Prevention and Treatment of Ovarian Hyperstimulation Syndrome

Abstract

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of ovarian stimulation. Although the milder form is more common, particularly among patients undergoing gonadotropin stimulation for assisted reproductive technology, the severe form is rare. Classification schemes are clinically directed and useful in diagnosis and management of moderate and severe cases. The ovarian renin-angiotensin system, as well as vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) offers attractive theories as to the pathogenesis of this disorder. Unfortunately, clinical applications of these findings are not yet available. Possible prevention measures would include identification of patients at high risk, withholding human chorionic gonadotropin (hCG), using a gonadotropin-releasing hormone agonist to trigger ovulation, using a smaller dose of hCG, controlled gonadotropin drift, or avoidance of fresh embryo transfer by cryopreservation and frozen embryo transfer at a later date. Management of moderate to severe OHSS rests upon the principles of expanding intravascular volume and maintaining adequate urine output.

Haematocrit, leukocyte and platelet counts and the severity of the ovarian hyperstimulation syndrome

“…OHSS is secondary to a circulatory dysfunction due to the simultaneous occurrence of increased vascular permeability and marked arteriolar vasodilation which lead to ascites formation, arterial hypotension, tachycardia, increased cardiac output, reduced peripheral vascular resistance, marked stimulation of the renin-angiotensin and sympathetic nervous systems and ADH, haemoconcentration, oliguria, sodium retention, hyponatraemia, and in extreme cases, renal failure and thrombotic events (Schenker and Weinstein, 1978;Golan et al, 1989;Lancet, 1991;Rizk and Aboulghar, 1991;Balasch et al, 1994;Dourron and Williams, 1996;Elchalal and Schenker, 1997).…”

“…The presence of ascites, pleural effusion and even peripheral oedema, and the development of haemoconcentration with increased haematocrit have been the main arguments to support the contention that increased capillary permeability, mainly of the ovarian vessels, is the pathogenic mechanism of severe OHSS (Schenker and Weinstein, 1978;Rizk and Aboulghar, 1991;Elchalal and Schenker, 1997). The high plasma concentrations of renin subsequently observed in severe OHSS were also considered to be of ovarian origin since both mature ovarian follicles and the corpus luteum are capable of synthesizing renin (Bergh and Navot, 1992;Dourron and Williams, 1996;Elchalal and Schenker, 1997). According to this pathogenic hypothesis, the occurrence of thromboembolic phenomena has been related to the rapid body fluid shift leading to haemoconcentration and increased blood viscosity (Schenker and Weinstein, 1978;Rizk and Aboulghar, 1991;Elchalal and Schenker, 1997).…”

Circulatory Dysfunction in Asymptomaticin VitroFertilization Patients. Relationship with Hyperestrogenemia and Activity of Endogenous Vasodilators1

“…Several findings in the present study are in keeping with the latter hypothesis: 1) all our patients, which were asymptomatic throughout the IVF, developed the circulatory dysfunction that characterizes the OHSS, namely decreased mean arterial pressure and peripheral vascular resistance, increased cardiac output, and a marked increase in PRA and plasma norepinephrine concentrations (22,26), 7 days after the administration of hCG; 2) the degree of activation of the renin-aldosterone and sympathetic nervous system observed in the cases included in the current study, although intense, was much lower than that observed in patients with severe OHSS studied by our group using identical laboratory techniques (22,26); and 3) circulatory dysfunction after hCG injection in patients included in the present study occurred at the time when clinical manifestations of severe OHSS usually develop (3,5,6).…”

“…IVF implies the pharmacological induction of multiple follicular selection and ovulation. Approximately 2% of women undergoing ovulation induction for IVF develop severe ovarian hyperstimulation syndrome (OHSS) (3)(4)(5)(6). This is an acute and self-limiting but potentially life-threatening condition appearing within the first week after ovulation is induced.…”

Prevention and Management of Ovarian Hyperstimulation Syndrome

“…On the molecular levels a variety of factors have been investigated including the ovarian rennin-angiotensin system, prostaglandins, histamine, prolactin, and vascular endothelial factor. [19][20][21][22][23][24][25][26] Estradiol levels have been correlated with the development of OHSS but administration of high doses of estradiol cannot induce the syndrome in an animal model. 27 In addition, a severe form of OHSS has been reported in a patient with 17-20 desmolase deficiency and very low estradiol levels.…”