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Oxytocin and cabergoline alleviate ovarian hyperstimulation syndrome (OHSS) by suppressing vascular endothelial growth factor (VEGF) in an experimental model

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Ovarian hyperstimulation syndrome (OHSS) is a life-threatening complication of ovarian stimulation in reproductive medicine. Here, we aimed to investigate the role of oxytocin (OT) and cabergoline in the prevention and alleviation of the OHSS in an animal model.

Methods

Thirty-five female immature Wistar rats were randomly assigned to five groups. The control group (n = 7) received saline only for five consecutive days. Remaining twenty-eight rats received 10 IU of pregnant mare serum gonadotropin (PMSG) followed by 30 IU of human chorionic gonadotropin (hCG) to induce OHSS. Group 2 (n = 7) was managed with no additional intervention after the induction of OHSS. Group 3 (n = 7) received 100 μg/kg cabergoline 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Group 4 (n = 7) and group 5 (n = 7) received 80 μg/kg and 160 μg/kg OT after induction of OHSS, respectively. Oxytocin was administered 2 h before the PMSG injection for four consecutive days and 2 h before the hCG injection on the fifth day. Body and ovary weight, vascular permeability (VP), VEGF expression in the ovaries, and levels of VEGF in the peritoneal fluids were examined in all animals.

Results

Cabergoline and OT reduced body weight, ovary weight, and VP compared to that of the OHSS group (p < 0.05). VEGF expressions in ovaries and peritoneal VEGF levels were decreased in cabergoline and OT groups compared to that of the OHSS groups (p < 0.001 for cabergoline and OT—80 μg/kg; p < 0.00001 for OT—160 μg/kg). However, there was no statistically significant difference in these parameters between the OT and cabergoline groups.

Conclusion

Both OT and cabergoline were active in the alleviation of OHSS through suppression of VEGF and VP. Overall, we conclude that OT is effective for downregulation for VEGF and improvement in vascular permeability in OHSS.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Ege University School of Medicine, Bornova, 35100, Izmir, Turkey

    Ismet Hortu, Gokay Ozceltik, Erol Tavmergen & Ege Nazan Tavmergen Goker

  2. Department of Stem Cell, Ege University Institute of Health Sciences, Bornova, 35100, Izmir, Turkey

    Ismet Hortu

  3. Department of Biochemistry, Ege University School of Medicine, Izmir, Turkey

    Elif Karadadas

  4. Department of IVF Research Center, Ege University School of Medicine, Izmir, Turkey

    Erol Tavmergen & Ege Nazan Tavmergen Goker

  5. Department of Histology and Embryology, Mugla Sıtkı Kocman University School of Medicine, Mugla, Turkey

    Gurkan Yigitturk

  6. Department of Physiology, Demiroglu Bilim University School of Medicine, Istanbul, Turkey

    Oytun Erbas

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  1. Ismet Hortu
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Contributions

IH contributed to conception and design, data extraction, and writing manuscript; EK and GO collected the data and performed interpretation and statistical analysis; GY done the histological analysis; ET and ENTG helped in supervising and critical revision; OE contributed to conception and design and performed the experiment.

Corresponding author

Correspondence to Ismet Hortu.

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Conflict of interest

All the authors declare that there is no conflict of interest.

Ethical approval

The present study was approved by the Committee for Animal Research of Ege University, Izmir, Turkey. All procedures performed in studies involving animals were in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

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The informed consent is not applicable for the current study.

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Hortu, I., Karadadas, E., Ozceltik, G. et al. Oxytocin and cabergoline alleviate ovarian hyperstimulation syndrome (OHSS) by suppressing vascular endothelial growth factor (VEGF) in an experimental model. Arch Gynecol Obstet 303, 1099–1108 (2021). https://doi.org/10.1007/s00404-020-05855-1

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  • DOI: https://doi.org/10.1007/s00404-020-05855-1

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