Maternal Risk of Cardiovascular Disease After Use of Assisted Reproductive Technologies

Author:

Magnus Maria C.1,Fraser Abigail23,Håberg Siri E.1,Rönö Kristiina4,Romundstad Liv Bente5,Bergh Christina6,Spangmose Anne Lærke7,Pinborg Anja7,Gissler Mika89,Wennerholm Ulla-Britt6,Åsvold Bjørn Olav101112,Lawlor Deborah A.23,Opdahl Signe11

Affiliation:

1. Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway

2. Population Health Sciences, Bristol Medical School, Bristol, United Kingdom

3. MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom

4. Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

5. Spiren Fertility Clinic, Trondheim, Norway

6. Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden

7. Fertility Department, Copenhagen University Hospital, Rigshospitalet, Denmark, Copenhagen

8. Finnish Institute for Health and Welfare, Helsinki, Finland, Region Stockholm, Academic Primary Health Care Centre, Stockholm, Sweden

9. Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden

10. K. G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway

11. Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway

12. Department of Endocrinology, Clinic of Medicine, St Olavs Hospital, Trondheim University 1 Hospital, Trondheim, Norway

Abstract

ImportanceThe use of assisted reproductive technologies (ARTs) is steadily increasing worldwide. The outcomes associated with treatment for an individual’s long-term health, including risk of cardiovascular disease (CVD), remain largely unknown, due to the small number of studies and their limited follow-up time.ObjectiveTo study whether the risk of CVD is increased among individuals who have given birth after ART compared with those who have given birth without ART.Design, Setting, and ParticipantsA registry-based cohort study was conducted using nationwide data from Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1985-2015). Data analysis was conducted from January to August 2022. 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.ExposuresData on ART conception were available from ART quality registries and/or medical birth registries.Main Outcomes and MeasuresInformation on CVD was available from patient and cause of death registries. The risk of CVD was estimated with Cox proportional hazards regression, adjusting for age, calendar year of start of follow-up, parity, diagnosis of polycystic ovary syndrome, diabetes, chronic hypertension, and country.ResultsMedian follow-up was 11 (IQR, 5-18) years. The mean (SD) age of women with no use of ART was 29.1 (4.9) years, and the age of those who used ART was 33.8 (4.7) 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% CI, 0.91-1.02), with evidence of heterogeneity between the countries (I2 = 76%; P = .01 for heterogeneity). No significant differences in the risk of ischemic heart disease, cerebrovascular disease, stroke, cardiomyopathy, heart failure, pulmonary embolism, or deep vein thrombosis were noted with use of ART. However, there was a tendency for a modest reduction in the risk of myocardial infarction (AHR, 0.80; 95% CI, 0.65-0.99), with no notable heterogeneity between countries.Conclusions and RelevanceThe findings of this study suggest that women 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. Longer-term studies are needed to further examine whether ART is associated with higher risk of CVD.

Publisher

American Medical Association (AMA)

Subject

Cardiology and Cardiovascular Medicine

Reference29 articles.

1. International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014.;Chambers;Hum Reprod,2021

2. ART in Europe, 2018: results generated from European registries by ESHRE.;Wyns;Hum Reprod Open,2022

3. Estradiol- and progesterone-related increases in the renin-aldosterone system: studies during ovarian stimulation and early pregnancy.;Sealey;J Clin Endocrinol Metab,1994

4. Infertility, fertility treatment, and risk of hypertension.;Farland;Fertil Steril,2015

5. Incidence of pulmonary and venous thromboembolism in pregnancies after in vitro fertilisation: cross sectional study.;Henriksson;BMJ,2013

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