Mechanisms of adverse pregnancy outcomes in women with PCOS and
ways to prevent these outcomes by knowing more about these mechanisms
Sedigheh Hantoushzadeh (1), Maasoumeh Saleh* (2),
Sepehr Aghajanian (3), Mahboubeh Saleh (4)
1-Professor of Maternal-Fetal Medicine, Department of Obstetrics and
Gynecology, Maternal-Fetal Neonatal Research Center, Tehran University
of medical sciences, Valiasr Hospital, Tehran, Iran.
2-Fellowship of Maternal-Fetal Medicine, Department of Obstetrics and
Gynecology, Tehran University of Medical Sciences, Shariati hospital,
Tehran, Iran.
3-Department of Community Medicine, School of Medicine, Alborz
University of Medical Sciences, Karaj, Iran.
4-MD, Department of Urogynecology, Fasa University of Medical Sciences,
Fars, Iran.
Corresponding author*: Maasoumeh Saleh,
E-Mail:
salehmaasoumeh@yahoo.com
Dear editor,
We have read the study by Valgeirsdottir et al. (1), and wanted to
congratulate the authors for this prosperous article on risk of
stillbirth in polycystic ovarian syndrome (PCOS) women and make some
minor contributions.
PCOS is a complex disorder with unclear exact etiology. It involves
cardiovascular (CV), metabolic, endocrine, and reproductive system.
Several studies have reported an increase in adverse maternal and fetal
outcomes for women with PCOS, independent of the use of reproductive
technology or body mass index (BMI). PCOS is strongly associated with
preeclampsia (PE), gestational diabetes mellitus (GDM), very preterm
birth (PTB), large for gestational age fetuses (LGA), and asphyxia
during labor (2). In the study by Valgeirsdottir et al. (1), PCOS had a
50% increased risk of stillbirth compared to women without PCOS,
especially at term. In this study, the mechanisms of stillbirth are well
explained, which include the following: 1-Hyperandrogenism and
associated insulin resistance 2-Obesity 3-Hypertensive disorders
4-Placental diseases, fetal anomalies and umbilical cord abnormalities
5-Fetal growth restriction (FGR) 6-Gestational diabetes 7-Chronic
inflammation, oxidative state and mitochondrial dysfunction.
Serum concentration of homocysteine (Hcy) decreases during pregnancy due
to physiologic fall in albumin, as well as folic acid supplementation
(3). High serum Hcy level in PCOS women is an independent risk factor
for atherosclerotic vascular disease and thromboembolic disorders (4)
and it is associated with insulin resistance (5) and adverse pregnancy
outcomes, including PE, PTB, and low birth weight (LBW) (6). Elevated
C-reactive protein (CRP) levels indicate a low-grade inflammation in
PCOS, it is the most sensitive predictor of CV morbidity (7) and also it
is associated with adverse pregnancy outcomes (8). These two important
mechanisms, including high Hcy serum level and inflammation can play a
role in the adverse pregnancy consequences. So, the measurement of serum
Hcy level and CRP may be helpful in PCOS patient’s risk stratification
for pregnancy complications.
Another important issue is to suggest ways to prevent these adverse
pregnancy consequences in PCOS patients. Possible options are:
1-Lifestyle modification 2-pharmacological options: metformin, statins,
aspirin and high dose folic acid. The possible mechanisms by which
aspirin prevents adverse pregnancy outcomes are: 1-improvement in the
placentation 2-inhibition of platelet aggregation and its antithrombotic
effect 3-antiinflammatory effects and endothelial stabilization (9).
Metformin has beneficial effects on endothelial function and improve
insulin resistance (10). Statins reverses the pregnancy-specific
angiogenic imbalance and improve endothelial function (11). High dosage
of folic acid reduces Hcy concentration (12), and through this mechanism
may be effective in reducing pregnancy complications. Various studies
have been performed with these goals. But in the future, more extensive
studies on methods of preventing adverse pregnancy consequences by
focusing on their mechanisms are recommended in PCOS women.