HOW TO COAX NEW LIFE

On any playground, in any nursery school, Brittany Abshire and West Redington would blend in perfectly with the other kids and the schoolyard clamor. Brittany, 2 1/2, is a chubby, mischievous chatterbox, and West, who turned one in August, is a grinning, inquisitive toddler who loves clambering up steps and the back of the sofa. As far as the world can see, there is nothing special about either of them. Wonderfully ordinary though they may be, however, young West and Brittany were conceived under extraordinary circumstances by parents who could barely believe the feat was possible. Just five years ago, in fact, it would not have been possible. Without recent key advances in genetics and reproductive biology, the Abshires and the Redingtons–and thousands of others afflicted with fertility problems–would never have been able to bring children into the world.

Their new hope can be traced to the birth of Louise Brown in England in 1978. Louise was the world’s first test-tube baby, conceived by means of in vitro fertilization, in which, after her mother’s egg and father’s sperm were united in a laboratory, the resulting embryo was implanted in her mother’s womb. Louise’s subsequent, internationally celebrated birth launched a new branch of medicine that has come to be known as “assisted reproductive technology.”

The first in vitro baby in the U.S. was born three years later, and since then the procedure has been responsible for 26,000 more births in America alone. For women with blocked or scarred Fallopian tubes that prevent eggs from reaching the uterus, the technology has been a godsend. But for others, particularly those in whom doctors cannot find the reason for infertility, in vitro can be an exercise in frustration. It is expensive (about $7,800 for each attempt, three or four of which are often needed to achieve success) and not covered by many insurance plans. It is also quite unpleasant for most women, who become bloated and sore and sometimes suffer mood swings from the powerful hormones they must take. Finally, the procedure produces children for only 18% of the couples who try it, as 40,000 did in the U.S. last year.

Still, in vitro has had an astounding ripple effect that has reached many branches of infertility research. Twenty years of manipulating human eggs, embryos and sperm have led researchers to solutions to problems that in vitro alone cannot help. Couples carrying severe genetic disorders and infertile men have become parents as a result, and methods are being explored to restore fertility in both men and women who are undergoing cancer treatment. The same technique can be used for women who postpone childbearing to a point in their lives when their fertility would naturally diminish.

Disorders in men, the problem in 40% of infertile couples, used to be considered a lost cause. “Until two years ago, couples in which the man was infertile were told to find a sperm donor,” says Dr. Michael McClure, chief of the reproductive-sciences branch at the National Institute of Child Health and Human Development. “Or they were essentially advised about adoption. Things were that dismal. But now a significant portion of male infertility may be treatable.”

Among the first to benefit from the new techniques were Jim and Sarah Redington, of Hot Springs, Virginia. By 1994, after eight years of waiting, they had nearly given up hope of having a second child. Jim, a family physician, was treated for testicular cancer in 1985 while Sarah was pregnant with their daughter Rebecca. He could no longer produce sperm, and the samples he had stored at a sperm bank before his cancer treatment had failed to make Sarah pregnant again. Not even the in vitro process resulted in conception. “The doctor said it didn’t work and never would,” recalls Jim. “We were crushed.”

Their specialist did hold out one faint hope. In the future, he said, for men with few or sluggish sperm that could not penetrate egg cells on their own, scientists might be able to help fertilization take place by injecting a single sperm cell into an egg. At the time, that sounded futuristic even to a medical man like Jim. But he and Sarah took their doctor’s advice, stopped trying to conceive through in vitro and kept Jim’s last remaining samples frozen at the sperm bank.

Finally, in 1994, the year Sarah turned 38, a new procedure became available at the Eastern Virginia Medical School in Norfolk. She and Jim were among the first patients to try it there, using a sample of Jim’s sperm that had been frozen since 1985. And in August 1995, the couple got back the future that Jim’s illness had nearly taken from them: Sarah gave birth to their blond, gray-green-eyed son West.

