目的:卵巢刺激的推荐处理是什么,基于文献中现有的最佳证据
■指南制定小组制定了84条建议,回答了18个关于卵巢刺激的关键问题。
■IVF/ICSI的卵巢刺激已在美国国家健康与护理卓越研究所关于生育问题的指南中进行了简要讨论,澳大利亚和新西兰皇家妇产科学院发表了关于辅助生殖中卵巢刺激的声明。有,根据我们的知识,没有专门针对卵巢刺激过程的循证指南。
■该指南是根据ESHRE指南制定的结构化方法制定的。在一组专家提出关键问题后,进行了文献检索和评估.包括截至2018年11月8日发表并以英文撰写的论文。该指南的关键结果是每个开始周期的累积活产率或每个开始周期的活产率的有效性。以及中度和/或重度卵巢过度刺激综合征(OHSS)发生率方面的安全性。
■根据收集到的证据,我们制定并讨论了相关建议,直至指南小组达成共识.草案定稿后,组织了一次利益攸关方审查。最终版本由指南小组和ESHRE执行委员会批准。
■该指南提供了84条建议:关于刺激前管理的7条建议,40关于LH抑制和促性腺激素刺激的建议,关于卵巢刺激期间监测的11条建议,关于触发最终卵母细胞成熟和黄体支持的18条建议和关于预防OHSS的8条建议。其中包括61项基于证据的建议——其中只有21项被制定为强有力的建议——以及19项良好做法要点和4项仅研究建议。该指南包括强烈建议使用窦卵泡计数或抗苗勒管激素(而不是其他卵巢储备测试)来预测对卵巢刺激的高反应和低反应。该指南还包括强烈建议在一般IVF/ICSI人群中使用GnRH拮抗剂方案而不是GnRH激动剂方案。基于可比的疗效和更高的安全性。对于预测的不良反应者,同样推荐GnRH拮抗剂和GnRH激动剂。关于激素预处理和其他辅助治疗(二甲双胍,生长激素(GH),睾丸激素,脱氢表雄酮,阿司匹林和西地那非),指南组得出的结论是,不建议增加疗效或安全性.
■一些较新的干预措施尚未得到很好的研究。对于大多数这些干预措施,在证据不足的基础上,提出了反对干预措施的建议或只针对研究的建议.未来的研究可能需要对这些建议进行修订。
■该指南为临床医生提供了关于卵巢刺激的最佳实践的明确建议,基于现有的最佳证据。此外,提供了一系列研究建议,以促进卵巢刺激的进一步研究。
■该指南由ESHRE制定和资助,支付与指南会议相关的费用,随着文献检索和指南的传播。准则组成员未收到付款。F.B.报告Ferring的研究资助和默克公司的咨询费,套圈,GedeonRichter和默克公司的演讲者费用。N.P.报告了Ferring的研究资助,MSD,罗氏诊断,Theramex和BesinsHealthcare;MSD的咨询费,Ferring和IBSA;以及Ferring的演讲者费用,MSD,默克·塞罗诺,IBSA,Theramex,BesinsHealthcare,GedeonRichter和罗氏诊断。A.L.M报告了Ferring的研究资助,MSD,IBSA,默克·塞罗诺,GedeonRichter和TEVA以及罗氏的咨询费,Beckman-Coulter.G.G.报告MSD的咨询费,套圈,默克·塞罗诺,IBSA,菲诺克斯,Theramex,Gedeon-Richter,Glycotope,雅培,Vitrolife,Biosilu,ReprodWissen,Obseva和PregLem以及MSD的演讲者费用,套圈,默克·塞罗诺,IBSA,菲诺克斯,TEVA,GedeonRichter,Glycotope,雅培,Vitrolife和Biosilu。E.B.reportsresearchgrantsfromGedeonRichter;consultingandspeaker\'sfeesfromMSD,套圈,Abbot,GedeonRichter,默克·塞罗诺,罗氏诊断和IBSA;以及IVI-RMS瓦伦西亚的所有权权益。P.H.报告了GedeonRichter的研究资助,默克,IBSA和Ferring和MSD的演讲者费用,IBSA,默克公司和GedeonRichter.J.U.报告IBSA和Ferring的演讲者费用。N.M.报告了MSD的研究资助,默克公司和IBSA;MSD的咨询费,默克,IBSA和Ferring和MSD的演讲者费用,默克,IBSA,GedeonRichter和Theramex.M.G.报告默克·塞罗诺的演讲者费用,套圈,GedeonRichter和MSD。S.K.S.报告默克公司的发言人费用,MSD,Ferring和Pharmasure。E.K.报告默克·塞罗诺的演讲者费用,安杰利尼制药和MSD。M.K.报告费林的发言人费用。T.T.报告默克公司的演讲者费用,MSD和MLD。其他作者报告没有利益冲突。
■本指南代表了ESHRE的观点,这是在仔细考虑准备时可用的科学证据后获得的。在某些方面缺乏科学证据的情况下,有关ESHRE利益相关者之间已达成共识。遵守这些临床实践指南并不能保证成功或特定的结果。它也没有建立护理标准。临床实践指南并不取代将临床判断应用于每个个体陈述的需要,也不是基于地点和设施类型的变化。ESHRE不做任何担保,明示或暗示,关于临床实践指南,并特别排除对特定用途或目的的适销性和适用性的任何保证。(完整的免责声明可在www。eshre.欧盟/准则。)÷ESHRE页面内容未经外部同行评审。该手稿已获得ESHRE执行委员会的批准。
OBJECTIVE: What is the recommended management of ovarian stimulation, based on the best available evidence in the literature?
