Clinica Valle Giulia, Genera Center for Reproductive Medicine, Rome, Italy.
Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
Hum Reprod. 2021 Jan 25;36(2):305-317. doi: 10.1093/humrep/deaa317.
What is the global variability in recurrent implantation failure (RIF) definition, investigation and therapy, currently offered to patients undergoing IVF?
Definitions, diagnostic investigations and treatments offered to RIF patients differ widely amongst assisted reproduction healthcare professionals and clinical guidelines on RIF are urgently needed.
RIF affects around 10% of patients undergoing IVF worldwide. There is no consensus on the definition of RIF, its diagnostic investigations or the therapeutic options, which leads to inconsistencies in clinical practice.
STUDY DESIGN, SIZE, DURATION: A cross-sectional study of clinicians and embryologists was conducted between May and June 2020. The survey included 43 questions aimed at understanding participants' background and their current practice with regards to defining, investigating and managing RIF. The questions were designed by the European Society of Human Reproduction and Embryology (ESHRE) Special Interest Group (SIG) on implantation and early pregnancy following three consensus meetings.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 8579 ESHRE members from 6916 IVF centers were invited to participate using two global email calls based on their pre-specified interest in implantation and early pregnancy. SurveyMonkey and SPSS were used for data collection and analysis, respectively. Furthermore, differences were reported in the answers of European and non-European professionals, as well as between public and private settings and among clinicians clustered according to the average number of RIF patients treated per year.
The final data set included 735 clinicians and 300 embryologist or IVF-biologists. The majority defines RIF based on the number of failed embryo transfers (ETs) with the most common threshold adopted being three ETs both fresh and frozen. More than two-thirds take lifestyle factors into account, mainly drugs, smoking and BMI. The highest consensus on which diagnostic investigations should be performed was reached for anatomical malformations and gynecological aspects focusing on hydrosalpinx, Asherman's syndrome, endometrial thickness and endometriosis. Concerning treatment of RIF patients, the highest consensus was reached for preconceptional therapies, including BMI adjustment, smoking and endometritis followed by therapies during IVF procedures.
LIMITATIONS, REASONS FOR CAUTION: The response rate was relatively low, but comparable to other surveys.
A consensus on definition, diagnosis and treatment of RIF would help to reduce costly, time-consuming and poorly validated approaches.
STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. B.T. received support from Bayer for Clinical trials concerning endometriosis and Ferring for clinical trials concerning ovarian stimulation. She received reimbursement for travel expenses from Astropharm, Ferring. Dr Kade and is a shareholder of Reprognostics. She is a board member of the Austrian Society for Obstetrics and Gynecology (OEGGG), the associate head of the 'Reproduktionsmedizinische Zentren Baden-Württemberg' (RZBW), a member of guideline group of the German Society for Obstetrics and Gynecology (DGGG) and an editorial board member of the following journals: American Journal of Reproductive Immunology (AJRI), Archives of Gynecology and Obstetrics. All the other authors declare no conflict of interest.
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目前，在接受体外受精的患者中，反复着床失败（RIF）的定义、检查和治疗在全球范围内有何差异？
提供给 RIF 患者的定义、诊断性检查和治疗方法在辅助生殖医疗专业人员和临床指南之间存在很大差异，因此迫切需要制定 RIF 临床指南。
RIF 影响全球约 10%的接受 IVF 的患者。目前对于 RIF 的定义、诊断性检查或治疗方案尚无共识，这导致了临床实践中的不一致。
研究设计、规模、持续时间：2020 年 5 月至 6 月期间，对临床医生和胚胎学家进行了横断面研究。该调查包括 43 个问题，旨在了解参与者的背景以及他们目前在定义、检查和管理 RIF 方面的实践情况。这些问题是由欧洲人类生殖与胚胎学会（ESHRE）着床和早期妊娠特别兴趣小组（SIG）根据他们在着床和早期妊娠方面的预先指定的兴趣，通过三次共识会议设计的。
参与者/材料、设置、方法：根据他们在着床和早期妊娠方面预先指定的兴趣，通过两次全球电子邮件呼吁，邀请了来自 6916 个 IVF 中心的 8579 名 ESHRE 成员参加。SurveyMonkey 和 SPSS 分别用于数据收集和分析。此外，欧洲和非欧洲专业人员、公共和私人环境以及根据每年治疗的 RIF 患者数量进行分组的临床医生之间的回答也存在差异。
最终数据集包括 735 名临床医生和 300 名胚胎学家或 IVF 生物学家。大多数人根据失败的胚胎移植（ET）次数来定义 RIF，最常见的采用的阈值是新鲜和冷冻胚胎移植各三次。超过三分之二的人考虑生活方式因素，主要是药物、吸烟和 BMI。对于应进行哪些诊断性检查，达成了最高共识，重点是解剖学畸形和妇科方面，包括输卵管积水、Asherman 综合征、子宫内膜厚度和子宫内膜异位症。关于 RIF 患者的治疗，在 preconceptional 治疗方面达成了最高共识，包括 BMI 调整、吸烟和子宫内膜炎，其次是在 IVF 过程中的治疗。
局限性、谨慎的原因：回复率相对较低，但与其他调查相当。
在 RIF 的定义、诊断和治疗方面达成共识将有助于减少昂贵、耗时和验证效果不佳的方法。
研究资金/利益冲突：未使用外部资金。B.T. 获得了拜耳公司用于子宫内膜异位症临床试验和费森尤斯公司用于卵巢刺激临床试验的支持。她收到了阿斯法姆、费森尤斯的旅行费用报销。博士卡德是 Reprognostics 的股东。她是奥地利妇产科协会（OEGGG）的董事会成员，是“巴登-符腾堡生殖医学中心”（RZBW）的联合负责人，是德国妇产科协会（DGGG）指南小组的成员，也是以下期刊的编辑委员会成员：美国生殖免疫学期刊（AJRI）、妇产科档案。其他所有作者均无利益冲突。
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