S Mahalingaiah1, J E Hart2, F Laden3, L V Farland4, M M Hewlett5, J Chavarro6, A Aschengrau7, S A Missmer8. 1. Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, MA 02118, USA shruthi@bu.edu. 2. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. 3. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. 4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. 5. Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston, MA 02118, USA. 6. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. 7. Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA. 8. Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Abstract
STUDY QUESTION: Is there an association between air pollution exposures and incident infertility? SUMMARY ANSWER: Increased exposure to air pollution is associated with an increased incidence of infertility. WHAT IS KNOWN ALREADY: Exposures to air pollution have been associated with lower conception and fertility rates. However, the impact of pollution on infertility incidence is unknown. STUDY DESIGN, SIZE, DURATION: Prospective cohort study using data collected from 116 430 female nurses from September 1989 to December 2003 as part of the Nurses' Health Study II cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertility was defined by report of attempted conception for ≥12 months without success. Participants were able to report if evaluation was sought and if so, offer multiple clinical indications for infertility. After exclusion, 36 294 members were included in the analysis. Proximity to major roadways and ambient exposures to particulate matter less than 10 microns (PM10), between 2.5 and 10 microns (PM2.5-10), and less than 2.5 microns (PM2.5) were determined for residential addresses for the 36 294 members between the years of 1993 and 2003. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable adjusted Cox proportional hazard models with time-varying covariates. MAIN RESULTS AND THE ROLE OF CHANCE: Over 213 416 person-years, there were 2508 incident reports of infertility. Results for overall infertility were inconsistent across exposure types. We observed a small increased risk for those living closer to compared to farther from a major road, multivariable adjusted HR = 1.11 (CI: 1.02-1.20). This was consistent for those reporting primary or secondary infertility. For women living closer to compared to farther from a major road, for primary infertility HR = 1.05 (CI: 0.94-1.17), while for secondary infertility HR = 1.21 (CI: 1.07-1.36). In addition, the HR for every 10 µg/m(3) increase in cumulative PM2.5-10 among women with primary infertility was 1.10 (CI: 0.96-1.27), and similarly was 1.10 (CI: 0.94-1.28) for those with secondary infertility. LIMITATIONS, REASONS FOR CAUTION: Within the 2 year window of infertility diagnosis, we do not have the exact date of diagnosis or the exact timing of the start of attempting conception. As infertility status and subtypes of infertility were prospectively collected biennially, we were unable to tightly examine the timing of exposures on incidence of infertility. In terms of exposure quantification, we used ambient air pollution exposures as a proxy for personal exposures, potentially leading to exposure misclassification. However, several studies suggest that ambient measurements are an acceptable surrogate for individual level exposures in most populations. WIDER IMPLICATIONS OF THE FINDINGS: We observed an association between all size fractions of PM exposure, as well as traffic-related air pollution, and incidence of infertility. Of note, the strongest association was observed between cumulative average exposures over the course of follow-up and the risk of infertility, suggesting that chronic exposures may be of greater importance than short-term exposures. STUDY FUNDING/COMPETING INTERESTS: The work for this paper was supported by the following: S.M.: Reproductive Scientist Development Program HD000849, and the Building Interdisciplinary Research Careers in Women's Health HD043444, the Boston University CTSI 1UL1TR001430, and a research grant from the Boston University Department of Obstetrics and Gynecology, S.A.M.: R01HD57210 from the National Institute of Child Health and Human Development and the Massachusetts Institute of Technology Center for Environmental Health Sciences Translational Pilot Project Program, R01CA50385 from the National Cancer Institute, J.E.H. and F.L.: 5R01ES017017 from the National Institute for Environmental Health Sciences, 5 P42 ES007381 from the National Institute of Environmental Health at the National Institute of Health. L.V.F.: T32HD060454 in reproductive, perinatal, and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Nurses' Health Study II is additionally supported by infrastructure grant UM1CA176726 from the National Cancer Institute, NIH, U.S. Department of Health and Human Services. The authors have no actual or potential competing financial interests to disclose.
STUDY QUESTION: Is there an association between air pollution exposures and incident infertility? SUMMARY ANSWER: Increased exposure to air pollution is associated with an increased incidence of infertility. WHAT IS KNOWN ALREADY: Exposures to air pollution have been associated with lower conception and fertility rates. However, the impact of pollution on infertility incidence is unknown. STUDY DESIGN, SIZE, DURATION: Prospective cohort study using data collected from 116 430 female nurses from September 1989 to December 2003 as part of the Nurses' Health Study II cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS:Infertility was defined by report of attempted conception for ≥12 months without success. Participants were able to report if evaluation was sought and if so, offer multiple clinical indications for infertility. After exclusion, 36 294 members were included in the analysis. Proximity to major roadways and ambient exposures to particulate matter less than 10 microns (PM10), between 2.5 and 10 microns (PM2.5-10), and less than 2.5 microns (PM2.5) were determined for residential addresses for the 36 294 members between the years of 1993 and 2003. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariable adjusted Cox proportional hazard models with time-varying covariates. MAIN RESULTS AND THE ROLE OF CHANCE: Over 213 416 person-years, there were 2508 incident reports of infertility. Results for overall infertility were inconsistent across exposure types. We observed a small increased risk for those living closer to compared to farther from a major road, multivariable adjusted HR = 1.11 (CI: 1.02-1.20). This was consistent for those reporting primary or secondary infertility. For women living closer to compared to farther from a major road, for primary infertility HR = 1.05 (CI: 0.94-1.17), while for secondary infertility HR = 1.21 (CI: 1.07-1.36). In addition, the HR for every 10 µg/m(3) increase in cumulative PM2.5-10 among women with primary infertility was 1.10 (CI: 0.96-1.27), and similarly was 1.10 (CI: 0.94-1.28) for those with secondary infertility. LIMITATIONS, REASONS FOR CAUTION: Within the 2 year window of infertility diagnosis, we do not have the exact date of diagnosis or the exact timing of the start of attempting conception. As infertility status and subtypes of infertility were prospectively collected biennially, we were unable to tightly examine the timing of exposures on incidence of infertility. In terms of exposure quantification, we used ambient air pollution exposures as a proxy for personal exposures, potentially leading to exposure misclassification. However, several studies suggest that ambient measurements are an acceptable surrogate for individual level exposures in most populations. WIDER IMPLICATIONS OF THE FINDINGS: We observed an association between all size fractions of PM exposure, as well as traffic-related air pollution, and incidence of infertility. Of note, the strongest association was observed between cumulative average exposures over the course of follow-up and the risk of infertility, suggesting that chronic exposures may be of greater importance than short-term exposures. STUDY FUNDING/COMPETING INTERESTS: The work for this paper was supported by the following: S.M.: Reproductive Scientist Development Program HD000849, and the Building Interdisciplinary Research Careers in Women's Health HD043444, the Boston University CTSI 1UL1TR001430, and a research grant from the Boston University Department of Obstetrics and Gynecology, S.A.M.: R01HD57210 from the National Institute of Child Health and Human Development and the Massachusetts Institute of Technology Center for Environmental Health Sciences Translational Pilot Project Program, R01CA50385 from the National Cancer Institute, J.E.H. and F.L.: 5R01ES017017 from the National Institute for Environmental Health Sciences, 5 P42 ES007381 from the National Institute of Environmental Health at the National Institute of Health. L.V.F.: T32HD060454 in reproductive, perinatal, and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The Nurses' Health Study II is additionally supported by infrastructure grant UM1CA176726 from the National Cancer Institute, NIH, U.S. Department of Health and Human Services. The authors have no actual or potential competing financial interests to disclose.
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