Quantitative ultramorphological analysis of human sperm: fifteen years of experience in the diagnosis and management of male factor infertility

Abstract

The advantages of quantitative ultramorphological (QUM) sperm analysis in the diagnosis and treatment of male infertility are presented. The QUM methodology is based on three elements: complementary scanning electron microscopy and transmission electron microscopy observations of 7 sperm cell subcellular organelles (acrosome, postacrosomal lamina, nucleus, neck, axoneme, mitochondrial sheath, and outer dense fibers); systematic classification of the specific ultramorphological malformations into 4 pathological and the normal categories, indicating the morphological state of each subcellular organelle; and comparison between well-defined reference groups with opposite fertility status or treatment conditions. QUM has established 2 indices for the in vivo and in vitro male fertility potential: (1) Natural Fertility Index (NFI), with accurate prediction (97% sensitivity and 90% specificity) of 80% of the male patients; and (2) IVF score, with prediction of 76% of the nonfertilizing and 90% of fertilizing IVF groups. QUM has enabled assessment of ultramorphological indications for varicocele and radiation exposure. Varicocele causes defects in sperm head organelles related to early spermatid development, whereas ionizing radiation causes amorphous head shape. QUM established criteria for specific non-in-vitro therapeutic interventions, including varicocelectomy, follicle-stimulating hormone (FSH) administration, and acupuncture. The varicocele index enabled correct classification of 79 and 89% of patients with and without varicocele. Males with idiopathic impairment of sperm acrosome and nucleus are potential responders to FSH treatment, whereas patients exhibiting low sperm activity are candidates for acupuncture treatment. Patients with a low Natural Fertility Index are recommended for an assisted reproduction technique (ART). based on the ultramorphology of the tail axoneme. Patients who achieved pregnancy following intrauterine insemination or in vitro fertilization and those whose wives conceived only following intracytoplasmic sperm injection were classified with accuracy of 78 and 74%, respectively. QUM sperm analysis is clinically informative, nontraumatic, and cost-effective, and is recommended when the male infertility factor cannot be clearly diagnosed by routine tests prior to first ART trial.