In-Vitro Fertilization
The first baby conceived by in-vitro fertilization (IVF) was born in England in 1978. Since then, more than 3,000 babies conceived in this way have been born. The term in vitro literally means "in glass"; the fertilization takes place outside the body in a glass petri dish. The term is used in contrast to in-vivo--"in the living body"--fertilization. In vitro fertilization is indicated when women have no functional Fallopian tubes, the male cannot produce enough sperm to fertilize an egg in vivo, premature menopause (which requires an egg from a donor), and other infertility problems. IVF is made up of four major steps: Development (maturation) of the egg while still in the ovary; retrieving the egg upon its release; fertilizing the egg and growing it to the embryonic stage; and transferring the embryo into the uterus.
Early attempts at IVF were made over a century ago, with successful rabbit embryo transfer carried out by Walter Heape in England. Gregory Pincus (1903-1967) and Enzmann performed further IVF experiments in the 1930s. An editorial in the New England Journal of Medicine in 1937 suggested IVF as a treatment for infertility in women. Although human IVF experiments were carried out in the 1940s and 1950s by John Rock, Menkin, and Landrum Shettles, knowledge of reproductive physiology was too limited for the IVF procedures to be successful. Then it was discovered that sperm had to undergo capacitation--changes in the plasma membrane--after ejaculation in order to be capable of fertilization, and that the oocyte (egg) also is not ready for fertilization until just before ovulation occurs. Armed with this knowledge, researchers successfully fertilized rabbit oocytes in vitro. Min-Chueh Chang went a step further and implanted in vitro fertilized oocytes into female rabbits. IVF for many other species followed.
The final advance was made by British physicians Robert Edwards and Patrick Steptoe, who began collaborating in 1968. They developed a method of stimulating ovulation with hormone treatment, then retrieving the nearly mature ova and placing them in culture for the several hours needed for full maturation. Meanwhile, a fresh specimen of male sperm was treated so it underwent capacitation, then it was added to the oocytes in the petri dish, where fertilization took place. After undergoing initial division, the eight-celled embryo was introduced into the woman's uterus, where, in successful IVF procedures, it would implant. An English couple underwent this IVF procedure and, in 1978, Louise Brown--the first human baby conceived outside the womb--was born. Since then, IVF has become a widely used method of infertility treatment, offered by hundreds of medical centers around the world. Since the mid-1980s, cryopreservation (freezing) of embryos has become common as a way of saving extra fertilized eggs in the event the initial IVF attempt fails. Thorny legal and ethical questions have resulted, however, dramatized by the 1984 plane crash death of a husband and wife who left behind cyropreserved embryos in Australia. Who has the right to dispose of cyropreserved embryos? How long can they be stored? Who owns them? Is an embryo an heir of its parents?
Several variations on IVF are also an option: One is gamete intrafallopian transfer (GIFT), in which oocytes and sperm are gathered and prepared as in IVF but are placed into the fallopian tube, uniting there rather than in the petri dish. Another is zygote intrafallopian transfer (ZIFT) in which one or more zygotes--fertilized eggs before they start to divide--are transferred to the fallopian tubes. Because they are invasive and expensive, and because higher pregnancy rates are being obtained with three-day uterine transfer, these methods have widely been abandoned.
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