Long-term risk of cardiovascular disease after assisted reproductive technology and infertility
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Background
The use of Assisted Reproductive Technology (ART) is increasing worldwide. These treatments involve ovarian stimulation to enable multiple follicle recruitment, hence inducing supraphysiological estrogen levels. While most long-term follow-up of women undergoing ART has concerned cancer incidence, the long-term safety regarding cardiovascular and metabolic diseases remains under-explored. This study was performed to assess the risk of acute myocardial infarction, cerebral ischemic conditions, intracranial hemorrhage, type 2 diabetes mellitus, heart failure, aortic aneurysm or dissection, and chronic kidney disease in women that conceived with ART, and to investigate the role of the underlying infertility and its risk factors.
Methods and Findings
Swedish national registers allowed us to follow a nationwide cohort of 380,756 women from their first birth between 1992 and 2002 until the end of 2023. The safety of ART was evaluated by comparing women with infertility who conceived with and without ART, while adjusting for baseline differences in age, body mass index, country of origin, socioeconomic factors, pre-existing comorbidity, smoking and year. The role of infertility was additionally explored by comparing all women with and without infertility adjusting for age, as well as the aforementioned baseline characteristics. Cumulative risks were plotted using inverse-probability weighted Kaplan-Meier curves. To facilitate the comparison of groups we also estimated risk differences and ratios at 10-, 20-, and 30-years of follow-up. Use of ART was not associated with cardiovascular disease except for an excess risk of cerebral ischemic conditions, with a 30 year risk ratio of 1.43 (1.09; 1.89). With the exception of cerebral ischemic conditions, intracranial hemorrhage, aortic dissection, and chronic kidney disease, women with a history of infertility exhibited consistently higher risk of all outcomes, adjustment for differences in baseline characteristics explained some but not all of these elevated risks.
Conclusions
With the exception of ischemic cerebral conditions, the findings provide reassurance regarding the long-term cardiometabolic safety of ART use, while adding to the growing literature suggesting that infertility can act as a marker of women’s cardiovascular and metabolic disease.
AUTHOR SUMMARY
Why Was This Study Done?
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Assisted reproductive technology is an increasingly common infertility treatment, accounting for up to 5% of children born per year in some countries.
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The treatment often exposes women to high doses of hormones, which raises concerns about potential negative effects on the cardiovascular system.
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It is currently unclear whether use of assisted reproductive technology increases a woman’s long-term risk of cardiovascular diseases.
What Did the Researchers Do and Find?
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We conducted a study including all women who gave birth in Sweden from 1992 to 2002 [380,756], with ability to track the occurrence of heart disease and stroke through 2023.
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We compared women who conceived with and without assisted reproductive technology after experiencing infertility, with adjustment for differences in background characteristics. We also compared overall risks to women with and without infertility.
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Use of assisted reproductive technology was associated with a 43% higher risk of cerebral ischemic conditions, but not with any other studied outcomes. After 30 years follow-up, women with infertility were found at 36% higher risk of acute myocardial infarction, 34% higher risk of type 2 diabetes, and 25% higher risk of heart failure, compared to women with similar background characteristics.
What Do These Findings Mean?
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While the fidings are largely reassuring with respect to long-term cardiovascular health following use of ART, an excess risk of cerebral ischemic conditions warrants further consideration.
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The results suggest that women with infertility are at elevated risk of cardiovascular issues later in life.
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Limitations of the study include the relatively small number of women treated with these technologies and a lack of data on women who underwent treatment which did not result in birth.
