THE NEW REVOLUTION IN MAKING BABIES

By MICHAEL D. LEMONICK

The medical practice known as Reproductive Biology Associates, located in the Atlanta suburb of Dunwoody, is pretty typical of the 315 fertility clinics in the U.S. and of the hundreds more in other countries around the world. Most of its patients--couples, mainly, but also single women--are here on this crisp, bright autumn day because they have tried in vain to have babies the old-fashioned way. Now they hope that medical science can help them satisfy that most basic of instincts, programmed into the brain and body by millions of years of evolution: the urge to bear children.

The depth of that feeling is shown in the expressions of anticipation and determination on the patients' faces, in the hands clasped tightly together, in the urgent, hushed murmurs of their voices. And the evidence that their hope may be realized is displayed prominently all around them: the hallway is lined with bulletin boards covered with the photographs of babies born to men and women who have sat in the clinic over the years.

Yet the one set of pictures that would make clear how R.B.A. stands out from other fertility practices has never been posted. In October, a patient here gave birth to twin boys conceived from eggs--another woman's--that had been frozen for more than two years. Unlike Bobbi McCaughey, this woman could not be helped by fertility drugs. She had suffered ovarian failure and could produce no eggs, no matter how much medication she took. Her best option would have been to accept a fresh egg from a donor. But she had agreed to this experimental procedure instead, on the condition that her privacy would be jealously guarded.

If she anticipated that the world might be, well, curious about her case, she was right. Infertility rates in industrialized countries have been rising for three decades, mostly as a result of women delaying childbirth. From 1988 to 1995 alone, the number of American women of childbearing age who suffered from fertility problems jumped from 4.9 million to 6.1 million, a 25% increase. Any breakthrough that could do something about this trend would be big news indeed.

And this birth--the first of its kind in the U.S. and one of the first in the world--wasn't just any breakthrough. A woman's eggs are more fragile than a man's sperm, and over the years, attempts to freeze and thaw them have almost always ended in failure. R.B.A.'s success, though it may not have been quite as dramatic as the birth of septuplets, within days had made headlines all over the world. Within weeks, the Atlanta clinic had fielded calls from fertility experts and infertile couples as far away as England and Germany.

No wonder. Doctors have been trying for centuries to improve on nature's way of perpetuating the human species. The first successful artificial insemination took place during the presidency of George Washington. And since 1978, when the world's first test-tube baby was born, researchers have assembled a battery of medicines and high-tech procedures that have utterly transformed the treatment of infertility. More than 33,000 babies have been born in the U.S. thanks to in-vitro (literally, "in glass") fertilization, or IVF--nearly 7,000 in 1994 alone, the most recent year for which numbers are available.

IVF, fertility drugs and other techniques have, in short, revolutionized conception. And the revolution is far from over. In the R.B.A. laboratories and in a handful of other research labs around the world, scientists are pushing the technology of assisted reproduction even further, offering new hope to childless couples and new opportunity to women who want to postpone childbearing.

If egg freezing can be perfected, for example, a woman who faces the loss of her egg-bearing ovaries through radiation therapy or disease could preserve her eggs for later insemination. Or, given that aging eggs rather than aging bodies are the leading cause of female infertility, a young woman who wants a career before she starts her family--or even before she chooses a mate--could freeze her eggs in their prime, then use them later.

Egg freezing is just one of the fertility breakthroughs that are moving through the pipeline from lab to clinic. Doctors are removing and cold-storing ovarian and testicular tissue for later reimplantation, coaxing test-tube embryos to grow stronger before they are put into the womb, even performing microscopic surgery to transfer chromosomes from old, worn-out eggs into young, robust ones. All these techniques have a single purpose: to beat the odds nature has stacked against a woman's ability to bear children.

Americans will undoubtedly be the biggest consumers of these new procedures, just as they are of current treatments. However, many existing assisted-reproduction therapies were developed overseas. The world's first in-vitro baby, Louise Brown, was born in England. The first baby born from a frozen embryo is Australian. And it was in a Belgian lab that researchers found a way to inject sperm directly into an egg cell, enabling men with insufficient, slow-moving or feeble sperm to become fathers--a powerful new technique known as intracytoplasmic sperm injection, or ICSI.

Which of these or half a dozen other procedures a specialist will call upon depends largely on the reason a patient or couple is infertile. For Anita and Vincent Bielicki, both Chicago police officers, the problem was in Vincent's sperm. Before turning to more elaborate measures, the couple tried several courses of therapy, in which Anita took ovulation-stimulating drugs (a la Bobbi McCaughey) and fertilization was to occur inside the body.