The technique their physician had predicted, is known as ICSI–for intracytoplasmic sperm injection–and had first been performed successfully in Belgium in 1992. Injecting a sperm cell into an egg may sound like a simple procedure, but attempts had failed until researchers figured out how to manipulate the sperm and egg without damaging them. U.S. clinics now do thousands of icsi procedures a year, with a success rate of about 24%. The technique can help men with low sperm counts or motility, and even those who cannot ejaculate or have no live sperm in their semen as a result of vasectomy, chemotherapy or a medical disorder.

The one concern that both doctors and patients express about ICSI is that by fertilizing eggs with sperm that cannot make their own way naturally, the procedure might preserve defective sperm cells that nature would have eliminated. Men with low sperm counts may also have a higher incidence of chromosomal abnormalities and may be at higher risk of passing on genetic defects. But clinical studies so far provide no evidence to support these fears. Belgian scientists have examined a thousand babies born as a result of the technique and found no higher rate of birth defects than in the general population. Nonetheless, the procedure is still considered experimental.

Other avenues of ongoing research on sperm and eggs suggest eerily futuristic scenarios–much as ICSI did just a few years ago. At the University of Pennsylvania School of Veterinary Medicine, biologist Ralph Brinster has been working for several years with sperm stem cells, or spermatogonia, the cells deep within the testes that produce sperm. Working with mice, Brinster and his colleagues have found that the stem cells can be transplanted from a healthy animal to a sterile one, enabling the second animal to father offspring. More recently, the team has found that stem cells can be frozen, thawed and transplanted, and still produce apparently normal sperm.

Brinster’s work has profound implications for humans. Some researchers suggest that it might be possible to enhance fertility in men with low sperm counts by removing some of their stem cells, getting them to multiply in the laboratory, and returning them in greater numbers to their owner. Also, human spermatogonia will probably freeze well, so that men about to undergo chemotherapy might be able to have stem cells frozen and later transplanted back into their testes. Unlike frozen sperm samples, which can be used up, stem cells provide, theoretically at least, an inexhaustible supply of sperm.

Experiments with sperm stem cells, however, are bound to raise disturbing moral and ethical questions. The cells could, for instance, be transplanted from one man to another, enabling the second man to father children that, genetically speaking, are not his. Someday human stem cells might even be transplanted into animals, enabling researchers to study sperm production and development and perhaps gain fresh insights into infertility and contraception.

Taking the technology several steps further, a man with a genetic defect might one day be able to have some of his stem cells removed, treated for their defect by some yet-to-be-discovered means of gene therapy, and returned to him so that he could then father healthy children. “Now that’s Star Trek,” says McClure. “These are enormously inflammatory issues with tremendous potential for use and abuse. There’s nowhere near the knowledge and technology yet to do this.”

Researchers have also begun to take bolder approaches to the handling of human eggs. The standard method with IVF has been to dose a woman with hormones to trick her ovaries into releasing many mature eggs at once. But now researchers have begun to experiment with immature eggs, which can be harvested from the ovaries without hormone therapy, matured in culture in the laboratory and then fertilized and transferred back into the womb. That technique, first successful in South Korea in 1991, could spare the woman costly and unpleasant hormone treatments.

Another advantage of the technique is that immature eggs survive freezing better than mature ones, thus opening the possibility of preserving fertility in women who must undergo cancer treatments that cause sterility. When the tissue is thawed, either the eggs can be grown to maturity for ivf or the tissue itself can be grafted back onto the ovary so that the eggs can mature in the woman’s body. Says Dr. Roger Gosden, who pioneered the technique at England’s Leeds University: “This is an experimental procedure, and until someone has a pregnancy as a result of getting the tissue back, it will remain so.”

