The Effects of Supraphysiological Estrogen Levels Observed During In Vitro Fertilization Treatment on Cardiac Electrophysiology

ABSTRACT Supraphysiological estradiol (E2) levels during in vitro fertilization (IVF) may influence cardiac electrophysiology, but this effect is not well defined. We prospectively evaluated the impact of high E2 concentrations induced by controlled ovarian hyperstimulation (COH) on electrocardiographic (ECG) parameters of atrial conduction and ventricular repolarization. To our knowledge, this is the first study to examine these detailed electrophysiological indices in the context of supraphysiological E2. This prospective observational study included 62 healthy women undergoing an IVF protocol. Standard 12‐lead ECGs and serum hormone levels were obtained before stimulation (baseline E2 < 50 pg/mL) and at peak E2 concentration. Changes in PR interval, corrected QT (QTc) interval, J‐Tpeak (J‐Tp) distance, and Tpeak‐Tend (Tp‐e) interval were analyzed with paired tests. COH produced a marked rise in E2 and significant prolongations in all cardiac intervals. From baseline to peak E2, PR increased from 138.50 ± 20.59 to 144.53 ± 19.31 ms ( p = 0.007), QTc from 410.0 to 422.0 ms ( p = 0.003), J‐Tp from 208.74 ± 30.52 to 216.56 ± 30.98 ms ( p = 0.005), and Tp‐e from 80.00 to 83.50 ms ( p < 0.001). Supraphysiological E2 levels during IVF are associated with alterations in cardiac electrophysiology, including prolongation of atrial conduction and ventricular repolarization intervals. Although values remained within normal limits in healthy women, the observed QTc and Tp‐e prolongation suggest a potential pro‐arrhythmic substrate and highlight the importance of cardiac monitoring in IVF patients, particularly those with cardiovascular risk. Trial Registration: ClinicalTrials.gov identifier: NCT07007416