Abstract
Purpose
A systematic review was conducted to (1) collate and synthesise the available evidence for the role of cortisol in relation to IVF treatment outcomes; (2) to establish the strength of an association between cortisol and IVF; and (3) to assess the overall quality of the studies and guide future research in this area.
Methods
Seven electronic databases, including the reference lists of published papers, were searched. Inclusion criteria qualified any prospective/observational cohort study that reported original data. Quality assessment of eligible studies was conducted using the STROBE statement, which was used to assess the risk of bias and the quality of observational studies included in this review.
Result(s)
A total of eight studies reported a significant association between cortisol and IVF outcomes. Three studies found that higher cortisol may be associated with more favourable IVF outcomes, whereas five studies found that lower cortisol levels may be conducive to IVF success. Eleven of all studies included in this review were regarded as low quality publications.
Conclusion(s)
Study findings were that the evidence for the role of cortisol in relation to IVF outcomes is currently mixed. Future researchers are encouraged to consider the methodological limitations highlighted in this review and to utilise more robust assessment methods when examining the influence that chronic, rather than acute, stress may have on IVF outcomes.
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References
Lord S, Robertson N. The role of patient appraisal and coping in predicting distress in IVF. Reprod Inf Psychol. 2005;23:319–32.
Boivin J, Giffiths E, Venetis C. Emotional distress in infertile women and failure of assisted reproductive technologies: a meta analysis of prospective psychosocial studies. BMJ. 2007;342:d223.
Mathiesen SMS, Frederiksen Y, Ingerlev JJ, Zachariae R. Stress, distress and outcome of assisted reproductive technology (ART): a meta-analysis. Hum Reprod. 2011;26:1763–2776.
Dickerson S, Kemeny ME. Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull. 2004;3:355–9.
Marieb EN, Hoehn K. Human anatomy & Physiology. 7th ed. San Francisco: Benjamin Cummings; 2007.
Fateh M, Ben-Rafeal Z, Benadiva CA, Mastroianni L, Flickinger GL. Cortisol level in human follicular fluid. Fertil Steril. 1989;55:538–41.
Demyttenaere K, Nijs P, Evers-Kieboums G, Koninckx PR. Coping and the ineffectiveness of coping influence the outcome of in vitro fertilisation through stress responses. Pychoneuroendocrinology. 1992;19:655–65.
Micheal AE, Collins TD, Norgate DP, Gregory L, Wood PJ, Cooke BA. Relationship between diurnal cortisol: cortisone ratios and the clinical outcome of in vitro fertilisation and embryo transfer (IVF-ET). Clin Endocrin. 1999;5:535–40.
Csemiczky G, Landgren BM, Collins A. The influence of stress and state anxiety on the outcome of IVF treatment. Psychological and endocriniological assessment of Swedish women entering IVF treatment. Acta Obstst Gynecol Scand. 2000;79:113–8.
Lewicka S, Von Hagens C, Hettinger U, Grunwald K, Vecsali P, Runnebaum B. Cortisol and cortisone in human follicular fluid and serum and the outcome of IVF treatment. Hum Reprod. 2003;18:1613–7.
An Y, Sun Z, Li L, Zhang Y, Ji M. Relationship between psychological stress and reproductive outcome in women undergoing in vitro fertilisation treatment: psychological and neurohormonal assessment. J Assist Reprod Genet. 2011;30:35–41.
Rabin BS. Introduction to immunology and immune-endocrine interactions. In: Vedhara K, Irwin MR, editors. Human psychoneuroimmunology. Oxford: Oxford University Press; 2005. p. 1–24.
Andersen CY, Hornnes P. Intrafollicular concentrations of free cortisol close to follicular rupture. Hum Reprod. 1994;9:1944–9.
Keay SD, Harlow CR, Wood PJ, Jenkins JM, Cahill DJ. Higher cortisol: cortisone ratios in the preovulatory follicle of completely unstimulated IVF cycles indicate oocytes with increased pregnancy potential. Hum Reprod. 2002;9:2410–4.
Thurston LM, Norgate DP, Jonas KC, Gregory L, Wood PJ, Cooke BA, Micheal AE. Ovarian modulators of type 1 11B: hydroxysteriod dehydrogenase (11BHSD) activity and intra follicular cortisol: cortisone ratios correlate with clinical outcome of IVF. Hum Reprod. 2003;18:1603–12.
Lovely LP, Meyer WR, Ekstrom D, Golden RN. Effect of stress on pregnancy outcome among women undergoing assisted reproduction procedures. South Med J. 2003;96:548–51.
Smeenk JMJ, Verhaak CM, Vingerhoets AJJM, Sweep CGJ, Merkus JMWM, Williamson SJ, Van Minnen A, Staatman H, Braat DDM. Stress and outcome success in IVF: the role of self-reports and endocrine variables. Hum Reprod. 2005;20:991–6.
Nouri K, Litschauer B, Huber JC, Buerkle B, Tiringer D, Tempfer CB. Saliva cortisol and subjective stress are not associated with number of oocytes after controlled ovarian hyperstimulation in patients undergoing in vitro fertilization. Fertil Steril. 2011;96:69–72.
