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Stress and reproductive failure: past notions, present insights and future directions

  • REPRODUCTIVE IMMUNOLOGY
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Problem

Maternal stress perception is frequently alleged as a cause of infertility, miscarriages, late pregnancy complications or impaired fetal development. The purpose of the present review is to critically assess the biological and epidemiological evidence that considers the plausibility of a stress link to human reproductive failure.

Methods

All epidemiological studies published between 1980 and 2007 that tested the link between stress exposure and impaired reproductive success in humans were identified. Study outcomes were evaluated on the basis of how associations were predicted, tested and integrated with theories of etiology arising from recent scientific developments in the basic sciences. Further, published evidence arising from basic science research has been assessed in order to provide a mechanistic concept and biological evidence for the link between stress perception and reproductive success.

Results

Biological evidence points to an immune–endocrine disequilibrium in response to stress and describes a hierarchy of biological mediators involved in a stress trigger to reproductive failure. Epidemiological evidence presents positive correlations between various pregnancy failure outcomes with pre-conception negative life events and elevated daily urinary cortisol. Strikingly, a relatively new conceptual approach integrating the two strands of evidence suggests the programming of stress susceptibility in mother and fetus via a so-called pregnancy stress syndrome.

Conclusions

An increasing specificity of knowledge is available about the types and impact of biological and social pathways involved in maternal stress responses. The present evidence is sufficient to warrant a reconsideration of conventional views on the etiology of reproductive failure. Physicians and patients will benefit from the adaptation of this integrated evidence to daily clinical practice.

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Acknowledgements

Valuable assistance to KLK was provided by Dr. James Tansey, Assistant Professor and Chair of Business Ethics at the Sauder School of Business, UBC. The authors are grateful for the support provided by Mirjam Ruecke and Ronny Schwierzinski in performing a prospective cohort trial.

Author information

Authors and Affiliations

  1. Interdisciplinary Studies Graduate Program, University of British Columbia, 6201 Cecil Green Park Road, Vancouver, BC, V6T 1Z1, Canada

    Katrina Nakamura

  2. Department of Health Care and Epidemiology, University of British Columbia, Vancouver, Canada

    Sam Sheps

  3. Western Regional Training Center for Health and Policy Research, University of British Columbia, Vancouver, Canada

    Sam Sheps

  4. Charité University Medicine, Berlin, Germany

    Petra Clara Arck

  5. Brain Body Institute, McMaster University, Hamilton, Canada

    Petra Clara Arck

Authors
  1. Katrina Nakamura
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  2. Sam Sheps
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  3. Petra Clara Arck
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Corresponding author

Correspondence to Katrina Nakamura.

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Capsule

Scientific evidence in synthesis supports the plausibility of a stress trigger to human reproductive failure; higher risk may be explained by pregnancy stress syndrome.

Appendix

Appendix

Box 1

Stress and human reproductive failure: recommendations for future research

Prospective study design with multiple evaluation time points during pregnancy and a large number of patients (500 or more)

Development of measurable indices for pregnancy stress syndrome

Psychometric tools

Biological markers such as neurohormones (urinary cortisol, CRH), neuropeptides (substance P), sex/pregnancy-related hormones (progesterone, estradiol, βHCG)

Environmental risk assessment (noise, chemical exposure)

Indicators of increased susceptibility or resilience to a stress risk to pregnancy failure via hereditary, cultural/ethnic and gender factors

Genetic profile

Cultural/ethnic context of the study population

Consideration of risk subgroups combining variables suspected to confer high risk, for example

High stress perception with low social support, age over 30 years, low BMI, low progesterone and smoking

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Nakamura, K., Sheps, S. & Clara Arck, P. Stress and reproductive failure: past notions, present insights and future directions. J Assist Reprod Genet 25, 47–62 (2008). https://doi.org/10.1007/s10815-008-9206-5

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  • DOI: https://doi.org/10.1007/s10815-008-9206-5

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