Assisted reproductive technology in women with adult congenital heart disease compared to controls: a large national registry study

Abstract Background/Introduction Survival rates for patients with congenital heart disease have improved, leading to more pregnancies among women with adult congenital heart disease (ACHD). Many patients now seek fertility treatments, including assisted reproductive technology (ART), but the short-term cardiovascular safety remains largely unknown. Purpose We sought to study the fertility rate and proportion of ART, as well as related complications and outcome among women with ACHD, in a large national retrospective matched case-control study. Methods We studied all women 18 years of age with ACHD in The Swedish Registry of Congenital Heart Disease compared to matched controls in Medical Birth Registry, respectively, the national registry of ART, the National Patient Register and the Cause of Death register between 2007 and 2020. Major adverse cardiovascular events (MACE) were studied from the start of first ART until 6 months after delivery, stillbirth/miscarriage or last treatment. MACE was defined as the presence of at least one of the following: CVD mortality, arrhythmia, thromboembolism (either during hospitalisation or in outpatient care), hospitalisation with a main diagnosis of either ischaemic heart disease, ischaemic stroke, peripheral artery disease, heart failure or aortic dissection. We excluded ART cycles due to preimplantation genetic diagnosis and due to sperm insemination and/or sperm donation (as a proxy for male factor infertility). Results We studied cycles of ART in women with ACHD (720 cycles) and controls (6221 cycles) from 2007 through 2020 (Table 1, Figure 1). More pregnancies in women with ACHD were facilitated by ART (3.9%) compared to controls (3.2%), but time from the start of the first treatment until delivery of a neonate did not differ. The total number of neonates, regardless of ART or spontaneous conception, was the same in women with ACHD and controls (1.7 neonates per woman). More women with ACHD gave birth prematurely before week 28 (2.5%) compared to controls (0.3%). Pregnancies in women with ACHD had an increased risk of congenital malformations (6.3%) compared to controls (3.2%). During and 6 months after ART, women with ACHD had an increased risk of MACE (n=9, 3.6%), odds ratio 2.84 (95% CI 1.15- 6.97), compared to controls (n=17, 1.1%). This was primarily driven by hospitalisation due to arrhythmias, mostly consisting of supraventricular tachyarrhythmias. No women died of cardiovascular mortality. Conclusion This is the first large national study investigating complications due to ART in women with ACHD compared to matched controls. Women with ACHD conceiving by ART may have an increased risk of prematurity, congenital malformations and non-fatal adverse cardiovascular events compared to controls. However, caution and careful optimism are still warranted, as our results cannot be applied directly to women with more complex ACHD.Table 1.