A novel system for non-invasive selection of single spermatozoa with high DNA integrity for clinical in vitro fertilization (IVF) - Phase 1 I2I application

全球范围内，每六对夫妇中就有一对与不孕不育作斗争。卵胞浆内单精子注射(ICSI)是一种广泛用于治疗不育夫妇的程序，是一种选择单个精子并将其注射到带有微小锐化玻璃管的卵子中的技术。用于ICSI的单个精子中存在精子DNA损伤或碎裂，会降低受精率并增加流产。我们如何选择DNA完整性最好的精子进行ICSI？如果我们进行标准的测试来评估DNA的完整性，目前，精子必须在这个过程中被销毁，不能用于ICSI。自1992年ICSI发明以来，胚胎学家通过对单个精子的活力和形态进行经验显微镜观察来选择单个精子进行ICSI，这涉及到很大的主观性和不一致性。目前，还没有一种技术能够非侵入性地量化单个精子的活力和形态，或者将这些测量与DNA完整性联系起来。*本项目旨在开发第一种非侵入性选择具有高DNA完整性的单个精子的定量技术。我们正在开发新的计算机视觉显微镜和自动化技术，以全面测量单个活精子的运动和形态参数。然后，这些精确测量的单个精子的特征将与相同精子的DNA碎片相关。这些数据将被用来建立机器学习模型，使用个体精子的运动性和形态特征来预测其DNA完整性。这项新技术将消除目前ICSI精子选择的主观性和不一致性，并标准化选择具有高DNA完整性的单个精子，最终提高接受体外受精治疗的患者的怀孕率和后代的健康。

One in six couples struggles with infertility worldwide. Intracytoplasmic sperm injection (ICSI), a procedure widely used to treat infertile couples, is a technique in which a single sperm is selected and injected into an egg with a tiny sharpened glass tube. The presence of sperm DNA damage or fragmentation in the single sperm used for ICSI lowers the fertilization rates and increases miscarriages. How do we choose the sperm with the best DNA integrity for ICSI? If we perform a standard test to assess the DNA integrity, presently, the sperm has to be destroyed in the process and cannot be used for ICSI. Since the invention of ICSI in 1992, single sperm selection for ICSI has been made by embryologists using empirical microscopic observation of single sperms' motility and morphology, which involves significant subjectivity and inconsistency. Currently, there is no technique capable of non-invasively quantifying both motility and morphology of individual sperms, or to correlate these measures with DNA integrity.****This project aims to develop the first quantitative technology for the non-invasive selection of single sperms with high DNA integrity. We are developing new computer vision microscopy and automation techniques to comprehensively measure motility and morphology parameters of single live sperms. These precisely measured characteristics of individual sperm will then be correlated to the same sperm's DNA fragmentation. The data will be used to establish machine learning models using the individual sperm motility and morphology characteristics to predict its DNA integrity. This new technology will eliminate the current subjectivity and inconsistency of sperm selection for ICSI, and standardize the selection of a single sperm with high DNA integrity to ultimately improve pregnancy rates and the health of offspring for patients undergoing IVF treatment.