Department of Reproductive Genetics, Juno Genetics, Rome, Italy.
Unit of Medical Genetics, Centre for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Hum Reprod. 2024 Aug 1;39(8):1844-1855. doi: 10.1093/humrep/deae131.
STUDY QUESTION: What is the current practice and views on (expanded) carrier screening ((E)CS) among healthcare professionals in medically assisted reproductive (MAR) practices in Europe? SUMMARY ANSWER: The findings show a limited support for ECS with less than half of the respondents affiliated to centres offering ECS, and substantial variation in practice between centres in Europe. WHAT IS KNOWN ALREADY: The availability of next-generation sequencing, which enables testing for large groups of genes simultaneously, has facilitated the introduction and expansion of ECS strategies, currently offered particularly in the private sector in the context of assisted reproduction. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey evaluating practice and current views among professionals working in MAR practice in different European countries was designed using the online SurveyMonkey tool. The web-based questionnaire included questions on general information regarding the current practice of (E)CS in MAR and questions on what is offered, to whom the test is offered, and how it is offered. It consisted mostly of multiple-choice questions with comment boxes, but also included open questions on the respondents' attitudes/concerns relevant to (E)CS practice, and room to upload requested files (e.g. guidelines and gene panels). In total, 338 responses were collected from 8 February 2022 to 11 April 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: The online survey was launched with an invitation email from the ESHRE central office (n = 4889 emails delivered) and the European Society of Human Genetics (ESHG) central office (n = 1790 emails delivered) sent to the ESHRE and ESHG members, and by social media posts. The survey was addressed to European MAR centres or gamete banks and to centres located in non-European countries participating in the European IVF-monitoring Consortium. Two reminder emails were sent. After exclusion of 39 incomplete responses received (e.g. only background information), 299 respondents from 40 different countries were included for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 42.5% (127/299) of respondents were affiliated to centres offering ECS. The perceived responsibility to enable prospective parents to make informed reproductive decisions and preventing suffering/burden for parents were the main reasons to offer ECS. A single ECS panel is offered by nearly 45% (39/87 received answers) of the centres offering ECS, 25.3% (22/87) of those centres offer a selection of ECS panels, and 29.9% (26/87) offer whole exome sequencing and a large in silico panel. Different ranges of panel sizes and conditions were included in the ECS panel(s) offered. Most of the respondents (81.8%; 72/88 received answers) indicated that the panels they offer are universal and target the entire population. Pathogenic variants (89.7%; 70/78 received answers), and to a lesser extent, likely pathogenic variants (64.1%%; 50/78 received answers), were included in the ECS report for individuals and couples undergoing MAR with their own gametes. According to 87.9% (80/91 received answers) of the respondents, patients have to pay to undergo an ECS test. Most respondents (76.2%; 61/80 received answers) reported that counselling is provided before and after the ECS test. Preimplantation genetic testing, the use of donor gametes, and prenatal diagnostic testing were the three main reproductive options discussed with identified carrier couples. The main reason, according to the respondents, for not offering ECS in their centre, was the lack of professional recommendations supporting ECS (52.5%; 73/139 received answers) and the high cost for couples or reimbursement not being available (49.6%; 69/139). The challenges and moral dilemmas encountered by the respondents revolved mainly around the content of the offer, including the variants classification and the heterogeneity of the panels, the counselling, and the cost of the test. LIMITATIONS, REASONS FOR CAUTION: Although the total number of respondents was acceptable, the completion rate of the survey was suboptimal. In addition, the heterogeneity of answers to open-ended questions and the ambiguity of some of the answers, along with incomplete responses, posed a challenge in interpreting survey results. It is also plausible that some questions were not easily understood by the respondents. For this reason, response and non-response bias are acknowledged as further limitations of the survey. WIDER IMPLICATIONS OF THE FINDINGS: The results of this survey could aid in identifying potential challenges or areas for improvement in the current practice of ECS in the MAR field and contribute to the discussion on how to address them. The results underline the need to stimulate a more knowledge-based debate on the complexity and the pros and cons of a possible implementation of ECS in MAR. STUDY FUNDING/COMPETING INTEREST(S): All costs relating to the development process were covered from European Society of Human Reproduction and Embryology and European Society of Human Genetics funds. There was no external funding of the development process or manuscript production. A.C. is full-time employee of Juno Genetics. L.H. declared receiving a research grant during the past 36 months from the Netherlands Organisation for Health Research and Development. She has also participated in a Health Council report of the Netherlands on preconception carrier screening and collaborated with the VSOP Dutch Genetic Alliance (patient umbrella organization on rare and genetic disorders). L.H. and C.v.E. are affiliated with Amsterdam University Medical Centre, a hospital that offers ECS in a non-commercial setting. R.V. received honoraria for presentations from Merck Academy and is unpaid board member of the executive committee of the Spanish Fertility Society. The other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.
