Long-term CV Risk in Women Prescribed Fertility Therapy
Long-term CV Risk in Women Prescribed Fertility Therapy
Objectives The purpose of the study was to investigate whether fertility therapy might contribute to subsequent cardiovascular disease.
Background Fertility medications are used for 1% of births yet may also lead to endothelial injury with long-term adverse consequences for the mother.
Methods A population-based cohort analysis was performed of women who gave birth in Ontario, Canada, between July 1, 1993, and March 31, 2010, distinguishing those who did and did not receive fertility therapy in the 2 years before delivery. Cox proportional models were derived to estimate hazard ratios with and without adjustment for baseline characteristics. The primary outcome was a composite cardiovascular endpoint of death, nonfatal coronary ischemia, stroke, transient ischemic attack, thromboembolism, or heart failure.
Results Among 1,186,753 women who delivered during the study period, 6,979 gave birth after fertility therapy. After 9.7 years of median follow-up, women who delivered after fertility therapy had fewer cardiovascular events than controls (103 vs. 117 events per 100,000 person-years), equivalent to an unadjusted hazard ratio of 0.96 (95% confidence interval: 0.72 to 1.29, p = 0.79) and an adjusted hazard ratio of 0.55 (95% confidence interval: 0.41 to 0.74, p < 0.0001). An apparent relative lower risk was observed across all age and income groups. Women who received fertility therapy also had lower risk-adjusted all-cause mortality, thromboembolic events, subsequent depression, alcoholism, and self-harm (p < 0.01 for each).
Conclusions Successful fertility therapy was not associated with an increased risk of cardiovascular disease later in life.
Infertility affects approximately 1 in 8 reproductive-age couples globally and can lead to enormous personal stress. General reproductive assistance improves the chance of pregnancy through medications that stimulate ovulation and now represents approximately 1% of all infants born annually in North America. Many industrialized countries support fertility therapy under national health insurance programs. In addition, some American states and Canadian provinces guarantee access to affordable fertility care whereas others offer no such programs.
Fertility therapy focuses attention toward achieving pregnancy rather than long-term health Clinical decision making, to an extreme degree, prioritizes a successful pregnancy, yet unintended toxicity can occur. One concern is that fertility therapy might lead to downstream cardiovascular events due to increased risks of maternal metabolic syndromes (e.g., gestational diabetes mellitus and hypertension), direct endothelial dysfunction, and prothrombotic effects from ovarian hyperstimulation with hyperestrogenemia. Nevertheless, long-term data are lacking on the health effects associated with fertility therapy for women who have a successful pregnancy, in part because of a lack of uniform reporting of adverse outcomes after fertility therapy and legislation sometimes prohibiting health data linkage.
The potential association between fertility therapy and subsequent cardiovascular disease is increasingly relevant given societal trends for women to delay pregnancy until older age, and with a higher likelihood of baseline heart disease. We questioned whether fertility therapy might contribute to increased cardiovascular events after successful pregnancy. The goal of the GRAVID (General Reproductive Assistance and Vascular Illness Downstream) study was to assess the long-term risk of premature cardiovascular disease for women after successful fertility drug treatment.
Abstract and Introduction
Abstract
Objectives The purpose of the study was to investigate whether fertility therapy might contribute to subsequent cardiovascular disease.
Background Fertility medications are used for 1% of births yet may also lead to endothelial injury with long-term adverse consequences for the mother.
Methods A population-based cohort analysis was performed of women who gave birth in Ontario, Canada, between July 1, 1993, and March 31, 2010, distinguishing those who did and did not receive fertility therapy in the 2 years before delivery. Cox proportional models were derived to estimate hazard ratios with and without adjustment for baseline characteristics. The primary outcome was a composite cardiovascular endpoint of death, nonfatal coronary ischemia, stroke, transient ischemic attack, thromboembolism, or heart failure.
Results Among 1,186,753 women who delivered during the study period, 6,979 gave birth after fertility therapy. After 9.7 years of median follow-up, women who delivered after fertility therapy had fewer cardiovascular events than controls (103 vs. 117 events per 100,000 person-years), equivalent to an unadjusted hazard ratio of 0.96 (95% confidence interval: 0.72 to 1.29, p = 0.79) and an adjusted hazard ratio of 0.55 (95% confidence interval: 0.41 to 0.74, p < 0.0001). An apparent relative lower risk was observed across all age and income groups. Women who received fertility therapy also had lower risk-adjusted all-cause mortality, thromboembolic events, subsequent depression, alcoholism, and self-harm (p < 0.01 for each).
Conclusions Successful fertility therapy was not associated with an increased risk of cardiovascular disease later in life.
Introduction
Infertility affects approximately 1 in 8 reproductive-age couples globally and can lead to enormous personal stress. General reproductive assistance improves the chance of pregnancy through medications that stimulate ovulation and now represents approximately 1% of all infants born annually in North America. Many industrialized countries support fertility therapy under national health insurance programs. In addition, some American states and Canadian provinces guarantee access to affordable fertility care whereas others offer no such programs.
Fertility therapy focuses attention toward achieving pregnancy rather than long-term health Clinical decision making, to an extreme degree, prioritizes a successful pregnancy, yet unintended toxicity can occur. One concern is that fertility therapy might lead to downstream cardiovascular events due to increased risks of maternal metabolic syndromes (e.g., gestational diabetes mellitus and hypertension), direct endothelial dysfunction, and prothrombotic effects from ovarian hyperstimulation with hyperestrogenemia. Nevertheless, long-term data are lacking on the health effects associated with fertility therapy for women who have a successful pregnancy, in part because of a lack of uniform reporting of adverse outcomes after fertility therapy and legislation sometimes prohibiting health data linkage.
The potential association between fertility therapy and subsequent cardiovascular disease is increasingly relevant given societal trends for women to delay pregnancy until older age, and with a higher likelihood of baseline heart disease. We questioned whether fertility therapy might contribute to increased cardiovascular events after successful pregnancy. The goal of the GRAVID (General Reproductive Assistance and Vascular Illness Downstream) study was to assess the long-term risk of premature cardiovascular disease for women after successful fertility drug treatment.
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