Doxycycline inhibits vascular leakage and prevents ovarian hyperstimulation syndrome in a murine model

Objective: To determine whether doxycycline would inhibit the development of ovarian hyperstimulation syndrome (OHSS) in a murine model. Design: Testing the effect of oral doxycycline treatment on gonadotropin-induced peritoneal capillary leakage in mice. Setting: Animal research facility. Animal(s): Four-week-old female C57Bl/6 mice. Intervention(s): Ovarian hyperstimulation syndrome was induced in mice by administering gonadotropins for 3 days followed by human chorionic gonadotropin. Peritoneal vascular leakage was quantified using the Miles vascular permeability assay. Mice were treated with daily oral doxycycline or vehicle. Main Outcome Measure(s): The concentration of dye in abdominal fluid extracted by peritoneal lavage was measured spectrophotometrically. Ascites volume was determined using dye dilution. Result(s): Doxycycline inhibited peritoneal vascular leakage and ascites accumulation in the hormonally stimulated mice. Doxycycline treatment did not inhibit ovarian stimulation or ovulation when compared with controls, as indicated by similar ovarian morphology, ovarian weights, and corpora lutea counts. Importantly, vessel density within the corpora lutea was similar in the two groups. Conclusion(s): Doxycycline prevents OHSS in a murine model without compromising ovarian stimulation. This effect is caused by inhibition of vascular leakage. Doxycycline's potential in preventing human OHSS is promising and warrants further studies. (Fertil Steril (R) 2009;92:1701-5. (C) 2009 by American Society for Reproductive Medicine.)