The purpose of this study was to evaluate the effectiveness of combined approach on the prevention of severe ovarian hyperstimulation syndrome (OHSS) in high risk patients undergoing controlled ovarian hyperstimulation for IVF. The combined approach consisted of: (1) step-down administration of gonadotropins; (2) lowering the dose of human chorionic gonadotropin; (3) intravenous albumin infusion at the time of oocyte retrieval and (4) progesterone use for luteal support. Total of 87 high risk patients with a serum estradiol level >11,010 pmol/l or 3000 pg/ml on HCG day were managed by this combined approach and their results were compared with 274 low risk patients. In all high risk patients, the gonadotrophin dose were decreased starting as early as on day 4 of ovarian stimulation as necessary, ovulation was triggered by a decreased HCG dose of 5000-7000 IU according to the level of estradiol, intravenous infusion of 20% human albumin, 50-100ml were given just 1h before the oocyte retrieval and luteal support was provided either by 50mg progesterone in oil, IM or 600 mg micronized progesterone orally or vaginally until the day of beta-HCG determination. All patients were followed by serial ultrasonographic examinations and complete blood count analysis after embryo transfer to detect the early signs of OHSS and to allow early intervention. Age and duration of infertility were similar in both groups. Although the number of gonadotrophin ampoules used (22.7 +/- 4.7 versus 27.8+/-3.7; P<0.05) was significantly lower, estradiol levels (16,764 +/- 6936 pmol/l versus 8870 +/- 2456 pmol/l; P<0.05) and mean number of oocytes (18.3 +/- 5.9 versus 10.6+/-5.4; P<0.05) were significantly higher in study group. There was no significant difference between groups in terms of the mean number of transferred embryos (3.2 +/- 1.1 versus 3.4+/-1.1) and rate of pregnancies (50.5% versus 40.1%). There was only one moderate and no severe OHSS case in the high risk group, while five moderate and one severe OHSS cases developed in the control group consisting of low risk patients. In conclusion, intravenous albumin combined with low dose HCG, early step-down administration of gonadotropins and progesterone use for luteal support, so called combined approach, proved to be effective in the prevention of severe ovarian hyperstimulation syndrome in documented high risk patients.