Feng Qian, Li Wentao, Li Wanlin, Wang Rui, Crispin James, Longobardi Salvatore, D'Hooghe Thomas, Mol Ben W
Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia.
National Perinatal Epidemiology and Statistics Unit (NPESU), Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.
Hum Reprod. 2025 Apr 1;40(4):654-663. doi: 10.1093/humrep/deaf022.
How frequently do infertility trials report live birth and pregnancy, and how consistently were their definitions reported?
One-third of 1425 infertility trials published in the last decade reported live birth, with one in eight reporting clinical pregnancy, ongoing pregnancy, and live birth concurrently; absent, ambiguous, or heterogeneous definitions were common.
Absent or inconsistent outcome definitions in randomized controlled trials (RCTs) limit their interpretation and complicate subsequent evidence synthesis. While reporting live birth in infertility trials has been a long-running recommendation, the extent to which this is adhered to, and the temporal trend of adherence, is unclear. Furthermore, it is unknown if outcome reporting in infertility trials is clear and consistent.
STUDY DESIGN, SIZE, DURATION: We studied all RCTs in infertility published between 2012 and 2023. We aimed to assess (i) whether biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth were reported; the temporal trends in reporting these pregnancy outcomes, and compare the characteristics of trials reporting each type of outcome; (ii) whether and how these pregnancy outcomes were defined.
PARTICIPANTS/MATERIALS, SETTING, METHODS: We systematically searched Embase, Medline, and CENTRAL for RCTs in infertility from January 2012 to August 2023. RCTs involving infertile women that reported either biochemical pregnancy, clinical pregnancy, ongoing pregnancy, or live birth were eligible. Secondary analyses, interim analyses, or conference abstracts were not eligible. Two authors independently screened articles. We extracted pregnancy definitions and trial characteristics primarily using text mining in R, a programming environment for data analysis, and supplemented by manual checking. The accuracy of extracted data was validated in a random sample of 50 articles, with sensitivity and specificity all at or above 90%.
We included 1425 infertility RCTs. Among these, 419 (29.4%) reported biochemical pregnancy. While 1359 (95.4%) RCTs reported clinical pregnancy, 404 (28.4%) reported ongoing pregnancy, and 484 (34.0%) reported live birth, only 174 (12.2%) reported all three outcomes. The proportion of trials reporting live birth increased from 23.1% in 2012 to 33.7% in 2023. Trials reporting up to biochemical pregnancy or clinical pregnancy were more likely to be unregistered, smaller, single-centered, and published in non-first quarter journals. Definitions for biochemical, clinical, ongoing pregnancy, and live birth were provided in 68.5% (287/419), 64.5% (876/1359), 70.5% (285/404), and 41.1% (199/484) of articles reporting on these outcomes. Among 876 clinical pregnancy definitions, 63.4% (n = 555) specified the pregnancy confirmation timing. Of the 220 definitions that reported gestational weeks (ranging from 4 to 16 weeks), the most common cut-off was 6 weeks, used in 48.2% (n = 106) of cases. For ongoing pregnancy definitions, 96.1% (n = 274) of the 285 definitions included gestational age in weeks (ranging from 6 to 32 weeks), with 12 weeks being the most common cut-off used in 49.1% (n = 140) of definitions. Among 199 live birth definitions, 62.3% (n = 124) used a gestational age threshold (ranging from 20 to 37 weeks), with 24 weeks being the most common cut-off, used in 28.6% (n = 57) of trials.
LIMITATIONS, REASONS FOR CAUTION: Due to the vast data we needed to extract, we used text-mining supplemented by manual data extraction. While we optimized the text-mining algorithm attempting to identify all types of outcome definitions and manually curated all extracted definitions, definitions were missed in less than 10% of randomly checked studies, which is a limitation of this study. We only described definition patterns in published RCTs, and our results cannot be extrapolated to unpublished RCTs.
Despite long-standing recommendations to report live birth in infertility trials, in the last decade only a third of RCTs did so. This highlights a disconnection between the advocated outcome and what researchers are reporting. We observed an encouraging trend that there has been a consistent rise in the proportion of trials reporting live birth. Furthermore, the significant lack and variability of pregnancy definitions underscore the imperative to increase the dissemination and uptake of standardized pregnancy outcomes.
STUDY FUNDING/COMPETING INTEREST(S): No funding was received for the study. Q.F. reports receiving a PhD scholarship from Merck. B.W.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.M. reports consultancy, travel support, and research funding from Merck and consultancy for Organon and Norgine. B.W.M. holds stock from ObsEva. W.T.L. is supported by an NHMRC Investigator grant (GTN2016729). W.L.L. reports receiving a PhD scholarship from the China Scholarship Council. T.D.H and S.L. are employees of Merck Healthcare KGaA, Darmstadt, Germany. R.W. is supported by an NHMRC Investigator grant (GTN2009767). The other author has no conflict of interest to declare.
