The union of sperm and egg constitutes fertilization. The apparent simplicity and frequency of this phenomenon belie the complexity of the process. For fertilization to be accomplished, appropriate maturation of an oocyte in a dominant follicle must occur, ovulation must successfully release the egg, and sperm capable of fertilization must be present in adequate numbers. Even all of these events are not sufﬁcient to accomplish either fertilization or pregnancy.
Following ovulation, the egg is picked up by the ﬁmbrial end of the fallopian tube for transport to the uterine cavity. When the egg enters the fallopian tube, it is surrounded by a cumulus of granulosa cells and intimately surrounded by a clear zona pellucida. Within the zona pellucida are both the egg (in metaphase II stage) and the ﬁrst polar body. Meanwhile, spermatozoa are transported through the cervical mucus and the uterus and into the fallopian tubes. During this transport period, the sperm undergo two changes: capacitation and acrosome reaction. These changes activate enzyme systems within the sperm head and make it possible for the sperm to cross the cumulus and the zona pellucida.
Once sperm and egg encounter each other (generally in the ampulla of the fallopian tube), the sperm are attracted to an egg through chemotaxis, made possible by capacitation of the sperm and binding of progesterone to a surface receptor on the sperm. These increase sperm motility, helping them pass the barrier of the cumulus and zona pellucida, where the sperm attaches to the cell membrane of the egg and enters the cytoplasm. When the sperm enters the cytoplasm, intracytoplasmic structures, the coronal granules, arrange themselves in an orderly fashion around the outermost portion of the cytoplasm just beneath the cytoplasmic membrane, and the sperm head swells and gives rise to the male pronucleus. Under this stimulus, the egg completes its second meiotic division, casting off the second polar body to a position also beneath the zona pellucida. The pronuclei, which contain the haploid sets of chromosomes of maternal and paternal origin, do not fuse, but the nuclear membranes surrounding them disappear, and the chromosomes arrange themselves on the developing spindle for the ﬁrst mitotic division. In this way, the diploid complement of chromosomes is rees-tablished, completing the process of fertilization.
Over the course of 20 hours following the attachment of the chromosomes to the spindle, cell division (cleavage) occurs, giving rise to the two-cell embryo. A signiﬁcant number of fertilized ova do not complete cleavage for a number of reasons, including failure of chromosome arrangement on the spindle, speciﬁc gene defects that prevent the formation of the spindle, and environmental factors.
Over the course of 3 to 4 days, the dividing cell mass passes down the fallopian tube toward the endometrial cavity. Early trophoblastic cells formed during the blastula stage of development digest away the zona pellucida to allow the embryo to burrow into the thickened endometrium. Implantation of the embryo generally takes place about 3 days after the embryo enters the uterine cavity. Through most of this process, exposure to toxic agents (teratogens or radiation) is usually either completely destructive or causes little or no effect. Twinning may occur at any time from the two-cell stage until th formation of the blastula just prior to implantation.