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加尼瑞克与预防过早促黄体生成素激增

Ganirelix and the prevention of premature luteinizing hormone surges.

作者信息

Mannaerts Bernadette

机构信息

Organon Pharma BV, Molenstraat, Oss, the Netherlands.

出版信息

F S Rep. 2023 Feb 24;4(2 Suppl):56-61. doi: 10.1016/j.xfre.2023.02.009. eCollection 2023 Jun.

Abstract

Ganirelix is a gonadotropin-releasing hormone (GnRH) antagonist with high antagonistic activity that blocks the GnRH receptor by competitive binding. A daily dose of 0.25 mg of ganirelix was sel5ected after a phase II study because it was the minimal, effective daily dose to prevent premature luteinizing hormone surges and this dose yielded the highest ongoing pregnancy rate per started cycle. After subcutaneous administration, ganirelix is rapidly absorbed, reaching peak levels within 1-2 hours (t), and has a high absolute bioavailability (>90%). Prospective, comparative studies have demonstrated the advantages of GnRH antagonists over long GnRH agonist treatment in assisted reproduction, including the immediate reversibility of drug effects, a requirement for less follicle-stimulating hormone, a shortened duration of stimulation, a reduced incidence of ovarian hyperstimulation syndrome, and reduced patient burden. Combined analyses concluded that in the general in vitro fertilization population, there is a trend for a slightly lower ongoing pregnancy rate and a lower risk of ovarian hyperstimulation syndrome that is largely eliminated when considering triggering with GnRH agonist instead of human chorionic gonadotropin. Regardless of all the research, it is still not fully elucidated why the long GnRH agonist protocol has a trend for higher pregnancy rates after fresh transfer of the same number of good-quality embryos.

摘要

加尼瑞克是一种具有高拮抗活性的促性腺激素释放激素(GnRH)拮抗剂,它通过竞争性结合来阻断GnRH受体。在一项II期研究后,选择了每日0.25 mg的加尼瑞克剂量,因为这是预防过早促黄体生成素激增的最小有效日剂量,且该剂量在每个启动周期中产生的持续妊娠率最高。皮下给药后,加尼瑞克迅速吸收,在1 - 2小时内达到峰值水平(t),并且具有高绝对生物利用度(>90%)。前瞻性对比研究已经证明了GnRH拮抗剂在辅助生殖中优于长效GnRH激动剂治疗的优势,包括药物作用的立即可逆性、对促卵泡激素的需求减少、刺激持续时间缩短、卵巢过度刺激综合征的发生率降低以及患者负担减轻。综合分析得出,在一般体外受精人群中,存在持续妊娠率略低的趋势,以及卵巢过度刺激综合征风险较低的情况,当考虑用GnRH激动剂而非人绒毛膜促性腺激素进行触发时,这种情况在很大程度上得以消除。尽管有所有这些研究,但仍未完全阐明为什么在新鲜移植相同数量的优质胚胎后,长效GnRH激动剂方案的妊娠率有更高的趋势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14bc/10201301/8dff3c70bd55/gr1.jpg

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