Ovarian hyperstimulation syndrome inhibition by targeting VEGF, COX-2 and calcium pathways: a preclinical randomized study

Gynecol Endocrinol. 2014 Aug;30(8):587-92. doi: 10.3109/09513590.2014.910191. Epub 2014 May 13.


Objective: The efficacy of vascular endothelial growth factor (VEGF), COX-2, calcium and aromatase inhibitors in an ovarian hyperstimulation syndrome (OHSS) rat model was tested.

Methods: One hundred and eight female Wistar rats were randomly divided in nine groups. The control group received saline, while the OHSS group received rec-FSH for 4 consecutive days. The other seven groups received rec-FSH (4d) and Bevacizumab twice, Parecoxib daily, Verapamil daily, Parecoxib daily and Bevacizumab twice, Verapamil daily and Bevacizumab twice, Parecoxib and Verapamil daily, Letrozole and Meloxicam daily, respectively. All groups received also hCG at the 5th day.

Results: All intervention groups were characterized by reduced vascular permeability compared to the OHSS group, which in the groups of Verapamil (Calcium inhibition) and Parecoxib + Verapamil (COX-2 + Calcium inhibition) presented significant statistical difference. The Verapamil group showed the lowest corpus luteum formation, while the Parecoxib (COX-2 inhibition), the Parecoxib + Verapamil (COX-2 + Calcium inhibition), the Bevacizumab + Parecoxib (VEGF + COX-2 inhibition) and the Bevacizumab + Verapamil (VEGF + Calcium inhibition) groups were also characterized by lower corpus luteum numbers compared to the OHSS group. Furthermore, lower graafian follicle formation was observed in the above groups, while the ovarian weight and the hormonal profile were not significantly affected.

Conclusions: Studying the different check points of the VEGF pathway, we conclude that targeting calcium pathways could be beneficial for the vascular permeability control in an OHSS animal model.

Keywords: Calcium inhibition; Cox-2 inhibition; VEGF inhibition; ovarian hyperstimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Bevacizumab
  • Calcium Signaling* / drug effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Drug Evaluation, Preclinical
  • Female
  • Isoxazoles / administration & dosage*
  • Molecular Targeted Therapy / methods
  • Ovarian Hyperstimulation Syndrome / prevention & control*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Verapamil / administration & dosage*


  • Antibodies, Monoclonal, Humanized
  • Cyclooxygenase 2 Inhibitors
  • Isoxazoles
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Bevacizumab
  • parecoxib
  • Verapamil