Noninvasive amino acid turnover predicts human embryo aneuploidy

Abstract

Assisted reproduction technology has two significant problems: low success rates and multiple pregnancies. Because of these problems, the priority in IVF clinics is to develop a potential diagnostic test that can be used to select the embryos with the ultimate developmental competence. Aneuploidy screening as embryo selection criteria will ensure that the transferred embryos are euploid and high implantation rate. We hypothesize that aneuploidy in human preimplantation embryos could be discriminated by their amino acid metabolism profile in the spent culture media. Preimplantation genetic testing for aneuploidy results and spent embryo culture medium amino acid content were analyzed for 58 couples. The next-generation sequencing technique was used and coupled with TE biopsy. Forty euploid and 71 aneuploid blastocysts were evaluated. Embryos were cultured individually until day 5 or 6 of embryo development. Spent culture medium was collected after finishing the culture. There was no statistical difference between D3 and D5 embryo morphology between euploid and aneuploid embryos (p > .05). Eight amino acids, including SER, GLY, HIS, ARG, THR, ALA, PRO, and TYR, were detected in the culture medium from the blank control group, euploid group, and aneuploid group. Only TYR amino acid concentration was found significantly higher in the aneuploid group compared to the euploid group (p < .003). Tyrosine amino acid levels equal to and above 76.38 µmol/L could be considered aneuploid. Aneuploid embryos demonstrate altered amino acid turnover in vitro relative to euploid counterparts. A noninvasive method of amino acid profiling will be of value as a tool for routine preimplantation embryo selection among all patient groups.

摘要

辅助生殖技术有两个重大问题：成功率低和多胎妊娠。由于这些问题, 辅助生殖诊所的首要任务是开发一种诊断性预测手段, 用于选择具有最终发育能力的胚胎。非整倍体筛选作为胚胎选择的标准将确保移植胚胎是整倍体和高着床率。本研究假设, 人类植入前胚胎中的非整倍体可以通过其在废培养基中的氨基酸代谢谱来区分。本研究纳入58对夫妇的非整倍体植入前遗传学检测结果和废胚胎培养基氨基酸含量进行了分析。采用下一代测序技术, 并结合TE活检。评估了40个整倍体囊胚和71个非整倍体囊胚。胚胎分别培养至胚胎发育第5天或第6天。培养结束后收集废培养基。整倍体和非整倍体胚胎D3和D5胚胎形态差异无统计学意义（p>0.05）。在空白对照组、整倍体组和非整倍体组的培养基中检测到8种氨基酸, 包括丝氨酸（SER）、甘氨酸（GLY）、组氨酸（HIS）、精氨酸（ARG）、苏氨酸（THR）、丙氨酸（ALA）、脯氨酸（PRO）和酪氨酸（TYR）。与整倍体组相比, 非整倍体组中只有酪氨酸氨基酸浓度显著高于整倍体组（p<0.003）。酪氨酸氨基酸水平等于或高于76.38 mmol /L可视为非整倍体。非整倍体胚胎在体外相对于整倍体胚胎表现出氨基酸周转的改变。一种非侵入性的氨基酸分析方法对于所有患者群体的常规植入前胚胎选择具有重要价值。

Keywords:

• Aneuploidy; amino acid turnover; embryo culture media

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Funding

The author(s) reported there is no funding associated with the work featured in this article.