Ovarian hyperstimulation syndrome (OHSS). Aspects on immune and endocrine mechanisms

Abstract

The ovarian hyperstimulation syndrome (OHSS) is a well-known side effect of ovarian stimulation for ovulation induction or for in vitro fertilisation. The syndrome is characterised by massively enlarged ovaries and a hyperpermeable/procoagulant state, giving rise to diverse symptoms such as abdominal pain, nausea, ascites, hypovolemia and thromboembolism. Patients with severe OHSS need hospitalisation with intensive care. The aims of this study were to study the OHSS prevalence in a cohort of IVF patients, find factors (patient characteristics, clinical parameters) that may help to identify a risk population, and to compare blood samples of OHSS patients and control patients to identify biochemical markers of OHSS with predictive and pathophysiological importance.A 6-month cohort of 428 patients undergoing controlled ovarian hyperstimulation (COH) was followed prospectively. Patient characteristics and clinical/laboratory data were evaluated in patients with different classes of OHSS and compared with the remainder populations. Eighteen patients (4.2 %) developed severe OHSS and 7.3 % developed a mild/moderate form of OHSS. The OHSS patients were significantly younger, received lower doses of gonadotrophins, presented with ovaries containing a higher number of total and large follicles, had a higher number of retrieved oocytes and a higher pregnancy rate. Patients with severe OHSS additionally had increased prevalence of allergy and were more likely to have children born.The ovarian-derived hormones inhibin A and inhibin B, as putative predictors of OHSS development, were evaluated. Fifteen patients with severe OHSS were compared with matched (age, follicle numbers, pregnancy) controls. Inhibin A levels in the OHSS group were significantly higher at the time point when OHSS had developed and the levels declined during OHSS treatment. The levels of inhibin B were significantly higher in OHSS patients before oocyte aspiration. Thus, inhibins may be of pathophysiological significance in OHSS and measurements of these hormones may be useful in the prediction and monitoring of OHSS.The blood levels of immunosuppressive cytokines were compared in OHSS patients and matched control patients. Levels of interleukin (IL)-4, IL-10, IL-13, were measured. Lower levels of IL-10 were seen at the start of gonadotrophin stimulation in OHSS patients as compared to the controls. The lower levels of IL-10 at start of stimulation in OHSS patients may be of pathophysiological importance by allowing for an enhanced TH1 type immune response during gonadotrophin stimulation and thereby increased and generalised inflammation.The OHSS is characterized by increased permeability of the ovaries and thus the plasma levels of vascular endothelial growth factor (VEGF165) during COH were evaluated. There were no differences between OHSS and control patients in plasma VEGF165 levels at any time points. A positive correlation between VEGF165 and follicle numbers and progesterone were seen only in the control group.Plasma levels of nitrate, a metabolite of nitric oxide (NO), were analysed in women to evaluate possible fluctuations during the menstrual cycle, during COH and also in OHSS patients. The levels during the menstrual cycle showed a peak at ovulation and during COH the levels increased to a plateau after gonadotrophin start. The levels of nitrate in the OHSS patients were similar to those during COH. This data indicates hormonal influence on NO production.