}, issn = {1460-2350}, doi = {10.1093/humrep/deq322}, author = {Mumford, Sunni L and Schisterman, Enrique F and Anna Maria Siega-Riz and Gaskins, Audrey J and Steiner, Anne Z and Daniels, Julie L and Olshan, Andrew F and Hediger, Mary L and Hovey, Kathleen and Wactawski-Wende, Jean and Trevisan, Maurizio and Bloom, Michael S} } @article {610428, title = {Effect of dietary fiber intake on lipoprotein cholesterol levels independent of estradiol in healthy premenopausal women}, journal = {Am J Epidemiol}, volume = {173}, number = {2}, year = {2011}, month = {2011 Jan 15}, pages = {145-56}, abstract = {High-fiber diets are associated with improved lipid profiles. However, pre- and postmenopausal women respond differently to fiber intake, suggesting that endogenous estradiol mediates the effect. The authors{\textquoteright} objective was to determine the direct effect of fiber intake on lipoprotein cholesterol levels independent of estradiol among premenopausal women. The BioCycle Study, a prospective cohort study conducted at the State University of New York at Buffalo from 2005 to 2007, followed 259 healthy women for up to 2 complete menstrual cycles. Serum lipoprotein and hormone levels were measured at 16 visits timed using fertility monitors. Fiber intake was assessed by 8 24-hour recalls. Marginal structural models with inverse probability weights for both lipoprotein and estradiol levels were used to estimate controlled direct effects of the highest category of fiber intake (>=22 g/day vs. , keywords = {Adolescent, Adult, Cholesterol, Dietary Fiber, Estradiol, Female, Humans, Linear Models, Lipoproteins, Menstrual Cycle, Prospective Studies, Young Adult}, issn = {1476-6256}, doi = {10.1093/aje/kwq388}, author = {Mumford, Sunni L and Schisterman, Enrique F and Anna Maria Siega-Riz and Gaskins, Audrey J and Wactawski-Wende, Jean and VanderWeele, Tyler J} } @article {610426, title = {Realignment and multiple imputation of longitudinal data: an application to menstrual cycle data}, journal = {Paediatr Perinat Epidemiol}, volume = {25}, number = {5}, year = {2011}, month = {2011 Sep}, pages = {448-59}, abstract = {Reproductive hormone levels are highly variable among premenopausal women during the menstrual cycle. Accurate timing of hormone measurement is essential, especially when investigating day- or phase-specific effects. The BioCycle Study used daily urine home fertility monitors to help detect the luteinising hormone (LH) surge in order to schedule visits with biologically relevant windows of hormonal variability. However, as the LH surge is brief and cycles vary in length, relevant hormonal changes may not align with scheduled visits even when fertility monitors are used. Using monitor data, measurements were reclassified according to biological phase of the menstrual cycle to more accurate cycle phase categories. Longitudinal multiple imputation methods were applied after reclassification if no visit occurred during a given menstrual cycle phase. Reclassified cycles had more clearly defined hormonal profiles, with higher mean peak hormones (up to 141\%) and reduced variability (up to 71\%). We demonstrate the importance of realigning visits to biologically relevant windows when assessing phase- or day-specific effects and the feasibility of applying longitudinal multiple imputation methods. Our method has applications in settings where missing data may occur over time, where daily blood sampling for hormonal measurements is not feasible, and in other areas where timing is essential.}, keywords = {Adolescent, Adult, Cohort Studies, Data Interpretation, Statistical, Estradiol, Female, Fertility, Follicle Stimulating Hormone, Humans, Longitudinal Studies, Luteinizing Hormone, Menstrual Cycle, new york, Ovulation Prediction, Progesterone, Prospective Studies, Time Factors, Young Adult}, issn = {1365-3016}, doi = {10.1111/j.1365-3016.2011.01204.x}, author = {Mumford, Sunni L and Schisterman, Enrique F and Gaskins, Audrey J and Pollack, Anna Z and Perkins, Neil J and Whitcomb, Brian W and Ye, Aijun and Wactawski-Wende, Jean} } @article {610430, title = {Adherence to a Mediterranean diet and plasma concentrations of lipid peroxidation in premenopausal women}, journal = {Am J Clin Nutr}, volume = {92}, number = {6}, year = {2010}, month = {2010 Dec}, pages = {1461-7}, abstract = {BACKGROUND: A Mediterranean diet has been associated with a reduced risk of cardiovascular disease and mortality. A possible mechanism is through a decrease in lipid peroxidation (LPO); however, evidence linking the Mediterranean diet with lower LPO in premenopausal women is