A Brave New World? : New Technique Increases Fertility, but Raises Fears About Genetic Engineering

Before Peter Bastone underwent chemotherapy for Hodgkin’s disease, the 27-year-old visited several Los Angeles sperm banks.

He knew that the chemotherapy most likely would leave him sterile and that saving a sample of his sperm probably would be his only hope to someday have a biological child.

Seven years later, Bastone’s farsighted planning--and his faith in technology--paid off.

With a very limited quantity of sperm to work with, experts used a new in vitro fertilization (IVF) technique called micromanipulation to create several embryos. They were implanted in his wife, Julie, last spring, and the couple is expecting a child in December.

“Since we only had a limited supply of sperm, we wanted to utilize the best technology available,” says Peter Bastone, the administrator of Daniel Freeman Memorial Hospital.

With micromanipulation, experts can cut through the outer shell surrounding the egg, allowing abnormal, misshapen or a scant amount of sperm a better chance to fertilize it. The procedure uses a computerized microscope and precision instruments to handle the pinhead-size egg and even smaller sperm.

But in the whirlwind world of reproductive science, this use of micromanipulation is already old news. The latest buzz concerns the use of the technique to screen the embryo for genetic diseases before it is implanted.

In this procedure, specialists can take a fertilized embryo at an early stage of development (and still in the petri dish) and remove a cell to “biopsy.” Using sophisticated techniques in molecular biology, technicians can look for genetic markers that reveal the presence of some inheritable diseases. If the biopsy uncovered the gene for cystic fibrosis, for instance, that embryo would not be implanted; disease-free embryos would.

In essence, the technology ushers in an era during which embryos might be tested for certain traits--sex, diseases, even eye color--thus giving a couple the choice of which embryos they want implanted.

It’s brave-new-world stuff, but ethical questions are evolving as fast as the technology.

“The advances have left us all breathless,” says David L. Hill, director of the Center for Reproductive Medicine at Century City Hospital in Los Angeles and the Bastones’ doctor. “And if it’s difficult for me to assimilate, I would imagine it’s difficult for most people outside the field to understand. But we are all going to be dealing with the ethical questions.”

Micromanipulation marks a turning point in infertility treatment, experts say. When the first scholarly paper about it appeared in the late 1980s, Hill says, it hit “like a bomb.”

The procedure evolved from the need to address male infertility, which accounts for about 40% of all infertility cases. Because of birth defects, viruses, diseases or environmental toxins, sperm can become abnormally shaped or immobile and cannot penetrate the egg.

In traditional IVF, concentrated sperm are placed in a dish with an egg, but the sperm must still be able to fertilize the egg. Too often, that did not happen.

“There was a large number of patients we couldn’t help,” says Hill. “We were at a loss to improve the sperm’s ability to penetrate all the cells and membranes around the egg. Up until micromanipulation, if you had bad sperm, that was it. This will help a significant number of our couples.”

With micromanipulation, sperm considered 100% abnormal can still fertilize an egg, says Hill, whose center has produced about 10 pregnancies with the technique. (Even if a sperm is abnormal, the genetic material inside the sperm--the DNA--can be normal and create a healthy child.)

During micromanipulation, a concentrated drop of sperm is placed under a microscope and the best-looking of the bunch, perhaps five or 10 sperm, are caught in a sliver-thin, hollow glass needle.

The egg is then placed under the enclosed, temperature-controlled microscope and held with a tiny, suction-like device. The glass needle is used to pierce the layer of cells and membranes that make up the zona, the egg’s outer shell. (Because the microscope is computerized, the movements of the embryologist’s hands are automatically scaled down to a fraction of the actual movement.)

The embryologist then releases the sperm through the needle into the space surrounding the egg. The egg itself is not touched. It’s now up to the sperm and egg to fuse.

“Once you’ve injected sperm, (the success) still relies on one of the sperm to fertilize the egg. That part you still have to leave to nature,” says Dr. Joel H. Batzofin, co-medical director of the Huntington Reproductive Center in Pasadena.

Micromanipulation can also be used to open a crack in the shell before implanting a fertilized egg in the womb, thus improving chances that the embryo will “hatch.”

Instead of using a needle, experts at UCI Medical Center and the Beckman Laser Institute in Irvine are using a laser beam to bore holes in the egg’s shell. They can even move sperm around with a special kind of “vacuum” laser.

“The laser may be more precise,” says Dr. Ricardo Asch, a reproductive specialist at UCI. “You can control the exact place in which to produce a tear in the (zona).”

Asch and his colleagues are attempting to use a laser to fuse the egg and sperm so that the sperm need not penetrate the egg on its own. That research is still experimental.

With fine tuning, some experts predict micromanipulation’s success rate could match regular IVF. Although statistics vary drastically among centers, couples have about a 14% chance of ending up with a baby for each attempt with regular IVF.

