Dhillon R K, McLernon D J, Smith P P, Fishel S, Dowell K, Deeks J J, Bhattacharya S, Coomarasamy A
School of Clinical and Experimental Medicine, University of Birmingham, Academic department, Birmingham Women's Hospital, Birmingham B15 2TG, UK
Division of Applied Health Sciences, School of Medicine and Dentistry, Foresterhill, Aberdeen AB25 2ZD, UK.
Hum Reprod. 2016 Jan;31(1):84-92. doi: 10.1093/humrep/dev268. Epub 2015 Oct 25.
Which pretreatment patient variables have an effect on live birth rates following assisted conception?
The predictors in the final multivariate logistic regression model found to be significantly associated with reduced chances of IVF/ICSI success were increasing age (particularly above 36 years), tubal factor infertility, unexplained infertility and Asian or Black ethnicity.
The two most widely recognized prediction models for live birth following IVF were developed on data from 1991 to 2007; pre-dating significant changes in clinical practice. These existing IVF outcome prediction models do not incorporate key pretreatment predictors, such as BMI, ethnicity and ovarian reserve, which are readily available now.
STUDY DESIGN, SIZE, DURATION: In this cohort study a model to predict live birth was derived using data collected from 9915 women who underwent IVF/ICSI treatment at any CARE (Centres for Assisted Reproduction) clinic from 2008 to 2012. Model validation was performed on data collected from 2723 women who underwent treatment in 2013. The primary outcome for the model was live birth, which was defined as any birth event in which at least one baby was born alive and survived for more than 1 month.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from 12 fertility clinics within the CARE consortium in the UK. Multivariable logistic regression was used to develop the model. Discriminatory ability was assessed using the area under receiver operating characteristic (AUROC) curve, and calibration was assessed using calibration-in-the-large and the calibration slope test.
The predictors in the final model were female age, BMI, ethnicity, antral follicle count (AFC), previous live birth, previous miscarriage, cause and duration of infertility. Upon assessing predictive ability, the AUROC curve for the final model and validation cohort was (0.62; 95% confidence interval (CI) 0.61-0.63) and (0.62; 95% CI 0.60-0.64) respectively. Calibration-in-the-large showed a systematic over-estimation of the predicted probability of live birth (Intercept (95% CI) = -0.168 (-0.252 to -0.084), P < 0.001). However, the calibration slope test was not significant (slope (95% CI) = 1.129 (0.893-1.365), P = 0.28). Due to the calibration-in-the-large test being significant we recalibrated the final model. The recalibrated model showed a much-improved calibration.
LIMITATIONS, REASONS FOR CAUTION: Our model is unable to account for factors such as smoking and alcohol that can affect IVF/ICSI outcome and is somewhat restricted to representing the ethnic distribution and outcomes for the UK population only. We were unable to account for socioeconomic status and it may be that by having 75% of the population paying privately for their treatment, the results cannot be generalized to people of all socioeconomic backgrounds. In addition, patients and clinicians should understand this model is designed for use before treatment begins and does not include variables that become available (oocyte, embryo and endometrial) as treatment progresses. Finally, this model is also limited to use prior to first cycle only.
To our knowledge, this is the first study to present a novel, up-to-date model encompassing three readily available prognostic factors; female BMI, ovarian reserve and ethnicity, which have not previously been used in prediction models for IVF outcome. Following geographical validation, the model can be used to build a user-friendly interface to aid decision-making for couples and their clinicians. Thereafter, a feasibility study of its implementation could focus on patient acceptability and quality of decision-making.
STUDY FUNDING/COMPETING INTEREST: None.
哪些预处理患者变量对辅助受孕后的活产率有影响?
最终多变量逻辑回归模型中的预测因素显示,与体外受精/卵胞浆内单精子注射(IVF/ICSI)成功率降低显著相关的因素包括年龄增长(尤其是36岁以上)、输卵管因素不孕症、不明原因不孕症以及亚洲或黑人种族。
用于预测IVF后活产的两个最广泛认可的预测模型是基于1991年至2007年的数据开发的;早于临床实践的重大变化。这些现有的IVF结局预测模型没有纳入关键的预处理预测因素,如体重指数(BMI)、种族和卵巢储备,而这些因素现在很容易获得。
研究设计、规模、持续时间:在这项队列研究中,使用从2008年至2012年在任何一家辅助生殖中心(CARE)诊所接受IVF/ICSI治疗的9915名女性收集的数据推导了一个预测活产的模型。对2013年接受治疗的2723名女性收集的数据进行了模型验证。该模型的主要结局是活产,定义为至少有一个婴儿存活且存活超过1个月的任何分娩事件。
参与者/材料、环境、方法:从英国CARE联盟内的12家生育诊所收集数据。使用多变量逻辑回归来开发模型。使用受试者操作特征(AUROC)曲线下面积评估判别能力,并使用大样本校准和校准斜率检验评估校准情况。
最终模型中的预测因素为女性年龄、BMI、种族、窦卵泡计数(AFC)、既往活产、既往流产、不孕原因和不孕持续时间。在评估预测能力时,最终模型和验证队列中的AUROC曲线分别为(0.62;95%置信区间(CI)0.61 - 0.63)和(0.62;95%CI 0.60 - 0.64)。大样本校准显示对活产预测概率存在系统性高估(截距(95%CI)= -0.168(-0.252至-0.084),P < 0.001)。然而,校准斜率检验不显著(斜率(95%CI)= 1.129(0.893 - 1.365),P = 0.28)。由于大样本校准检验显著,我们对最终模型进行了重新校准。重新校准后的模型显示校准有了很大改善。
局限性、谨慎原因:我们的模型无法考虑可能影响IVF/ICSI结局的因素,如吸烟和饮酒,并且在一定程度上仅限于代表英国人群的种族分布和结局。我们无法考虑社会经济地位,而且可能由于75%的人群为其治疗支付私人费用,结果不能推广到所有社会经济背景的人群。此外,患者和临床医生应明白,此模型设计用于治疗开始前,不包括治疗过程中出现的变量(卵母细胞、胚胎和子宫内膜)。最后,该模型也仅限于仅在第一个周期之前使用。
据我们所知,这是第一项提出一个新颖、最新模型的研究,该模型包含三个易于获得的预后因素;女性BMI、卵巢储备和种族,这些因素以前未用于IVF结局的预测模型。经过地理验证后,该模型可用于构建一个用户友好的界面,以帮助夫妇及其临床医生进行决策。此后,对其实施的可行性研究可侧重于患者的可接受性和决策质量。
研究资金/利益冲突:无。