PCOS found an independent risk factor for adverse outcomes in pregnancy

Published 22 June 2020

A huge population study of more than 9 million pregnancies has shown that the risk of metabolic complications in pregnancy is higher in women with PCOS than in controls and is associated independently with PCOS.

The health implications of polycystic ovary syndrome stretch far beyond fertility and conception. Indeed, the third ESHRE/ASRM consensus, following agreements on diagnosis in 2004 and treatment in 2008, considered the wide-ranging ‘health aspects’ of PCOS, notably insulin resistance and other metabolic disorders, type 2 diabetes, cardiovascular diseases and cancers.(1,2,3) Among the ‘pregnancy complications’ were gestational diabetes, pre-eclampsia and the birth of small-for-gestational age babies. 

Now, ‘the largest study in the literature to date’ in assessing PCOS as a risk factor for the metabolic complications of pregnancy has confirmed that women with PCOS are indeed at a two-fold higher risk of developing gestational diabetes than women without PCOS, at a 50% increased risk of developing gestational hypertension, and a 30% increased risk of pre-eclampsia.(4)

The results come from analysis of the largest inpatient cohort in the USA (the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database) in which deliveries to women with diagnosed PCOS between 2004 and 2014 (n = 14,882) were compared with a non-PCOS reference group of more than 9 million deliveries. While the results appear to echo those of earlier (and smaller) studies, the authors state that this study avoids much of the formers’ heterogeneity and confounding from inadequate statistical power. Thus, in their opinion these earlier studies (even a large meta-analysis from 2019) were unable to isolate PCOS as an independent risk factor for all metabolic complications of pregnancy. 

First, in terms of metabolic characteristics, the study showed that pregnant women with PCOS were at baseline more obese than controls (22.3% vs 3.5%), had greater prevalence of chronic hypertension (8.4% vs 1.8%) and had more pregestational diabetes (4.1% vs 0.9%). All these differences were statistically significant. There was also a higher rate of IVF conception in the PCOS women (2.4% vs 0.1%) and more multiple pregnancies (5.9% vs 1.5%), which seemed largely explained by IVF. 

However, in all pregnancies the women with PCOS were more likely to develop gestational diabetes (adjusted OR 2.19), pregnancy-associated hypertension (aOR 1.38), and pre-eclampsia (aOR 1.29) than controls. The adjustments controlled for age, income level, obesity, smoking and chronic disease. The study also controlled for ‘insurance type’, which was significantly different between the two groups and may explain a possibility of underdiagnosis in women belonging to lower socioeconomic groups and receiving their care through Medicaid.

The adjustments proved important in the findings, indicating, for example, that the two-fold added risk of gestational diabetes was independently associated with PCOS and not confounded by obesity (or other confounding factors). ‘Currently,’ the authors write, ‘most studies and meta-analyses suggest between a 2.5- to 4-fold increased risk of GDM in the PCOS population, with significant uncertainty about whether or not the attributable risk is from PCOS alone, or if it is related to obesity.’ The size of the study population and the study’s strict adjustments mean, they explain, that their results are a likely ‘accurate representation of the risk’.

As background to their report the authors note that hypertensive disorders of pregnancy complicate up to 10% of all pregnancies, a prevalence ‘over-represented’ in women with PCOS. This study indeed found all such disorders greater than in controls, with an adjusted odds ratio for pre-eclampsia of 1.29 (and pregnancy-associated hypertension of 1.38). The physiological processes behind these associations have been widely studied, but, say the authors, remain ‘relatively elusive’ but apparently related ‘to the similar pathophysiological processes that predispose PCOS women to higher rates of metabolic syndrome, such as central obesity and increased insulin resistance’.

As ever, multiple pregnancy is identified as one of the greatest risks of adverse pregnancy outcomes, whether in PCOS women or not. However, in this study women with PCOS had a four-fold higher incidence of multiples than non-PCOS (5.9% vs 1.5%) and an almost 6-fold higher rate of IVF use in multiple pregnancies complicated by PCOS (12.3% vs. 2.3%). However, the authors stress that, while multiple pregnancy may confer more risk than PCOS (either alone or in combination with PCOS), it does not completely remove or modify the independent risk of PCOS. ‘Our data support this assertion,’ they write, ‘because the increased adjusted ORs for adverse metabolic pregnancy outcomes that were significant for all pregnancies remained statistically significant in the singleton pregnancy group’. Thus, PCOS remained a clinically significant independent risk factor for adverse outcomes (gestational diabetes, pre-eclampsia) even in the presence of other risk factors such as multiplicity. 

Such findings, they conclude, that PCOS represents a genuine independent risk factor for adverse pregnancy complications, should ‘ensure that women with PCOS, regardless of other pre-existing conditions, will receive appropriate care in the prevention and management of their pregnancies’. 

1. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19: 41-47.
2. The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod 2008; 23: 462-477.
3. The Amsterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on women's health aspects of polycystic ovary syndrome (PCOS). Hum Reprod 2012; 27: 14-24.
4. Mills G, Badeghiesh A, Suarthana E, et al. Polycystic ovary syndrome as an independent risk factor for gestational diabetes and hypertensive disorders of pregnancy: a population-based study on 9.1 million pregnancies. Hum Reprod 2020;

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