Original articleThe impact of periconceptional maternal stress on fecundability
Introduction
Perceived stress has long been hypothesized to reduce the probability of conception. The belief that stress decreases fertility can be partially attributed to studies reporting natural conception by infertile couples soon after the adoption of a child [1], [2] and, more recently, increased probability of pregnancy among in vitro fertilization patients undergoing stress reduction interventions [3], [4], [5].
An effect of stress on conception may be the consequence of overactivation of the hypothalamic-pituitary-adrenal (HPA) axis. Stress may affect ovulation by causing a rise in plasma glucocorticoid levels, which consequently suppress gonadotrophin releasing hormone (GnRH) [6]. Increased HPA axis function and high concentrations of glucocorticoids can be detrimental to the developing endometrium [7]. The process of implantation is a form of uterine inflammation, and intracellular cytokines such as uterine NFkappaB are critical during implantation [8]. However, if glucocorticoids suppress NFkappaB and the local inflammation, then they are indirectly compromising the process of implantation [9].
Only a few prospective epidemiologic studies have rigorously investigated the hypothesis behind stress and fecundability, with varied results [10], [11], [12], [13]. None of the studies compared the effects of stress across different windows of the menstrual cycle. If stress affects the process of ovulation or fertilization, then stress in the follicular phase (especially during the ovulatory window) may affect fecundability; rather, if stress interferes with implantation, then stress during the luteal phase would affect fecundability.
More research is clearly needed to quantify the effects of perceived stress on fecundability. The objective of this study is to examine the association between self-reported stress and fecundability and identify the window(s) of highest susceptibility during the menstrual cycle, using a large daily data set from a prospective pregnancy study of women office workers.
Section snippets
Study population and eligibility
The Mount Sinai Study of Women Office Workers was a prospective study originally designed to evaluate the reproductive health of women office workers 40 years of age and younger. Through 1990–1994, women were enrolled from 14 companies and government agencies in New England [14], [15]. Women who were sexually active while using inconsistent or no contraceptives in the month before the baseline questionnaire were eligible. Women using intrauterine devices, having a hysterectomy, or diagnosed
Study population
Women who had completed at least one daily diary (N = 563) were eligible for inclusion in the prospective pregnancy study. Excluded from the current analysis were 76 women who had less than 30 days of stress information (resulting in N = 487). The final sample size for analysis was 400 women after excluding 87 additional participants with missing data for any of the following covariates at baseline: age, intention to conceive, parity, marital status, or education. The 87 women excluded from the
Main findings on fecundability
This is the first prospective cohort study to examine the association between self-reported stress and fecundability during specific windows of susceptibility during the menstrual cycle. Higher stress during the estimated ovulatory window was statistically significantly associated with a 46% decrease in fecundability. This effect is large enough to be considered clinically significant, as it translates to more than a 3-month delay in conception. The American Society of Reproductive Medicine
Conclusion
Findings from this study support a significant reduction in fecundability during the ovulatory window for women experiencing higher levels of stress before conception. These findings—that specific windows during the menstrual cycle may be particularly vulnerable to stress—are important for two reasons: they pave the way to pinpointing specific biological mechanisms that could be tested (e.g., in animal models or in longitudinal epidemiologic studies with daily measures of reproductive hormone
Acknowledgments
The authors thank the participants of the MSSWOW study. The authors thank Emily Steinmetz for reviewing the final article.
The National Institutes of Health (R01-HD24618, R01-ES012458) supported this work.
Authors' contributions: S.A. and K.T. planned the analysis, conducted analyses, interpreted the results, and drafted and edited the article. M.M. was the PI responsible for designing the study and implementing data and biospecimen collection for the MSSWOW study. She also reviewed and edited
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2019, PsychoneuroendocrinologyCitation Excerpt :While the PSS (Cohen et al., 1983) has been widely used around the world to study the role of chronic psychological stress in the etiology of adverse health outcomes, several researchers have been questioning its appropriateness for studies assessing women’s menstrual cycle and fecundability (Lynch et al., 2012; Nakamura et al., 2008; Schliep et al., 2015). Given that reproductive outcomes are known to be sensitive to critical windows of exposure, measuring daily perceived stress over the course of the menstrual cycle may more precisely capture the physical responses to daily hassles in women compared to measuring a single baseline stress (Akhter et al., 2016; Bolger et al., 2003; Schliep et al., 2015). Indeed, one recent study, conducted among 259 premenopausal women found a significant inverse relationship between daily perceived stress and total estradiol, luteal progesterone, and ovulatory function, whereas there was no association when using the baseline PSS-14 or the cycle PSS-4 (Schliep et al., 2015).
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There are no conflicts of interest to declare.