title: Preconception stress increases the risk of infertility: results from a couple-based prospective cohort study--the LIFE study.
abstract: OBJECTIVE
  Are women's stress levels prospectively associated with fecundity and infertility?
  
  
  CONCLUSIONS
  Higher levels of stress as measured by salivary alpha-amylase are associated with a longer time-to-pregnancy (TTP) and an increased risk of infertility.
  
  
  BACKGROUND
  Data suggest that stress and reproduction are interrelated; however, the directionality of that association is unclear.
  
  
  METHODS
  In 2005-2009, we enrolled 501 couples in a prospective cohort study with preconception enrollment at two research sites (Michigan and Texas, USA). Couples were followed for up to 12 months as they tried to conceive and through pregnancy if it occurred. A total of 401 (80%) couples completed the study protocol and 373 (93%) had complete data available for this analysis.
  
  
  METHODS
  Enrolled women collected saliva the morning following enrollment and then the morning following their first observed study menses for the measurement of cortisol and alpha-amylase, which are biomarkers of stress. TTP was measured in cycles. Covariate data were captured on both a baseline questionnaire and daily journals.
  
  
  RESULTS
  Among the 401 (80%) women who completed the protocol, 347 (87%) became pregnant and 54 (13%) did not. After adjustment for female age, race, income, and use of alcohol, caffeine and cigarettes while trying to conceive, women in the highest tertile of alpha-amylase exhibited a 29% reduction in fecundity (longer TTP) compared with women in the lowest tertile [fecundability odds ratios (FORs) = 0.71; 95% confidence interval (CI) = (0.51, 1.00); P < 0.05]. This reduction in fecundity translated into a >2-fold increased risk of infertility among these women [relative risk (RR) = 2.07; 95% CI = (1.04, 4.11)]. In contrast, we found no association between salivary cortisol and fecundability.
  
  
  CONCLUSIONS
  Due to fiscal and logistical concerns, we were unable to collect repeated saliva samples and perceived stress questionnaire data throughout the duration of follow-up. Therefore, we were unable to examine whether stress levels increased as women continued to fail to get pregnant. Our ability to control for potential confounders using time-varying data from the daily journals, however, minimizes residual confounding.
  
  
  CONCLUSIONS
  This is the first US study to demonstrate a prospective association between salivary stress biomarkers and TTP, and the first in the world to observe an association with infertility.
  
  
  BACKGROUND
  This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts #N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358). There are no conflicts of interest to declare.
  
  
  BACKGROUND
  Not applicable.
authors.affiliation: The Ohio State University College of Medicine, 395 W. 12th Avenue, Room 580, Columbus, OH 43210, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Lynch
authors.forename: R
authors.initials: R
authors.lastname: Sundaram
authors.forename: J M
authors.initials: JM
authors.lastname: Maisog
authors.forename: A M
authors.initials: AM
authors.lastname: Sweeney
authors.forename: G M
authors.initials: GM
authors.lastname: Buck Louis
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D011247:Pregnancy; D011446:Prospective Studies; D055291:Salivary alpha-Amylases / Q000032:analysis; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology; D061685:Time-to-Pregnancy; D055815:Young Adult
chemical_list: D015415:Biomarkers; D055291:Salivary alpha-Amylases
keywords: alpha-amylase; cortisol; fecundity; infertility; stress