首页 > 学术动态 > 辅助生殖治疗使用GnRH拮抗剂,GnRH拮抗剂的好处是什么?


分类:学术动态   |   来源:美福生命   |   4910阅读数

  Author:Efstratios M.Kolibianakis and Georg Griesinger
  作者:Efstratios M.Kolibianakis and Georg Griesinger
  Book:Human Assisted Reproductive Technology
  Editors:David K.Gardner,Botros RMB Rizk and Tommaso Falcone
  主编:David K.Gardner,Botros RMB Rizk和Tommaso Falcone
  Gonadotropin releasing hormone(GnRH)analogs have been used since 1984 for the purpose to inhibit premature luteinizing hormone(LH)surge in ovarian stimulation.In contrast to GnRH antagonists,GnRH agonists are characterized by a lack of immediate suppression of endogenous gonadotropins,requiring a long pretreatment period prior to initiation of gonadotropn stimulation.Despite this significant disadvantage,they were used exclusively to control endogenous LH secretion until the end of the 1990s,since they were the only clinically available analog.
  The availability of GnRH antagonists did not only offer clinicians an alternative to GnRH agonists but,more importantly,has led to the development of new concepts aiming to increase safety and simplicity in ovarian stimulation.These include the modified natural cycle,mild IVF,the use of GnRH agonist for triggering of final oocyte maturation,the administration of antagonists during the luteal phase for management of severe OHSS,as well as control of endogenous LH with GnRH antagonists in intrauterine insemination cycles.
  Scheme of GnRH antagonist administration
  Administration of GnRH antagonists can be performed by either a single dose or by using a daily scheme.Administration of a single-dose antagonist is effective in suppressing endogenous LH for 4 days.If the criteria to trigger final oocyte maturation have not been met by the end of this time period(which was the case for about 10%of patients in a large phase III trial),daily antagonist dose can be administered accordingly.
  Apparently,the single-dose administration is patient friendlier compared to the daily dose,since it is associated with a decreased number of antagonist injections.However,theoretically it might result in unnecessary antagonist administration.In this respect,although daily antagonist necessitates multiple injections,it allows using the minimally necessary dose of antagonist in a given treatment cycle.
  Until today only two comparative RCTs between the two schemes of antagonist administration have been published,including 215 patients.Stratified analysis of these two trials shows no difference in the probability of clinical pregnancy.However,since they are based on a small number of patients,the results are not conclusive.Nevertheless,the majority of published antagonist studies have been performed with the daily dose protocol.
  Optimal dose of GnRH antagonist
  Three RCTs were performed by the ganirelix dose-finding study group to establish the dose under which GnRH antagonists should be used in IVF.Results reported in 1998 showed that the optimal dose was 0.25mg for the daily dose scheme and 3mg for the single dose scheme.
  Higher antagonist doses for daily administration have been associated with very low LH levels and a lower probability of pregnancy.Moreover,they lead to detectable antagonist in circulation by the day of embryo transfer,which has been suggested to be detrimental for embryo implantation.
  Timing of GnRH antagonist administration
  Antagonist administration was performed in the initial comparative trials between GnRH agonists and GnRH antagonists with a fixed scheme,starting on day 6 of stimulation.Optimization of this fixed antagonist protocol,based on data regarding endogenous LH control,has recently moved antagonist initiation to an earlier time point,e.g.to day 5 of stimulation.
  In the flexible antagonist scheme,antagonist is started when an LH surge is likely to occur.Since there is significant heterogeneity between individual treatment cycles,different criteria have been used to guide antagonist initiation,which are based on either ultrasound and/or hormonal criteria.
  Fixed compared to flexible antagonist initiation is a simpler protocol that requires less monitoring.On the other hand,it might lead to unnecessary antagonist administration,since in a proportion of patients an LH surge is unlikely to occur on day 5 of stimulation due to absence of follicular development.
  Both the fixed(day 6 of stimulation)and the flexible protocol(using different criteria for antagonist initiation)have been compared in four RCTs,the results of which have been summarized in a meta-analysis that did not show a significant difference in clinical pregnancy rates between the two protocols.However,all studies showed the same direction of effect,which was not in favor of the flexible protocol.

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