Fertilization normally occurs within the ampullary portion of the fallopian tubes. During the middle of the female menstrual cycle the cervical mucus changes, becoming more abundant and watery. These changes facilitate the entry of sperm into the uterus and protect the sperm from the highly acidic vaginal secretions. Within the female reproductive tract, sperm undergo physiologic changes, generally referred to as capacitation. After sperm contact with the egg, a new type of flagellar motion is initiated, termed hyperactive motility, characterized by large, lashing motions of the sperm tail. Sperm release lytic enzymes from the acrosome region to help penetrate the egg investments, termed the acrosome reaction. Direct contact between the sperm and egg appears to be mediated by specific receptors on the surface of each gamete. As a result of the interactions and changes, the sperm is incorporated into the cytoplasm of the egg.

After penetration of the egg, a “zona reaction” occurs in which the zona pellucida becomes impenetrable to more sperm, providing a block to polyspermy. In addition, the egg resumes its meiosis and begins to form a metaphase II spindle. The sperm centriole within the midpiece is crucial for early spindle formation within the fertilized egg.