Author + information
- Natalie Dayan, MD, MSc†,
- Carl A. Laskin, MD‡,
- Karen Spitzer, MSc‡,
- Jennifer Mason, RN†,
- Jacob A. Udell, MD, MPH†,
- Rachel M. Wald, MD†,
- Samuel C. Siu, MD, MS†,§,
- Theodora Iten-Scott, BSc† and
- Candice K. Silversides, MD, MS†∗ ()
- †University of Toronto, Department of Medicine, Obstetric Medicine and Pregnancy and Heart Disease Program, Mount Sinai Hospital, University Health Network, and Women’s College Hospital, Toronto, Ontario, Canada
- ‡LifeQuest Centre for Reproductive Medicine, and Departments of Medicine and Obstetrics & Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada
- §University of Western Ontario, Department of Medicine, University Hospital, London, Ontario, Canada
- ↵∗700 University Ave, 3rd Floor, Mount Sinai Hospital, OPG Building, Room 3-912, Toronto, Ontario M5G 1Z5, Canada
A growing number of women seek infertility treatment with assisted reproductive technologies (ART), such as in vitro fertilization (IVF) or intrauterine insemination (IUI), in conjunction with ovarian stimulation treatments (1). Although ART improve the chances of successful pregnancy, there are potential risks for the mother and offspring, including ovarian hyperstimulation syndrome (OHSS), venous thrombosis, multiple gestations, pre-eclampsia, and pre-term delivery (1). Women with heart disease have an increased baseline risk of these obstetric and perinatal complications (2,3). They may not tolerate additional risks imposed by ART. However, complications in pregnant women with heart disease treated with ART have not been described, despite parallel trends of delayed childbearing and increasing prevalence of heart disease among reproductive-aged women. Therefore, we aimed to describe adverse outcomes in a series of pregnant women with heart disease treated with ART.
Medical records of women followed in the Pregnancy and Heart Disease Program at our center and enrolled in our long-standing pregnancy outcomes study were reviewed to identify use of ART between September 2007, and August 2013. Information on cause of infertility, type of ART, superovulation protocols, and ART complications was obtained by self-report from each participant via telephone or face-to-face interview. Qualitative comparisons of the frequency of adverse outcomes were made using data from published reference populations.
Of the 20 women with 22 pregnancies included, 15 (75%) were white, with a mean age of 37 ± 4 years. Fifteen pregnancies (68%) were in women with a congenital heart defect, and 7 (32%) with acquired heart disease. Most pregnancies were first births (nulliparity, 64%), and 2 (9%) were multiples. Pregnancy was achieved by IUI without hormonal stimulation (n = 1), IUI with hormonal stimulation (n = 3), and IVF including cycles using donor oocytes (n = 18).
All pregnancies resulted in live births, except 1 that was electively terminated at 17 weeks due to fetal omphalocele. Overall, 73% of pregnancies were associated with at least 1 complication. Adverse outcomes are shown in Table 1. OHSS was common compared with rates reported in a population-based study of deliveries resulting from prescribed fertility treatments (18% vs. 1%) (4), although this comparison should be interpreted cautiously because the populations and definitions for OHSS may differ. Adverse cardiac maternal outcomes (27% vs. 13%) and fetal or neonatal outcomes (45% vs. 20%) were more common in this series compared with pregnant women with heart disease not conceiving with ART (2). Pre-maturity also was more common among infants in this series compared with infants in a reference ART population (32% vs. 13%) (5).
This is the first report of pregnancy outcomes in women with heart disease conceiving by ART. This report highlights the complex medical issues facing modern maternal demographics. The results presented in this small series underscore the need for updated information on outcomes in ART-treated women with high-risk medical conditions.
OHSS is a potentially serious complication of ART that may result in fluid shifts, maternal hypotension, thromboembolism, and death. Even mild forms of OHSS may be poorly tolerated in women with ventricular dysfunction, left ventricular outflow tract obstruction, Fontan circulation, or pulmonary arterial hypertension. Moreover, women with heart disease may seek medical attention sooner than those free of heart disease, leading to a high frequency of reported OHSS. Although only women with successful pregnancies were included in this study, ART-treated women with vulnerable heart lesions are at risk of OHSS and thromboembolism, even if pregnancy is not achieved.
Multiple gestations are common in ART pregnancies and are associated with a higher cardiac output compared with single pregnancies. This increased hemodynamic burden can be problematic in women with significant left-sided obstructive valve lesions or left ventricular systolic dysfunction. Multiple pregnancies have higher rates of pre-eclampsia and other morbidities that are poorly tolerated in the setting of pre-existing heart disease.
Pregnancies in women with heart disease are associated with adverse fetal and neonatal outcomes (2,3); the frequency of these complications may be even higher in the presence of ART. Putative mechanisms include suboptimal endometrial function at the time of implantation and compromised uteroplacental perfusion.
This study is limited by its retrospective design. It is likely that not all women who had ART during the time period studied were identified by chart review because recruitment occurred in a cardiac clinic where ART information was not routinely collected.
Current practice guidelines address pregnancy risks in women with heart disease. However, more information is urgently needed to help guide medical and obstetric management of women with heart disease treated with ART. The additional potential risks conferred by ART in conjunction with cardiac-specific maternal and fetal risks must be weighed against the desire for pregnancy. Modified ART protocols and close antenatal surveillance at a center with expertise in pregnancy and heart disease are recommended because of high complication rates.
The authors thank Kyle Pasternac for his assistance with this project.
Please note: The Canadian Institute of Health Research supported the study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Allen V.M.,
- Wilson R.D.,
- Cheung A.
- Siu S.C.,
- Sermer M.,
- Colman J.M.,
- et al.
- Drenthen W.,
- Boersma E.,
- Balci A.,
- et al.
- Udell J.A.,
- Lu H.,
- Redelmeier D.A.
- Sazonova A.,
- Kallen K.,
- Thurin-Kjellberg A.,
- et al.