Related Experiment Video
Updated: Apr 30, 2026
Fertility Preservation Through Oocyte Vitrification: Clinical and Laboratory Perspectives
Published on: September 16, 2021
Ovarian hyperstimulation syndrome inhibition by targeting VEGF, COX-2 and calcium pathways: a preclinical randomized
Chrysoula Kitsou1, Ioannis Kosmas, Leandros Lazaros
1Genetics and IVF Unit, Department of Obstetrics and Gynecology, Medical School, Ioannina University , Ioannina , Greece .
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.
Insights
Targeting calcium pathways effectively reduced vascular permeability in an ovarian hyperstimulation syndrome (OHSS) rat model. This study investigated VEGF, COX-2, and calcium inhibitors for OHSS treatment strategies.
Area of Science:
- Reproductive endocrinology and pharmacology.
- Animal models for human disease research.
Background:
- Ovarian hyperstimulation syndrome (OHSS) is a significant complication of assisted reproductive technologies.
- Current treatments for OHSS primarily focus on symptom management, necessitating research into novel therapeutic targets.
Purpose of the Study:
- To evaluate the efficacy of vascular endothelial growth factor (VEGF), COX-2, calcium, and aromatase inhibitors in mitigating OHSS.
- To identify specific molecular pathways that can be targeted for improved OHSS management.
Main Methods:
- An OHSS rat model was induced using recombinant follicle-stimulating hormone (rec-FSH) and human chorionic gonadotropin (hCG).
- Rats were randomized into nine groups, including control, OHSS, and seven treatment groups receiving various inhibitors (Bevacizumab, Parecoxib, Verapamil, Letrozole, Meloxicam).
- Vascular permeability, corpus luteum formation, and graafian follicle development were assessed.
Main Results:
- All inhibitor groups demonstrated reduced vascular permeability compared to the OHSS group.
- Significant reductions in vascular permeability were observed with Verapamil (calcium inhibition) and Parecoxib + Verapamil (COX-2 + calcium inhibition).
- Calcium and COX-2 inhibition, along with VEGF inhibition, led to decreased corpus luteum and graafian follicle formation.
Conclusions:
- Targeting calcium pathways shows promise for controlling vascular permeability in OHSS.
- Inhibiting calcium channels may be a beneficial strategy in managing OHSS, warranting further clinical investigation.
- VEGF and COX-2 pathways also play roles, but calcium inhibition appears particularly effective for vascular permeability.
