Objective: Ovarian hyperstimulation syndrome (OHSS) is a rare iatrogenic complication of ovarian stimulation usually occurring during the luteal phase or during the early part of pregnancy. OHSS is a potential complication of ovarian induction by almost every agent used for ovarian stimulation. Today, due to aggressive treatment protocols including the development of in vitro fertilization and cryopreservation with the goal of obtaining sufficient numbers of oocytes and embryos, an increased risk of developing OHSS is present. OHSS is now becoming increasingly more recognized due to the higher number of women undergoing assisted reproductive techniques. Design: Review of the literature regarding ovarian hyperstimulation syndrome. Methods: A review of the epidemiology, pathophysiology, risk factors, classification, clinical features, and treatment and prevention of OHSS. Conclusion: OHSS can be thought of as the loss of control over the hyperstimulation of the ovaries. Although the prevalence of the severe form of OHSS is small, it is important to remember that OHSS is usually an iatrogenic complication of a nonvital treatment that has the potential for a fatal outcome. Therefore, critical care physicians play an integral part in the care of these patients and therefore should be familiar with and recognize the various clinical manifestations and potential outcomes of this entity.

Ovarian hyperstimulation syndrome.

Diagnosis, prevention and management of ovarian hyperstimulation syndrome

The ovarian hyperstimulation syndrome (OHSS) is a rare iatrogenic complication of ovarian stimulation occurring during the luteal phase or during early pregnancy. This complication is unusual as it is not the consequence of a treatment which is vital or mandatory for the patient's health. Nevertheless, it can be accompanied by severe morbidity and may even be fatal. Data pertaining to the clinical course and consequences of OHSS in women and its treatment were searched using Medline, Current Contents and PubMed. To date, only a few studies have collected a large number of cases of OHSS. The clinical course of OHSS may involve, according to its severity and the occurrence of pregnancy, electrolytic imbalance, neurohormonal and haemodynamic changes, pulmonary manifestations, liver dysfunction, hypoglobulinaemia, febrile morbidity, thromboembolic phenomena, neurological manifestations and adnexal torsion. Treatment of the acute phase relies only on an empirical and symptomatic approach. The general approach will be adapted to the levels of severity. Specific approaches such as paracentesis, pleural puncture, surgical approach of OHSS and specific medication during OHSS were evaluated sporadically. More adequate treatment methods would require a better understanding of the underlying pathophysiological mechanisms, to promote an aetiological therapeutic approach. Properly conducted studies, including large numbers of patients are required in order to determine the best method of prevention and management.

Review of clinical course and treatment of ovarian hyperstimulation syndrome (OHSS)

Ovarian hyperstimulation syndrome (OHSS) is a dramatic complication of ovulation induction. In its most severe form, OHSS is characterized by massive cystic enlargement of the ovaries associated with third space fluid shift, resulting in the formation of ascites and pleural effusion. Ascites developes because of increased peritoneal capillary permeability. In this study we examined the role of vascular endothelial growth factor (VEGF) and interleukins in the pathogenesis of increased capillary permeability. VEGF is a member of the family of heparin binding proteins that act directly on endothelial cells to induce proliferation and angiogenesis. VEGF mRNA and protein are expressed by human ovarian granulosa and theca cells late in follicular development and subsequent to ovulation by granulosa and theca cells. Therefore, VEGF is ideally positioned to provoke the increased permeability of theca blood vessels that occurs shortly before ovulation. Hybridization studies in the rat and primate ovary have demonstrated VEGF mRNA expression predominantly after the luteinizing hormone (LH) surge known to be essential for OHSS. The gonadotrophin-releasing hormone antagonist results in a decreased mRNA expression, implying such expression is dependent on LH. The expression of VEGF mRNA has been recently shown to be enhanced by human chorionic gonadotrophin (HCG) in a dose- and time-dependent fashion. These studies confirm the timely association between VEGF and HCG that has been clinically known for many years to be integral in the development of OHSS. VEGF concentrations in serum, peritoneal fluid and follicular fluid of patients at risk for OHSS have been shown to be significantly related to the development of the syndrome. Furthermore, the kinetics of VEGF in the plasma of patients who actually develop severe OHSS are closely correlated with the clinical course of the syndrome and with certain biological characteristics of OHSS and of capillary leakage, such as leukocytosis and increased hematocrit. Studies on ascitic fluid from patients with sever OHSS have proved that VEGF is the major capillary permeability agent. Incubation with VEGF antiserum decreased the vascular permeability activity by 70%. Interleukin-2 (IL-2) is the first of a series of lymphocytotrophic hormones to be recognized as pivotal for the regulation of immune response. However, hard data to confirm its central role in the pathogenesis of OHSS are still lacking, despite the fact that some preliminary studies suggest a positive association between the pooled follicular fluid IL-2 concentration and the development of OHSS. IL-6 is a mediator of the acute phase response to injury, a systemic reaction characterized by leukocytosis, increased vascular permeability and increased synthesis of acute phase proteins by the liver. Significantly higher serum and ascites IL-6 concentrations were seen in OHSS patients. The immunohistochemical localization pattern suggested that IL-6 is LH or HCG dependent. However, the use of IL-6 as a predictor for the occurrence of OHSS has not been successful. The kinetics of IL-6 in patients with severe OHSS are correlated with the clinical symptoms and the biochemical parameters known to be associated with the severity of the syndrome, suggesting a possible role for IL-6. Further molecular biology studies similar to those performed on VEGF are needed to confirm if this interleukin is central in the cascade of events. IL-8 is a chemoattractant, activating cytokine and a potent angiogenic agent. The peritoneal fluid levels is increased in patients with severe OHSS; its concentration in peritoneal fluid is increased inpatients with severe OHSS. The place of this interleukin in the cascade of events is as yet undetermined and further studies are needed. In conclusion, molecular biology and clinical studies strongly suggest that VEGF is the principal mediator by which HCG might increase capillary permeability in OHSS.

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The role of vascular endothelial growth factor and interleukins in the pathogenesis of severe ovarian hyperstimulation syndrome

Complications of assisted reproductive techniques

Despite advances in monitoring techniques, severe ovarian hyperstimulation syndrome still occurs in 1% of patients treated with ovulation induction for assisted conception techniques. The seriousness of this iatrogenic syndrome is reflected in the fact that deaths have been reported following it. We report a patient who developed severe OHSS and a potentially lethal complication, following ovulation induction for gamete intra-Fallopian transfer

Simon Meagher

Papers

Severe ovarian hyperstimulation syndrome and cerebrovascular accidents

Edwards' syndrome after the replacement of cryopreserved-thawed embryos.