Diet and Lifestyle in the Prevention of Ovulatory Disorder I... : Obstetrics & Gynecology

OBJECTIVE: To evaluate the relation of a dietary pattern and other lifestyle practices to risk of ovulatory disorder infertility. METHODS: We followed a cohort of 17,544 women without a history of infertility for 8 years as they tried to become pregnant or became pregnant. A dietary score based on factors previously 6/17/13 1:11 PM Diet and Lifestyle in the Prevention of Ovulatory Disorder I... : Obstetrics & Gynecology Page 2 of 13 http://journals.lww.com/greenjournal/Fulltext/2007/11000/Diet_and_Lifestyle_in_the_Prevention_of_Ovulatory.17.aspx related to lower ovulatory disorder infertility (higher consumption of monounsaturated rather than trans fats, vegetable rather than animal protein sources, low glycemic carbohydrates, high fat dairy, multivitamins, and iron from plants and supplements) and other lifestyle information was prospectively related to the incidence of infertility. RESULTS: Increasing adherence to a “fertility diet” pattern was associated with a lower risk of ovulatory disorder infertility. The multivariable-adjusted relative risk of ovulatory disorder infertility comparing women in the highest with women in the lowest quintile of the “fertility diet” pattern score was 0.34 (95% confidence interval 0.23–0.48; P for trend<.001). This inverse relation was similar in subgroups defined by women’s age, parity, and body weight. A combination of five or more low-risk lifestyle factors, including diet, weight control, and physical activity was associated with a 69% lower risk of ovulatory disorder infertility and an estimated population attributable risk of 66% (95% confidence interval 29–86%). CONCLUSION: Following a “fertility diet” pattern may favorably influence fertility in otherwise healthy women. Further, the majority of infertility cases due to ovulation disorders may be preventable through modifications of diet and lifestyle. LEVEL OF EVIDENCE: II Infertility is a common condition affecting one of six couples during their reproductive lifetime.1 Among these couples, problems with ovulation can be identified in 18–30% of the cases.1–3 Although treatment options for infertility are available, their large cost4,5 and frequency of adverse events6,7 have motivated the identification of potentially modifiable risk factors. We have previously found that body weight,8,9 physical activity,9 and dietary factors, such as intakes of specific fatty acids,10 protein (Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Protein intake and ovulatory infertility. Am J Obstet Gynecol. In press), carbohydrates (Chavarro JE, RichEdwards JW, Rosner BA, Willett WC. A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility. Eur J Clin Nutr. In press), dairy foods,11 iron,12 and multivitamins,13 are related to infertility due to ovulation disorders. These findings suggest that an overall dietary and lifestyle pattern aimed at increasing the intake of certain micronutrients and improving insulin sensitivity through the modification of diet composition, weight control, and increased physical activity may help prevent ovulatory disorder infertility. However, the degree to which a fertility-promoting dietary pattern, by itself or in combination with changes in body weight and physical activity, may reduce infertility is unknown, as is the proportion of cases that could be prevented. To address these questions, we conducted a prospective observational analysis of diet, physical activity, and body weight in relation to incident infertility due to ovulation disorders among apparently healthy women enrolled in the Nurses’ Health Study II. MATERIALS AND METHODS The Nurses’ Health Study II is prospective cohort study started in 1989 when more than 116,000 female registered nurses aged 25–42 years completed a mailed baseline questionnaire. Participants 6/17/13 1:11 PM Diet and Lifestyle in the Prevention of Ovulatory Disorder I... : Obstetrics & Gynecology Page 3 of 13 http://journals.lww.com/greenjournal/Fulltext/2007/11000/Diet_and_Lifestyle_in_the_Prevention_of_Ovulatory.17.aspx have been followed biennially since then with mailed questionnaires. The study was approved by the Institutional Review Board of Brigham and Women’s Hospital. Follow-up for the current analysis started in 1991, when diet was first measured, and concluded in 1999. Every 2 years participants were asked if they had tried to become pregnant for more than 1 year without success since the previous questionnaire administration and to indicate whether their inability to conceive was caused by tubal blockage, ovulatory disorder, endometriosis, cervical mucus factor, male factor, or was not found, was not investigated, or