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

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 kn...

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Autores principales: Elia, E.M., Quintana, R., Carrere, C., Bazzano, M.V., Rey-Valzacchi, G., Paz, D.A., Pustovrh, M.C.
Formato: Artículo publishedVersion
Lenguaje:Inglés
Publicado: 2013
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rat
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_17572215_v6_n1_p_Elia
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spelling paperaa:paper_17572215_v6_n1_p_Elia2023-06-12T16:51:20Z Metformin decreases the incidence of ovarian hyperstimulation syndrome: An experimental study J. Ovarian Res. 2013;6(1) Elia, E.M. Quintana, R. Carrere, C. Bazzano, M.V. Rey-Valzacchi, G. Paz, D.A. Pustovrh, M.C. cyclooxygenase 2 estradiol Evans blue metformin nitric oxide synthase progesterone vasculotropin animal experiment animal model article blood vessel permeability body weight controlled study enzyme linked immunosorbent assay female immunohistochemistry nonhuman ovary follicle ovary hyperstimulation pathophysiology priority journal protein expression rat Western blotting 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. © 2013 Elia et al.; licensee BioMed Central Ltd. Fil:Elia, E.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Paz, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Pustovrh, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_17572215_v6_n1_p_Elia
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language Inglés
orig_language_str_mv eng
topic cyclooxygenase 2
estradiol
Evans blue
metformin
nitric oxide synthase
progesterone
vasculotropin
animal experiment
animal model
article
blood vessel permeability
body weight
controlled study
enzyme linked immunosorbent assay
female
immunohistochemistry
nonhuman
ovary follicle
ovary hyperstimulation
pathophysiology
priority journal
protein expression
rat
Western blotting
spellingShingle cyclooxygenase 2
estradiol
Evans blue
metformin
nitric oxide synthase
progesterone
vasculotropin
animal experiment
animal model
article
blood vessel permeability
body weight
controlled study
enzyme linked immunosorbent assay
female
immunohistochemistry
nonhuman
ovary follicle
ovary hyperstimulation
pathophysiology
priority journal
protein expression
rat
Western blotting
Elia, E.M.
Quintana, R.
Carrere, C.
Bazzano, M.V.
Rey-Valzacchi, G.
Paz, D.A.
Pustovrh, M.C.
Metformin decreases the incidence of ovarian hyperstimulation syndrome: An experimental study
topic_facet cyclooxygenase 2
estradiol
Evans blue
metformin
nitric oxide synthase
progesterone
vasculotropin
animal experiment
animal model
article
blood vessel permeability
body weight
controlled study
enzyme linked immunosorbent assay
female
immunohistochemistry
nonhuman
ovary follicle
ovary hyperstimulation
pathophysiology
priority journal
protein expression
rat
Western blotting
description 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. © 2013 Elia et al.; licensee BioMed Central Ltd.
format Artículo
Artículo
publishedVersion
author Elia, E.M.
Quintana, R.
Carrere, C.
Bazzano, M.V.
Rey-Valzacchi, G.
Paz, D.A.
Pustovrh, M.C.
author_facet Elia, E.M.
Quintana, R.
Carrere, C.
Bazzano, M.V.
Rey-Valzacchi, G.
Paz, D.A.
Pustovrh, M.C.
author_sort Elia, E.M.
title Metformin decreases the incidence of ovarian hyperstimulation syndrome: An experimental study
title_short Metformin decreases the incidence of ovarian hyperstimulation syndrome: An experimental study
title_full Metformin decreases the incidence of ovarian hyperstimulation syndrome: An experimental study
title_fullStr Metformin decreases the incidence of ovarian hyperstimulation syndrome: An experimental study
title_full_unstemmed Metformin decreases the incidence of ovarian hyperstimulation syndrome: An experimental study
title_sort metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study
publishDate 2013
url http://hdl.handle.net/20.500.12110/paper_17572215_v6_n1_p_Elia
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AT carrerec metformindecreasestheincidenceofovarianhyperstimulationsyndromeanexperimentalstudy
AT bazzanomv metformindecreasestheincidenceofovarianhyperstimulationsyndromeanexperimentalstudy
AT reyvalzacchig metformindecreasestheincidenceofovarianhyperstimulationsyndromeanexperimentalstudy
AT pazda metformindecreasestheincidenceofovarianhyperstimulationsyndromeanexperimentalstudy
AT pustovrhmc metformindecreasestheincidenceofovarianhyperstimulationsyndromeanexperimentalstudy
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