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

全世界每六对夫妇中就有一对在与不孕症作斗争。卵胞浆内单精子注射（ICSI）是一种广泛用于治疗不育夫妇的手术，是一种选择单个精子并用微小的尖锐玻璃管注射到卵子中的技术。在用于ICSI的单个精子中存在精子DNA损伤或片段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？如果我们进行标准测试来评估DNA完整性，目前，精子必须在过程中被破坏，不能用于ICSI。自1992年ICSI技术发明以来，单精子的选择一直是由胚胎学家通过显微镜观察单精子的运动能力和形态来进行的，这涉及到很大的主观性和不一致性。目前，还没有技术能够非侵入性地量化单个精子的运动性和形态，或者将这些测量与DNA完整性相关联。该项目旨在开发第一种用于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。这些精确测量的单个精子的特征将与同一精子的DNA片段相关联。这些数据将用于建立机器学习模型，使用个体精子的运动力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，以最终提高接受IVF治疗的患者的妊娠率和后代的健康。

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.