ICSI with Testicular Sperm in Non-Azoospermic Men: Expert Opinion and Practical Algorithm

Biological RationaleHuman spermatozoa are uniquely vulnerable to reactive oxygen species (ROS) due to limited cytoplasm, abundant polyunsaturated fatty acids in membranes, and highly condensed chromatin with residual nicks.Clinically relevant ROS sources include varicocele, genital tract infection, febrile illness, environmental toxins, metabolic disease, smoking, and advanced paternal age (1, 2).ROS attack lipids and DNA, producing oxidative adducts such as 8-oxo-deoxyguanosine (8-oxo-dG) (3, 4).The OGG1 glycosylase removes 8-oxo-dG, creating an abasic site that, in the absence of downstream base-excision repair machinery-which mature sperm lack-renders DNA susceptible to strand breaks (4, 5).Following fertilization, the oocyte's repair systems must correct paternal lesions before syngamy.When the paternal lesion burden is high or the oocyte's repair reserve is diminished (such as in advanced maternal age and diminished ovarian reserve), incomplete repair may manifest as delayed paternal DNA replication, impaired embryo development, implantation failure, miscarriage, and potentially intergenerational effects (4, 6).Testicular sperm typically carry far less DNA damage than sperm exposed to the epididymis, vas deferens, and ejaculate (4, 7-13).The key factor appears to be the minimization of oxidative stress encountered during transit and after ejaculation (14, 15).This biology and collective data provide a mechanistic basis for preferring testicular sperm-less exposed to post-testicular oxidative stress-in specific clinical contexts.