Main investigator: Prof. Antonio Pellicer Martínez
Investigator: Dr. Raúl Gómez
Phd Student: Hortensia Ferrero
Financing Obtained: SAF2008-03546
Research description
During assisted reproduction cycles and in order to obtain a higher number of oocytes women are administered Gonadotrophins..
Most of patients do not offer adverse response, nevertheless, nearly 5% develop the syndrome of ovarian hiperestimulation (SHO), characterized by the increase of vascular permeability that causes exit and accumulation of blood fluids in peritoneal and pulmonary cavity.
During the first three years we developped an animal model of SHO on which we could assign the increased permeability to increased vascular endothelial growth factor (VEGF) that occurs almost exclusively on ovarian levels. We rehearsed in the past the inhibition of VEGF protein as a possible treatment for the syndrome in an animal in a successful way by which we had been awarded internationally..
Nevertheless we discovered that anti-VEGF drugs trade can also alter fertility in laboratory animals, which led us to give up its application in humans.
During the last four years we have been seeking for new non aggressive treatment that could block the protein VEGF without altering the fertility.
The result of this effort has been expressed in the development of treatments based on dopamine agonists. These compounds have been used routinely and continuously in clinic as a treatment for different pathologies (hiperprolactinemias, parkinson, low libido) since the years 60.
They are not toxic, they do not affect the ovarian function neither the development of the fetus but in them we discover an enormous potential to block the increases of permeability induced by VEGF and with it the SHO. All support the use of dopamine agonists in women with SHO, whose successful results have led our group to be pioneer in the specific, effective and not toxic treatment of the syndrome..
Though we have reduced the original incident of the SHO in a 75% yet we are not completely satisfied. Inherent ito the human changeability some patients show deficiencies in the expression of the receptor 2 of dopamine that limit the effectiveness of the treatment with dopamine for the SHO in them.
In the next years we intend to characterize which are the ovarian cell populations that espress the receptor 2 of the dopamine, how they vary their levels during the process of luteinization and if there are differences in ovarian pathologies associated to the SHO as the polycystic ovary síndrome.
With all that we intend to focus to the maximum our search of intermediaries in the signaling pathways of the dopamine receptor in order to develop medicines more effective if suitable for the the syndrome treatment.
Posted Items
Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohí J, Simón C.
The pathogenesis of ovarian hyperstimulation syndrome: in vivo studies investigating the role of interleukin-1? , interleukin-6, and vascular endothelial growth factor. Fertil Steril. 71: 482-489. (1999)
Garrido N, Albert C, Krüssel J, O'Connor JE, Remohí J, Simón C, Pellicer A.
Expression, production, and secretion of vascular endothelial growth factor and interleukin-6 by granulosa cells in comparable in women with and without endometriosis. Fertil. Steril. 76,3 :568-575. (2001)
Gomez R, Simon C, Remohi J, Pellicer A.
Vascular endothelial growth factor receptor-2 activation induces vascular permeability in hyperstimulated rats, and this effect is prevented by receptor blockade. Endocrinology. 143(11):4339-48. (2002)
Gomez R, Lima I, Simon C, Pellicer A.
Administration of low-dose LH induces ovulation and prevents vascular hyperpermeability and vascular endothelial growth factor expression in superovulated rats . Reproduction. 127:483-9. (2004)