The use of frozen eggs raises ethical questions, particularly since it presents the possibility of lifting nature’s age limit on motherhood. A young woman, for instance, might wish to have some eggs frozen, in case she chooses to become pregnant later in life. For most women past 35, fertility declines sharply, simply because their eggs have become too old to be viable. But their bodies can still sustain a pregnancy, and many could give birth if they could just get access to healthy eggs. Until now the only option has been to use an egg from a younger donor, but some day they may be able to use their own frozen eggs.

Of all the studies involving immature eggs, surely the most controversial–and, to some ethicists, downright repugnant–is the work on ovarian tissue. Researchers have been performing experiments aimed ultimately at transplanting such tissue from fetuses–either aborted or miscarried–into infertile women. Fetal tissue is a rich source of eggs. A five-month fetus has cells that can produce about 7 million eggs, in contrast to the mere 400,000 or so that survive to a woman’s puberty. Researchers have suggested using this tissue to establish egg banks for infertile women, who could then give birth to children who did not carry their genes–children whose biological mothers had in fact never been born.

One of the most extraordinary offshoots of in vitro research is a technique, offered to people carrying severe genetic diseases, that can ensure that their children will not inherit their defective genes. Couples in this situation are not technically infertile, but their options have been limited to an uncertain pregnancy or, if testing shows the presence of a defective gene, an abortion. Some people, opposed to abortion entirely, or unwilling to go through it again after one or more experiences, have decided never to have children.

Renee and David Abshire, a couple from DeRidder, Louisiana, made that decision in 1989 after the death of their three-year-old daughter Maigon from Tay-Sachs disease, a hereditary disorder that causes blindness, retardation, seizures and a relentless deterioration of the nervous system. Once Maigon’s illness was diagnosed, the Abshires, though both healthy themselves, learned that they each carried one copy of the deadly Tay-Sachs gene.

The inheritance pattern of the disease dictated that any child the Abshires conceived would have a 1-in-4 chance of developing Tay-Sachs. As members of the Pentecostal Assembly of God, the couple could not countenance abortion, yet neither could Renee risk conceiving a child who might suffer and die as Maigon had. Still in their 20s, they opted for childlessness.

Then, in 1991, Renee received a phone call from Gary Hodgen, president of the Jones Institute for Reproductive Medicine at the Eastern Virginia Medical School. The Institute had developed a procedure that could enable her and David to have a healthy child, and Hodgen wanted them to try it. The procedure, called preimplantation genetic diagnosis, is a marriage of in vitro fertilization and high-tech genetic testing. PGD begins with a standard in vitro fertilization, but then, when the embryos have divided to between four and eight cells, technicians remove one or two cells and test them for the harmful gene carried by the parents. The embryos develop normally even though cells have been removed, and once the test results come back, the defective embryos are discarded. Only healthy ones are transferred into the woman’s uterus.

Despite their earlier reservations, the Abshires decided to risk the procedure. “The thing in my mind was, this could be my last chance,” says Renee. Brittany Nicole Abshire was born on Jan. 26, 1994, the first child in the world born as a result of PGD for Tay-Sachs. Not only is she healthy, but she is not a carrier of Tay-Sachs and so will never have to face the decisions that her parents did.

Worldwide, only about 76 babies have been born as a result of PGD. So far the procedure has produced healthy children for parents who were carriers of cystic fibrosis, hemophilia, Duchenne muscular dystrophy and other even rarer genetic conditions. But the procedure is still experimental, and mistakes can be tragic. At least one child has been born with cystic fibrosis as a result of laboratory error.

There is also the fear that PGD will be misused to make “perfect babies” by selecting for genetic traits that have nothing to do with disease. Genes have not been found for good looks, high IQ or artistic talent, but if they ever are, prospective parents are sure to want them. PGD is already in demand for sex selection, though doctors refuse to use it unless there is a clear medical reason. For now the technique is being employed to bring healthy children into the world. Whether those children prove to be smart or good looking will still have to depend, at least for the present, on the roll of the genetic dice.

–Reported by Hannah Bloch/Washington and Helen Gibson/London