sparse. OBJECTIVE: We investigated whether adherence to a Mediterranean diet was associated with lower LPO concentrations in premenopausal women. DESIGN: Two hundred fifty-nine healthy women aged 18-44 y were followed for <= 2 menstrual cycles. Plasma concentrations of F(2)-isoprostane (8-iso-PGF2α), 9-hydroxyoctadecadieneoic acid (9-HODE), and thiobarbituric acid reactive substances (TBARS) were measured <= 8 times per cycle at visits scheduled by using fertility monitors. Diet was assessed <= 4 times per cycle by using 24-h dietary recalls. The alternate Mediterranean Diet Score (aMED) (range: 0-9) was calculated on the basis of intake of vegetables, legumes, fruit, nuts, whole grains, red and processed meat, fish, and alcohol and the ratio of monounsaturated to saturated fat. RESULTS: A 1-unit increase in aMED was associated with a 4.50\% decrease in 8-iso-PGF2α concentrations (95\% CI: -6.32\%, -2.65\%) and a 14.01\% decrease in 9-HODE concentrations (95\% CI: -17.88\%, -9.96\%) after adjustment for energy intake, age, race, body mass index, plasma ascorbic acid, and serum cholesterol. No significant association was observed between aMED and TBARS. A 1-unit increase in aMED was associated with a 1.39\% increase (95\% CI: 0.07\%, 2.72\%) in plasma ascorbic acid concentrations. CONCLUSIONS: Adherence to a Mediterranean diet is associated with lower LPO and higher ascorbic acid concentrations. These results confirm that decreased LPO is a plausible mechanism linking a Mediterranean diet to reduced cardiovascular disease risk.}, keywords = {Adolescent, Adult, Ascorbic Acid, Diet, Mediterranean, Dinoprost, Female, Humans, Linoleic Acids, Conjugated, Lipid Peroxidation, Lipids, Premenopause, Young Adult}, issn = {1938-3207}, doi = {10.3945/ajcn.110.000026}, author = {Gaskins, Audrey J and Rovner, Alisha J and Mumford, Sunni L and Yeung, Edwina and Browne, Richard W and Trevisan, Maurizio and Perkins, Neil J and Wactawski-Wende, Jean and Schisterman, Enrique F} } @article {610431, title = {Influence of endogenous reproductive hormones on F2-isoprostane levels in premenopausal women: the BioCycle Study}, journal = {Am J Epidemiol}, volume = {172}, number = {4}, year = {2010}, month = {2010 Aug 15}, pages = {430-9}, abstract = {Endogenous reproductive hormones and oxidative stress have been independently linked to risk of chronic disease but mostly in postmenopausal women. The interplay between endogenous reproductive hormones and oxidative stress among premenopausal women, however, has yet to be clearly elucidated. The objective of this study was to investigate the association between endogenous reproductive hormones and F(2)-isoprostanes in the BioCycle Study. Women aged 18-44 years from western New York State were followed prospectively for up to 2 menstrual cycles (n = 259) during 2005-2007. Estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, F(2)-isoprostanes, and thiobarbituric acid-reactive substances were measured up to 8 times per cycle at clinic visits timed by using fertility monitors. F(2)-Isoprostane levels had an independent positive association with estradiol (beta = 0.02, 95\% confidence interval: 0.01, 0.03) and inverse associations with sex hormone-binding globulin and follicle-stimulating hormone (beta = -0.04, 95\% confidence interval: -0.07, -0.003; beta = -0.02, 95\% confidence interval: -0.03, -0.002, respectively) after adjustment for age, race, age at menarche, gamma-tocopherol, beta-carotene, total cholesterol, and homocysteine by inverse probability weighting. Thiobarbituric acid-reactive substances, a less specific marker of oxidative stress, had similar associations. If F(2)-isoprostanes are specific markers of oxidative stress, these results call into question the commonly held hypothesis that endogenous estradiol reduces oxidative stress.}, keywords = {Adolescent, Adult, Biomarkers, F2-Isoprostanes, Female, Fertility, Gonadal Steroid Hormones, Humans, Menstrual Cycle, Oxidative Stress, Premenopause, Prospective Studies, Young Adult}, issn = {1476-6256}, doi = {10.1093/aje/kwq131}, author = {Schisterman, Enrique F and Gaskins, Audrey J and Mumford, Sunni L and Browne, Richard W and Yeung, Edwina and Trevisan, Maurizio and Hediger, Mary and Zhang, Cuilin and Perkins, Neil J and Hovey, Kathleen and Wactawski-Wende, Jean} } @article {610433, title = {A longitudinal study of serum lipoproteins in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study}, journal = {J Clin Endocrinol Metab}, volume = {95}, number = {9}, year = {2010}, month = {2010 Sep}, pages = {E80-5}, abstract = {CONTEXT: Exogenous estrogens have been