Lynch · Human reproduction (Oxford, England) 2014 · prospective cohort study · n=373

Preconception stress increases the risk of infertility: results from a couple-based prospective cohort study--the LIFE study.

Cited 203 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective cohort study tracking preconception stress biomarkers to pregnancy outcomes over 12 months

PubMed 24664130 · doi:10.1093/humrep/deu032 · record verified 2026-08-26

What was done

Couples (n = 501 enrolled, 401 completed protocol) trying to conceive in Michigan and Texas were followed prospectively for up to 12 months in the LIFE study (2005–2009). Women collected morning saliva samples on the day following enrollment and the day after their first observed menses during the study to measure salivary alpha-amylase and cortisol. Time-to-pregnancy (measured in cycles) and infertility (failure to conceive within 12 months) were evaluated in 373 women with complete data, adjusting for age, race, income, and time-varying alcohol, caffeine, and cigarette use.

What was found

Among 401 women completing follow-up, 347 (87%) conceived and 54 (13%) did not. Women in the highest tertile of salivary alpha-amylase experienced a 29% reduction in fecundability compared with the lowest tertile (fecundability odds ratio = 0.71, 95% CI 0.51 to 1.00, P < 0.05) and a more than two-fold increased risk of infertility (relative risk = 2.07, 95% CI 1.04 to 4.11). Salivary cortisol showed no statistically significant association with fecundability.

Why it matters

This study provides prospective human evidence linking sympathetic nervous system activation, measured via alpha-amylase, with increased time-to-pregnancy and doubled risk of clinical infertility.

Limits

Saliva sampling and stress measures were only collected at enrollment and the first observed menses rather than repeatedly throughout the 12-month follow-up, preventing assessment of reverse causality where prolonged failure to conceive increases stress. Findings were restricted to alpha-amylase while cortisol showed no association, and unmeasured lifestyle or biological confounders cannot be fully ruled out.

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