Dietary Fat Intake and Fecundability in 2 Preconception Cohort Studies

American Journal of Epidemiology © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: . Vol. 187, No. 1 DOI: 10.1093/aje/kwx204 Advance Access publication: June 8, 2017 Original Contribution Dietary Fat Intake and Fecundability in 2 Preconception Cohort Studies * Correspondence to Dr. Lauren A. Wise, Department of Epidemiology, Boston University School of Public Health, Talbot Building, 4th Floor, Boston, MA, 02118 (e-mail: ). Initially submitted September 7, 2016; accepted for publication March 15, 2017. The association between dietary fat and fertility is not well studied. We evaluated intakes of total fat, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, trans fatty acids (TFA), ω-3 fatty acids, and ω-6 fatty acids in relation to fecundability in Danish and North American preconception cohort studies. Women who were attempting to become pregnant completed a validated food frequency questionnaire at baseline. Pregnancy status was updated bimonthly for 12 months or until pregnancy. Fecundability ratios (FR) and 95% confidence intervals were estimated using multivariable proportional probabilities regression. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and ω-6 fatty acids were not appreciably associated with fecundability. TFA intake was associated with reduced fecundability in North American women (for the fourth quartile vs. the first, FR = 0.86, 95% confidence interval (CI): 0.71, 1.04) but not Danish women (for the fourth quartile vs. the first, FR = 1.04, 95% CI: 0.86, 1.25), though intake among Danish women was low. In North America, ω-3 fatty acid intake was associated with higher fecundability, but there was no dose-response relationship (among persons who did not use fish oil supplements: for the fourth quartile vs. the first, FR = 1.40, 95% CI: 1.13, 1.73); no association was found in Danish women, among whom low intake was rare. In the present study, high TFA intake and low ω-3 fatty acid intake were associated with reduced fecundity. fatty acids; fertility; internet; prospective studies; trans fatty acids Abbreviations: BMI, body mass index; CI, confidence interval; FFQ, food frequency questionnaire; FR, fecundability ratio; LMP, last menstrual period; MET, metabolic equivalent; MUFA, monounsaturated fatty acid; PRESTO, Pregnancy Study Online; PUFA, polyunsaturated fatty acid; SD, standard deviation; SF, Snart Foraeldre; SFA, saturated fatty acid; TFA, trans fatty acid; TTP, time to pregnancy. acids (TFAs) was associated with ovulatory infertility (5) and endometriosis (6). In animal studies, a higher intake of ω-3 fatty acids has been associated with improved markers of fertility (7–9), particularly in male rodents (8, 9), but evidence in humans is limited (10–14). We assessed the association between dietary fat consumption and time to pregnancy (TTP) among women participating in preconception cohort studies in Denmark and North America. Specifically, we examined total dietary fat intake and intakes of major subtypes of fatty acids, including saturated fatty acid (SFA), polyunsaturated fatty acid (PUFA), monounsaturated fatty acid (MUFA), TFA, ω-3 fatty acids, and ω-6 fatty acids in relation to fecundability. Approximately 10%–15% of couples experience infertility, which is clinically defined as inability to conceive after 12 months of unprotected intercourse (1). Fats comprise 30%– 40% of daily energy intake in Western countries. They are essential components of cell membranes and can modulate the expression of enzymes involved in the metabolism of prostaglandins and steroid hormones, which are critical for reproduction (2). The association between dietary fat intake and fertility has not been studied extensively. Fat-rich diets have been associated with poor oocyte development, possibly related to the induction of oxidative stress in the follicular environment (3, 4). However, the type of fat likely matters. In a prospective cohort study of female nurses, a higher intake of trans fatty 60 Am J Epidemiol. 2018;187(1):60–74 Lauren A. Wise*, Amelia K. Wesselink, Katherine L. Tucker, Shilpa Saklani, Ellen M. Mikkelsen, Heidi Cueto, Anders H. Riis, Ellen Trolle, Craig J. McKinnon, Kristen A. Hahn, Kenneth J. Rothman, Henrik Toft Sørensen, and Elizabeth E. Hatch Dietary Fat Intake and Fertility METHODS Study population Am J Epidemiol. 2018;187(1):60–74 status, self-administered online follow-up questionnaires were completed every 8 weeks for 12 months or until a reported conception. Assessment of fatty acid intake Dietary fat intake was estimated using the nutrient composition of all food items in the FFQ and validated in each population (17, 19). Total dietary fat intake was calculated by summing all servings of fat from individual foods and mixed recipes. In SF, information about the fat content of specific foods was obtained from the Danish nutrient database (20). In PRESTO, we used the National Cancer Institute’s DIET*CALC software (version 1.5.0) (21) to estimate fat consumption. In the SF dietary validation study, deattenuated correlation coefficients when comparing the FFQ data to 4-day food records were 0.63 for total fat, 0.61 for SFA, 0.59 for MUFA, and 0.49 for PUFA (17). In the Dietary Health Questionnaire II validation study, deattenuated correlation coefficients when comparing the FFQ data to repeated 24-hour dietary recalls were 0.66 for total fat, 0.66 for SFA, 0.62 for MUFA, and 0.64 for PUFA (19). Assessment of TTP We estimated TTP using data from the baseline and followup questionnaires. Women with regular menstrual cycles were asked to report their usual menstrual cycle length. Among women with irregular cycles, we estimated menstrual cycle length based on date of LMP at baseline and prospectively reported LMP dates during follow-up. We estimated TTP, in discrete menstrual cycles, using the following formula: [(reported cycles of pregnancy attempt time at baseline) + [(LMP date from most recent followup questionnaire − date of baseline questionnaire)/cycle length] + 1]. TTP was rounded to the nearest whole number. Assessment of covariates Information on potential confounders (including age, race/ ethnicity (PRESTO only), educational level, household income, height, weight, physical activity level, smoking, alcohol consumption, marital status, last method of contraception, parity, and use of supplements (including fish oil supplements)) was reported on the baseline questionnaire. We calculated body mass index (BMI) as weight in kilograms divided by height in meters squared. In SF, total metabolic equivalent (MET)–hours per week were calculated using the International Physical Activity Questionnaire short-form by summing the MET-hours from walking, moderate physical activity, and vigorous physical activity (hours/week × 3.3 METs, 4 METs, and 8 METs, respe (...truncated)