Currently, however, micromanipulation is still chancy and national success rates are unavailable. Each procedure is labor intensive and costly--from $500 to $2,000 above standard IVF charges of $5,000 to $10,000. Plus, experts still don’t know why it works or fails, orwhich couples would most likely benefit. The technology is in a “phase of sporadic success,” says Dr. Jon W. Gordon of the Mount Sinai (N. Y.) School of Medicine in a recent medical journal.

Still, for some couples, micromanipulation offers a chance where there was none.

One Los Angeles couple endured seven years of infertility treatments, including traditional IVF, but the husband had abnormal sperm and the procedures failed.

“Out of the blue (they) called me up one day and said, ‘We want to do IVF with donor sperm,’ ” Batzofin says. “I said, ‘You know, we have this new procedure.’ They came in, and we used micromanipulation and she got pregnant. It worked the first time.”

Another Los Angeles couple, Susan and Tim, went through four years of infertility treatments, including two IVF attempts. After spending about $60,000 to no avail, they were “very jaded, bitter and cynical” with the field of reproductive medicine, says Tim.

Batzofin attributed their infertility to two problems: sperm that failed to penetrate the egg, and antibodies in Susan that tended to kill the sperm. Batzofin suggested micromanipulation.

“We were depressed,” Susan says. “But this was our last chance. I felt like this is the highest-tech technology. This was our best chance.”

Four embryos were implanted and, nine months later, Susan gave birth to twins.

Although she is an ecstatic new mother, Susan is somewhat incredulous about the technology.

“The whole process was as unnatural as possible,” she says. “They were literally selecting the sperm that would make our baby!”

Some people are uneasy with this level of intrusion. Micromanipulation virtually eliminates the natural selection from conception. If medical experts can choose the egg and sperm, and then test the embryo for its genetic makeup before implanting the embryo, what’s next?

Later this month, the ethics board of the American Fertility Society will meet in Birmingham, Ala., to wrestle with the moral quandaries creamted by micromanipulation.

One goal may be to suggest a less sinister-sounding name for the technology, says Joyce Zeitz, a society spokeswoman.

“ Micromanipulation smacks of genetic engineering,” she says.

But micromanipulation could open the door for that.

Beginning early next year, couples who wish to have a child but who both carry the gene for Tay-Sachs disease can participate in an experiment at the Jones Institute for Reproductive Medicine in Norfolk, Va., to test their embryos for that disease before implantation.

Embryos that are free of the gene or that only carry one gene (which would make the child a carrier) would be implanted. But embryos that carry both genes, and which would be stricken with the disease, would not be implanted, says Dr. Gary D. Hodgen, president of the institute and a leading researcher in preimplantation screening.

These couples are not infertile. But Hodgen says most couples expected to enter the study have already lost a child to Tay-Sachs, and micromanipulation will allow for genetic screening before risking another pregnancy.

Tay-Sachs occurs mainly in people of East European Jewish descent. The afflicted baby appears normal at birth, but the brain begins to degenerate at three to six months. Blindness and arrested development occur, and the child often dies by age 3 or 4.

“We picked Tay-Sachs because it is one of the most devastating of inheritable diseases,” Hodgen says. “We thought this was necessary on ethical grounds. We want the public to know that we give great value to every preembryo (an embryo before implantation), fetus and child. But we believe parents need a choice. We believe this information would be valuable to know even before a woman becomes pregnant.”

The Genetics and IVF Institute in Fairfax, Va., has preimplantation genetic screening for couples whose offspring are at high risk for cystic fibrosis and the so-called “X-linked” chromosomal disorders that cause profound retardation.

But so far there have been no takers for the technology, says Director Joseph D. Schulman.

“The major limitation we have in our program is it is costly,” Schulman says. “We’ve had a number of inquires from couples who are interested but are unable to afford this type of testing. It is not yet something that insurance companies will pay for. The current view is that it is cheaper for patients to have amniocentesis or chorionic villi sampling and terminate the pregnancy.”

But Hodgen and Schulman argue that preimplantation screening spares high-risk couples from significant anxiety and trauma.

And Hodgen believes that geneticists will someday be able to repair any defective gene in the embryo before implanting it, gradually eliminating inherited diseases:

“If it’s worth eradicating smallpox, why isn’t it worth eradicating these inheritable diseases?”

Some people, however, worry that the procedure could be used to screen non-medical characteristics--such as eye color or height--or potential illnesses, such as a tendency to develop heart disease or alcoholism. Many diseases are believed to result from a combination of flawed genes and the individual’s environment.

“There will be questions raised, and they must be clarified on an as-we-go basis,” Hodgen says. “If used for good, (the technology) would not be applied to frivolous, non-medical purposes. It would not be used to manipulate the genes to make people changed in a cosmetic, inappropriate way. It would be used to help parents have medically healthy children.”

What is objectionable to most is the idea that “children are commodities to order up the way you want them,” says USC ethicist Alexander M. Capron.

But how the technology is controlled will depend on how both society and medical experts view it, he says:

“Will we, as individuals with our own ethical guideposts, make good decisions?

“That remains to be seen.”