研究问题:在欧洲的医学辅助生殖(MAR)实践中,医疗保健专业人员对(扩展)携带者筛查((E)CS)的当前实践和观点是什么?
总结答案:研究结果表明,对 ECS 的支持有限,只有不到一半的受访者隶属于提供 ECS 的中心,而且欧洲各中心之间的实践存在很大差异。
已知情况:下一代测序技术的出现使同时检测大量基因成为可能,这促进了 ECS 策略的引入和扩展,目前主要在辅助生殖的私人部门提供。
研究设计、规模、持续时间:使用在线 SurveyMonkey 工具设计了一项评估不同欧洲国家 MAR 实践中专业人员实践和当前观点的横断面调查。该网络问卷包括关于 MAR 中 ECS 当前实践的一般信息问题,以及提供哪些测试、向谁提供测试以及如何提供测试的问题。它主要由多项选择题和评论框组成,但也包括与 ECS 实践相关的受访者态度/关注点的开放问题,以及上传所需文件(例如指南和基因面板)的空间。总共从 2022 年 2 月 8 日至 2022 年 4 月 11 日收集了 338 份来自欧洲生育协会(ESHRE)和欧洲人类遗传学协会(ESHG)会员的回复。
参与者/材料、设置、方法:ESHRE 中央办公室(发送了 4889 封电子邮件)和 ESHG 中央办公室(发送了 1790 封电子邮件)向 ESHRE 和 ESHG 成员以及社交媒体帖子发送了一份邀请电子邮件,发起了在线调查。该调查针对欧洲 MAR 中心或配子库以及参与欧洲 IVF 监测联盟的非欧洲国家的中心进行。发送了两封提醒电子邮件。在排除收到的 39 份不完整回复(例如,仅背景信息)后,共有 299 名来自 40 个不同国家的受访者被纳入分析。
主要结果和机会的作用:总体而言,42.5%(127/299)的受访者隶属于提供 ECS 的中心。提供知情的生殖决策和为父母预防痛苦/负担的能力是提供 ECS 的主要原因。近 45%(收到 87 个答案中的 39 个)提供 ECS 的中心提供了一个单一的 ECS 面板,25.3%(87 个答案中的 22 个)的中心提供了一个 ECS 面板的选择,29.9%(87 个答案中的 26 个)提供全外显子组测序和大型的体外面板。提供的 ECS 面板包含不同范围的面板大小和条件。大多数受访者(81.8%;收到 88 个答案中的 72 个)表示他们提供的面板是通用的,针对整个人群。在接受 MAR 并使用自己配子的个体和夫妇中,致病性变异(89.7%;收到 78 个答案中的 70 个)和致病性变异(64.1%;收到 78 个答案中的 50 个)被包含在 ECS 报告中。根据 87.9%(收到 91 个答案中的 80 个)的受访者,患者必须付费进行 ECS 测试。大多数受访者(76.2%;收到 80 个答案中的 61 个)报告说,在 ECS 测试前后都提供咨询。在确定携带者夫妇中,讨论的主要生殖选择是植入前遗传检测、使用供体配子和产前诊断检测。受访者不提供 ECS 的主要原因是缺乏专业推荐支持 ECS(52.5%;收到 139 个答案中的 73 个)和夫妇的费用过高或没有报销(49.6%;收到 139 个答案中的 69 个)。受访者遇到的挑战和道德困境主要围绕着提供的内容,包括变体分类和面板的异质性、咨询以及测试的成本。
局限性、谨慎的原因:尽管回复总数是可以接受的,但调查的完成率不理想。此外,对开放式问题的回复存在异质性和模糊性,以及不完整的回复,这给解释调查结果带来了挑战。一些问题也可能不容易被受访者理解,这也是一个限制。因此,承认存在回复和非回复偏差是调查的进一步限制。
更广泛的影响:这项调查的结果可以帮助确定 MAR 领域 ECS 实践中的潜在挑战或改进领域,并有助于讨论如何解决这些问题。结果强调需要激发关于可能在 MAR 中实施 ECS 的复杂性和利弊的更基于知识的辩论。
研究资金/利益冲突:开发过程的所有费用均由欧洲人类生殖与胚胎学协会和欧洲人类遗传学协会承担。没有外部资金用于开发过程或手稿制作。A.C. 是 Juno Genetics 的全职员工。L.H. 报告说,在过去 36 个月内,她从荷兰卫生研究与发展组织获得了一项研究资助。她还参与了荷兰关于孕前携带者筛查的健康委员会报告,并与 VSOP 荷兰遗传联盟(罕见和遗传疾病患者伞式组织)合作。L.H. 和 C.v.E. 隶属于阿姆斯特丹大学医学中心,该医院在非商业环境中提供 ECS。R.V. 因演讲从 Merck Academy 获得了荣誉酬金,并且是西班牙生育协会执行委员会的无薪董事会成员。其他作者没有什么可透露的。
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