Houghton Franchesca D, Hawkhead Judith A, Humpherson Peter G, Hogg Jan E, Balen Adam H, Rutherford Anthony J, Leese Henry J
Department of Biology, University of York, PO Box 373, York YO10 5YW, UK.
Hum Reprod. 2002 Apr;17(4):999-1005. doi: 10.1093/humrep/17.4.999.
IVF is limited by low success rates and a confounding high multiple birth rate contributing to prematurity, increased neonatal mortality and child handicap. These problems could be overcome if single embryos of known developmental competence could be selected for transfer on day 2/3 of development, but current methods, which rely on morphological appearance, are poor predictors of viability.
We have measured non-invasively the depletion/appearance (i.e. turnover) of a physiological mixture of 18 amino acids by single human embryos during in-vitro culture using high performance liquid chromatography.
From the time of transfer (day 2/3), embryos with future competence to develop to the blastocyst stage (day 5/6) exhibit amino acid flux patterns distinct from those of embryos with similar morphological appearance which arrest. Significantly, the profiles of Ala, Arg, Gln, Met and Asn flux predict blastocyst potentiality at >95%. The amino acid most consistently depleted throughout development by those embryos which form blastocysts was leucine. Of the amino acids which were produced, the most striking was alanine, which appeared in increasing amounts throughout development.
Non-invasive amino acid profiling has the potential to select developmentally competent single embryos for transfer, thereby increasing the success rate and eliminating multiple births in IVF.
体外受精(IVF)受限于低成功率以及令人困扰的高多胎出生率,后者会导致早产、新生儿死亡率增加和儿童残疾。如果能够挑选出已知发育能力的单个胚胎在发育的第2/3天进行移植,这些问题或许可以得到解决,但目前依赖形态外观的方法对胚胎存活能力的预测效果不佳。
我们使用高效液相色谱法,在体外培养过程中对单个人类胚胎非侵入性地测量了18种氨基酸的生理混合物的消耗/出现情况(即周转率)。
从移植时间(第2/3天)起,未来有能力发育到囊胚阶段(第5/6天)的胚胎,其氨基酸通量模式与形态外观相似但发育停滞的胚胎不同。值得注意的是,丙氨酸、精氨酸、谷氨酰胺、蛋氨酸和天冬酰胺的通量模式预测囊胚发育潜力的准确率超过95%。在发育过程中,形成囊胚的胚胎最持续消耗的氨基酸是亮氨酸。在产生的氨基酸中,最显著的是丙氨酸,其在整个发育过程中含量不断增加。
非侵入性氨基酸分析有潜力挑选出发育能力良好的单个胚胎进行移植,从而提高体外受精的成功率并避免多胎生育。