shown to affect the lipid profile, leading to the hypothesis that endogenous estrogens may have similar effects. OBJECTIVE: The objective of the study was to evaluate the association between endogenous estrogen and serum lipoproteins across the menstrual cycle. DESIGN: This was a prospective cohort study. SETTING: The study was conducted at the University at Buffalo, 2005-2007. PARTICIPANTS: Participants included 259 healthy, regularly menstruating women aged 18-44 yr. MAIN OUTCOME MEASURES: Serum levels of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and triglycerides measured up to eight times per cycle for up to two cycles were measured. RESULTS: Total and LDL cholesterol were lower during the luteal phase as compared with the follicular phase (P < 0.001), and HDL levels were highest around ovulation (P < 0.001). More women were classified above the desirable range (LDL > or =130 mg/dl or total cholesterol > or =200 mg/dl) when measured during the follicular phase. Estradiol was positively associated with HDL in acute effects models [beta = 0.019, 95\% confidence interval (CI) 0.015, 0.022] and inversely associated with total (beta = -0.017, 95\% CI -0.020, -0.014) and LDL cholesterol (beta = -0.023, 95\% CI -0.027, -0.018) and triglycerides (beta = -0.041, 95\% CI -0.054, -0.029) in persistent effects models. CONCLUSIONS: Endogenous estrogen, like exogenous estrogen, appears to have beneficial effects on the lipid profile. Because lipoprotein cholesterol levels vary across the menstrual cycle, cyclic variations in lipoprotein levels may need to be considered in the design and interpretation of studies in reproductive-age women and in the clinical management of women{\textquoteright}s cholesterol.}, keywords = {Adolescent, Adult, Cohort Studies, Female, Gonadal Steroid Hormones, Humans, Lipoproteins, Longitudinal Studies, Menstrual Cycle, Triglycerides, Young Adult}, issn = {1945-7197}, doi = {10.1210/jc.2010-0109}, author = {Mumford, Sunni L and Schisterman, Enrique F and Anna Maria Siega-Riz and Browne, Richard W and Gaskins, Audrey J and Trevisan, Maurizio and Steiner, Anne Z and Daniels, Julie L and Zhang, Cuilin and Perkins, Neil J and Wactawski-Wende, Jean} } @article {610432, title = {Whole grains are associated with serum concentrations of high sensitivity C-reactive protein among premenopausal women}, journal = {J Nutr}, volume = {140}, number = {9}, year = {2010}, month = {2010 Sep}, pages = {1669-76}, abstract = {In premenopausal women, elevated C-reactive protein (CRP) concentrations have been associated with an increased risk of negative reproductive outcomes. Whole grain consumption has been associated with lower CRP concentrations in older women; however, less is known about this relationship in younger women. We investigated whether whole grain intake was associated with serum high sensitivity CRP (hs-CRP) concentrations in young women. BioCycle was a prospective cohort study conducted at the University of Buffalo from 2005 to 2007, which followed 259 healthy women aged 18-44 y for , keywords = {Adolescent, Adult, C-Reactive Protein, Cohort Studies, Diet, Diet Surveys, Edible Grain, Feeding Behavior, Female, Food Analysis, Humans, new york, Premenopause, Young Adult}, issn = {1541-6100}, doi = {10.3945/jn.110.124164}, author = {Gaskins, Audrey J and Mumford, Sunni L and Rovner, Alisha J and Zhang, Cuilin and Chen, Liwei and Wactawski-Wende, Jean and Perkins, Neil J and Schisterman, Enrique F} } @article {610435, title = {Effect of daily fiber intake on reproductive function: the BioCycle Study}, journal = {Am J Clin Nutr}, volume = {90}, number = {4}, year = {2009}, month = {2009 Oct}, pages = {1061-9}, abstract = {BACKGROUND: High-fiber diets have been associated with decreased breast cancer risk, likely mediated by the effect of fiber on lowering circulating estrogen concentrations. The influence of fiber on aspects of reproduction, which include ovulation, has not been well studied in premenopausal women. OBJECTIVE: The objective was to determine if fiber consumption is associated with hormone concentrations and incident anovulation in healthy, regularly menstruating women. DESIGN: The BioCycle Study was a prospective cohort study conducted from 2004 to 2006 that followed 250 women aged 18-44 y for 2 cycles. Dietary fiber consumption was assessed < or =4 times/cycle by using 24-h recall. Outcomes included concentrations of estradiol, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which were measured < or =8 times/cycle, and incident anovulation. RESULTS: Dietary fiber consumption was inversely associated with hormone