Blocking VEGFR2ph, the first step in VEGF downstream signaling, is able to avoid iVP in OHSS, but specific antiVEGFR2 drugs are toxic. D binding to its receptor 2 (R2)diminishes iVP in tumors and is thought to internalize VEGFR2 in close proximity to R2 in endothelial cells. Because our microarray analysis showed Tyrosine hydroxylase (TH) ( key enzyme in D synthesis) downregulation (dR) as a condition of OHSS ovaries, we aimed to 1) block iVP in OHSS bypassing the TH dR with the administration of DA) and 2) Elucidate if decreased (Dc)VP was debt to Dc VEGFR2ph or to luteolysis, related to OHSS resolution and (LX) induced in immature rats by DA inhibition of prolactin (Pr) secretion, which is needed to maintain corpus luteum. Immature wistar rats, 22 day(d)s old, were injected with PMSG 10 UI (d 22–25) and hCG 30 IU (d 26) to develop OHSS and treated, with different doses of the DA bromocriptine (Br) or cabergoline (Cb) 24 hours (h) later (d 27). The effects of DA on VP were measured (n=8 each dose) 48 h after hCG (maximal VP) (d 28). At the same time point serum samples (sp) were collected to quantify functional (f)LX by measuring P4 and Pr (n=8 each dose). Both ovaries were frozen too,one of them was used to quantify VEGFR2ph and mRNA expression (n=4 each dose) and the other for structural (st)LX studies (n=3 each dose). VP was expressed as the extravasation of EB dye (μg EB/100g weight ±SEM) previously injected by the vein. The housekeeping gene GAPDH and VEGFR2 were amplified with RT/QF-PCR and the ratio VEGFR2/GAPDH in arbitrary fluorescence units (AFU), used to compare VEGFR2mRNA expression between (bw)sp. VEGFR2ph was quantified by western blot analysis in which band signal densities of a phosporilated (pY)VEGFR2 antibody (ab) were normalized with those corresponding to a “whole” VEGFR2 ab and the ratio pYVEGFR2/VEGFR2 (in AFU) used to compare VEgr2ph bw sp. Apoptosis and vascularization as parameters of stLX were detected by in situ TdT enzyme labelling and with CD31 ab staining respectively. We used image analysis software to quantify apoptotic cells per bright field and CD31area. Pr and P4 levels were quantified by RIA and ELISA respectively. ANOVA or Mann-Whitney tests were used, depending on variance homogeneity, for statiscal analysis. In a first set, Placebo (PL),Cb at 0.6, 3, 6,30 or Br at 0,75, 150, 300, 600 μg doses were administered in a single dose 24 h after hCG(d27). DA had no effect on stLX and VEGFR2mRNA expression. The minimal doses to avoid iVP compared to PL (30.03+4.07) were Br 150 μg (12.01±2.07; p=0.042) and Cb 3 μg (9.63±1.67, p=0.037)), and were related with a 60% Dc pYVEGFR2/VEGFR2 ratio but couldn’t be impaired from fLX in Cb 3μg[P4]=121±17; p=0.047 or Br2 150 μg[P4]=137±28; p=0.063 vs PL[P4]=202±47ng/ml. In a second set, to isolate the role of VEGFR2 ph on VP, we avoided LX in OHSS DA treated rats by implanting them with pellets containing Pr 10mg, to maintain 80 ng/ml circulating levels as seen in OHSS DA untreated rats. After 24 h rats received PL, Cb2 at 3, 6 or Br2 at 150, 300 μg doses and 24 h later VP was measured to show that although[P4] levels were similar in PL (198±37ng/ml) or DA treated (range 173–225 ng/ml) rats, VP and VEGFR2ph were Dc to a 65% and 50 % level vs PL rats in the absence of fLX. iVP in OHSS can be specifically treated without LX by blocking VEGFR2ph with non-toxic DA, that’s why, Cb started to be administered in January to ovum donors in our center in a prospective double blind study expected to finish in 7 months.