Stress and success: data from a prospective cohort investigating the impact of early life stress on IVF outcomes

Women who experienced early life stress (ELS) have aberrant hypothalamic-pituitary-adrenal and autonomic responses as well as an increased inflammatory response to induced stress when compared to ELS naïve women. The impact of ELS on infertile women is largely unknown. We sought to determine the prevalence of ELS in the infertile population and the impact of this dysregulated stress reactivity on IVF cycle characteristics and outcomes. Prospective cohort study. Women aged 18-42 were recruited for enrollment prior to initiating an autologous IVF cycle. Patients pursuing third party reproduction or fertility preservation were excluded. Consenting participants provided demographic information and completed the CDC-Kaiser Adverse Childhood Experience Questionnaire. Those who indicated 2+/10 positive responses were considered to be ELS positive. A power analysis indicated that a sample size of 277 subjects would provide at least 80% power with an alpha of 0.05 to detect a 40% relative difference in live birth rates between groups. Continuous variables were compared using Student’s t-test or Mann–Whitney U test based on normality, while χ2 or Fisher’s exact tests were used to compare categorical variables by ELS status. Logistic regression was used to assess for predictors of live birth and early pregnancy failure adjusting for confounders as appropriate. The prevalence of ELS positivity in this infertile cohort was 29.2% (n=83/284). ELS positive women and controls were similar in age, race/ethnicity, and history of anxiety/depression, however higher BMIs were observed in the ELS positive group (mean BMI 27.4 vs 25.6 kg/m2, p=.02). There were no differences in infertility diagnosis, pregnancy history, number of prior IVF cycles or ovarian reserve parameters. While live birth rates were similar in the two groups (37% vs 35%; aOR 1.13, 95% CI 0.65-1.95, p=0.658), ELS positive women had significantly higher rates of early pregnancy loss (EPL) per transfer (28% vs 17%, p=.04). This association persisted when the analysis was restricted to patients undergoing their first IVF cycle and excluding cycles in which preimplantation genetic testing was performed. After controlling for BMI and parity, ELS positivity remained significantly associated with EPL (aOR 1.95, 95% CI 1.05-3.62, p=0.03). However, when EPL rates were considered only among those who achieved a pregnancy (positive pregnancy test), no difference was observed between groups. Early life stress has a longstanding impact on adult health. While IVF cycle parameters and pregnancy rates do not seem to be impacted, infertile women who experienced ELS have significantly higher rates of early pregnancy loss per transfer. Further studies are needed to elucidate the precise mechanisms of these findings to identify risk reduction methods in this unique, potentially vulnerable, subpopulation of patients pursuing fertility services.