| 1. |
- Cesta, Carolyn E., et al.
(author)
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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
- 2018
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In: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 97:3, s. 258-268
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Journal article (peer-reviewed)abstract
- IntroductionWomen undergoing fertility treatment experience high levels of stress. However, it remains uncertain if and how stress influences in vitro fertilization (IVF) cycle outcome. This study aimed to investigate whether self-reported perceived and infertility-related stress and cortisol levels were associated with IVF cycle outcomes.Material and methodsA prospective cohort of 485 women receiving fertility treatment was recruited from September 2011 to December 2013 and followed until December 2014. Data were collected by online questionnaire prior to IVF start and from clinical charts. Salivary cortisol levels were measured. Associations between stress and cycle outcomes (clinical pregnancy and indicators of oocyte and embryo quality) were measured by logistic or linear regression, adjusted for age, body mass index, education, smoking, alcohol and caffeine consumption, shiftwork and night work. ResultsUltrasound verified pregnancy rate was 26.6% overall per cycle started and 32.9% per embryo transfer. Stress measures were not associated with clinical pregnancy: when compared with the lowest categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest categories of the perceived stress score was 1.04 (95% CI 0.58-1.87), infertility-related stress score was OR = 1.18 (95% CI 0.56-2.47), morning and evening cortisol was OR = 1.18 (95% CI 0.60-2.29) and OR = 0.66 (95% CI 0.34-1.30), respectively.ConclusionsPerceived stress, infertility-related stress, and cortisol levels were not associated with IVF cycle outcomes. These findings are potentially reassuring to women undergoing fertility treatment with concerns about the influence of stress on their treatment outcome.
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| 2. |
- Cesta, Carolyn E., et al.
(author)
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Maternal polycystic ovary syndrome and risk of neuropsychiatric disorders in offspring : prenatal androgen exposure or genetic confounding?
- 2020
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In: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 50:4, s. 616-624
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Journal article (peer-reviewed)abstract
- BACKGROUND: Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.METHODS: A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.RESULTS: PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.CONCLUSIONS: Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.
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| 3. |
- Cesta, Carolyn E, et al.
(author)
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Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and heritability in a nationwide Swedish cohort.
- 2016
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In: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 73, s. 196-203
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Journal article (peer-reviewed)abstract
- Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 5-15% of reproductive-aged women and characterized by high levels of circulating androgens. Given that androgens have been implicated in the aetiology of several psychiatric disorders, it was hypothesized that women with PCOS have high risk for psychiatric comorbidity. We aimed to investigate this risk amongst women with PCOS, as well as in their siblings, to elucidate if familial factors underlie any potential associations. Using the Swedish national registers, we identified all women diagnosed with PCOS between 1990 and 2013 (n=24,385), their full-siblings (n=25,921), plus matched individuals (1:10/100) from the general population and their full-siblings. Psychiatric disorder diagnoses were identified including schizophrenia, bipolar disorder, depressive and anxiety disorders, eating disorders, personality and gender identity disorder, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), tics, attempted and completed suicide. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression and adjusted ORs (AOR) were determined by adjustment for comorbid psychiatric disorders. Overall, women with PCOS had an increased odds of having at least one psychiatric disorder (OR=1.56 [95CI%, 1.51-1.61]). Crude ORs showed associations with nearly all psychiatric disorders included in this study. Following adjustment for comorbid psychiatric disorders, women with PCOS were still at a significantly increased risk for bulimia, schizophrenia, bipolar disorder, depressive and anxiety disorders, personality disorders, with the highest AORs for ASD (AOR=1.55 [95%CI, 1.32-1.81]) and tics (AOR=1.65 [95%CI, 1.10-2.47]). Significantly higher AORs were found for ASD in both brothers and sisters of women with PCOS, and for depressive, anxiety, and schizophrenia spectrum disorders in the sisters only. Notably, the crude ORs for attempted suicide were 40% higher in women with PCOS and 16% higher in their unaffected sisters. However, the AORs were greatly attenuated indicating that underlying psychiatric comorbidity is important for this association. Women with PCOS had higher risks for a range of psychiatric disorders not shown before. Elevated risk in their siblings suggests shared familial factors between PCOS and psychiatric disorders. This study is an important first step towards identifying the underlying mechanisms for risk of psychiatric disorders in women with PCOS. Health professionals treating women with PCOS should be aware that these patients - as well as their family members - are important targets for mental health care.
