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

Autores
Elia, Evelin Mariel; Quintana, Ramiro; Carrere, Carlos; Bazzano, María Victoria; Rey Valzacchi, Gastón; Paz, Dante Agustin; Pustovrh, María Carolina
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Elia, Evelin Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Quintana, Ramiro. Procrearte Medicina Reproductiva y Molecular; Argentina
Fil: Carrere, Carlos. Procrearte Medicina Reproductiva y Molecular; Argentina
Fil: Bazzano, María Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rey Valzacchi, Gastón. Procrearte Medicina Reproductiva y Molecular; Argentina
Fil: Paz, Dante Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Pustovrh, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad del Valle. Fundación Samanea; Colombia
Materia
Síndrome de hiperestimulación ovarica
Metformina
VEGF
Permeabilidad vascular
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/21097
Acceder
id CONICETDig_254c14e70e99902b065f57643e9da3fb
oai_identifier_str oai:ri.conicet.gov.ar:11336/21097
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental studyElia, Evelin MarielQuintana, RamiroCarrere, CarlosBazzano, María VictoriaRey Valzacchi, GastónPaz, Dante AgustinPustovrh, María CarolinaSíndrome de hiperestimulación ovaricaMetforminaVEGFPermeabilidad vascularhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: 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.Fil: Elia, Evelin Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Quintana, Ramiro. Procrearte Medicina Reproductiva y Molecular; ArgentinaFil: Carrere, Carlos. Procrearte Medicina Reproductiva y Molecular; ArgentinaFil: Bazzano, María Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rey Valzacchi, Gastón. Procrearte Medicina Reproductiva y Molecular; ArgentinaFil: Paz, Dante Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Pustovrh, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad del Valle. Fundación Samanea; ColombiaBioMed Central2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/21097Elia, Evelin Mariel; Quintana, Ramiro; Carrere, Carlos; Bazzano, María Victoria; Rey Valzacchi, Gastón ; et al.; Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study; BioMed Central; Journal of Ovarian Research; 6; 1; 9-2013; 62-70; 621757-2215CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/1757-2215-6-62info:eu-repo/semantics/altIdentifier/url/https://ovarianresearch.biomedcentral.com/articles/10.1186/1757-2215-6-62info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:21:13Zoai:ri.conicet.gov.ar:11336/21097instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:21:14.083CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study
title Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study
spellingShingle Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study
Elia, Evelin Mariel
Síndrome de hiperestimulación ovarica
Metformina
VEGF
Permeabilidad vascular
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
dc.creator.none.fl_str_mv Elia, Evelin Mariel
Quintana, Ramiro
Carrere, Carlos
Bazzano, María Victoria
Rey Valzacchi, Gastón
Paz, Dante Agustin
Pustovrh, María Carolina
author Elia, Evelin Mariel
author_facet Elia, Evelin Mariel
Quintana, Ramiro
Carrere, Carlos
Bazzano, María Victoria
Rey Valzacchi, Gastón
Paz, Dante Agustin
Pustovrh, María Carolina
author_role author
author2 Quintana, Ramiro
Carrere, Carlos
Bazzano, María Victoria
Rey Valzacchi, Gastón
Paz, Dante Agustin
Pustovrh, María Carolina
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Síndrome de hiperestimulación ovarica
Metformina
VEGF
Permeabilidad vascular
topic Síndrome de hiperestimulación ovarica
Metformina
VEGF
Permeabilidad vascular
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Elia, Evelin Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Quintana, Ramiro. Procrearte Medicina Reproductiva y Molecular; Argentina
Fil: Carrere, Carlos. Procrearte Medicina Reproductiva y Molecular; Argentina
Fil: Bazzano, María Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rey Valzacchi, Gastón. Procrearte Medicina Reproductiva y Molecular; Argentina
Fil: Paz, Dante Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Pustovrh, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. Universidad del Valle. Fundación Samanea; Colombia
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.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/21097
Elia, Evelin Mariel; Quintana, Ramiro; Carrere, Carlos; Bazzano, María Victoria; Rey Valzacchi, Gastón ; et al.; Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study; BioMed Central; Journal of Ovarian Research; 6; 1; 9-2013; 62-70; 62
1757-2215
CONICET Digital
CONICET
url http://hdl.handle.net/11336/21097
identifier_str_mv Elia, Evelin Mariel; Quintana, Ramiro; Carrere, Carlos; Bazzano, María Victoria; Rey Valzacchi, Gastón ; et al.; Metformin decreases the incidence of ovarian hyperstimulation syndrome: an experimental study; BioMed Central; Journal of Ovarian Research; 6; 1; 9-2013; 62-70; 62
1757-2215
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/1757-2215-6-62
info:eu-repo/semantics/altIdentifier/url/https://ovarianresearch.biomedcentral.com/articles/10.1186/1757-2215-6-62
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846782664875442176
score 12.982451

Publicaciones similares