Reducing the Risk of Pre-Eclampsia in Women with Polycystic Ovary Syndrome Using a Combination of Pregnancy Screening, Lifestyle, and Medical Management Strategies

Abstract

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labor, and pre-eclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This narrative synthesis summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidence-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early-pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

Keywords: PCOS; angiogenic ratio; lifestyle; nutrition; pathophysiology; placenta; pre-eclampsia; pregnancy; screening.

Figure 1

Factors influencing bidirectional fetal–maternal placentation. A schematic model showing the potential impact of nutritional and environmental factors at all stages of pregnancy, including gametogenesis, decidualization, implantation, and placental and fetal development. In normal placental development extravillous cytotrophoblasts proliferate in anchoring columns to successfully invade through the decidua and engage in bidirectional communication with maternal decidual natural killer cells, macrophages, stromal, dendritic, endometrial gland epithelial, and T cells (1). Extravillous cytotrophoblasts transform the distal spiral arteries (2) and these changes mediate high volume flow at low pressure into the intervillous space (3). The blue arrows represent the paternal, maternal, and fetal components. Nutritional and environmental factors influence sperm maturation and development in males [82]. Once sperm enter the reproductive tract, they release signaling molecules that interact with decidual cells prior to fertilization [70]. Human oocytes develop in the mother during embryonic development and are subject to nutritional and environmental factors that influence epigenetic developmental programming [83]. Maternal and paternal nutritional and environmental factors can therefore influence sperm and oocytes prior to fertilization and have the potential to alter bidirectional communication signals during placentation. The red arrows represent the effect of nutritional and environmental factors in maternal pathophysiology and their impact on decidualization, placentation, and embryogenesis. Following fertilization, the zygote and morula receive nutrition from maternal secretions in the fallopian tube [24]. During implantation and throughout the first trimester, both the placenta and embryo obtain nutrition from histotroph fluid that is derived from maternal endometrial gland secretions [24]. These secretions provide glucose, lipids, glycoproteins, and growth factors that stimulate the rapid proliferation of villous trophoblasts, extravillous trophoblast invasion, spiral artery remodeling, and normal development of the placenta [77,84]. At the start of the second trimester, blood enters the intervillous space, resulting in hemotrophic nutritional exchange between the maternal and fetal circulations [85]. Accumulating evidence suggests that pathophysiological changes in women with PCOS, such as insulin resistance, chronic inflammation, and hyperandrogenism, may influence the composition and quality of histotrophic and hemotrophic nutrition, alter bidirectional communication between decidual and placental cells, and effect normal placentation and fetal development. The central diagram in blue is adapted with permission from Kingdom and Drewlo 2011 [86].

Figure 2

Algorithm for pre-eclampsia screening, lifestyle, and medical management of women with polycystic ovary syndrome in pregnancy. First-trimester multivariable screening is based on references [32,44,231,245]. The use of the sFlt-1:PlGF ratio is based on references [32,35,43,246,247]. Mean arterial pressure (MAP); uterine artery pulsatility index (UtAPI); placental growth factor (PlGF); soluble fms-like tyrosine kinase-1 (sFlt-1).