Deep Learning-based Automated Rare Sperm Identification from Testes Biopsies

Non-obstructive azoospermia (NOA), the most severe form of male infertility, is currently treated using microsurgical sperm extraction (microTESE) to retrieve sperm cells for in vitro fertilization via intracytoplasmic sperm injection (IVF-ICSI). The success rate of this procedure for NOA patients is currently limited by the ability of andrologists to identify a few rare sperm cells among millions of background testis cells. To improve this success rate, we developed a convolution neural network (CNN) to detect rare sperm from low-resolution microscopy images of microTESE samples. Our CNN uses the U-Net architecture to perform pixel-based classification on image patches from brightfield microscopy, which is followed by morphological analysis to detect individual sperm instances. This CNN is trained using microscopy images of fluorescently labeled sperm, which is fixed to eliminate their motility, and doped into testis biopsies obtained from NOA patients. We initially tested this algorithm using purified sperm samples at different imaging magnifications in order to determine the upper bounds of performance. We then tested this algorithm by doping rare sperm cells into testis biopsy samples from NOA patients and found a sperm detection F1 score of 85.2%. These results demonstrate the potential to use automated microscopy to dramatically increase the amount of testis biopsy tissue that could be comprehensively examined, which greatly increases the chance of finding rare viable sperm, and thereby increases the success rates of IVF-ICSI for couples with NOA.