CONCLUSIONS: The guideline development group formulated 84 recommendations answering 18 key questions on ovarian stimulation.
BACKGROUND: Ovarian stimulation for IVF/ICSI has been discussed briefly in the National Institute for Health and Care Excellence guideline on fertility problems, and the Royal Australian and New Zealand College of Obstetricians and Gynaecologist has published a statement on ovarian stimulation in assisted reproduction. There are, to our knowledge, no evidence-based
guidelines dedicated to the process of ovarian stimulation.
UNASSIGNED: The guideline was developed according to the structured methodology for development of ESHRE
guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 8 November 2018 and written in English were included. The critical outcomes for this guideline were efficacy in terms of cumulative live birth rate per started cycle or live birth rate per started cycle, as well as safety in terms of the rate of occurrence of moderate and/or severe ovarian hyperstimulation syndrome (OHSS).
METHODS: Based on the collected evidence, recommendations were formulated and discussed until
consensus was reached within the guideline group. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline group and the ESHRE Executive Committee.
RESULTS: The guideline provides 84 recommendations: 7 recommendations on pre-stimulation management, 40 recommendations on LH suppression and gonadotrophin stimulation, 11 recommendations on monitoring during ovarian stimulation, 18 recommendations on triggering of final oocyte maturation and luteal support and 8 recommendations on the prevention of OHSS. These include 61 evidence-based recommendations-of which only 21 were formulated as strong recommendations-and 19 good practice points and 4 research-only recommendations. The guideline includes a strong recommendation for the use of either antral follicle count or anti-Müllerian hormone (instead of other ovarian reserve tests) to predict high and poor response to ovarian stimulation. The guideline also includes a strong recommendation for the use of the GnRH antagonist protocol over the GnRH agonist protocols in the general IVF/ICSI population, based on the comparable efficacy and higher safety. For predicted poor responders, GnRH antagonists and GnRH agonists are equally recommended. With regards to hormone pre-treatment and other adjuvant treatments (metformin, growth hormone (GH), testosterone, dehydroepiandrosterone, aspirin and sildenafil), the guideline group concluded that none are recommended for increasing efficacy or safety.
CONCLUSIONS: Several newer interventions are not well studied yet. For most of these interventions, a recommendation against the intervention or a research-only recommendation was formulated based on insufficient evidence. Future studies may require these recommendations to be revised.
CONCLUSIONS: The guideline provides clinicians with clear advice on best practice in ovarian stimulation, based on the best evidence available. In addition, a list of research recommendations is provided to promote further studies in ovarian stimulation.
BACKGROUND: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payment. F.B. reports research grant from Ferring and consulting fees from Merck, Ferring, Gedeon Richter and speaker\'s fees from Merck. N.P. reports research grants from Ferring, MSD, Roche Diagnositics, Theramex and Besins Healthcare; consulting fees from MSD, Ferring and IBSA; and speaker\'s fees from Ferring, MSD, Merck Serono, IBSA, Theramex, Besins Healthcare, Gedeon Richter and Roche Diagnostics. A.L.M reports research grants from Ferring, MSD, IBSA, Merck Serono, Gedeon Richter and TEVA and consulting fees from Roche, Beckman-Coulter. G.G. reports consulting fees from MSD, Ferring, Merck Serono, IBSA, Finox, Theramex, Gedeon-Richter, Glycotope, Abbott, Vitrolife, Biosilu, ReprodWissen, Obseva and PregLem and speaker\'s fees from MSD, Ferring, Merck Serono, IBSA, Finox, TEVA, Gedeon Richter, Glycotope, Abbott, Vitrolife and Biosilu. E.B. reports research grants from Gedeon Richter; consulting and speaker\'s fees from MSD, Ferring, Abbot, Gedeon Richter, Merck Serono, Roche Diagnostics and IBSA; and ownership interest from IVI-RMS Valencia. P.H. reports research grants from Gedeon Richter, Merck, IBSA and Ferring and speaker\'s fees from MSD, IBSA, Merck and Gedeon Richter. J.U. reports speaker\'s fees from IBSA and Ferring. N.M. reports research grants from MSD, Merck and IBSA; consulting fees from MSD, Merck, IBSA and Ferring and speaker\'s fees from MSD, Merck, IBSA, Gedeon Richter and Theramex. M.G. reports speaker\'s fees from Merck Serono, Ferring, Gedeon Richter and MSD. S.K.S. reports speaker\'s fees from Merck, MSD, Ferring and Pharmasure. E.K. reports speaker\'s fees from Merck Serono, Angellini Pharma and MSD. M.K. reports speaker\'s fees from Ferring. T.T. reports speaker\'s fees from Merck, MSD and MLD. The other authors report no conflicts of interest.
CONCLUSIONS: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a
consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/
guidelines.) †ESHRE Pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.