Li Wenqiang, Jia Nanxi, Chi Hongbin, Zhan Siyan, Zeng Lin
Research Center of Clinical Epidemiology, Peking University Third Hospital, Haidian District, Beijing, China.
Ministry of Education, Key Laboratory of Epidemiology of Major Diseases (Peking University), Haidian District, Beijing, China.
Hum Reprod. 2025 Jan 1;40(1):85-95. doi: 10.1093/humrep/deae255.
Do the infertility core outcome set and standardized definitions affect the outcome selection for randomized controlled trials, and what aspects should be further improved in the future?
Intrauterine pregnancy demonstrated the highest uptake level, whereas others were low, especially in neonatal outcomes; as time progresses, the target sample size increases, and with prospective registration, the consistency between outcomes reported in registrations and infertility core outcome set improves significantly.
The infertility core outcome set, published on 30 November 2020, aims to standardize outcome reporting and prevent selective reporting bias; however, there is a paucity of research evaluating its actual adoption, which is crucial for the timely promotion of transparency, standardization, adjustment of development strategies, and efficient resource utilization.
STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 1673 eligible randomized controlled trial registrations for infertility in 18 registries from March 2004 to July 2024 based on registry entries.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 4625 infertility-related studies from 1 November 1999 to 26 July 2024 were retrieved in the World Health Organization International Clinical Trials Registry Platform. Finally, 1673 randomized controlled trial registrations were selected and divided into four period groups. Period, target sample size, prospective registration, blinding, support, and countries/regions were potential influencing factors. The consistency of outcomes, definitions, and standardized denominators of randomized controlled trial registry entries with the recommendations of the infertility core outcome set were the main outcomes. Independent retrieval, screening, data extraction, and consistency evaluations by two assessors and expert consultations were conducted to assess the uptake and potential influencing factors of the infertility core outcome set in randomized controlled trials involving infertile patients undergoing in vitro fertilization.
Results reveal that the reporting level in the pregnancy domain was significantly higher than that in the neonatal domain (13.6% vs 5.7%). Intrauterine pregnancy (66.9%), live birth (27.6%), and miscarriage (26.5%) had relatively high uptake levels. The uptake of most core outcomes and domains, as well as the total number of reported core outcomes, showed statistically significant differences based on period, target sample size, and prospective registration. Multivariable analyses supported the above finding. Reasons responsible for the results may be attributed to the lack of effective promotional measures, as well as the limited researcher awareness regarding this core outcome set.
LIMITATIONS, REASONS FOR CAUTION: Some results in this study may have been influenced by the subjective judgment of the evaluators due to the complexity of the information in registries.
Uptake of most core outcomes or domains is increasing but is not yet ideal. Moreover, the upward trend cannot be solely attributed to the publication of the infertility core outcome set. The key to promoting uptake is to thoroughly explore and recognize the factors that both facilitate and hinder the uptake of the infertility core outcome set, further expand and publicize the core outcome set, and foster multidisciplinary or multiple stakeholder cooperation.
STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Capital's Funds for Health Improvement and Research (CFH 2024-2G-4097), as well as the special fund of Beijing Key Clinical Specialty Construction Project. The authors have no conflicts of interest to declare.
不孕症核心结局集及标准化定义是否会影响随机对照试验的结局选择，未来还应在哪些方面进一步改进？
宫内妊娠的纳入水平最高，而其他结局的纳入水平较低，尤其是新生儿结局方面；随着时间推移，目标样本量增加，且进行前瞻性注册后，注册中报告的结局与不孕症核心结局集之间的一致性显著提高。
2020年11月30日发布的不孕症核心结局集旨在规范结局报告并防止选择性报告偏倚；然而，评估其实际应用情况的研究较少，而这对于及时提高透明度、实现标准化、调整发展策略以及有效利用资源至关重要。
研究设计、规模、持续时间：这项横断面研究基于注册记录，纳入了2004年3月至2024年7月期间18个注册机构中1673项符合条件的不孕症随机对照试验注册记录。
参与者/材料、设置、方法：在世界卫生组织国际临床试验注册平台检索了1999年11月1日至2024年7月26日期间共4625项不孕症相关研究。最终，选取了1673项随机对照试验注册记录并分为四个时间段组。时间段、目标样本量、前瞻性注册、盲法、资助情况以及国家/地区为潜在影响因素。随机对照试验注册记录的结局、定义及标准化分母与不孕症核心结局集建议的一致性为主要结局。由两名评估人员进行独立检索、筛选、数据提取及一致性评估，并进行专家咨询，以评估不孕症核心结局集在涉及接受体外受精的不孕患者的随机对照试验中的应用情况及潜在影响因素。
结果显示，妊娠领域的报告水平显著高于新生儿领域（13.6%对5.7%）。宫内妊娠（66.9%）、活产（27.6%）和流产（26.5%）的纳入水平相对较高。大多数核心结局及领域的纳入情况以及报告的核心结局总数在时间段、目标样本量和前瞻性注册方面存在统计学显著差异。多变量分析支持上述发现。导致这些结果的原因可能是缺乏有效的推广措施，以及研究人员对该核心结局集的认识有限。
局限性、需谨慎的原因：由于注册记录中的信息复杂，本研究的一些结果可能受到评估人员主观判断的影响。
大多数核心结局或领域的纳入情况正在增加，但仍不理想。此外，上升趋势不能仅归因于不孕症核心结局集的发布。促进纳入的关键在于深入探索和认识促进及阻碍不孕症核心结局集纳入的因素，进一步扩大并宣传核心结局集，并促进多学科或多利益相关方的合作。
研究资金/利益冲突：本研究得到了首都卫生发展科研专项（CFH 2024 - 2G - 4097）以及北京市重点临床专科建设项目专项资金的支持。作者声明无利益冲突。
http://www.comet - initiative.org/Studies/Details/3184
