Polycystic Ovary Syndrome and Pregnancy : Prenatal Exposures and Pregnancy Complications

Abstract: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of fertile age. The aetiology of PCOS is not fully understood and might be affected by foetal exposures. Women with PCOS have an increased risk of pregnancy complications, but information on rare severe complications is scarce.The overall aim of this thesis was to gain further knowledge of the association between the intrauterine environment and development of PCOS in offspring, and the association between maternal PCOS and adverse pregnancy outcomes, with a focus on preterm birth and stillbirth.This thesis includes three nationwide register-based cohort studies and one matched cohort study including early second-trimester blood samples. Associations were estimated with multivariate Cox, logistic and linear regression models, with adjustment for confounders including body mass index. Correlations were estimated with Spearman’s rank correlation coefficient.It was found that maternal overweight and obesity, and smoking during pregnancy, were associated with increased risk for female offspring to develop PCOS later in life compared with offspring of normal weight and non-smoking mothers, respectively. Size at birth was not associated with the risk of PCOS development. During pregnancy, women with PCOS had higher second-trimester levels of anti-Müllerian hormone (AMH) and testosterone than non-PCOS women, and AMH levels were positively correlated with total testosterone levels. High AMH levels were not associated with an increased risk of pregnancy complications. Women with PCOS seemed at increased risk of extremely, very, and moderately preterm birth compared with non-PCOS women. The association was strongest for extremely preterm birth of spontaneous onset. Women with PCOS also seemed at increased risk of stillbirth compared with non-PCOS women, and the rate of stillbirth in PCOS women was particularly high in term pregnancy.In conclusion, increased maternal BMI and maternal smoking may increase the risk of PCOS in offspring. Even though second-trimester AMH levels are higher in pregnant women with PCOS than controls, AMH seems not to be a mediator of increased risk for pregnancy complications in PCOS women. PCOS should be considered a risk factor for severe pregnancy complications such as extremely preterm birth and stillbirth.