Dose-finding study of daily gonadotropin-releasing hormone (GnRH) antagonist for the prevention of premature luteinizing hormone surges in IVF/ICSI patients: antide and hormone levels
Dose-finding study of daily gonadotropin-releasing hormone (GnRH) antagonist for the prevention of premature luteinizing hormone surges in IVF/ICSI patients: antide and hormone levels
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DOI：
10.1093/humrep/deh357
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发表时间：
2004-10-01
影响因子：
6.1
通讯作者：
Lambalk, CB
中科院分区：
文献类型：
--
作者：
Huirne, JAF;van Loenen, ACD;Lambalk, CB
背景：本研究的目的是确定抗毒素（Iturelix）的最小有效剂量，以防止体外受精（IVF）患者体内黄体生成素（LH）过早激增。方法：在一项前瞻性、单中心研究中，144 名 IVF/ICSI 患者从周期第 2 天和周期第 6 天开始接受 r-hFSH 刺激，并每日联合治疗 2 mg/2 ml (n=30)、1 mg/ml (n=30)、0.5 mg/ml (n=31)、0.5 mg/0.5 ml (n=23) 和 0.25 mg/ml (n=30) GnRH 拮抗剂（抗药）。在抗解剂施用期间每天采集三次血清样本以评估抗解剂和激素水平。最小有效剂量定义为最低剂量组（12.4 IU/l，孕酮>2 ng/ml）。结果：血清抗药水平、每天平均 LH 和 E2 水平及其曲线下面积与抗药剂量相关。在较大体积稀释后，抗解剂的生物利用度几乎加倍。在 GnRH 拮抗剂治疗期间，注射前 LH 水平逐渐升高。 LH 激增发生在最低剂量组 0.5 mg/ml (3.2%)、0.5 mg/0.5 ml (6.7%) 和 0.25 mg/ml (13.3%)。因此，0.5 mg/ml 被认为是最小有效剂量。 Antide 总体耐受性良好且安全。结论：0.5 mg/ml 抗药是预防 r-hFSH 刺激的 IVF 患者 LH 过早激增的最小有效剂量。
BACKGROUND: The aim of this study was to define the minimal effective dose of antide (Iturelix) to prevent premature luteinizing hormone (LH) surges in in vitro fertilization (IVF) patients. METHODS: In a prospective, single centre study, 144 IVF/ICSI patients were stimulated with r-hFSH from cycle day 2 and from cycle day 6 onwards, cotreated with daily 2 mg/2 ml (n=30), 1 mg/ml (n=30), 0.5 mg/ml (n=31), 0.5 mg/0.5 ml (n=23) and 0.25 mg/ml (n=30) GnRH antagonist (antide). Serum samples were taken three times daily during antide administration to assess antide and hormone levels. The minimal effective dose was defined as the lowest dose group with 12.4 IU/l and progesterone >2 ng/ml). RESULTS: Serum antide levels, mean LH and E2 levels per day and their area under the curves were dose-related to antide. The bioavailability of antide almost doubled after dilution in larger volumes. Pre-injection LH levels gradually increased during GnRH antagonist treatment. LH surges occurred in the lowest dose groups 0.5 mg/ml (3.2%), 0.5 mg/0.5 ml (6.7%) and 0.25 mg/ml (13.3%). Hence, 0.5 mg/ml is considered to be the minimal effective dose. Antide was overall well tolerated and safe. CONCLUSIONS: 0.5 mg/ml antide is the minimal effective dose to prevent an untimely LH surge in IVF patients stimulated with r-hFSH.