After six unsuccessful tries, the Bielickis decided to go for what Anita calls "the whole banana"--in-vitro fertilization at Chicago's Center for Human Reproduction. It worked the first time, and in 1993 Anita gave birth to Andrea. Later attempts were unsuccessful, so the following year they tried ICSI. Result: their second daughter, Elizabeth, now 2.

For Sheila and Rick Burski of Rice, Minn., the outcome was equally happy. Because Sheila's fallopian tubes were blocked, a problem in about 35% of female-infertility cases, IVF was the only option. The first try at the Midwest Center for Reproductive Health in Minneapolis ended in a miscarriage, and the second, using leftover embryos that had been frozen, didn't take at all. "We had some real downer weeks, particularly after the second attempt," says Rick, an excavation contractor.

Finally, after a third failure, they tried a different approach: doctors retrieved a fresh batch of eggs, and this time they used assisted zona hatching, in which the egg's membrane, known as the zona pellucida, is chemically weakened so sperm can penetrate more easily. (Another way to do this is to drill a tiny hole in the egg; both methods are less tricky than full-fledged ICSI.) Their son, Eric Richard, was born in October.

Like most couples, the Bielickis and the Burskis didn't need the newest assisted-reproduction therapies. That's just as well: these procedures have not entered the mainstream of clinical practice. Some, including R.B.A.'s egg-freezing technique. may never do so. A second patient in the Atlanta clinic is pregnant thanks to a frozen egg; so, reportedly, are three women in Italy, and births have previously been reported in Australia, Germany and Italy. But the success rate is still very low--only two births in 23 tries in Atlanta, so far--and the technique is expensive. So R.B.A. is not yet offering the procedure to healthy women who simply want to postpone childbearing--though scientists hope that will change within a few years.

The same holds true for many other experimental therapies emerging from the lab. One of the most promising is a technique that keeps embryos growing for a few extra days in a Petri dish. Until recently, clinicians had to put in-vitro embryos into the uterus when they were just one or two days old and relatively fragile. After that, the embryos' metabolism changes, rendering standard growth mixtures useless for nourishing them. That's why clinics insert several at once, which raises the odds of success but often produces triplets, quads and even quints.

Australian embryologist David Gardner and his colleagues at the Colorado Center for Reproductive Medicine in Englewood have come up with a mixture that keeps cells growing in vitro for up to five days, making it much easier to pick out the strongest embryos. So instead of three or four or five embryos, doctors can implant one or two. The technique could be a standard practice by next spring.

Another intriguing method involves harvesting not a woman's eggs but bits of her egg-bearing ovarian tissue. Like egg freezing, this procedure could preserve fertility for women who know they are about to lose their ovaries. It could be used on females who are far too young to produce mature eggs--girls who are undergoing radiation treatments, for example. In theory, the tissue could eventually be placed back in the body and lead to successful pregnancies. (This has been done in sheep but not yet in humans.) Men's sperm-generating testicular tissue could also be removed, and presumably re-implanted--though this too has been done only in animals. Routine human therapy using any of these tissue-preserving methods is probably five or 10 years away.

Yet another fertility-boosting procedure sounds almost as if it came from science fiction. Researchers know that older women's eggs are less fertile than those of younger women, and suspect that the fault lies not in the chromosomes but in the biological machinery that controls cell division. To test this idea, Dr. Jamie Grifo, director of reproductive endocrinology at New York University Medical Center, and his colleague, Dr. John Zhang, have microsurgically transplanted the chromosome-containing nuclei from older women's eggs into younger women's eggs from which the nuclei have been removed. The transplants took, and while 40% to 50% of older eggs show chromosomal abnormalities, says Grifo, "the rate was only 15% with the transplants."

Grifo's eggs have not yet resulted in any births, but an upside-down version of the procedure has succeeded. At the St. Barnabas Medical Center in Livingston, N.J., Drs. Richard Scott and Jacques Cohen have been taking cytoplasm--the nonnuclear part of a cell--out of young women's eggs and injecting it into the eggs of older women. One egg with refurbished cyotoplasm has grown into babyhood; another birth is expected next spring.

While all these new techniques could mean more reproductive choices for the infertile, they could also create tricky ethical and legal issues. Indeed, almost every clinical advance in assisted reproduction leads to unforeseen dilemmas. Take ICSI, which on its face seems utterly benign. In some cases, male infertility may be caused by a genetic defect; helping a man with such a defect reproduce could result in passing the defect on to his son. Also, since sperm can be obtained surgically, they have in a few cases been recovered from men killed in accidents, and then used to father children--a legal quagmire, since the dead cannot give consent.

Egg freezing may actually ease one ethical dilemma. When clinics freeze test-tube embryos for later use, what happens if that use never takes place? If the parents divorce or die, who gets custody of the embryos? Courts have addressed both these thorny situations in specific cases, but no nationwide policy exists in the U.S.

