Cardiovascular Changes in Women Undergoing Medicated and Natural Frozen Embryo Transfer Cycles: A Prospective Observational Cohort Study

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Background: Frozen embryo transfer (FET) use in assisted reproductive technology (ART) has increased globally, with multiple reviews linking FET—particularly medicated cycles—to higher risks of obstetric complications including hypertensive disorders of pregnancy (HDP). Given that HDP is a sex-specific risk factor for future cardiovascular disease (CVD), this study aimed to assess acute cardiovascular changes in medicated versus natural modified FET cycles. Methods: This was a prospective observational cohort study at a fertility centre in London. Patients were recruited from May 2021 to March 2022. Maternal demographics including age, body mass index, smoking status, ethnicity and parity were recorded. Cardiovascular parameters including blood pressure along with measures of left ventricular systolic and diastolic function, assessed by transthoracic echo, were analysed at baseline in the luteal phase of the preceding cycle and on the day of embryo transfer, in medicated and natural modified FET cycles. Repeat measures analysis of the cardiac variables for the two time points, comparing the two protocols after controlling for maternal demographics, was performed by linear mixed models. Results: Seventy-two healthy patients were included in the analysis; of those, 59 (82%) underwent the medicated protocol. For both protocols, after controlling for maternal demographic characteristics, the left atrial area significantly increased (p = 0.004) from baseline to embryo transfer with a mean difference of 0.98 (95% CI [0.33, 1.63]). When comparing the interaction between the protocols between the two time points, whilst no effect could be seen on haemodynamic variables or left ventricular diastolic/systolic function, medicated FET cycles were associated with a statistically significant improvement in mean average global longitudinal strain (GLS) (p = 0.024) with a mean difference of −2.24 (95% CI [−4.17, −0.31]), whereas natural modified cycles demonstrated a slight shift toward more positive strain values. Conclusions: In this cohort of healthy patients undergoing FET, both protocols were associated with a significant increase in left atrial area from baseline to embryo transfer possibly resulting from an increased preload due to progesterone administration. The improvement in left ventricular average GLS seen in medicated FET cycles may reflect protocol-related physiological effects, potentially mediated by sustained exogenous oestrogen exposure and its influence on vascular loading conditions and myocardial relaxation.

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