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Journal of Ovarian Research
Published in: Journal of Ovarian Research 1/2013

Open Access 01-12-2013 | Research

Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study

Authors: Evelin M Elia, Ramiro Quintana, Carlos Carrere, María V Bazzano, Gastón Rey-Valzacchi, Dante A Paz, María C Pustovrh

Published in: Journal of Ovarian Research | Issue 1/2013

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Abstract

Background

In assisted reproduction cycles, gonadotropins are administered to obtain a greater number of oocytes. A majority of patients do not have an adverse response; however, approximately 3-6% develop ovarian hyperstimulation syndrome (OHSS). Metformin reduces the risk of OHSS but little is known about the possible effects and mechanisms of action involved.

Objective

To evaluate whether metformin attenuates some of the ovarian adverse effects caused by OHSS and to study the mechanisms involved.

Material and methods

A rat OHSS model was used to investigate the effects of metformin administration. Ovarian histology and follicle counting were performed in ovarian sections stained with Masson trichrome. Vascular permeability was measured by the release of intravenously injected Evans Blue dye (EB). VEGF levels were measured by commercially immunosorbent assay kit. COX-2 protein expression was evaluated by western blot and NOS levels were analyses by immunohistochemistry.

Results

Animals of the OHSS group showed similar physiopathology characteristics to the human syndrome: increased body weight, elevated progesterone and estradiol levels (P<0.001), increased number of corpora lutea (P<0.001), higher ovarian VEGF levels and vascular permeability (P<0.001 and P<0.01); and treatment with metformin prevented this effect (OHSS+M group; P<0.05). The vasoactive factors: COX-2 and NOS were increased in the ovaries of the OHSS group (P<0.05 and P<0.01) and metformin normalized their expression (P<0.05); suggesting that metformin has a role preventing the increased in vascular permeability caused by the syndrome.

Conclusion

Metformin has a beneficial effect preventing OHSS by reducing the increase in: body weight, circulating progesterone and estradiol and vascular permeability. These effects of metformin are mediated by inhibiting the increased of the vasoactive molecules: VEGF, COX-2 and partially NOS. Molecules that are increased in OHSS and are responsible for a variety of the symptoms related to OHSS.
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Metadata
Title
Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study
Authors
Evelin M Elia
Ramiro Quintana
Carlos Carrere
María V Bazzano
Gastón Rey-Valzacchi
Dante A Paz
María C Pustovrh
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2013
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/1757-2215-6-62

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