Failed Fertilization in ART: What are the Causes and Methods to Improve Fertilization

Abstract

Introduction of clinical ICSI made a revolution in achieving higher fertilization in ART programs. However, ICSI does not completely eliminate the risk of fertilization failure as total fertilization failure (TFF) occurs in 1-3% of ICSI cycles. TFF leads to unexpected premature termination of the ART treatment, inflicting a substantial psychological and financial burden on patients. The potential reasons for TFF include inability of the oocyte to activate the cascade of fertilization events, suboptimal oocytes or sperm quality, and technical issues in performing ICSI. Specifically, oocyte-related factors include oocyte cytoplasmic immaturity caused by insufficient protein synthesis or aberrant signalling pathways, spindle abnormalities, and defective proteins involved in fertilization. Sperm-related factors are primarily associated with abnormalities in the structure, expression, and localization pattern of PLC[Formula: see text]. Several laboratory approaches involving pharmacological agents help in activation of the oocytes thereby prevent the fertilization failure. However, as of now, there is no conclusive evidence to demonstrate the benefit of artificial oocyte activation hence, TFF following ICSI remains an ongoing and significant challenge in ART laboratory.