Center for Reproduction and Genetics, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China.
University of Science and Technology of China, Hefei, 230026, Anhui, P. R. China.
Reprod Biol Endocrinol. 2024 Mar 20;22(1):32. doi: 10.1186/s12958-024-01203-z.
The objective was to construct a model for predicting the probability of recurrent implantation failure (RIF) after assisted reproductive technology (ART) treatment based on the clinical characteristics and routine laboratory test data of infertile patients. A model was developed to predict RIF. The model showed high calibration in external validation, helped to identify risk factors for RIF, and improved the efficacy of ART therapy.
Research on the influencing factors of RIF has focused mainly on embryonic factors, endometrial receptivity, and immune factors. However, there are many kinds of examinations regarding these aspects, and comprehensive screening is difficult because of the limited time and economic conditions. Therefore, we should try our best to analyse the results of routine infertility screenings to make general predictions regarding the occurrence of RIF.
STUDY DESIGN, SIZE, DURATION: A retrospective study was conducted with 5212 patients at the Reproductive Center of the First Affiliated Hospital of USTC from January 2018 to June 2022.
PARTICIPANTS/MATERIALS, SETTING, METHODS: This study included 462 patients in the RIF group and 4750 patients in the control group. The patients' basic characteristics, clinical treatment data, and laboratory test indices were compared. Logistic regression was used to analyse RIF-related risk factors, and the prediction model was evaluated by receiver operating characteristic (ROC) curves and the corresponding areas under the curve (AUCs). Further analysis of the influencing factors of live births in the first cycle of subsequent assisted reproduction treatment in RIF patients was performed, including the live birth subgroup (n = 116) and the no live birth subgroup (n = 200).
(1) An increased duration of infertility (1.978; 95% CI, 1.264-3.097), uterine cavity abnormalities (2.267; 95% CI, 1.185-4.336), low AMH levels (0.504; 95% CI, 0.275-0.922), insulin resistance (3.548; 95% CI, 1.931-6.519), antinuclear antibody (ANA)-positive status (3.249; 95% CI, 1.20-8.797) and anti-β2-glycoprotein I antibody (A-β2-GPI Ab)-positive status (5.515; 95% CI, 1.481-20.536) were associated with an increased risk of RIF. The area under the curve of the logistic regression model was 0.900 (95% CI, 0.870-0.929) for the training cohort and 0.895 (95% CI, 0.865-0.925) for the testing cohort. (2) Advanced age (1.069; 95% CI, 1.015-1.126) was a risk factor associated with no live births after the first cycle of subsequent assisted reproduction treatment in patients with RIF. Blastocyst transfer (0.365; 95% CI = 0.181-0.736) increased the probability of live birth in subsequent cycles in patients with RIF. The area under the curve of the logistic regression model was 0.673 (95% CI, 0.597-0.748).
LIMITATIONS, REASONS FOR CAUTION: This was a single-centre regression study, for which the results need to be evaluated and verified by prospective large-scale randomized controlled studies. The small sample size for the analysis of factors influencing pregnancy outcomes in subsequent assisted reproduction cycles for RIF patients resulted in the inclusion of fewer covariates, and future studies with larger samples and the inclusion of more factors are needed for assessment and validation.
Prediction of embryo implantation prior to transfer will facilitate the clinical management of patients and disease prediction and further improve ART treatment outcomes.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the General Project of the National Natural Science Foundation of China (Nos. 82,201,792, 82,301,871, 81,971,446, and 82,374,212) and the Natural Science Foundation of Anhui Province (No. 2208085MH206). There are no conflicts of interest to declare.
This study was registered with the Chinese Clinical Trial Register (Clinical Trial Number: ChiCTR1800018298 ).
本研究旨在基于不孕患者的临床特征和常规实验室检测数据,构建预测辅助生殖技术(ART)治疗后复发性种植失败(RIF)概率的模型。
对 RIF 影响因素的研究主要集中在胚胎因素、子宫内膜容受性和免疫因素上。然而,这些方面有很多种检查,由于时间和经济条件的限制,综合筛查较为困难。因此,我们应该尽量分析常规不孕检查的结果,以便对 RIF 的发生做出一般预测。
研究设计、规模、持续时间:这是一项回顾性研究,纳入了 2018 年 1 月至 2022 年 6 月在中国科学技术大学附属第一医院生殖中心接受治疗的 5212 例患者,其中 462 例为 RIF 组,4750 例为对照组。比较了患者的基本特征、临床治疗数据和实验室检测指标。采用 logistic 回归分析 RIF 相关的危险因素,并通过接收者操作特征(ROC)曲线及其对应的曲线下面积(AUC)评估预测模型。进一步分析 RIF 患者后续辅助生殖治疗中首次周期活产的影响因素,包括活产亚组(n=116)和无活产亚组(n=200)。
(1)不孕时间延长(1.978;95%CI,1.264-3.097)、宫腔异常(2.267;95%CI,1.185-4.336)、低 AMH 水平(0.504;95%CI,0.275-0.922)、胰岛素抵抗(3.548;95%CI,1.931-6.519)、抗核抗体(ANA)阳性状态(3.249;95%CI,1.20-8.797)和抗β2-糖蛋白 I 抗体(A-β2-GPI Ab)阳性状态(5.515;95%CI,1.481-20.536)与 RIF 风险增加相关。logistic 回归模型的 AUC 曲线在训练队列中的值为 0.900(95%CI,0.870-0.929),在测试队列中的值为 0.895(95%CI,0.865-0.925)。(2)高龄(1.069;95%CI,1.015-1.126)是 RIF 患者后续辅助生殖治疗首次周期无活产的危险因素。囊胚移植(0.365;95%CI=0.181-0.736)增加了 RIF 患者后续周期活产的概率。logistic 回归模型的 AUC 曲线在训练队列中的值为 0.673(95%CI,0.597-0.748)。
局限性、谨慎的原因:这是一项单中心回归研究,其结果需要通过前瞻性大规模随机对照研究进行评估和验证。RIF 患者后续辅助生殖周期妊娠结局影响因素分析的样本量较小,纳入的协变量较少,需要更大样本量和更多因素的研究进行评估和验证。
在移植前预测胚胎着床将有助于患者的临床管理和疾病预测,并进一步提高辅助生殖技术的治疗效果。
研究基金/利益冲突:本研究得到了国家自然科学基金面上项目(Nos. 82,201,792, 82,301,871, 81,971,446, 和 82,374,212)和安徽省自然科学基金(No. 2208085MH206)的支持。没有利益冲突需要声明。
本研究在中国临床试验注册中心注册(临床试验编号:ChiCTR1800018298)。