Lynch C D, Sundaram R, Maisog J M, Sweeney A M, Buck Louis G M
The Ohio State University College of Medicine, 395 W. 12th Avenue, Room 580, Columbus, OH 43210, USA.
Hum Reprod. 2014 May;29(5):1067-75. doi: 10.1093/humrep/deu032. Epub 2014 Mar 23.
Are women's stress levels prospectively associated with fecundity and infertility?
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.
Data suggest that stress and reproduction are interrelated; however, the directionality of that association is unclear.
STUDY DESIGN, SIZE, DURATION: 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.
PARTICIPANTS/MATERIALS, SETTING, 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.
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.
LIMITATIONS, REASONS FOR CAUTION: 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.
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.
STUDY FUNDING/COMPETING INTEREST(S): 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.
Not applicable.
女性的压力水平与生育能力及不孕是否存在前瞻性关联？
唾液α-淀粉酶所测得的较高压力水平与较长的受孕时间（TTP）以及不孕风险增加有关。
数据表明压力与生殖相互关联；然而，这种关联的方向性尚不清楚。
研究设计、规模、持续时间：2005年至2009年，我们在美国两个研究地点（密歇根州和得克萨斯州）对501对夫妇进行了一项前瞻性队列研究，在孕前进行入组。夫妇们在尝试受孕期间接受长达12个月的随访，若怀孕则持续至孕期结束。共有401对（80%）夫妇完成了研究方案，373对（93%）有可供此分析的完整数据。
参与者/材料、设置、方法：入组女性在入组后的次日早晨以及首次观察到的研究月经后的次日早晨采集唾液，用于测量皮质醇和α-淀粉酶，这两种物质是压力的生物标志物。TTP按周期进行测量。协变量数据通过基线问卷和日常日志收集。
在完成方案的401名（80%）女性中，347名（87%）怀孕，54名（13%）未怀孕。在对女性年龄、种族、收入以及尝试受孕期间饮酒、咖啡因和吸烟情况进行调整后，α-淀粉酶处于最高三分位数的女性与最低三分位数的女性相比，生育能力降低了29%（TTP更长）[受孕几率比（FORs）=0.71；95%置信区间（CI）=(0.51, 1.00)；P<0.05]。生育能力的这种降低转化为这些女性不孕风险增加了两倍多[相对风险（RR）=2.07；95%CI=(1.04, 4.11)]。相比之下，我们未发现唾液皮质醇与受孕能力之间存在关联。
局限性、谨慎理由：由于财政和后勤方面的考虑，我们无法在整个随访期间收集重复的唾液样本和感知压力问卷数据。因此，我们无法研究随着女性持续未能怀孕压力水平是否会升高。然而，我们利用日常日志中的随时间变化数据控制潜在混杂因素的能力将残余混杂降至最低。
这是美国第一项证明唾液压力生物标志物与TTP之间存在前瞻性关联的研究，也是世界上第一项观察到与不孕存在关联的研究。
研究资金/利益冲突：本研究由尤妮斯·肯尼迪·施赖弗国家儿童健康与人类发展研究所的内部研究项目资助（合同编号#N01-HD-3-3355、N01-HD-3-3356、N01-HD-3358）。无利益冲突声明。
不适用。
