Can High Dose Aspirin Reduce Vascular Permeability in Ovarian Hyperstimulation Syndrome (OHSS) – A Mouse Model

Abstract

To study the effect of inhibition of cyclooxygenase pathway by Aspirin (ASA) in reducing vascular permeability in mice OHSS model. Animal experiment. 4-5 week old Swiss Webster (SW) female mice underwent ovarian stimulation using pregnant mare serum gonadotropin (PMSG) and/or human chorionic gonadotropins (HCG) with or without the administration of ASA. Twelve SW mice were divided into 4 groups: HCG, ASA+HCG, PMSG+HCG and ASA+PMSG+HCG. All medications were injected intra-peritoneally using an established OHSS model in Mice. The modified Miles Vascular permeability (VP) assay was used to quantify the degree of VP. 48 hours following HCG, 1μL of Evans Blue dye (EBS) was injected intra orbitally. 30 minutes later 2 mL of sterile saline was injected intraperitoneally followed by 1 minute of careful abdominal massage and collection of 1 ml of ascetic fluid into a 96-well ELISA plate. Absorbance was measured at 620 nm. Ovarian, uterine and total mouse weight- before and after stimulation were measured and a portion of each mouse' ovary and uterus were collected for histological analysis. Material and Methods: A WCMC IACUC was approved. Results:OHSS was determined by measuring post stimulation (5 days interval) mouse weight and assessing ovarian size (which was larger in the 2 mice groups receiving PMSG). Comparing both the HCG group and the PMSG+HCG group with the groups which received the same stimulation protocol along with ASA, vascular permeability was significantly attenuated in the groups treated with cyclooxygenase inhibitor aspirin (p<0.0004 and p<0.02, respectively).Tabled 1No. of MicePMSGAspirinhCGVP AssayWeight-beforeWeight-afterOvarian Weight310 IU0.42α25.9329.90.0293100μLX410 IU0.24α25.9526.150.021320 IU X310 IU0.46β26.7329.680.039320 IU X3100μLX410 IU0.23β27.2829.20.038α p<0.0004, β p<0.0216 Open table in a new tab α p<0.0004, β p<0.0216 Our study demonstrated that administration of Aspirin in OHSS mice significantly reduced VP. Future experiment ought to asses the patho-physiology in which Acetyl salicylic acid affects VP (i.e. via platelets activation). Further investigation is warranted to establish the dose and route at which ASA should be administered to achieve optimal effect.