Even trickier is the question of what to do with leftover embryos when the parents are done having children. In the U.S., clinics have parents specify beforehand how they want unused embryos handled. Some donate them to other infertile couples or to scientists for research. Others have them destroyed. But many individuals and institutions--most notably the Roman Catholic Church--consider these embryos to be human beings and their disposal equivalent to murder.

Substitute frozen eggs for embryos, however, and these problems go away. No one considers an unfertilized egg to be a human being (though the Catholic Church officially opposes IVF, as it does nearly all assisted-reproduction procedures, including artificial insemination). Moreover, there is no controversy about whom the egg belongs to. An unfertilized egg, after all, has no father.

But even as it eases one ethical controversy, egg freezing may exacerbate another. Menopause, doctors now know, simply marks the end of a woman's egg supply. Otherwise, her reproductive equipment can still function if supplied with hormone supplements. With IVF, hormones and another woman's egg, even a postmenopausal woman can give birth.

That this is precisely what has happened is no surprise, given the powerful human urge to procreate. Some 100 women ages 50 and older have borne children in the U.S., and so have many more in other countries. In fact, the 60-year-old barrier has been broken several times. Last spring, a 63-year-old California woman named Arceli Keh gave birth (she had allegedly lied to the clinic about her age); so, in 1994, did an Italian woman who was 62.

"Nobody's tried it in 70- or 80-year-olds yet," says Dr. Richard Paulson, head of reproductive endocrinology and infertility at the University of Southern California, where Keh was a patient, "but at present there's no evidence of an upper age limit." Inevitably, the prospect of using their own eggs, frozen years before, rather than a donor's genetically foreign eggs, will only increase the number of older women who want to give birth.

Even at 50, though, pregnancy and childbirth can put a terrible strain on a woman's body, and the demands of child rearing can do the same to both body and spirit. Some observers believe it is not fair to the child. "When that child is of college age," observes John Paris, professor of bioethics at Boston College and a Jesuit priest, speaking of the 62-year-old Italian woman's offspring, "his mother will be 80." That is, if she is still alive. "We're designing orphans by choice, and we say this is O.K.," he says.

Older mothers disagree, of course. People live longer nowadays, they argue, and stay healthy and strong well into their 70s and 80s. Besides, when an elderly man fathers a child--Strom Thurmond or Tony Randall, to name just two recent examples--many applaud his virility. When an older woman bears a child, she is seen as some sort of freak. Yet sexist as it may seem, most experts agree that the mother is usually the more crucial parent.

For all these reasons, only a handful of the hundreds of fertility clinics in the U.S. will treat women 50 and older. The ethics committee of the American Society for Reproductive Medicine has issued guidelines stating that "infertility should remain the natural characteristic of menopause." But the guidelines are voluntary; no law prevents doctors from starting a pregnancy in any woman who wants one.

Assisted reproduction is among the least regulated medical specialties in the U.S. Unlike most of Europe, the U.S. does not require fertility clinics to be licensed. Moreover, many U.S. clinics are interested above all in turning a buck. Thus, says Gladys White, executive director of the National Advisory Board on Ethics in Reproduction, "the U.S. has some of the best and some of the worst infertility centers in the world."

The insurance industry doesn't help matters. In most of the world, IVF is covered by national health insurance. Private insurers in the U.S., by contrast, often refuse to pay for it. Since each attempt costs an average of nearly $8,000, patients often risk multiple births in order to avoid having to pay for a second visit. Eight states now mandate IVF coverage, but in most of the U.S., high-quality assisted reproduction is only for the well-to-do.

Beyond the issues of affordability and fairness and concerns about aging mothers and disposing of frozen embryos, a single ethical question underlies all assisted reproduction, from fertility drugs to the still untested idea of human cloning: Have we the right to play God by intervening in this most basic of biological functions?

But playing God is an unfair description of assisted reproduction, says Dr. Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at New York Hospital/Cornell Medical Center. "All of us in medicine are facilitators, trying, essentially, to put things back to the way they work in nature," he says.

Whatever the concerns raised by their work, the scientists who are pushing the envelope on assisted reproduction reject any suggestion that the work is morally repugnant. And so, clearly, do the tens of thousands of infertile couples who seek their help.

--Reported by Leslie Everton Brice/Atlanta, Dan Cray/Los Angeles, James L. Graff/Chicago and Lawrence Mondi/New York

For information on how to choose a fertility clinic, visit time.com on the Web.

With reporting by LESLIE EVERTON BRICE/ATLANTA, DAN CRAY/LOS ANGELES, JAMES L. GRAFF/CHICAGO AND LAWRENCE MONDI/NEW YORK