Women with a history of infertility and pregnancy loss may be at increased risk of non-fatal and fatal stroke later in life, according to new research published in The BMJ.

While age-specific stroke rates are higher in men, women have more stroke events than men and are less likely to recover. In fact, in 2019, women lost a total of 10 million years of healthy life due to disability following a stroke - 44% more years than men did.

However, the reason for this increased risk is unclear. To investigate further, a group of researchers analysed data from 27 studies which looked at the link between infertility, miscarriage and stillbirth, and non-fatal and fatal stroke.

Having a history of recurrent pregnancy loss may be considered as a female-specific risk factor for stroke

Data from eight studies spanning seven countries (Australia, China, Japan, Netherlands, Sweden, UK, and the USA) and around 620,000 women were included in the analysis.

The studies used questionnaires and hospital data to gather information about the participants, all of whom were aged 32 to 73 at baseline.

In total, 275,863 women had data on non-fatal and fatal stroke, 54,716 women only had data on non-fatal stroke, and 288,272 only had data on fatal stroke. Among these, 9,265 (2.8%) women experienced a first non-fatal stroke at a median age of 62, and 4,003 (0.7%) had a fatal stroke at a median age of 71.

After accounting for several extraneous variables, the researchers found that infertility, miscarriage, and stillbirth were all associated with an increased risk of stroke, especially recurrent miscarriages (three or more) and stillbirths.

Multiple pregnancy losses significantly increased the risk of stroke

Miscarriage was also associated with an 11% higher risk of non-fatal stroke compared to women who had not had a miscarriage, and this risk increased with the number of miscarriages a woman had, with three miscarriages increasing stroke risk by 35%.

For women who had three or more miscarriages, the level of risk for non-fatal ischaemic and haemorrhagic stroke was 37% and 41% respectively. However, for the same group, the risk of fatal ischaemic and haemorrhagic stroke following three or more miscarriages rose to 83% and 84% respectively.

A history of stillbirth was also associated with a 30% higher risk of non-fatal stroke, rising to 80% for women who had two or more stillbirths. The study also found that recurrent stillbirth was associated with an over 40% higher risk of fatal stroke. 

Early monitoring and intervention for women with a history of pregnancy loss or infertility

The study is observational and can’t establish a cause, however, the researchers suggest that the link between pregnancy loss and stroke may be explained by endothelial dysfunction (narrowing of the heart’s blood vessels), while the link between infertility and increased stroke risk may be due to conditions such as polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI).

However, since unhealthy lifestyle choices (such as smoking or obesity) are also associated with pregnancy loss and infertility (which could contribute to an elevated risk of stroke) the researchers suggest that promoting healthy habits may help to lower their risk of stroke later in life.