concentrations (estradiol, progesterone, LH, and FSH; P < 0.05) and positively associated with the risk of anovulation (P = 0.003) by using random-effects models with adjustment for total calories, age, race, and vitamin E intake. Each 5-g/d increase in total fiber intake was associated with a 1.78-fold increased risk (95\% CI: 1.11, 2.84) of an anovulatory cycle. The adjusted odds ratio of 5 g fruit fiber/d was 3.05 (95\% CI: 1.07, 8.71). CONCLUSIONS: These findings suggest that a diet high in fiber is significantly associated with decreased hormone concentrations and a higher probability of anovulation. Further study of the effect of fiber on reproductive health and of the effect of these intakes in reproductive-aged women is warranted.}, keywords = {Adolescent, Adult, Anovulation, Diet, Diet Records, Dietary Fiber, Dose-Response Relationship, Drug, Estradiol, Female, Follicle Stimulating Hormone, Humans, Luteinizing Hormone, Progesterone, Prospective Studies, Risk Factors, Young Adult}, issn = {1938-3207}, doi = {10.3945/ajcn.2009.27990}, author = {Gaskins, Audrey J and Mumford, Sunni L and Zhang, Cuilin and Wactawski-Wende, Jean and Hovey, Kathleen M and Whitcomb, Brian W and Howards, Penelope P and Perkins, Neil J and Yeung, Edwina and Schisterman, Enrique F} } @article {610434, title = {The effect of lipid adjustment on the analysis of environmental contaminants and the outcome of human health risks}, journal = {Methods Mol Biol}, volume = {580}, year = {2009}, month = {2009}, pages = {371-81}, abstract = {Past literature on exposure to lipophilic agents such as organochlorines (OCs) is conflicting, posing challenges for the interpretation of their potential human health risks. Since blood is often used as a proxy for adipose tissue, it is necessary to model serum lipids when assessing health risks of OCs. Using a simulation study, we evaluated four statistical models (unadjusted, standardized, adjusted, and two-stage) for the analysis of polychlorinated biphenyls (PCBs) exposure, serum lipids, and health outcome risk. Eight candidate true causal scenarios, depicted by directed acyclic graphs, were used to illustrate the ramifications of misspecification of underlying assumptions when interpreting results. Biased results were produced when statistical models that deviated from the underlying causal assumptions were used with the lipid standardization method found to be particularly prone to bias. We concluded that investigators must consider biology, biological medium, laboratory measurement, and other underlying modeling assumptions when devising a statistical model for assessing health outcomes in relation to environmental exposures.}, keywords = {Environmental Exposure, Environmental Pollutants, Humans, Lipids, Models, Theoretical, Polychlorinated Biphenyls}, issn = {1940-6029}, doi = {10.1007/978-1-60761-325-1_20}, author = {Gaskins, Audrey J and Schisterman, Enrique F} } @article {610436, title = {Effects of low-dose aspirin in in-vitro fertilization}, journal = {Curr Opin Obstet Gynecol}, volume = {21}, number = {3}, year = {2009}, month = {2009 Jun}, pages = {275-8}, abstract = {PURPOSE OF REVIEW: In theory, use of aspirin in IVF is based on its anti-inflammatory, vasodilatory, and platelet aggregation inhibition properties, which improve blood flow to a woman{\textquoteright}s implantation site. It is hypothesized that this effect on blood flow will improve success rates. RECENT FINDINGS: Clinical studies investigating the use of low-dose aspirin (LDA) as an adjuvant therapy to IVF have produced conflicting results. The conflicting results have come as a consequence of the heterogeneous mixture of clinical trials with lack of adequate power. Even after multiple meta-analyses, differing estimates of effect were calculated as to whether aspirin should be used in conjunction with IVF. SUMMARY: Conflicting results leave the question of the effects of LDA in IVF unanswered. More trials are required for analysis to have adequate statistical power and until then the data remain unclear. At this point, there are not enough data to show that aspirin has a beneficial effect on the outcomes of IVF, but absence of effect is not adequate grounds to overturn the current clinical practice for those using LDA in efforts aimed at achieving success with IVF.}, keywords = {Aspirin, Cyclooxygenase Inhibitors, Dose-Response Relationship, Drug, Female, Fertilization in Vitro, Humans, Meta-Analysis as Topic, Pregnancy}, issn = {1473-656X}, doi = {10.1097/GCO.0b013e32832a0673}, author = {Schisterman, Enrique F and Gaskins, Audrey J and Whitcomb, Brian W} }