INVESTIGADORES
PARBORELL Maria Fernanda Agustina
congresos y reuniones científicas
Título:
The importance of Angiopoietin-1 (ANGPT-1) in ovarian stimulation protocols: poor and high responders
Autor/es:
SCOTTI L; ABRAMOVICH D; PASCUALI N; HORTON M; DE ZÚÑIGA I; BISIOLI C; TESONE M; F. PARBORELL
Lugar:
Estambul
Reunión:
Congreso; 28th Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE); 2012
Institución organizadora:
Society of Human Reproduction and Embryology
Resumen:
Introduction: Despite
the advances in assisted reproduction, poor and high ovarian response to gonadotropins
remains a problem. Patients
who fail to obtain an adequate number of mature follicles after
gonadotropin stimulation are considered to be poor responders. On the other
hand, the retrieval of >15 oocytes is one of the main criteria for deeming a
patient as high responder. In women, ovarian angiogenesis seems to be involved
in the selection of follicles during stimulated IVF cycles. Gonadotropins,
steroids and vasoactive substances such as vascular
endothelial growth factor (VEGF) and angiopoietin-1 (ANGPT1) are involved in the
regulation of vascularization. The ANGPTs/Tie-2 system acts in concert with
VEGF. ANGPT-1 is necessary to stabilize blood vessels while ANGPT2 and
the soluble receptor Tie-2 (sTie-2) act as natural antagonists for ANGPT1. The
balance between ANGPT1, ANGPT2 and sTie-2, and VEGF is important for
angiogenesis in the ovary. It is important to note that one of our previous
reports demonstrated that levels of ANGPT1 were
increased in follicular fluid (FF) from high responder patients undergoing ART in
comparison with those from normoresponder patients. Our objectives were: 1) To analyze
the levels of ANGPT1 and sTie-2
in FF from young poor responders and 2) To determine the
effect of ANGPT1 in high responder patients undergoing ART on endothelial cell
migration.
Material and methods: This study was performed
in 51 patients aged 25-39 years old undergoing ART. Written informed consent
was given by all the patients before recruitment. Patients with pelvic
pathologies such as endometriosis, uterine fibroids or pelvic inflammatory
disease were excluded from the study. Patients were classified into three
groups with respect to the number of aspirated oocytes: normoresponders (n=15;
8-13 oocytes), low responder (n=17; 0-5 oocytes) and
high responder (n=19; 15-25 oocytes). The FF was centrifuged immediately for 10
min at 2000 x g to remove cellular components and debris and then transferred
to sterile polypropylene tubes. The supernatant was stored at ?80º C until
assayed. The levels of ANGPT1 and sTie-2 were measured in FF by ELISA assay. To
assess the specific effect of ANGPT1 on ovarian angiogenesis, we evaluated the
effect of FF from high responders on endothelial cell migration in the presence
of a neutralizing antibody against ANGPT1. For this purpose, a wound healing
assay using the EA.hy926 endothelial cell line was performed.
Results: In FF from patients undergoing ART
with poor response, the levels of ANGPT1 were higher than in normoresponders
(Normoresponders: 165.1 ± 21.7 vs Poor responders: 318.5 ± 61.6 pg / ml,
p<0.05). No difference was found in the
levels of sTie-2 between
the groups analyzed. Incubation with FF from high responders in the
presence of an ANGPT1 antibody resulted in a significant decrease in cell
migration compared to FF without antibody (p<0.05). It is worth to note that
in the absence of neutralizing antibody against ANGPT1, endothelial migration
was significantly greater in the presence of FF from high responders than in
the presence of FF from normoresponders (p<0.001).
Conclusions: Our
results suggest that the levels of ANGPT1 are associated with the type of response to
gonadotropin therapy. Balanced levels of this protein appear to be crucial for a normal
ovarian response to gonadotropins. In addition, the results described regarding the levels of ANGPT1 in FF
and the altered endothelial cell migration in the presence of FF from high
responders with ANGPT1 antibody may provide new insights into the mechanisms by
which ANGPT1 has an effect on ovarian disorders such as poor ovarian responders
and OHSS.
Supported by: ANPCYT (PICT 2008/747).