Elsevier

Annals of Epidemiology

Volume 26, Issue 10, October 2016, Pages 710-716.e7
Annals of Epidemiology

Original article
The impact of periconceptional maternal stress on fecundability

https://doi.org/10.1016/j.annepidem.2016.07.015Get rights and content

Abstract

Purpose

To examine the association between periconceptional self-reported stress levels and fecundability in women.

Methods

Daily stress was reported on a scale from 1 to 4 (lowest to highest) among 400 women who completed daily diaries including data on lifestyle and behavioral factors, menstrual characteristics, contraceptive use, and intercourse for up to 20 cycles or until pregnancy. Discrete survival analysis was used to estimate the associations between self-reported stress during specific windows of the menstrual cycle and fecundability (cycles at risk until pregnancy), adjusting for potential confounders.

Results

One hundred thirty-nine women became pregnant. During the follicular phase, there was a 46% reduction in fecundability for a 1-unit increase in self-reported stress during the estimated ovulatory window (fecundability odds ratio [FOR] = 0.54; 95% confidence interval [CI] 0.35–0.84) and an attenuated trend for the preovulatory window (FOR = 0.73; 95% CI 0.48–1.10). During the luteal phase, higher stress was associated with increased probability of conception (FOR = 1.63, 95% CI 1.07–2.50), possibly due to reverse causality.

Conclusions

Higher stress during the ovulatory window may reduce probability of conception; however, once conception occurs, changes in the hormonal milieu and/or knowledge of the pregnancy may result in increased stress. These findings reinforce the need for encouraging stress management techniques in the aspiring and expecting mother.

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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    There are no conflicts of interest to declare.

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