New Prospective Cohort Study Reports the Association between Preconception Stress and Enhanced Infertility Risk

Literature evidence suggests a close inter-relationship between stress and reproduction, but its directionality is not clearly known. Recently, a US study demonstrated that increased stress levels in couples, as evaluated by salivary alpha-amylase, may lead to longer time-to-pregnancy (TTP) and a higher risk of infertility. The findings, touted to be the first in the world to prospectively link salivary stress markers with infertility, are published in the journal Human Reproduction.

Courtney Denning-Johnson Lynch, Director of Reproductive Epidemiology, The Ohio State University College of Medicine, Columbus, USA, and coworkers conducted the prospective cohort study on 501 couples who were trying to conceive, and followed them up to 1 year to investigate if conception occurred. The study protocol was completed by 80% of the couples (n=401), with the entire data available for analysis in 93% of the subjects. Saliva was collected from all the enrolled women in the morning after registration and also subsequent to their first study menses to compute the stress biomarkers, alpha-amylase, and cortisol. The scientists noted TTP in the cycles, and both baseline questionnaire and daily journals were used to capture covariate data.

The results showed that while 87% (347/401) women achieved pregnancy, the remaining did not succeed in their attempts. Moreover, there was a 29% decrease in fecundity in the women in the highest tertile of alpha-amylase, when compared to those in the lowest tertile, following adjustment for confounding factors like race, female age, alcohol usage, income, and cigarettes and caffeine use (fecundability odds ratios [FORs]=0.71; 95% CI=0.51 to 1.00; P<0.05). Considering this, the researchers reported >2 fold heightened risk for infertility in such women (relative risk [RR]=2.07; 95% CI=1.04 to 4.11). Contrastingly, no such relationship was established between fecundability and salivary cortisol.

In an earlier study, Louis et al (Fertility and Sterility, 2011) demonstrated that stress decreases the chances of conception across the fertile window. Analyzing 274 women, the researchers used basal saliva samples (collected on day 6 of every cycle) to measure salivary alpha-amylase and cortisol levels. The estimation of probability of pregnancy during fertile window and fecundity was done by Bayesian modeling and discrete-time survival techniques, respectively. The results indicated a negative association between fecundity in the first cycle and alpha-amylase concentrations (OR=0.85; 95% CI=0.67-1.09), following the adjustment for intercourse frequency, ages of couples, and alcohol consumption. However, there was no negative correlation between cortisol levels and fecundity.

Similarly, Park et al (Journal of the Korean Medical Association, 2011) observed that preconception stress affects the rate of infertility in women by 10-15%, with depression, rather than anxiety disorder, being the reason for the association. It was also found that the quality and density of sperm is adversely affected following disasters, thereby indicating the impact of stress on male infertility. Additionally, the study noted that increased stress both prior to and during pregnancy may lead to small-for-gestational age infants, preterm labor, and decreased infant weight. In the light of these findings, the researchers emphasized the importance of psychiatric care and treatment in order to relieve preconception distress.

Although maternal stress is implicated in a number of complications such as miscarriages, infertility, and impaired fetal development, there is an urgent need to reconsider the conventional opinion on the etiology of reproductive failure. Nakamura et al (Journal of Assisted Reproduction and Genetics, 2008) reviewed the biological and epidemiological evidence to determine the plausible link between reproductive failure and stress. The review suggested the following:

  • Stress creates immune-endocrine disequilibrium, as per biological evidence
  • Positive link of negative life events during preconception and increased daily urinary cortisol with pregnancy failure outcomes, as per epidemiological evidence
  • A conceptual approach, that integrates the two, indicates stress susceptibility programming in mother and fetus through pregnancy stress syndrome. Thus, the increased risk of reproductive failure could be attributed to pregnancy stress syndrome.

Integration of this knowledge into routine clinical practice, in conjunction with preconception care/treatment for all couples, may help in reducing the complications associated with stress.


  • Lynch CD, Sundaram R, Maisog JM, Sweeney AM, Buck Louis GM. Preconception stress increases the risk of infertility: results from a couple-based prospective cohort study–the LIFE study. Hum Reprod. 2014 May;29(5):1067-75.
  • Louis GM, Lum KJ, Sundaram R, et al. Stress reduces conception probabilities across the fertile window: evidence in support of relaxation. Fertil Steril. 2011 Jun;95(7):2184-9. doi: 10.1016/j.fertnstert.2010.06.078.
  • Park YC, Park SC, Park M-II. The preconception stress and mental health of couples. Taehan Uihak Hyophoe Chi. 2011 Aug;54(8):832-37.
  • Nakamura K, Sheps S, Arck PC. Stress and reproductive failure: past notions, present insights and future directions. J Assist Reprod Genet. 2008 Feb-Mar;25(2-3):47-62. doi: 10.1007/s10815-008-9206-5.

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