Lower serum level of hypoxia-inducible factor 1alpha during controlled ovarian stimulation is related to the higher risk of developing ovarian hyperstimulation syndrome.

The aim of the study was to evaluate hypoxia-inducible factor 1alpha (HIF-1α) concentrations in follicular fluid (FF) and serum of patients undergoing controlled ovarian stimulation during in vitro fertilization (IVF) procedure and their potential relationship with the development of ovarian hyperstimulation syndrome (OHSS). An observational case-control study was conducted over 3 years, including 148 patients undergoing IVF treatment: 48 patients in the natural cycle (control group), 49 patients in the GnRH agonist protocol group (group 2) and 51 women in the GnRH antagonist protocol group (group 3). Blood and FF samples were collected on the day of oocyte retrieval and HIF-1α concentrations were assessed using enzyme-linked immunosorbent assay (ELISA). OHSS was diagnosed according to the Golan classification. Binomial logistic regression was used to show the change in the probability of OHSS associated with the concentration of HIF-1α. Finally, the ROC curve was created to check the usefulness of HIF-1α in the identification of OHSS. In all groups HIF-1α concentrations were lower in serum than in FF. There was no difference between the groups in the HIF-1α FF concentrations. Serum HIF-1α level was significantly lower in group 2 and 3 in comparison to the control group (320.35±148.83 pg/ml vs. 287.86±111.03 pg/ml and respectively vs. 490.38±249.36; p=0.0003 and p<0.000001). The overall incidence of OHSS in the entire study was 18.9%. There was no case of OHSS in the control group and no difference between group 2 and 3 in the incidence of OHSS. The OR of serum HIF-1α levels for probability of developing OHSS was estimated on 0.997 (95% CI 0.995-0.99962, p=0.024). The ROC curve analysis showed the optimal cutpoint for HIF-1α of 1015 pg/ml (with the 54% sensitivity and 65% specificity). During controlled ovarian stimulation lower serum level of HIF-1α on the day of oocyte retrieval is related to the higher risk of developing OHSS.