Stress, depression, and other psychiatric disorders : an epidemiological approach to studying the causes and consequences for in vitro fertilization outcome and polycystic ovary syndrome

Reproductive epidemiology, psychiatric epidemiology, and pharmacoepidemiology come together in this thesis which is comprised of four studies and divided into two parts.

Part 1 examines the impact of stress and depression on the outcomes of infertility treatment in women undergoing in vitro fertilization (IVF). Up to 30% of couples will experience difficulties conceiving, and women undergoing infertility treatment report high levels of stress and symptoms of depression and anxiety. There is concern that stress affects the success of the infertility treatment, and little is known about the influence of depression and treatment with antidepressants on fertility.

Using the Swedish national registers, Study I investigated the association between depression, anxiety, and antidepressant use and IVF cycle outcome in 23,577 nulliparous women undergoing their first recorded IVF cycle. Overall, 4.4% of the women had a diagnosis of depression or anxiety, or a dispensation for antidepressants prior to IVF cycle start. Findings suggest that women with the most complex and severe cases of depression had reduced chances of becoming pregnancy, independent of treatment with antidepressants. Study II examined the influence of multiple measures of stress on IVF cycle outcomes in the Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study. Perceived life stress, infertility-related stress, and biological stress measured by cortisol were not associated with indicators of oocyte and embryo quality, or pregnancy rate in the UppStART participants, a finding which is potentially reassuring to both patients and clinicians.

Part 2 investigates psychiatric disorders in women with polycystic ovary syndrome (PCOS). PCOS is a common endocrine disorder, affecting up to 15% of reproductive-aged women and is often accompanied by metabolic disorders and depression.

Study III utilizes diagnoses recorded in the Swedish National Patient Register to investigate both common and rare psychiatric disorders in women with PCOS, as well as in their siblings. Women with PCOS were found to have a 50% increased odds of having a psychiatric disorder compared with women from the general population without PCOS. Higher odds for some psychiatric disorders in the sisters and brothers reveal that common familial factors could be responsible for these findings, and indirect evidence for the role of elevated androgens in the risk for psychiatric disorders was found. Study IV provides evidence of common genetic and environmental factors between PCOS and major depression by utilizing data in a cohort of Swedish female twins. Findings suggest that part of the comorbidity between depression and PCOS is attributable to common factors between these two traits and neuroticism – a personality trait associated with depression and also found to be higher in women with PCOS.

List of scientific papers

I. Cesta CE, Viktorin A, Olsson H, Johansson V, Sjölander A, Bergh C, Skalkidou A, Nygren KG, Cnattingius S, Iliadou AN. Depression, Anxiety, and Antidepressant Treatment in Women: Association with In-vitro Fertilization Outcome. Fertility and Sterility. 2016; 106: 1594-1602.
https://doi.org/10.1016/j.fertnstert.2016.01.036

II. Cesta CE, Johansson AL, Hreinsson J, Rodriguez-Wallberg KA, Olofsson JI, Holte J, Wramsby M, Cnattingius S, Skalkidou A, Iliadou AN. Perceived stress, infertilityrelated stress, and cortisol levels in women undergoing in vitro fertilization and its influence on embryo quality and cycle outcome. [Submitted]

III. Cesta CE, Månsson M, Palm C, Lichtenstein C, Iliadou AN, Landén M. Polycystic Ovary Syndrome and Psychiatric Disorders: Co-morbidity and Heritability in a Nationwide Swedish Cohort. Psychoneuroendocrinology. 2016; 73: 196-203.
https://doi.org/10.1016/j.psyneuen.2016.08.005

IV. Cesta CE, Kuja-Halkola R., Lehto K., Iliadou AN, Landén M. Polycystic Ovary Syndrome, Personality, and Depression: A Twin Study. [Submitted]