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Maternal CV Risk After Assisted Reproductive Technologies
Quick Takes
- The findings of this study suggest that women who gave birth after assisted reproductive technologies (ART) were not at increased risk of CVD over a median follow-up of 11 years compared with those who conceived without ART.
- There was weak evidence that frozen embryo transfer was associated with an increased incidence of stroke as compared to fresh embryo transfer.
- Longer-term studies with more information on techniques of ART and embryo transfer are needed to further examine whether ART is associated with a higher risk of CVD.
Study Questions:
Is there an elevated risk of cardiovascular disease (CVD) among individuals who have given birth after assisted reproductive technologies (ART) compared with those who have given birth without ART?
Methods:
A Nordic maternal data linkage registry-based cohort study was conducted using nationwide data from the 1990s to 2015 in Denmark, Finland, Norway, and Sweden. A total of 2,496,441 individuals with a registered delivery in the national birth registries during the study period were included, and 97,474 (4%) of these gave birth after ART. The main exposure was any delivery after using ART, and individuals were classified as exposed from the time of their first delivery from use of ART, including fertilization method (in vitro fertilization [IVF] with or without intracytoplasmic sperm injection [ICSI]), or the use of fresh versus frozen embryo transfer, compared with individuals who had not used ART.
The primary outcome was CVD defined as any registration of ischemic heart disease (including myocardial infarction [MI]), cerebrovascular disease (including stroke), cardiomyopathy, heart failure, pulmonary embolism, and deep vein thrombosis (DVT). Clinical characteristics such as age, parity, prepregnancy body mass index, traditional CVD risk factors, and information on adverse pregnancy outcomes such as hypertensive disorders of pregnancy (HDP) and preterm birth were also recorded. Multivariate regression models were created to ascertain the association between ART and CVD after controlling for clinical variables and risk factors. Separate sensitivity analysis was also performed.
Results:
Of 2,496,441 nulliparous women at the start of follow-up without pre-existing CVD, 97,474 (4%) gave birth after ART. The median follow-up time for all individuals was 11 years. The rate of any CVD was 153 per 100,000 person-years. Individuals who gave birth after using ART had no increased risk of CVD (adjusted hazard ratio [AHR], 0.97; 95% confidence interval [CI], 0.91-1.02), with evidence of heterogeneity between the countries (I2 = 76%; p = 0.01 for heterogeneity).
When examining subgroups of CVD, there was no significant difference between individuals who delivered with and without using ART in the risk of ischemic heart disease, cerebrovascular disease, stroke, cardiomyopathy, heart failure, pulmonary embolism, or DVT. However, there was a lower risk of MI (incidence rates, 14 vs. 12 per 100,000; combined HR, 0.80; 95% CI, 0.65-0.99) among individuals who had used ART.
There was weak evidence that frozen, but not fresh, embryo transfers were associated with an increased risk of stroke (HR, 1.59 [95% CI, 1.11-2.26] for frozen embryo transfer and 0.91 [95% CI, 0.80-1.05] for fresh embryo transfer). The association between frozen embryo transfer and risk of stroke persisted after further adjustment for pregnancy complications (AHR, 1.58 [95% CI, 1.10-1.04]).
Conclusions:
The findings of this large Nordic maternal data linkage study suggest that individuals who gave birth after ART were not at increased risk of CVD over a median follow-up of 11 years compared with those who conceived without ART.
Perspective:
An increasing number of individuals are using ART for conception. A prior meta-analysis showed a higher risk of cerebrovascular disease in individuals undergoing ART as compared to those not. These data are inconsistent and lack the differentiation on method of ART and type of embryo transfer. This large study from the Nordic region with about 11 years of follow-up did not show an increased risk of CVD including stroke, heart failure, and pulmonary embolism or DVT after ART. Some studies have shown an increased risk of HDP in individuals undergoing frozen embryo transfer versus fresh embryo transfer. This study showed weak evidence of increased stroke in frozen transfers as compared to fresh transfers. IVF should be considered an important part of pregnancy and reproductive history and clinicians should focus on optimizing CV risk factors in all pregnant individuals.
Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Hypertension
Keywords: Cardiomyopathies, Cerebrovascular Disorders, Embryo Transfer, Fertilization, Fertilization in Vitro, Heart Failure, Hypertension, Pregnancy-Induced, Infant, Newborn, Myocardial Infarction, Myocardial Ischemia, Parity, Pregnancy, Premature Birth, Primary Prevention, Pulmonary Embolism, Reproductive Techniques, Risk Factors, Sperm Injections, Intracytoplasmic, Stroke, Thrombosis, Vascular Diseases, Women
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