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Circulatory Dysfunction in Asymptomatic in Vitro Fertilization Patients. Relationship with Hyperestrogenemia and Activity of Endogenous Vasodilators¹

Department of Obstetrics and Gynecology (D.M., J.B., F.F., M.C., J.A.V.) Liver Unit, Institut Clínic of Digestive Diseases, Department of Medicine (V.A.) and Hormonal Laboratory (W.J., R.C.), Hospital Clínic i Provincial, Faculty of Medicine, University of Barcelona, Barcelona, Spain

Address all correspondence and requests for reprints to: Juan Balasch, Department of Obstetrics and Gynecology, Hospital Clínic i Provincial, C/Casanova 143, 08036-Barcelona, Spain.

Severe ovarian hyperstimulation syndrome (OHSS) is consistently associated with a circulatory dysfunction characterized by arterial hypotension, low peripheral vascular resistance, and increased activity of the renin-aldosterone system. To investigate whether circulatory dysfunction also occurs in asymptomatic patients undergoing controlled gonadotropin ovarian hyperstimulation under pituitary suppression for in vitro fertilization (IVF), 12 women without clinical manifestations of OHSS underwent sequential blood, urine, and hemodynamic measurements at five study points: the 7th day of the menstrual cycle preceding IVF (study point 1 or baseline), the day when pituitary suppression was shown (study point 2), the day of hCG ovulatory injection (study point 3), the day after hCG was injected (study point 4), and 7 days after hCG administration (study point 5). Mean arterial pressure, cardiac output, peripheral vascular resistance, plasma concentrations of estradiol (E₂) and aldosterone, and plasma renin activity (PRA) were measured at each study point in all women. Serum levels of nitrite/nitrate, and plasma concentration of atrial natriuretic peptide, norepinephrine, adrenomedullin, and cyclic guanosine 3'5'-monophosphate were measured in samples obtained at study points 1 and 5. Multiple follicular development during ovarian stimulation associated with increased plasma E₂ concentration (mean peak plasma E₂ level, 2430 ± 428 pg/mL, range 1630–3840 pg/mL) were observed in each woman.

All patients developed a significant increase in cardiac output and decrease in arterial pressure and peripheral vascular resistance, and a marked elevation in PRA and aldosterone, all indicating the development of arteriolar vasodilation. Changes in circulatory measurements were temporarily related with the increase in E₂ both being detected at study points 3–5. In contrast, there was a clear chronological dissociation between the increase in plasma E₂ concentration and the stimulation of the renin-aldosterone system. PRA and aldosterone only reached abnormal levels at study point 5 in association with a significant increase in plasma norepinephrine concentration. Serum levels of nitrite/nitrate and plasma concentrations of atrial natriuretic peptide, adrenomedullin, and cyclic GMP were similar at study points 1 and 5.

It is concluded that the circulatory dysfunction that characterizes severe OHSS is a universal event in patients undergoing controlled ovarian hyperstimulation for IVF. Although the increase in E₂ levels during IVF cycles is associated with significant circulatory changes, the circulatory dysfunction that characterizes severe OHSS is clearly unrelated to the onset of hyperestrogenemia. Arteriolar vasodilation during IVF cycles was not associated with an increased activity of the vasodilator substances atrial natriuretic peptide, adrenomedullin, and nitric oxide.

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