Pregnancy, in vitro fertilization and cardiovascular outcomes in women with Turner syndrome compared to controls: a retrospective register-based matched case-control study

Background

Women with Turner syndrome (TS) frequently associated with a congenital heart disease, such as bicuspid aortic valve, coarctation of the aorta and aortic dilatation which may increase the risk of cardiovascular complications during fertility treatment and pregnancy.

Purpose

To study in vitro fertilization (IVF) and pregnancy related complications and cardiovascular outcomes among women with TS compared to controls.

Methods

In this retrospective register-based case-control study, major adverse cardiovascular events (MACE) were evaluated in two settings. First, within 12 weeks after IVF cycles in women with TS (n=146) compared with matched controls (n=454). Second, within 1 year after delivery or intrauterine foetal death in women with TS (n=59) compared to controls (n=481). MACE was defined as cardiovascular mortality, arrhythmia, ischemic heart disease, stroke, heart failure, aortic dissection, peripheral arterial disease, or venous thrombosis.

Results

Women with TS were younger and had higher body mass index (BMI) at the time of IVF compared with the controls (Table 1). Oocyte donation was performed at a higher rate in women with TS. There were no occurrences of ovarian hyperstimulation syndrome, ovarian torsion, infection, or bleeding requiring hospitalization in either study group. Within 12 weeks after IVF, no MACE were recorded.

The prevalence of congenital malformations was the same in neonates delivered by women with and without TS (n=2; 3.3% vs. n=13; 2.6%). One intrauterine foetal death occurred within the control group (0.2 %). Women with TS, were older, had higher frequency of IVF, hypertension, chronic kidney disease, and lower rate of term delivery, compared with controls (Table 2). We found an increased incidence of infants born small for gestational age among women with TS compared with controls (n=6; 10.7% vs. n=11; 2.3%, P<0.001).

Women with TS had increased odds of Caesarean section (OR 2.0; 95% CI: 1.4-2.6) and prematurity (OR 3.3; 95% CI: 1.7-7.2) compared with controls. The risk of having a small for gestational age neonate was higher among women with TS (RR 3.6; 95% CI 1.8–7.2).

Within 1 year after a pregnancy, three MACE occurred in the control group. Two hospital admissions, one due to venous thrombosis and one due to ventricular extrasystoles and one outpatient visit for premature depolarizations. No cardiovascular mortality was observed.

Conclusions

In this nationwide register-based study, no cardiovascular mortality or other major adverse cardiac event occurred in our cohort of IVF or pregnancies in women with TS. Spontaneous pregnancy can occur in women with TS, but IVF is more common. Women with TS have higher rates of hypertensive disorders, Caesarean section, small-for-gestational-age neonates, and preterm delivery. Careful cardiovascular evaluation before fertility treatment and pregnancy remains essential.