Use of meloxicam for OHSS prevention

Abstract

OBJECTIVE: Vascular endothelial growth factor (VEGF) plays a central role in Ovarian hyperstimulation syndrome (OHSS) by increasing vascular permeability. Recently, we have demonstrated a beneficial effect of meloxicam by reducing ovarian weight and VEGF expression associated with OHSS in a rat model. This effect may be mediated by the Ciclooxigenase-2 (COX-2), which is inhibited by meloxicam. The objective is to assess the role of Meloxican in OHSS prevention in oocyte donors. DESIGN: Prospective randomized study. MATERIALS AND METHODS: 36 oocyte donors with OHSS risk after COH were randomized to either receive expectant clinical management and support (group 1, n=18), or Meloxicam treatment (15 mg/daily orally for 8 days starting on the day of oocyte retrieval) (Group 2, n=18). All donors met standard ASRM screening criteria (with written informed consent signed, age between 21 and 30 years, and basal FSH levels ≤ 12 IU/l). OHSS risk parameters as inclusion criteria were: ≥ 10 follicles at least 14 mm per ovary and E2 levels ≥ 2500 pg/ml on hCG day. All patients used agonist GnRh luteal phase protocol, with rFSH 250 IU/daily for 4 days followed by equal dose of hMG for ovarian stimulation. Both groups were clinically, hematologically and biochemically followed for signs and symptoms of OHSS and received supportive measures as required. Blood samples for VEGF measurement were obtained on the day of hCG and 7 days later. RESULTS: Mean age, BMI, oocytes retrieved and estradiol levels were comparable between both groups as well as plasma VEGF concentrations on hCG day (19.1 ± 8.9 pg/ml and 24.6 ± 12.1 pg/ml for Groups 1 and 2 respectively, NS); although seven days after hCG, VEGF plasma levels were significantly lower in the treatment group (22.3 ± 10.9 pg/ml vs 13.7 ±6.3 pg/ml for Groups 1 and 2 respectively; p<0.05). Additionally, we found less OHSS symptoms in Group 2 patients (4/18 with slight abdominal distention; 2/18 with mild ascites), while in Group 1 their symptoms persisted unchanged or slightly worse on day 7 (14/18 with slightly abdominal distention; 12/18 presenting ascitis). CONCLUSIONS: Our results suggest a beneficial effect of meloxicam in the prevention and treatment of OHSS and its complications in ART cycles when no embryos are transferred. More studies are necessary in order to analyze the risk-benefit ratio of meloxicam administration in IVF embryo-tranfer cycles, since its use has been related to an antiimplantatory effect.