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| 4. |
- Cesta, Carolyn E, et al.
(author)
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Polycystic ovary syndrome, personality, and depression: A twin study.
- 2017
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In: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 85, s. 63-68
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Journal article (peer-reviewed)abstract
- Women with polycystic ovary syndrome (PCOS) are at elevated risk for suffering from depression. Neuroticism is a personality trait that has been associated with an increased risk for developing major depressive disorder (MDD). The aim of the present study was to quantify and decompose the correlation between neuroticism, PCOS, and MDD into shared and unique genetic and environmental etiologies, by using quantitative genetic methods.In a cohort of 12,628 Swedish female twins born from 1959 to 1985, neuroticism, PCOS identified by symptoms of hyperandrogenemia (i.e., hirsutism) and oligo- and/or anovulation, and lifetime MDD status were determined through questionnaire responses. Structural equation modeling was used to study the genetic and environmental sources of the variation within, and covariation between neuroticism, PCOS, and MDD.Female twins with PCOS (n=752) had significantly higher levels of neuroticism than women without PCOS, and a 2-fold increase in odds for a lifetime prevalence of MDD. The phenotypic correlation between PCOS and MDD was 0.19, with 63% of the correlation attributable to common genetic factors between the two traits. When taking into account neuroticism, 41% was attributable to common genetic factors and 9% attributable to common environmental factors shared between all three traits, with the remainder attributable to components unique to PCOS and MDD.There are common genetic factors between neuroticism, PCOS, and MDD; however, neuroticism shares approximately half of the genetic and environmental components behind the phenotypic correlation between PCOS and MDD, providing some etiological evidence behind the comorbidity between PCOS and depression.
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| 5. |
- Cesta, Carolyn E
(author)
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Stress, depression, and other psychiatric disorders : an epidemiological approach to studying the causes and consequences for in vitro fertilization outcome and polycystic ovary syndrome
- 2017
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Doctoral thesis (other academic/artistic)abstract
- 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.
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| 6. |
- Iliadou, Anastasia N., et al.
(author)
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The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study
- 2019
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In: BMJ Open. - : BMJ PUBLISHING GROUP. - 2044-6055. ; 9
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Journal article (peer-reviewed)abstract
- Purpose: The Uppsala-Stockholm Assisted Reproductive Techniques (UppStART) study is a prospectively recruited sample of couples undergoing assisted reproduction in Stockholm and Uppsala county in Sweden. The study was initiated to (1) investigate possible changes in the epigenetic profile of infants inferred through the ART procedures and their consequence and (2) to assess the impact of lifestyle and health exposures on treatment outcome.Participants: Recruitment took place between September 2011 and December 2013, and in vitro fertilisation (IVF) cycles initiated and pregnancies conceived during this time were followed until December 2014. The cohort includes 971 participants (n= 514 women; n= 457 men), and 129 pregnancies were achieved from the first IVF cycle included in the study.Findings to date: Self-reported demographic, health and lifestyle data were collected from a baseline questionnaire, and to assess changes to lifestyle, a follow-up questionnaire was issued at the time of oocyte retrieval, and at subsequent IVF cycles. Questionnaire data were linked to data extracted from medical records. Biological samples were collected at baseline: blood for extraction of serum, plasma and DNA, morning and evening saliva samples for cortisol measurement and at delivery including samples of maternal blood, placenta and amniotic fluid, and cord blood for epigenetic analysis.Future plans: Through the unique identification number assigned to each Swedish citizen at birth or immigration, UppStART study participants will be linked to the Swedish population-based national and quality registers to provide data from prenatal, obstetrical, neonatal and infant care, and subsequent updates will provide data on childhood health and educational outcomes. Collaboration and use of UppStART data is encouraged, and more information about access can be found at www.ki.se/meb/uppstart
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| 7. |
- Risal, Sanjiv, et al.
(author)
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Prenatal androgen exposure and transgenerational susceptibility to polycystic ovary syndrome
- 2019
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In: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 25:12, s. 1894-1904
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Journal article (peer-reviewed)abstract
- How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F1-F3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F1-F3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.
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