Author + information
- Received June 9, 2017
- Revision received July 6, 2017
- Accepted July 10, 2017
- Published online August 28, 2017.
- Natalie Dayan, MD, MSca,b,c,∗ (, )
- Kristian B. Filion, PhDa,b,d,
- Marisa Okano, MScPHb,c,
- Caitlin Kilmartin, BScc,
- Shauna Reinblatt, MDe,f,
- Tara Landry, MLISg,
- Olga Basso, PhDb,f and
- Jacob A. Udell, MD, MPHh,i,j,∗∗ ()
- aDepartment of Medicine, McGill University Health Centre, Montreal, Canada
- bDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada
- cResearch Institute, McGill University Health Centre, Montreal, Canada
- dCentre for Clinical Epidemiology, Lady Davis Institute for Health Research, Jewish General Hospital, Montreal, Canada
- eDepartment of Reproductive Endocrinology and Infertility, McGill University Health Centre, Montreal, Canada
- fDepartment of Obstetrics and Gynecology, McGill University Health Centre, Montreal, Canada
- gMedical Library, Montreal General Hospital, Montreal, Canada
- hWomen’s College Research Institute and Cardiovascular Division, Women’s College Hospital, Toronto, Canada
- iPeter Munk Cardiac Centre, Toronto General Hospital, Toronto, Canada
- jUniversity of Toronto, Toronto, Canada
- ↵∗Address for correspondence:
Dr. Natalie Dayan, McGill University Health Centre - Research Institute, Centre for Outcomes Research and Evaluation, 5252 de Maisonneuve West, 2B.40 Montreal QC H4A 3S5.
- ↵∗∗Dr. Jacob A. Udell, Women’s College Hospital, 76 Grenville Street, Toronto, Ontario M5S 1B1, Canada.
Background The longer term cardiovascular effects of fertility therapy are unknown.
Objectives The aim of this study was to summarize data linking fertility therapy with subsequent cardiovascular outcomes.
Methods We systematically searched published reports for studies addressing the question “does fertility therapy increase the risk of longer term cardiovascular outcomes?” We included: 1) human studies; 2) case control, cohort, or randomized designs with 3) exposure to fertility therapy and 4) cardiovascular outcomes clearly reported; 5) presence of comparison group; 6) minimum 1-year follow-up; and 7) adjustment for age. Two independent reviewers screened abstracts, titles, and full texts, and assessed study quality. We used the DerSimonian and Laird random-effects models to pool hazard ratios (HRs) with 95% confidence intervals (CIs) of the following outcomes: acute cardiac event; stroke; venous thromboembolism; hypertension; and diabetes mellitus, comparing women who received fertility therapy with those who did not.
Results Six observational studies met inclusion criteria including 41,910 women who received fertility therapy and 1,400,202 women who did not. There was no increased risk of a cardiac event (pooled HR: 0.91; 95% CI: 0.67 to 1.25; I2 = 36.6%), or diabetes mellitus (pooled HR: 0.93; 95% CI: 0.87 to 1.001; I2 = 0%). Results were not pooled for hypertension (I2 = 95.0%) and venous thromboembolism (I2 = 82.3%). There was a trend toward higher risk of stroke (pooled HR: 1.25; 95% CI: 0.96 to 1.63; I2 = 0%).
Conclusions The small number of studies and significant heterogeneity precludes definitive reassurance about the longer term cardiovascular safety of these treatments, particularly stroke. Future studies are needed to address ongoing knowledge gaps in this area.
This study was funded by the Heart and Stroke Foundation of Canada Grant in Aid (grant number G-15-0009034). The study funder had no role in the study design or conduct of the study. Dr. Udell is supported in part by funding from a Heart and Stroke Foundation of Canada National New Investigator/Ontario Clinician Scientist Award; Ontario Ministry of Research and Innovation Early Researcher Award; Women’s College Research Institute and Department of Medicine, Women’s College Hospital; Peter Munk Cardiac Centre, University Health Network; Department of Medicine and Heart and Stroke Richard Lewar Centre of Excellence in Cardiovascular Research, University of Toronto.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 9, 2017.
- Revision received July 6, 2017.
- Accepted July 10, 2017.
- 2017 American College of Cardiology Foundation
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