SISMER, Reproductive Medicine Unit, via Mazzini 12, Bologna 40138, Italy.
Hum Reprod. 2013 May;28(5):1210-20. doi: 10.1093/humrep/det030. Epub 2013 Mar 5.
Is it feasible to identify factors that significantly affect the clinical outcome of IVF-ICSI cycles and use them to reliably design a predictor of implantation?
The Bayesian network (BN) identified top-history embryos, female age and the insemination technique as the most relevant factors for predicting the occurrence of pregnancy (AUC, area under curve, of 0.72). In addition, it could discriminate between no implantation and single or twin implantations in a prognostic model that can be used prospectively.
The key requirement for achieving a single live birth in an IVF-ICSI cycle is the capacity to estimate embryo viability in relation to maternal receptivity. Nevertheless, the lack of a strong predictor imposes several restrictions on this strategy.
STUDY DESIGN, SIZE, DURATION: Medical histories, laboratory data and clinical outcomes of all fresh transfer cycles performed at the International Institute for Reproductive Medicine of Lugano, Switzerland, in the period 2006-2008 (n = 388 cycles), were retrospectively evaluated and analyzed.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were unselected for age, sperm parameters or other infertility criteria. Before being admitted to treatment, uterine anomalies were excluded by diagnostic hysteroscopy. To evaluate the factors possibly related to embryo viability and maternal receptivity, the class variable was categorized as pregnancy versus no pregnancy and the features included: female age, number of previous cycles, insemination technique, sperm of proven fertility, the number of transferred top-history embryos, the number of transferred top-quality embryos, the number of follicles >14 mm and the level of estradiol on the day of HCG administration. To assess the classifier, the indicators of performance were computed by cross-validation. Two statistical models were used: the decision tree and the BN.
The decision tree identified the number of transferred top-history embryos, female age and the insemination technique as the features discriminating between pregnancy and no pregnancy. The model achieved an accuracy of 81.5% that was significantly higher in comparison with the trivial classifier, but the increase was so modest that the model was clinically useless for predictions of pregnancy. The BN could more reliably predict the occurrence of pregnancy with an AUC of 0.72, and confirmed the importance of top-history embryos, female age and insemination technique in determining implantation. In addition, it could discriminate between no implantation, single implantation and twin implantation with the AUC of 0.72, 0.64 and 0.83, respectively.
LIMITATIONS, REASONS FOR CAUTION: The relatively small sample of the study did not permit the inclusion of more features that could also have a role in determining the clinical outcome. The design of this study was retrospective to identify the relevant features; a prospective study is now needed to verify the validity of the model.
The resulting predictive model can discriminate with reasonable reliability between pregnancy and no pregnancy, and can also predict the occurrence of a single pregnancy or multiple pregnancy. This could represent an effective support for deciding how many embryos and which embryos to transfer for each couple. Due to its flexibility, the number of variables in the predictor can easily be increased to include other features that may affect implantation.
STUDY FUNDING/COMPETING INTERESTS: This study was supported by a grant, CTI Medtech Project Number: 9707.1 PFLS-L, Swiss Confederation. No competing interests are declared.
是否可以确定对 IVF-ICSI 周期的临床结果有显著影响的因素,并利用这些因素可靠地设计出一种着床预测器?
贝叶斯网络(BN)确定了顶级胚胎、女性年龄和授精技术是预测妊娠(AUC,曲线下面积为 0.72)发生的最相关因素。此外,它还可以在一个可以前瞻性使用的预后模型中区分无着床和单胎或双胎着床。
在 IVF-ICSI 周期中实现单次活产的关键要求是评估胚胎在与母体接受性方面的活力的能力。然而,缺乏强有力的预测器对这一策略施加了若干限制。
研究设计、规模、持续时间:对 2006 年至 2008 年期间在瑞士洛迦诺国际生殖医学研究所进行的所有新鲜转移周期的医疗记录、实验室数据和临床结果(n=388 个周期)进行了回顾性评估和分析。
参与者/材料、设置、方法:患者未按年龄、精子参数或其他不孕标准进行选择。在接受治疗之前,通过诊断性宫腔镜排除子宫异常。为了评估可能与胚胎活力和母体接受性相关的因素,类别变量被归类为妊娠与非妊娠,特征包括:女性年龄、以前的周期数、授精技术、已证明有生育能力的精子、转移的顶级胚胎数量、转移的顶级优质胚胎数量、>14mm 的卵泡数量和 HCG 给药日的雌二醇水平。为了评估分类器,通过交叉验证计算了性能指标。使用了两种统计模型:决策树和 BN。
决策树确定了转移的顶级胚胎数量、女性年龄和授精技术是区分妊娠和非妊娠的特征。该模型的准确率为 81.5%,与简单分类器相比显著提高,但提高幅度如此之小,以至于该模型在预测妊娠方面临床应用价值不大。BN 可以更可靠地预测妊娠的发生,AUC 为 0.72,并证实了顶级胚胎、女性年龄和授精技术在决定着床方面的重要性。此外,它还可以分别以 AUC 为 0.72、0.64 和 0.83 的准确率区分无着床、单着床和双着床。
局限性、谨慎的原因:该研究的样本量相对较小,无法纳入可能也会影响临床结果的更多特征。本研究的设计是回顾性的,旨在确定相关特征;现在需要进行前瞻性研究来验证该模型的有效性。
由此产生的预测模型可以合理可靠地区分妊娠和非妊娠,还可以预测单胎妊娠或多胎妊娠的发生。这可能为决定每个夫妇要转移多少个胚胎和哪些胚胎提供有效的支持。由于其灵活性,预测器中的变量数量可以很容易地增加,以包括可能影响着床的其他特征。
研究资金/利益冲突:本研究由 CTI Medtech 项目资助,瑞士联邦号 9707.1 PFLS-L。没有利益冲突。