Article| Volume 39, ISSUE 1, P93-101, July 2019

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Does stress affect IVF outcomes? A prospective study of physiological and psychological stress in women undergoing IVF

Published:January 31, 2019DOI:


      Research question

      What are the effects of physiological and psychological stress on fertility outcomes for women undergoing IVF?


      A prospective cohort study of 72 patients undergoing IVF in 2017 and 2018. Physiological stress was assessed by salivary cortisol measurements: (i) pretreatment, when the patient received the IVF protocol; (ii) before oocyte retrieval (follicular cortisol was also measured); and (iii) before embryo transfer. Emotional stress was evaluated at each assessment with the State-Trait Anxiety Inventory and a 1–10 Visual Analogue Scale (VAS, referred to as the ‘Stress Scale’. Correlations between cortisol concentrations, psychological stress and IVF outcome were assessed.


      Salivary cortisol concentrations increased by 28% from pretreatment phase (0.46 ± 0.28 μg/dl) to maximum concentration on oocyte retrieval day (0.59 ± 0.29 μg/dl, P = 0.029) and then decreased by 29% on embryo transfer day (0.42 ± 0.23 μg/dl, P = 0.0162). On embryo transfer day, cortisol among women in their first cycle was higher than women who underwent more than one treatment (P = 0.024). Stress Scale score increased by 39% from pretreatment to a maximum score on oocyte retrieval day and then decreased by 12% on embryo transfer day. Salivary cortisol and Stress Scale were not related to subsequent embryo transfer, fertilization rate, embryo quality or clinical pregnancy rate. Follicular cortisol concentration was positively correlated with fertilization rate (r = 0.4, P = 0.004).


      It can be cautiously concluded that physiological and psychological stress do not negatively affect IVF outcomes. Moreover, high follicular cortisol concentrations might have positive effects on pregnancy rates.