Von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–9.
Bider D, Shine S, Turkaspa I, Leuren J, Dor J. Cortisol concentrations in follicular fluid of low responder patients. Hum Reprod. 1998;1:27–9.
Milad MP, Klock SC, Moses S, Chatterton R. Stress and anxiety do not result in pregnancy wastage. Hum Reprod. 1998;13:2296–300.
Anderson YC, Morineau G, Fukuda M, Westergaard GL, Ingerslev JJ, Flet J, Buskov AG. Assessment of follicular cortisol: cortisone ratio. Hum Reprod. 1999;6:1563–8.
An Y, Sun ZZ, Li LA, Zhang YJ, JI HP. Relationship between psychological stress and reproductive outcome in women undergoing in vitro fertilisation treatment: psychological and neurohormonal assessment. J Assist Reprod Genet. 2013;30:35–41.
Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Salivary cortisol: a better measure of adrenal cortical function then serum cortisol. Ann Clin Biochem. 1989;20:329–35.
Kirschbaum C, Hellhammer DH. Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology. 1989;19:313–33.
Kirschbaum C, Hellhammer DH. Salivary cortisol in psychoneuroendocrine research: recent developments and applications. Psychoneuroendocrinology. 1994;19:313–33.
Smith RE, Maguire JA, Stein Oakley AN, Sasano H, Takahashi K, Fukushima Z, Krozowski S. Location of 11 beta hydroxysteriod dehydrogenase type II in human epithellal tissues. J Clin Endocrinol Metab. 1996;81:3244–8.
Van Uum SH, Walker BK, Hermus AR, Sweep CG, Smits P, De Leeuw PW, Lenders JW. Effect of glycyrrhetinic acid on 11 beta hydroxysteriod dehydrogenase activity in normotensive and hypertensive subjects. Clin Sci. 2002;102:203–11.
Fuxe K, Anderson K, Eneroth P, Harfstrand A, Agnoti LF. Neuroendocrine actions of nicotine and of exposure to cigarette smoke: medical implications. Psychoneuroendocrinology. 1989;989(14):19–41.
Weidenfield J, Bodoff M, Saphier D, Brenner T. Further studies on the stimulatory action of nicotine on andrenocortical function in the rat. Neuroendocrinology. 1989;50:132–8.
Sg Matta, Fu Y, Valentine JD, Sharp BM. Response of the hypothalamus pituitary adrenal axis to nicotine. Psychoneuroendocrinology. 1998;23:103–13.
Rosecrans JA, Karin LD. Effects of nicotine on the hypothalamic pituitary adrenal axis (HPA) and immune function: introduction to the sixth nictone round table satellite American society of addiction medicine conference. Psychoneuroendocrinology. 1997;23:95–102.
Lovallo WR, Whitsett TL, Wilson MF. Caffiene stimulation of cortisol secretion across the waking hours in relation to caffeine intake levels. Psychosom Med. 2005;67:734–9.
Rohleder N, Schomner NC, Hellhammer R, Engle R, Kirschbaum C. Sex differences in glucocorticoid sensitivity of proinflamatory cytokine production after psychosocial stress. Psychosom Med. 2001;63:966–72.
Champaneri S, Xu X, Carnethon MR, Bertoni AG, Seeman T, Desantis AS, Diez Roux A, Shrager S, Golden SH. Diurnal salivary cortisol is associated with BMI and waist circumference: the multiethnic study of atheroscelerosis. Obesity. 2013;21:56–63.
Mathieson SMS, Frederiksen Y, Ingerslev HS, Zachariae R. Stress, distress and outcome of assisted reproductive technology (ART): a meta-analysis. Hum Reprod. 2011;26:2763–76.
Kudielka BM, Hellhammer DH, Wust S. Why do we respond so differently? Determinants of human salivary cortisol responses to challenge. Psychoneuroendocrinology. 2009;34:2–18.
Ferin M. Clinical review: stress and the reproductive cycle. J Clin Endo Metab. 1999;84:1768–74.
Staufenbiel SM, Penninx WJH, Spijker AT, Elzinga BM, Van Rosseum EFC. Hair cortisol, stress exposure and mental health in humans: a systematic review. Psychoneuroendocrinology. 2013;8:1220–35.
Sauve B, Karen G, Walsh G, Tokmakejians S, Van Uum SH. Measurement of cortisol in human hair as a biomarker of systematic exposure. Clin Invest Me. 2007;30:183–9.
Russell E, Karen G, Rieder M, Van Uum S. Hair cortisol as a biological marker of chronic stress: current status, future directions and unanswered questions. Pyshoneuroendocrinology. 2012;37:589–601.
Acknowledgments
The review was funded by the University of Nottingham (UK).
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There are no conflicts of interest.
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(PROSPERO registration number: CRD42013003566).
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Massey, A.J., Campbell, B., Raine-Fenning, N. et al. The association of physiological cortisol and IVF treatment outcomes: a systematic review. Reprod Med Biol 13, 161–176 (2014). https://doi.org/10.1007/s12522-014-0179-z
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DOI: https://doi.org/10.1007/s12522-014-0179-z