CRD42024498624.
不孕症试验中报告活产和妊娠的频率如何，其定义的报告是否一致？
在过去十年发表的1425项不孕症试验中，三分之一报告了活产情况，八分之一的试验同时报告了临床妊娠、持续妊娠和活产情况；缺乏、模糊或不一致的定义很常见。
随机对照试验（RCT）中缺乏或不一致的结果定义限制了对其的解读，并使后续的证据综合变得复杂。虽然在不孕症试验中报告活产一直是一项长期建议，但遵循这一建议的程度以及遵循的时间趋势尚不清楚。此外，不孕症试验中的结果报告是否清晰一致也不得而知。
研究设计、规模、持续时间：我们研究了2012年至2023年间发表的所有不孕症随机对照试验。我们旨在评估：（i）是否报告了生化妊娠、临床妊娠、持续妊娠和活产；报告这些妊娠结局的时间趋势，并比较报告每种结局类型的试验特征；（ii）这些妊娠结局是如何定义的。
参与者/材料、设置、方法：我们系统检索了Embase、Medline和CENTRAL数据库，以获取2012年1月至2023年8月期间的不孕症随机对照试验。纳入涉及不孕女性且报告了生化妊娠、临床妊娠、持续妊娠或活产的随机对照试验。二次分析、中期分析或会议摘要不符合要求。两名作者独立筛选文章。我们主要使用R语言（一种数据分析的编程环境）中的文本挖掘方法提取妊娠定义和试验特征，并辅以人工核对。在50篇文章的随机样本中验证了提取数据的准确性，敏感性和特异性均达到或高于90%。
我们纳入了1425项不孕症随机对照试验。其中，419项（29.4%）报告了生化妊娠。虽然1359项（95.4%）随机对照试验报告了临床妊娠，404项（28.4%）报告了持续妊娠，484项（34.0%）报告了活产，但只有174项（12.2%）报告了所有三种结局。报告活产的试验比例从2012年的23.1%增加到2023年的33.7%。报告生化妊娠或临床妊娠的试验更有可能未注册、规模较小、为单中心试验，且发表在非第一季度的期刊上。在报告这些结局的文章中，分别有68.5%（287/419）、64.5%（876/1359）、70.5%（285/404）和41.1%（199/484）提供了生化妊娠、临床妊娠、持续妊娠和活产的定义。在876个临床妊娠定义中，63.4%（n = 555）明确了妊娠确认时间。在报告孕周（4至16周）的220个定义中，最常见的截止值是6周，48.2%（n = 106）的病例使用该值。对于持续妊娠的定义，285个定义中有96.1%（n = 274）包括了孕周（6至32周），其中12周是最常用的截止值，49.1%（n = 140）的定义使用该值。在199个活产定义中，62.3%（n = 124）使用了孕周阈值（20至37周），其中24周是最常用的截止值，28.6%（n = 57）的试验使用该值。
局限性、注意事项：由于我们需要提取大量数据，我们使用了文本挖掘并辅以人工数据提取。虽然我们优化了文本挖掘算法以试图识别所有类型的结局定义，并手动整理所有提取的定义，但在不到10%的随机检查研究中仍遗漏了定义，这是本研究的一个局限性。我们仅描述了已发表随机对照试验中的定义模式，我们的结果不能外推至未发表的随机对照试验。
尽管长期以来一直建议在不孕症试验中报告活产情况，但在过去十年中只有三分之一的随机对照试验这样做了。这凸显了所倡导的结局与研究人员报告内容之间的脱节。我们观察到一个令人鼓舞 的趋势，即报告活产的试验比例一直在持续上升。此外，妊娠定义的严重缺乏和变异性凸显了推广和采用标准化妊娠结局的紧迫性。
研究资金/利益冲突：本研究未获得资金支持。Q.F.报告获得默克公司的博士奖学金。B.W.M.得到澳大利亚国家卫生与医学研究委员会（NHMRC）的研究员资助（GNT1176437）。B.W.M.报告从默克公司获得咨询、差旅支持和研究资金，并为欧加农公司和诺金公司提供咨询服务。B.W.M.持有ObsEva公司的股票。W.T.L.得到NHMRC的研究员资助（GTN20167）。W.L.L.报告获得中国国家留学基金管理委员会的博士奖学金。T.D.H和S.L.是德国达姆施塔特默克医疗保健有限公司的员工。R.W.得到NHMRC的研究员资助（GTN）。其他作者声明无利益冲突。
CRD42024498624
