Assisted Sperm Fusion Insemination: A Fusion-Based Approach to Fertilization Without Mechanical Oolemma Penetration

Intracytoplasmic sperm injection (ICSI) is widely used in assisted reproductive technology and achieves fertilization by directly injecting a spermatozoon into the oocyte cytoplasm. However, it requires deliberate disruption of the oolemma and bypasses physiological sperm-oocyte membrane fusion. Assisted sperm fusion insemination (ASFI) was developed to achieve fertilization through gamete membrane fusion without penetrating the oolemma.

This review summarizes the biological basis of sperm fusion competence, including acrosomal exocytosis, zona pellucida interaction, and molecular mechanisms of gamete membrane fusion, and reviews the development, technical procedure, clinical evidence, and current limitations of ASFI.

ASFI uses motile zona pellucida-bound spermatozoa that are recovered and pressed against the oolemma to facilitate membrane adhesion and fusion. Clinical studies have demonstrated fertilization, blastocyst development, and live birth after ASFI. In a prospective sibling-oocyte study, ASFI achieved a higher normal fertilization rate than conventional ICSI (88.0% vs. 70.2%), with no oocyte degeneration (0% vs. 8.8%) and a higher usable embryo rate per MII oocyte (45.8% vs. 28.1%).

ASFI provides a fusion-based alternative to direct sperm injection and may reduce procedure-related oocyte degeneration. Further studies are required to establish zona-independent sperm selection, technical standardization, and reproducibility across centers.