In 1999, a 36-year-old woman in Australia decided to try in vitro fertilization after seven years of attempting to become pregnant. Doctors stimulated her ovaries with hormone shots, performed minor surgery to harvest eggs, which were fertilized in a petri dish and then transferred into her uterus. In four separate attempts, a total of eight embryos made from this same batch of eggs were transferred into her body. All failed to implant.The woman opted to try again. Researchers at her fertility clinic, Melbourne IVF, made nine new embryos but this time decided to check the chromosomes in each one. Nearly all embryos with too few or too many copies of some chromosome-rather than the normal complement of 23 pairs-will fail to implant or will miscarry shortly after implantation. (Down’s syndrome, by far the most common such abnormality among surviving infants, is caused by three copies of chromosome 21.) To assess the chromosomes, a team of scientists led by geneticist Leeanda Wilton removed one cell from each three-day-old embryo. To each cell they added fragments of DNA-labeled with fluorescent tags-that bound to complementary sequences on the five chromosomes most susceptible to abnormalities. The tags showed that all but two of the removed cells had either an extra or a missing copy of a chromosome. The researchers then transferred the two seemingly normal embryos. Neither took.
The woman went through yet a third cycle. This time, Wilton and her coworkers, taking no chances, turned to a new technique called comparative genomic hybridization to analyze each embryo’s entire set of chromosomes. Only one of the five embryos appeared normal-chromosomally speaking. “It wasn’t a particularly great-looking embryo,” Wilton says. Still, the lone normal embryo was transferred. Nine months later, the woman gave birth to a healthy daughter.
So-called preimplantation genetic diagnosis is now common practice at dozens of in vitro fertilization clinics around the world. The procedure, which was introduced in the early 1990s as a way to determine whether an embryo had inherited the genes that cause fatal diseases such as cystic fibrosis and Huntington’s, can now identify more than 50 different genetic diseases. And as the Australian case demonstrates, the technology is playing an ever expanding role in the success of fertility clinics, allowing physicians to detect severe chromosomal abnormalities and carefully choose embryos for implantation.
But this flood of new genetic information on the unborn is reaching far beyond the world of in vitro fertilization clinics. Amniocentesis and chorionic villus sampling, the two techniques that since the 1970s have been mainstays in the diagnosis of chromosomal problems in fetuses, both now incorporate a panoply of tests for inherited genetic diseases. At the same time, researchers are developing safer, noninvasive means of assessing fetal health, two of which have made inroads in clinics around the world: ultrasound screening of body features associated with genetic abnormalities, and blood tests for proteins and hormones that are markers for Down’s syndrome and other diseases.
All of these new tests vary in risk or usefulness, and some remain highly controversial. Yet they all serve the same purpose: to provide parents with the information needed to select an embryo or to determine the fate of a fetus on the basis of its genetic makeup. “The changes to come are going to be even more profound as we get into more sophisticated genetic testing,” says Rebecca Smith-Bindman, a radiologist at the University of California, San Francisco.