13 Accidental hyperstimulation during ovulation induction

Abstract

Clinical hyperstimulation is the most serious complication of ovulation induction, occurring in approximately 3% of cases (0.8% in the severe form). Paradoxically, it seems to be rare following in vitro fertilization, probably because all the follicles are aspirated. High-risk patients are those with polycystic ovarian disease, hyperprolactinaemia and hypothyroidism. All forms of ovulation induction have been implicated. Use of LHRH agonists have not reduced the incidence of hyperstimulation and they may even have increased it. An ongoing pregnancy seems to predispose to the occurrence of hyperstimulation, due to the secretion of hCG. Clinically, three stages of hyperstimulation have been described by the WHO (mild, moderate and severe). The pathophysiology is not completely understood, although prostaglandins, histamines and, especially, the ovarian renin-angiotensin system may be involved. Local ovarian complications and thromboembolic complications have also occurred. The treatment of severe hyperstimulation is both symptomatic (fluid replacement, aspiration of effusions, moderate sodium and water restriction, small doses of diuretics) and specific (corticosteroids, aspiration of ovarian cysts, even voluntary interruption of pregnancy in the most serious forms). If the hyperstimulation occurs in the absence of pregnancy, antihistamines or antiprostaglandins can be given. Prevention is exceedingly important. This can be helped by recognition of polycystic ovarian disease and stimulation of these cases by clomiphene citrate or pure FSH associated, for use in in vitro fertilization, with prolonged desensitization using LHRH agonists. Daily ultrasound and hormonal monitoring of ovulation induction is required. When there is excessive response to stimulation, it is prudent not to induce ovulation with hCG or, alternatively, to aspirate all the follicles and freeze the embryos obtained without giving further injections of hCG in the luteal phase. Clinical ovarian hyperstimulation is the classic form of iatrogenic disorder and is the most important complication of ovulation induction treatments, since it can be life-threatening in its most severe form. In this chapter we review current knowledge concerning the frequency, factors associated with its occurrence, clinical aspects, physiopathological mechanisms and, finally, the possibilities for treatment and prevention.