Alvarez Claudio, Martí-Bonmatí Luis, Novella-Maestre Edurne, Sanz Roberto, Gómez Raúl, Fernández-Sánchez Manuel, Simón Carlos, Pellicer Antonio
Instituto Valenciano de Infertilidad, University of Valencia, Plaza de la Policía Local, 3, 46015 Valencia, Spain.
J Clin Endocrinol Metab. 2007 Aug;92(8):2931-7. doi: 10.1210/jc.2007-0409. Epub 2007 Apr 24.
Ovarian hyperstimulation syndrome (OHSS) results from increased vascular permeability (VP) caused by ovarian hypersecretion of vascular endothelial growth factor (VEGF), which activates its receptor-2. In animals, the dopamine receptor 2 agonist cabergoline (Cb2) inactivates VEGF receptor-2 and prevents increased VP.
Our objective was to test whether Cb2 reduces VP and prevents OHSS in humans.
We conducted a prospective, randomized, double-blind study on oocyte donors at risk of developing OHSS (>20 follicles, >12 mm developed, and >20 oocytes retrieved).
Cb2 0.5 mg/d (n = 37) or a placebo (n = 32) was administered from the day of human chorionic gonadotropin (d 0) until d 8. Ascites (a pocket of peritoneal fluid > 9 cm(2) in lithotomy position), hemoconcentration, and serum prolactin were recorded. Pharmacokinetic studies with magnetic resonance employing the transfer constant rate (K(trans), measure of permeability) and the extravascular extracellular space (upsilon(e), marker of cellular leakage) were performed to measure VP objectively.
Hematocrit (P < 0.01), hemoglobin (P = 0.003), and ascites (P = 0.005) were significantly lower on d 4 and 6 after treatment with Cb2 as compared with placebo. The incidence of moderate OHSS was 20.0 and 43.8%, respectively (P = 0.04). Magnetic resonance studies showed an increase in VP and extravascular leakage of fluid 5 d after human chorionic gonadotropin injection that was significantly prevented with Cb2 (K(trans) P = 0.04 and upsilon(e) P = 0.001, respectively).
Given that Cb2 is a well-established and safe medication, this study provides proof of concept for the use of dopamine agonists in the prevention of OHSS in women undergoing assisted reproduction.
卵巢过度刺激综合征（OHSS）是由卵巢过度分泌血管内皮生长因子（VEGF）导致血管通透性（VP）增加引起的，VEGF会激活其受体-2。在动物中，多巴胺受体2激动剂卡麦角林（Cb2）可使VEGF受体-2失活并防止VP升高。
我们的目的是测试Cb2是否能降低人体的VP并预防OHSS。
我们对有发生OHSS风险（卵泡>20个、发育成熟的卵泡>12mm且获取的卵母细胞>20个）的卵母细胞捐赠者进行了一项前瞻性、随机、双盲研究。
从注射人绒毛膜促性腺激素当天（第0天）至第8天，给予Cb2 0.5mg/d（n = 37）或安慰剂（n = 32）。记录腹水（截石位时腹腔内液体囊袋面积>9cm²）、血液浓缩情况和血清催乳素水平。采用磁共振进行药代动力学研究，利用转运常数速率（K(trans)，通透性指标）和血管外细胞外间隙（υ(e)，细胞渗漏标志物）来客观测量VP。
与安慰剂相比，Cb2治疗后第4天和第6天，血细胞比容（P < 0.01）、血红蛋白（P = 0.003）和腹水（P = 0.005）均显著降低。中度OHSS的发生率分别为20.0%和43.8%（P = 0.04）。磁共振研究显示，人绒毛膜促性腺激素注射后5天，VP增加且液体出现血管外渗漏，而Cb2可显著预防这种情况（K(trans) P = 0.04，υ(e) P = 0.001）。
鉴于Cb2是一种成熟且安全的药物，本研究为多巴胺激动剂在预防接受辅助生殖的女性发生OHSS中的应用提供了概念验证。
