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在接受 IVF/ICSI 周期的女性中,整倍体囊胚的数量和比率强烈依赖于卵巢储备和女性年龄。

The number and rate of euploid blastocysts in women undergoing IVF/ICSI cycles are strongly dependent on ovarian reserve and female age.

机构信息

Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

Clinica Eugin, Modena, Italy.

出版信息

Hum Reprod. 2022 Sep 30;37(10):2392-2401. doi: 10.1093/humrep/deac191.

Abstract

STUDY QUESTION

Can the possibility of having at least one euploid blastocyst for embryo transfer and the total number of euploid blastocysts be predicted for couples before they enter the IVF programme?

SUMMARY ANSWER

Ovarian reserve and female age are the most important predictors of having at least one euploid blastocyst and the total number of euploid blastocysts.

WHAT IS KNOWN ALREADY

The blastocyst euploidy rate among women undergoing ART has already been shown to significantly decrease with increasing female age, and the total number of euploid embryos is dependent on the blastocyst cohort size. However, the vast majority of published studies are based on retrospective analysis of data.

STUDY DESIGN, SIZE, DURATION: This prospective analysis included 847 consecutively enrolled couples approaching their first preimplantation genetic testing for aneuploidies (PGT-A) cycle between 2017 and 2020. Only couples for whom ejaculated sperm was available and women with a BMI of <35 kg/m2 were included in the study. Only the first cycle was included for each patient.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was conducted at an IVF centre where, for all patients, the planned treatment was to obtain embryos at the blastocyst stage for the PGT-A programme. The impact of the following covariates was investigated: a woman's serum AMH level, age, height, weight and BMI and a man's age, height, weight, BMI, sperm volume and sperm motility and morphology. The analysis was performed with a machine learning (ML) approach. Models were fit on the training set (677 patients) and their predictive performance was then evaluated on the test set (170 patients).

MAIN RESULTS AND ROLE OF CHANCE

After ovarian stimulation and oocyte insemination, 40.1% of couples had at least one blastocyst available for the PGT-A. Of 1068 blastocysts analysed, 33.6% were euploid. Two distinct ML models were fit: one for the probability of having at least one euploid blastocyst and one for the number of euploid blastocysts obtained. In the training set of patients, the variable importance plots of both models indicated that AMH and the woman's age are by far the most important predictors. Specifically, a positive association between the outcome and AMH and a negative association between the outcome and female age appeared. Gradient-boosted modelling offers a greater predictive performance than generalized additive models (GAMs).

LIMITATIONS, REASONS FOR CAUTION: The study was performed based on data from a single centre. While this provides a robust set of data with a constant ART process and laboratory practice, the model might be suitable only for the evaluated population, which may limit the generalization of the model to other populations.

WIDER IMPLICATIONS OF THE FINDINGS

ML models indicate that for couples entering the IVF/PGT-A programme, ovarian reserve, which is known to vary with age, is the most important predictor of having at least one euploid embryo. According to the GAM, the probability of a 30-year-old woman having at least one euploid embryo is 28% or 47% if her AMH level is 1 or 3 ng/ml, respectively; if the woman is 40 years old, this probability is 18% with an AMH of 1 ng/ml and 30% with an AMH of 3 ng/ml.

STUDY FUNDING/COMPETING INTEREST(S): This study was supported by an unrestricted grant from Gedeon Richter. The authors declared no conflict of interests.

TRIAL REGISTRATION NUMBER

N/A.

摘要

研究问题

在夫妇进入体外受精(IVF)计划之前,是否可以预测他们至少有一个可用于胚胎移植的整倍体胚胎囊和整倍体胚胎囊的总数?

总结答案

卵巢储备和女性年龄是预测至少有一个整倍体胚胎囊和整倍体胚胎囊总数的最重要指标。

已知情况

已经表明,接受辅助生殖技术(ART)的女性的胚胎囊整倍体率随着女性年龄的增长而显著下降,并且整倍体胚胎的数量取决于胚胎囊队列的大小。然而,绝大多数已发表的研究基于对数据的回顾性分析。

研究设计、大小和持续时间:这项前瞻性分析包括 2017 年至 2020 年间接受胚胎植入前基因检测(PGT-A)的 847 对连续入组的夫妇。仅包括有可用的精液的夫妇和 BMI<35kg/m2的女性纳入研究。每位患者仅纳入第一周期。

参与者/材料、设置、方法:该研究在一个 IVF 中心进行,对于所有患者,计划的治疗方法是在囊胚阶段获得胚胎,用于 PGT-A 计划。研究了以下协变量的影响:女性的血清 AMH 水平、年龄、身高、体重和 BMI,以及男性的年龄、身高、体重、BMI、精子体积和精子活力和形态。使用机器学习(ML)方法进行分析。在训练集(677 名患者)上拟合模型,然后在测试集(170 名患者)上评估其预测性能。

主要结果和机会的作用

在卵巢刺激和卵母细胞授精后,40.1%的夫妇有至少一个胚胎囊可供 PGT-A 使用。在分析的 1068 个胚胎囊中,有 33.6%是整倍体。拟合了两个不同的 ML 模型:一个用于预测至少有一个整倍体胚胎囊的概率,另一个用于预测获得的整倍体胚胎囊的数量。在患者的训练集中,两个模型的变量重要性图都表明 AMH 和女性年龄是迄今为止最重要的预测指标。具体而言,结果与 AMH 呈正相关,与女性年龄呈负相关。梯度提升建模比广义加性模型(GAMs)提供更好的预测性能。

局限性、谨慎的原因:该研究是基于单一中心的数据进行的。虽然这提供了一组具有恒定的 ART 过程和实验室实践的强大数据,但该模型可能仅适用于评估的人群,这可能限制了模型在其他人群中的推广。

研究结果的更广泛影响

ML 模型表明,对于进入 IVF/PGT-A 计划的夫妇来说,卵巢储备是一个重要的预测指标,已知卵巢储备会随着年龄的增长而变化。根据 GAM,如果一个 30 岁的女性 AMH 水平为 1 或 3ng/ml,那么她至少有一个整倍体胚胎的概率分别为 28%或 47%;如果女性 40 岁,那么 AMH 为 1ng/ml 时,这种可能性为 18%,而 AMH 为 3ng/ml 时为 30%。

研究资金/竞争利益:本研究得到 Gedeon Richter 的一项无限制赠款的支持。作者没有声明利益冲突。

试验注册编号

N/A。

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