BIOPSIES are a pain. When they're medically necessary we put up with them. When they're not, most of us would just as soon remain un-punctured.
When the patient is a 3-day-old embryo, it's especially fair to ask for some evidence of a clear medical benefit.
Pre-implantation genetic diagnosis, or PGD, is a procedure sometimes performed in conjunction with in vitro fertilization to improve the quality of the embryos selected. It entails the careful isolation of one of a 3-day-old embryo's eight or so cells, then analysis of that cell's genetic contents. Based on what is found, IVF patients and doctors can decide which embryos to transfer into the woman's uterus.
Use of PGD has risen exponentially since its inception 17 years ago. In the U.S., where PGD isn't formally tracked, about 3,000 procedures were performed in 2005, according to a recent report from the Genetics & Public Policy Center, which is affiliated with Johns Hopkins University. Experts estimate its frequency is rising annually by 15% to 30%.
In Europe, where more accurate numbers are available, a reporting system found a more than 20-fold jump in PGD procedures between 1999 and 2003, the most recent year for which figures are available.
But specialists are concerned that much of the rise in PGD is for an unproven goal: improving the successful pregnancy rates of older women undergoing IVF. "There's a lot of controversy in the field as to how PGD should be appropriately applied," says Catherine Racowsky, director of the IVF lab at Boston's Brigham and Women's Hospital.
Virtually everyone in the fertility community agrees that PGD is valuable for its original use: preventing the transmission of certain serious inherited disorders. But many are far less confident about use of the costly procedure on the embryos of otherwise healthy mothers whose only problem is the decline in fertility that inevitably comes with advancing age.
Experts say there is a lack of solid evidence that PGD results in an actual increase in the so-called "take-home baby rate."
They say the procedure mostly makes sense for women who have experienced repeated miscarriages while undergoing in vitro fertilization and want to avoid any more of them.
Some experts also harbor suspicions that, just maybe, removing a cell from an early-stage embryo could be harmful, although there is not much evidence to support such a fear.
Performed for the original medical reasons, PGD works wonders. The first reported PGD procedures, published in the journal Nature in 1990, prevented transmission of serious genetic disorders caused by a defective gene on one of the mother's two X chromosomes. Such disorders almost exclusively affect boys because a girl has two copies of the X chromosome and, to get the disease, both would have to carry a defective copy of the gene. Researchers successfully selected healthy offspring by sex-typing single cells from early embryos (by determining if they had two X chromosomes or one X and one Y) and then transferring only female embryos to the mother's womb.
Since then, advances in molecular biology have allowed more detailed analysis of the DNA of embryos. Today, embryologists can hunt for mutations in single genes responsible for rare but deadly disorders such as Tay-Sachs disease or cystic fibrosis. This isn't cheap: Parents who are at risk of transmitting severe single-gene disorders but wouldn't otherwise need to use IVF, could easily spend $25,000 for the procedure. Still, for at-risk couples, shrinking the 25% or 50% prospect of an embryo's inheriting a debilitating disease often makes PGD worth it.
But recent surveys show that in about two-thirds of the cases, PGD isn't being used to detect genetic diseases. It's done, instead, to inspect embryos created in the lab for abnormal chromosome counts in cases in which parents with fertility problems are already undergoing IVF.
Such abnormal counts -- sometimes an extra chromosome, other times a missing one -- are far more common in the case of older mothers and can lead to higher rates of miscarriage and birth defects. The goal of PGD is to improve healthy-pregnancy rates by screening out embryos whose cells are carrying extra or missing chromosomes, before transferring them to the mom's uterus. The biopsy (removal of the cell) and subsequent analysis add about $3,000 to the cost of IVF.
Some practitioners, such as veteran researcher Yuri Verlinsky, director of the Chicago-based Reproductive Genetics Institute, maintain that PGD should be performed routinely for all IVF patients to help increase the success rate.
But growing numbers of specialists think PGD is being oversold -- and hopeful parents may be spending thousands without any increase in their chances of taking home a baby.