was due to another reason. In a validation study among members of this cohort, self-reported diagnosis of ovulatory disorder infertility was confirmed by review of medical records in 95% of the cases.8 Women were also asked if they became pregnant during the preceding 2-year period, including pregnancies resulting in miscarriages or induced abortions. Using this information, we identified a cohort of women most likely attempting to become pregnant. Only married women (whose pregnancies are more likely to be intentional14) without a history of infertility and with available information on diet, physical activity, height, and weight were eligible to enter the analysis. These women contributed information to the analysis during each 2-year period in which they reported a pregnancy or a failed pregnancy attempt and were followed until they reported infertility from any cause, reached menopause, or underwent a sterilization procedure (themselves or their partner), whichever came first. We excluded the 10 diabetic women meeting these criteria. In total, we identified 17,544 women without a history of infertility who tried to become pregnant or became pregnant during the study period. Reports of infertility due to ovulatory disorder were considered cases. All other events (pregnancies —resulting in live births, miscarriages, or induced abortions—and infertility due to other causes) were considered noncases. We calculated body mass index (weight in kilograms divided by height squared in meters) (BMI) using height reported in the 1989 baseline questionnaire and weight reported in the most recent follow-up questionnaire. Self-reported height and weight have high validity in this and similar cohorts.15,16 Physical activity information was collected in 1991 and 1997 using a previously validated instrument,17 in which women reported the average time spent in eight different activities. We summed the contribution of each activity to obtain the average daily time spent in moderate (4–5.9 metabolic equivalents/h) and vigorous physical activities (6 metabolic equivalents/h or more). Dietary information was collected in 1991 and 1995 using a validated food-frequency questionnaire.18,19 This questionnaire has been previously found to validly estimate nutrient intakes 4 years in the past.20 Participants were asked to report how often, on average, they consumed each of the foods, beverages, and supplements included in the food-frequency questionnaire during the previous year. The questionnaire offered nine options for frequency of intake for each food that ranged from “never or less than once per month” to “six or more times per day.” The nutrient content of each food and specified portion size was obtained from a nutrient database derived from the U.S. Department of Agriculture,21 with supplemental information from other sources.22 Dietary glycemic load was calculated as the product of total carbohydrate intake 6/17/13 1:11 PM Diet and Lifestyle in the Prevention of Ovulatory Disorder I... : Obstetrics & Gynecology Page 4 of 13 http://journals.lww.com/greenjournal/Fulltext/2007/11000/Diet_and_Lifestyle_in_the_Prevention_of_Ovulatory.17.aspx times the average dietary glycemic index.19 We maintained a strictly prospective analysis of these factors in relation to infertility. Body mass index information from 1991 was related to cases reported in 1993; the 1993 BMI information was used for cases reported in 1995, and so forth. Physical activity data reported in 1991 were related to the 1991–1997 follow-up period, and the data reported in 1997 were related to the remainder of follow-up. For dietary variables we calculated cumulative averaged intakes to reduce measurement error due to within-person variation over time.23 Thus, the 1991 diet was related to cases reported in 1993 and 1995, and the average of the 1991 and 1995 diets was related to cases reported in 1997 and 1999. A summary “fertility diet” score was calculated for each woman based on variables we had earlier found to predict ovulatory disorder infertility, assigning the highest score to the category with the lowest risk. Thus, for increasing monounsaturated/trans fat ratio, vegetable protein, high-fat dairy, iron, and multivitamins, we assigned from 1 to 5 points from the lowest to the highest category. For animal protein, glycemic load, and low-fat dairy, the point assignment was reversed; women in the lowest intake category received 5 points and women in the highest stratum received 1 point (Table 1). Points for each of the variables were added to obtain the “fertility diet” score, which ranged from 8 to 40. The median score was 24 points. Women were divided into five groups according to quintiles of this score.