Depression, anxiety, and psychotropic medication use and fecundability

Published:April 28, 2016DOI:


      The literature regarding the associations between depression, anxiety, and fecundity is inconsistent. While cross-sectional studies suggest that depression and/or anxiety may adversely affect fecundity, the sole cohort study showed only a small association.


      We sought to evaluate the association of self-reported depressive symptoms, self-reported diagnoses of depression and anxiety, and psychotropic medication use with fecundability in a prospective cohort study.

      Study Design

      Data were derived from Pregnancy Study Online (PRESTO), an Internet-based preconception cohort study of couples attempting to conceive in the United States and Canada. At baseline, female participants completed a survey that assessed demographic information, history of physician-diagnosed depression and anxiety, self-reported depressive symptoms (assessed by the Major Depression Inventory), and use of psychotropic medications. Women completed follow-up surveys every 8 weeks for up to 12 months or until reported conception to assess changes in exposures and pregnancy status. We estimated fecundability ratios and 95% confidence intervals using proportional probabilities regression models. The analysis was restricted to 2146 women who had been attempting to conceive for ≤6 cycles at study entry.


      Severe depressive symptoms at baseline, regardless of treatment, were associated with decreased fecundability compared with no or low depressive symptoms (fecundability ratio, 0.62; 95% confidence interval, 0.43–0.91). The fecundability ratio associated with a 10-unit increase in Major Depression Inventory score was 0.90 (95% confidence interval, 0.83–0.97). Women who reported moderate to severe depressive symptoms and had never received psychotropic medications (fecundability ratio, 0.69; 95% confidence interval, 0.48–0.99) or who were currently being treated with psychotropic medications (fecundability ratio, 0.72; 95% confidence interval, 0.44–1.20) had decreased fecundability relative to women who had no/mild depressive symptoms and had never used psychotropic medications. Former users of psychotropic medications had increased fecundability regardless of the presence of no/mild depressive symptoms (fecundability ratio, 1.22; 95% confidence interval, 1.06–1.39) or moderate to severe depressive symptoms (fecundability ratio, 1.18; 95% confidence interval, 0.80–1.76).


      We found an inverse association between depressive symptoms and fecundability, independent of psychotropic medication use. Use of psychotropic medications did not appear to harm fecundability.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Thoma M.E.
        • McLain A.C.
        • Louis J.F.
        • et al.
        Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach.
        Fertil Steril. 2013; 99: 1324-1331
        • Seeman M.V.
        Psychopathology in women and men: focus on female hormones.
        Am J Psychiatry. 1997; 154: 1641-1647
        • Weissman M.M.
        • Olfson M.
        Depression in women: implications for health care research.
        Science. 1995; 269: 799-801
        • Vreeburg S.A.
        • Hoogendijk W.J.
        • van Pelt J.
        • et al.
        Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study.
        Arch Gen Psychiatry. 2009; 66: 617-626
        • Ferin M.
        Stress and the reproductive cycle.
        J Clin Endocrinol Metab. 1999; 84: 1768-1774
        • Margolese H.C.
        • Assalian P.
        Sexual side effects of antidepressants: a review.
        J Sex Marital Ther. 1996; 22: 209-217
        • Timby E.
        • Hedström H.
        • Bäckström T.
        • Sundström-Poromaa I.
        • Nyberg S.
        • Bixo M.
        Allopregnanolone, a GABAA receptor agonist, decreases gonadotropin levels in women. A preliminary study.
        Gynecol Endocrinol. 2011; 27: 1087-1093
        • Lapane K.L.
        • Zierler S.
        • Lasater T.M.
        • Stein M.
        • Barbour M.M.
        • Hume A.L.
        Is a history of depressive symptoms associated with an increased risk of infertility in women?.
        Psychosom Med. 1995; 57: 509-513
        • Williams K.E.
        • Marsh W.K.
        • Rasgon N.L.
        Mood disorders and fertility in women: a critical review of the literature and implications for future research.
        Hum Reprod Update. 2007; 13: 607-616
        • Lynch C.D.
        • Sundaram R.
        • Buck Louis G.M.
        • Lum K.J.
        • Pyper C.
        Are increased levels of self-reported psychosocial stress, anxiety, and depression associated with fecundity?.
        Fertil Steril. 2012; 98: 453-458
        • Gorman J.M.
        Comorbid depression and anxiety spectrum disorders.
        Depress Anxiety. 1996-1997; 4: 160-168
        • Grodstein F.
        • Goldman M.B.
        • Ryan L.
        • Cramer D.W.
        Self-reported use of pharmaceuticals and primary ovulatory infertility.
        Epidemiology. 1993; 4: 151-156
        • Casilla-Lennon M.
        • Chantala K.
        • Meltzer-Brody S.
        • Steiner A.
        The effect of antidepressants on fertility.
        Fertil Steril. 2016;
        • Wise L.A.
        • Rothman K.J.
        • Mikkelsen E.M.
        • et al.
        Design and conduct of an Internet-based preconception cohort study in North America: pregnancy study online.
        Paediatr Perinat Epidemiol. 2015; 29: 360-371
        • Bech P.
        Quality of life instruments in depression.
        Eur Psychiatry. 1997; 12: 194-198
        • Bech P.
        • Wermuth L.
        Applicability and validity of the Major Depression Inventory in patients with Parkinson's disease.
        Nord J Psychiatr. 1998; 52: 305-310
        • Bech P.
        • Rasmussen N.A.
        • Olsen L.R.
        • Noerholm V.
        • Abildgaard W.
        The sensitivity and specificity of the Major Depression Inventory, using the Present State Examination as the index of diagnostic validity.
        J Affect Disord. 2001; 66: 159-164
        • Ainsworth B.E.
        • Haskell W.L.
        • Herrmann S.D.
        • et al.
        2011 Compendium of physical activities: a second update of codes and MET values.
        Med Sci Sports Exerc. 2011; 43: 1575-1581
        • Weinberg C.R.
        • Wilcox A.J.
        • Baird D.D.
        Reduced fecundability in women with prenatal exposure to cigarette smoking.
        Am J Epidemiol. 1989; 129: 1072-1078
        • Weinberg C.R.
        • Wilcox A.J.
        Reproductive epidemiology.
        in: Rothman K.J. Greenland S. Modern epidemiology. Lippincott Raven, Philadelphia (PA)1998
        • Therneau T.M.
        • Grambsch P.M.
        Modeling survival data: extending the Cox model.
        Springer-Verlag, New York2000
        • SAS Institute
        SAS/Stat 9.3 user's guide.
        SAS Institute, Cary (NC)2008
        • Zigmond A.S.
        • Snaith R.P.
        The Hospital Anxiety and Depression Scale.
        Acta Psychiatr Scand. 1983; 67: 361-370
        • Rothman K.J.
        Six persistent research misconceptions.
        J Gen Intern Med. 2014; 29: 1060-1064
        • Ziliak S.T.
        • McCloskey D.N.
        The cult of statistical significance.
        University of Michigan Press, Ann Arbor (MI)2008: 27
        • Kessler R.C.
        • Berglund P.
        • Demler O.
        • et al.
        The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).
        JAMA. 2003; 289: 3095-3105