Blood sugar levels are known to be a risk factor for conception and successful pregnancy. For women struggling with conception, stress levels are high, but these are linked to poor outcomes.

A new study in the Journal of the Endocrine Society explores stress in relation to glucose levels during treatment at a fertility center since this is likely to impact conception rates and pregnancy success.

Background

Stress levels are rising each year, as has been shown by epidemiologic studies. Women are more prone to higher levels of stress than men. Especially during fertility treatment, women are stressed.

However, such women are more likely to suffer from metabolic conditions such as polycystic ovarian syndrome (PCOS). Conversely, fertility treatment, in many cases, is itself a disrupter of normal metabolism, mostly via abnormal glucose metabolism.

Stress is linked to abnormal glucose homeostasis in pregnancy. Especially during the preconception window, environmental and lifestyle factors, including lack of physical activity, pollution, and poor diet quality, could impact gestational health and might precipitate conditions like pre-eclampsia.

The current study looked at the relationship between the woman’s perception of stress in the period immediately before conception and pregnancy glucose levels, stratifying them by socioeconomic status and by mode of conception, whether natural or by intrauterine insemination (IUI) or in vitro fertilization (IVF).

All women in the study were followed prospectively as part of the Environmental and Reproductive Health (EARTH) study at the Massachusetts General Hospital Fertility Center.

The participants filled out a survey to measure their mental stress levels prior to conception using the Perceived Stress Scale 4 (PSS-4). They also underwent blood glucose screening after a load of 50g glucose was given during late pregnancy screening for gestational diabetes mellitus (GDM).

The blood glucose levels were then analyzed for associations with total PSS-4 scores, adjusting for confounding variables like age, body mass index (BMI), ethnicity, smoking, physical activity, educational levels, parity, and mode of conception.

What did the study show?

The median BMI of the participants was 23.4 kg/m2, and the median age was 35 years. Seven out of eight were White, two-thirds had a college degree or higher, and almost 80% were never-smokers.

Three out of four women conceived, for a total of 300 pregnancies, using assisted reproductive technologies (ART), with about 60% and 16% doing so with IVF and IUI, respectively. Blood glucose levels after a glucose load were assessed at a median of approximately ten months after the stress assessment was done.

The median PSS-4 score was 5, and the mean glucose level 119 mg/dL 1 hour after 50 g glucose load. Hyperglycemia was present in a fifth of the women, at 140 mg/dL or higher.

The mean PSS-4 score was higher, at 6, among women with hyperglycemia, compared to a mean of 5 for women with normal glucose levels.

The results showed that psychological stress went up as abnormal glucose levels increased. The mean glucose levels, after accounting for other variables as listed above, still increased from the first to the third tertiles of stress. The levels moved from 115 mg/dL in the first, through 119 mg/dL in the second, to 124 mg/dL in the third.

The risk of hyperglycemia was increased by 4% in the second tertile of stress but by 13% in the third, compared to the first tertile.

Stress was linked to abnormal glucose levels during pregnancy, mostly among those with at least a college degree and those with higher education, as well as possibly among those who conceived via IUI.

What are the implications?

“Higher preconception psychological stress was associated with higher pregnancy blood glucose levels as well as the probability of having abnormal glucose levels during pregnancy.”

While higher educational levels and income seemed to be risk factors for gestational hyperglycemia, the association with IUI should be validated since the number of such women was low.

However, the lower perceived effectiveness of this ART method compared to IVF may account for the higher stress levels among the women in this study, especially since it is used to correct female factor infertility. Income and educational levels may be related to workplace demands that are more time- and energy-consuming, resulting in increased stress levels.

This agrees with earlier reports showing increased job stress in association with higher education and presumably with higher income as well. In addition, women in the workplace have the additional need to ensure that their roles as household managers and mothers and wives are balanced with their job demands, increasing their stress levels.

Stress acts on the hypothalamic-pituitary-adrenal (HPA) axis to pump higher levels of cortisol and other glucocorticoids into the system. This pushes up glucose levels in the blood and repeated or chronic stress could result in hyperglycemia with insulin resistance.

The results corroborate similar measures reported in pregnancy studies across other countries. Discrepant research has also been reported, possibly due to different assessment measures, gestational age, and glucose testing methods.

The findings thus emphasize the impact of preconceptional stress on cardiovascular health in pregnancy. Future studies should include women of other communities, ethnicities, and socioeconomic status to ensure that the results are validated and generalizable.