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American Society for Reproductive Medicine （67ｔｈ Annual Meeting）
Orland（USA）、2011.10.16-19 Cabergoline helps to prevent the development of severe OHSS Tomoko Inoue, Takao Himeno, Yoko Ohnishi, Keijiro Ito, Yoshiharu Nakaoka, Yoshiharu Morimoto The Center for Reproductive Medicine and Infertility, IVF Namba Clinic Objective: Ovarian hyperstimulation syndrome (OHSS) is one of serious complications in controlled ovarian stimulation for IVF/ICSI. Highly increased permeability of capillary in swelled ovaries responding to gonadotropins causes fluid shift from the intravascular space to third space components. Vascular endothelial growth factor (VEGF) is assumed to play a critical role in the development of this pathophysiology. VEGF is an angiogenic cytokine, by binding to its receptor (VEGFR2), which accelerates vascular permeability to induce OHSS symptoms, such as ascites, pleural effusion, or hemoconcentration. Dopamine receptor agonist cabergoline inactivates the VEGF/VEGFR2 binding, and then it suppresses the development of OHSS. According to previous studies, cabergoline is reported to reduce the incidence of OHSS, but not the severity of OHSS. We conducted the following study to confirm if administration of cabergoline reduces the risk of severe OHSS on a retrospective basis. Design: Retrospective controlled study Materials and methods: Sixty one women had prophylactic intervention of cabergoline. They had controlled ovarian hyperstimulation for IVF or ICSI program. Forty one of them are on long protocol, and twenty of them are on antagonist protocol. When at least two follicles reached 17mm in diameter by ultrasound monitoring, they had HCG 5000IU shot followed by OPU procedure after 36 hours later. Serum estrogen levels in the women on the HCG day showed more than 3500 pg/ml, which is recognized as high risk status of OHSS. So we made all embryos freeze instead of fresh transfer after OPU. They also had cabergoline 0.5mg every two days 3 times from the OPU day.
Total of 126 control group had same treatment as intervention group other than cabergoline administration. Two group’s characters are matched in age, number of picked up eggs, serum E2 level on the HCG day, and serum AMH. Both groups had screening tests of peripheral blood analysis and transvaginal ultrasound monitoring on the 7th day after OPU. The grade of OHSS is classified in 3 groups as mild, moderate, and severe. The mild OHSS is characterized by none or mild discomfort in their abdomen, ascites limited to small pelvis, ovarian sizes more than 6cm in diameter, and normal peripheral blood analysis. The moderate OHSS shows symptoms as nausea or vomit, moderately retained ascites, ovarian sizes more than 8cm in diameter, and mild abnormalities in peripheral blood analysis. The severe OHSS is characterized by abdominal pain, dyspnea, serious tension in abdomen cased by massive volume of ascites, ovarian sizes more than 12 cm in diameter, and blood analysis showed Ht>45% or WBC>15000/mm3. Patients are classified to higher grade groups, when any of their clinical aspects discord. The volumes of ovaries are estimated by a following equation as (longest diameter) x (shortest diameter)2 . The figures are from ultrasound monitoring on 7th day after OPU. We analyzed the data using Fisher’s exact test. Result: The average age, number of obtained eggs by OPU, serum E2, and AMH were 35.459 vs. 35.310, 18.852 vs. 19.230, 5358.7pg/ml vs. 5185.8pg/ml, and 31.048 vs. 34.344 in cabergoline group (n=61) vs. control group (n=126) respectively. There were no statistical differences between two groups. The incidence of all OHSS was 60% vs. 75% (p=0.109). The combined incidence of moderate and severe OHSS was 9% vs. 24% (p=0.04). The volume of ovaries after OPU was significantly shrunk in cabergoline group (98.383cm3 vs. 138.251cm3 p=0.0039). We analyzed the data according to COH methods, but no statistical difference was detected in long protocol group or in antagonist protocol group respectively. And also there was no difference in hematocrit value, WBC counts, and volume of ascites between the two groups. Conclusion: Prophylactic administration of cabergoline reduced the incidence of moderate and severe OHSS, although total incidence of OHSS was not different. Combined with embryo freezing method, cabergoline could make OHSS management much effective in high risk patients undergoing ART treatment.
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