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        • Baum A.
        Stress, Intrusive Imagery, and Chronic Distress.
        Heal. Psychol. 1990; 6: 653-675
        • Boivin J.
        • Griffiths E.
        • Venetis C.A.
        Emotional distress in infertile women and failure of assisted reproductive technologies: meta-analysis of prospective psychosocial studies.
        BMJ. 2011; 342 (23): d223
        • Bozovic D.
        • Racic M.
        • Ivkovic N.
        Salivary cortisol levels as a biological marker of stress reaction.
        Med. Arch. 2013; 67: 374-377
        • Bringhenti F.
        • Martinelli F.
        • Ardenti R.
        • La Sala G.
        Psychological adjustment of infertile women entering IVF treatment: differentiating aspect and influencing factors.
        Acta. Obs. Gynecol. Scand. 1997; 76: 431-437
        • Butts C.D.
        • Bloom M.S.
        • Frye C.A.
        • Walf A.A.
        • Parsons P.J.
        • Steuerwald A.J.
        • Ilonze C
        • Fujimoto F.V.
        Urine cortisol concentration as a biomarker of stress is unrelated to IVF outcomes in women and men.
        J. Assist. Reprod. Genet. 2014; 31: 1647-1653
        • Cesta C.E.
        • Johansson A.L.V.
        • Hreinsson J
        • Rodriguez-Wallberg K.A.
        • Olofsson J.I.
        • Holte J.
        • Wramsby H.
        • Wramsby M.
        • Cnattingius S.
        • Skalkidou A.
        • Nyman Iliadou A.
        A prospective investigation of perceived stress, infertility-related stress, and cortisol levels in women undergoing in vitro fertilization: influence on embryo quality and clinical pregnancy rate.
        Acta. Obs. Gynecol. Scand. 2018; 97: 258-268
        • Csemiczky G.
        • Landgren B.M.
        • Collins A.
        The influence of stress and state anxiety on the outcome of IVF-treatment: Psychological and endocrinological assessment of Swedish women entering IVF-treatment.
        Acta. Obs. Gynecol. Scand. 2000; 79: 113-118
        • Demyttenaere K.
        • Bonte L.
        • Gheldof M.
        • Vervaeke M.
        • Meuleman C.
        • Vanderschuerem D.
        • D'Hooghe T.
        Coping style and depression level influence outcome in in vitro fertilization.
        Fertil. Steril. 1998; 69: 1026-1033
        • Dennerstein L.
        • Morse C.
        A review of psychological and social aspects of in vitro fertilization.
        Psychosom. Obs. Gynaecol. 1988; 9: 159-170
        • Harlow C.R.
        • Jenkins J.M.
        • Winston R.M.
        Increased follicular fluid total and free cortisol levels during the luteinizing hormone surge.
        Fertil. Steril. 1997; 68: 48-53
        • Harlow C.
        • Fahy U.
        • Talbot W.
        • Wardle P.
        • Hull M.
        Stress andstress-related hormones during in vitro fertilization treat-ment.
        Hum. Reprod. 1996; 11: 274-279
        • Keay S.D
        • Harlow C.R
        • Wood P.J
        • Jenkins J.M
        • Cahill D.
        Higher cortisol: cortisone ratios in the preovulatory follicle of completely unstimulated IVF cycles indicate oocytes with increased pregnancy potential.
        Hum. Reprod. 2002; 9: 2410-2414
        • Lord S.
        • Robertson N.
        The role of patient appraisal and coping in predicting distress in IVF.
        J. Reprod. Infant. Psychol. 2005; 23: 319-332
        • Massey A.J.
        • Campbell B.
        • Raine-Fenning N.
        • Aujla N.
        • Vedhara K.
        The association of physiological cortisol and IVF treatment outcomes: a systematic review.
        Reprod. Med. Biol. 2014; 13: 161-176
        • Massey A.J.
        • Campbell B.K.
        • Raine-Fenning N.
        • Pincott-Allen C.
        • Perry J.
        • Vedhara K.
        Relationship between hair and salivary cortisol and pregnancy in women undergoing IVF.
        Psychoneuroendocrinology. 2016; 74: 397-405
        • Matthiesen S.M.
        • Frederiksen Y
        • Ingerslev H.J
        • Zachariae R.
        Stress, distress and outcome of assisted reproductive technology (ART): a meta-analysis.
        Hum. Reprod. 2011; 26: 2763-2776
        • Micheal A.E.
        • Collins T.D.
        • Norgate D.P.
        • Gregory L
        • Wood P.
        Relationship between diurnal cortisol: cortisone ratios and the clinical outcome of in vitro fertilization and embryo transfer (IVF-ET).
        Clin. Endocrinol. (Oxf). 1999; 5: 535-540
        • Milad M.P.
        • Klock S.C.
        • Moses S
        • Chatterton R.
        Stress and anxiety do not result in pregnancy wastage.
        Hum. Reprod. 1998; 13: 2296-2300
        • Nouri K.
        • Litschauer B.
        • Huber J.C.
        • Buerkle B.
        • Tiringer D.
        • Tempfer C.
        Saliva cortisol levels and subjective stress are not associated with number of oocytes after controlled ovarian hyperstimulation in patients undergoing in vitro fertilization.
        Fertil. Steril. 2018; 96: 69-72
        • Ohnhaus E.E.
        • Adler R.
        Methodological problems in the measurement of pain: a comparison between the verbal rating scale and the visual analogue scale.
        Pain. 1975; 1: 379-384
        • Spielberger C.D.
        • Gorsuch R.L.
        • Lushene R.
        Manual for the State/Trait Anxiety Inventory.
        Consulting Psychologists Press,, Palo Alto, CA1970
        • Umeda T.
        • Hiramatsu R.
        • Iwaoka T.
        • Shimada T.
        • Miura F.
        • Sato T.
        Use of saliva for monitoring unbound free cortisol levels in serum.
        Clin. Chim. Acta. 1981; 110: 2
        • Weerth C.D
        • Buitelaar J.K
        Cortisol awakening response in pregnant women.
        Psychoneuroendocrinology. 2005; 30: 902-907
        • Yuan A.
        • Zhuangzhuang S.
        • Linan L.
        • Yajuan Z.
        • Hongping J.
        Relationship between psychological stress and reproductive outcome in women undergoing in vitro fertilization treatment: Psychological and neurohormonal assessment.
        J. Assist. Reprod. Genet. 2013; 30: 35-41


      Dr Netanella Miller is an OBGYN Resident at Meir Medical Center, Israel. She earned her medical degree from the Technion School of Medicine and studied acupuncture at Broshim Campus, specialising in Chinese gynaecology. Her research is in obstetrics and reproductive endocrinology and she has published several papers in leading journals.
      Key message
      Physiological and psychological stress do not negatively affect IVF outcomes. These findings might reassure women who are concerned that their stress level will affect their IVF outcomes.