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通过下一代测序估计胚胎囊胚非整倍体率随年龄的下降:一种新预测模型的建立。

Estimation of age-dependent decrease in blastocyst euploidy by next generation sequencing: development of a novel prediction model.

机构信息

Andrology and Human Reproduction Clinic, ANDROFERT, Campinas, Brazil -

Faculty of Health, Aarhus University, Aarhus, Denmark -

出版信息

Panminerva Med. 2019 Mar;61(1):3-10. doi: 10.23736/S0031-0808.18.03507-3. Epub 2018 Jun 28.

DOI:10.23736/S0031-0808.18.03507-3
PMID:29962186
Abstract

BACKGROUND

We developed a model to estimate the female age-dependent decrease in blastocyst euploidy and the impact of blastocyst cohort size on the likelihood of having at least one euploid blastocyst for transfer.

METHODS

Retrospective analysis of 1296 trophectoderm biopsies by next-generation sequencing analysis from 436 infertile couples undergoing intracytoplasmic sperm injection and preimplantation genetic testing for aneuploidy. A logistic regression model was fit to the data. The dependent and independent variables were embryo genetic status and female age, respectively. The method of fitting was quadratic on age, and the model was validated with cross validation by a data splitting technique.

RESULTS

The decrease in the probability of blastocyst euploidy follows an age-dependent binomial distribution, progressing with every year of female age, from 1.2% to 24.5% in 28-44 years-old women (P<0.0001). The minimum number of blastocysts needed to obtain at least one euploid blastocyst for transfer was computed for different probabilities and female ages. At the age of 28 years, a total of three blastocysts is required to obtain at least one euploid blastocyst with 90% probability, whereas it is 4, 5, 6, 9, 16 and 29 for ages 35, 37, 39, 41, 43, and 45, respectively.

CONCLUSIONS

A novel prediction model estimates the probability of blastocyst euploidy and the number of blastocysts required to obtain at least one euploid embryo for transfer. This new resource based on f emale age and blastocyst cohort size will aid clinicians counsel and plan treatment of infertile couples undergoing IVF/ICSI.

摘要

背景

我们开发了一个模型来估计囊胚整倍体率随女性年龄的下降趋势,以及囊胚队列大小对获得至少一个可移植整倍体囊胚的可能性的影响。

方法

对 436 对接受胞浆内精子注射和胚胎植入前遗传学检测非整倍体的不孕夫妇的 1296 个滋养外胚层活检进行了下一代测序分析的回顾性分析。将逻辑回归模型拟合到数据中。因变量和自变量分别为胚胎遗传状态和女性年龄。年龄的拟合方法为二次方,通过数据分割技术的交叉验证来验证模型。

结果

囊胚整倍体率的下降遵循年龄相关的二项式分布,随着女性年龄的每增加 1 岁而逐渐增加,从 28-44 岁女性的 1.2%到 24.5%(P<0.0001)。为不同的概率和女性年龄计算了获得至少一个可移植整倍体囊胚所需的最小囊胚数量。在 28 岁时,总共需要三个囊胚才能以 90%的概率获得至少一个整倍体囊胚,而在 35、37、39、41、43 和 45 岁时,分别需要 4、5、6、9、16 和 29 个囊胚。

结论

一个新的预测模型估计了囊胚整倍体率和获得至少一个可移植整倍体胚胎所需的囊胚数量。这个基于女性年龄和囊胚队列大小的新资源将有助于临床医生为接受体外受精/胞浆内单精子注射的不孕夫妇提供咨询和治疗计划。

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