Jodi Peterson, 36, still can't believe it has come to this. After eight months of failing to conceive right after her 1991 marriage, she found herself in the maw of the infertility machine. She and her husband, who live in suburban Maryland, endured a year of tests, from semen analysis to injection of a dye to see if her fallopian tubes were blocked. Their clean bill of health was, in the mirror world of infertility, perhaps the worst news they could have received: it meant the doctor had no idea why Peterson wasn't conceiving. So she went through months of daily infertility drugs. She put up with nine intrauterine inseminations (IUIs), in which sperm are shuttled by catheter directly to the uterus. Her bills had topped $40,000, and insurance covered nothing. Then her doctor discovered that Peterson's tubes, contrary to what she had been told, were hopelessly blocked: she had undergone a year of treatments that can work only with healthy tubes. So Peterson tried in vitro fertilization (IVF), in which eggs are retrieved with an ultrathin needle, fertilized in the lab and inserted into the uterus, bypassing the tubes. That resulted in a potentially fatal ectopic pregnancy. She has now had three more IVFs. "Do I have second thoughts?" Peterson asks. "You bet -- every time I write out a $2,500 check for fertility drugs. Now I accept the fact that we're not going to have biological children. I've grieved enough. I have to move on."
First they live by the unbending rule of the calendar, keeping their doctor-ordered appointments for conjugal relations on the prescribed three days of every month . . . even though it now brings them all the joy of taking out the trash. Then they become human pincushions, their rear ends sore from twice-a-day hormone shots that sometimes make their ovaries inflate to the size of baseballs. They spend at least $10,000, and as much as $100,000, on diagnostic tests and fertility drugs and the crapshoot known as assisted-reproductive techniques--a.k.a. test-tube babies. They cringe when friends counsel them to "give it time" when time is their relentless foe. They fume at insurers who regard infertility treatments as experimental, or even as a frivolity on a par with a nose job. They are childless. And more and more of them are mad--fighting, suing, e-mail-flaming mad--at an infertility industry that offers a lot of hype, a lot of hope and not enough babies. After 20 years of scientific advances, nearly three out of four couples seeking assisted reproduction still go home to an empty crib.
That sobering statistic underlies a new revisionism sweeping through the field of infertility. For years an inability to conceive has been portrayed as just another hurdle that an informed, determined couple could overcome with the help of the fertility cavalry: expensive drugs, cutting-edge science and adroit surgeons. Television specials on "older mothers" always seemed to end with a happy 40-year-old beaming over an occupied bassinet; the walls of infertility clinics were papered with photos of patients turned parents. Exhibit A: the more than 40,000 test-tube babies born in the United States since 1981. But from 1991 to today, the Federal Trade Commission has obtained cease-and-desist orders against 11 clinics whose advertising implied that a baby was almost as easy to get as a tattoo. This June, one of the country's renowned fertility specialists was accused of unethical experiments at his Irvine, Calif., IVF clinic (NEWSWEEK, June 12), a reminder that the infertility industry is largely un-regulated. The scientific basis of high-tech treatments remains weak, and clinical evidence that new techniques are significantly better than old ones is scarce. But the strongest impetus for the reassessment has been one little number. In 1993, the 267 clinics reporting to the American Society for Reproductive Medicine started 41,209 assisted-reproduction procedures. Of these, 8,741 resulted in live births. That's a success rate of 21.2 percent.
The low odds couldn't have come at a worse time. Today there are 5.3 million infertile couples in the United States. The percentage of childless, infertile couples has increased from 14.4 in 1965 to 18.5 now, according to the National Center for Health Statistics. Some of the increase is due to the greater number of thirty- and forty somethings. Fecundity declines with age, though exactly how steeply remains controversial. Some of the rise is due to changes in sexual habits. The greater the number of partners, the greater the risk of sexually transmitted diseases that can impair fertility. In 40 percent of the cases, it is the woman's infertility that prevents conception; in 40 percent, it is the man's; in 20 percent it is both partners'; or of unknown cause.
More than 3 million couples will seek medical help for infertility this year. (The others adopt, reconcile themselves to being childless or keep trying to conceive without help.) Most infertile couples need only low-tech intervention. The men receive advice to wear looser shorts (a scrotum with an internal temperature above about 95 degrees inhibits sperm formation); the women get drugs to regularize ovulation. But for a few percent of infertile couples, the last and probably only chance for a biological child lies in high-tech, assisted reproduction. Last year about 40,000 couples tried one or another of these techniques (chart, page 41). Most women treated at the clinics are under 35; 84 percent are under 40, and with good reason. In 1992, in women over 40, only 7.2 percent of successful egg retrievals resulted in a live birth when there was no male infertility. When the man also had a problem, the success rate for these women was 4.9 percent.
As childless couples know, the menu of test-tube-baby options has grown to bewildering lengths. In the beginning was plain-vanilla in vitro fertilization. The woman typically begins a monthlong drug regimen that superactivates her ovaries. If they produce eggs -- a dozen, ideally -- the physician extracts them, once they are mature, with a needle inserted through the vagina into the follicle. A technician mixes the husband's sperm, if they are healthy, with the eggs; otherwise donor sperm are used. Of these attempts, 86 percent yield a fertilized egg. The resulting zygotes are incubated for two to three days. Once the embryos have divided two to four times, forming four to 32 cells, two to four embryos (in most cases) are inserted through a catheter in the cervix into the woman's uterus.
One reason IVF fails more than four times out of five may be the trauma that inserting the zygote causes the uterus. Two variations circumvent this problem. In GIFT (gamete intrafallopian transfer), an egg and sperm are deposited separately in a fallopian tube through a tiny incision in the abdomen while the woman lies sedated under general anesthesia. Egg and sperm are supposed to meet up, fuse, drift to the uterus and start a baby. In ZIFT (zygote intrafallopian transfer), which also requires general anesthesia, a four-cell embryo produced by IVF is implanted into a tube, from which it floats gently into the womb.
To treat male infertility, a micropipette sucks as few as 100 sperm from a man's ejaculate and shoots a single one into the egg, which is then put into the womb or fallopian tubes. Intracytoplasmic sperm injection helps when sperm are too sluggish or too few to fertilize an egg unassisted. And in a procedure so new it isn't even named, Dr. Richard Sherins of the Genetics and IVF Institute in Fairfax, Va., has developed a way to remove immature sperm from the testes, using a thin needle, and fertilize an egg with a single one. This technique can bring fatherhood to men who, because of tubal blockages, ejaculate no sperm at all.
Such treatments for male infertility often work like a charm. One day, some of the still-experimental treatments for female problems might work like fertility goddesses, too (page 42), but there is little evidence that the "advances" available today are any such thing. The few well-controlled studies that have been done couldn't show big differences between new procedures, such as GIFT and ZIFT, and IVF, says Edmond Confino, a reproductive endocrinologist and director of IVF at Northwestern Memorial Hospital in Chicago. Unlike drugs, most new medical procedures do not need government approval. Only after they have been in widespread use for years might the data be robust enough to draw conclusions about how well they work. Because GIFT and ZIFT are so new, and have not been subject to controlled clinical testing, not even specialists agree on which procedure offers couples the best shot. Consider:
In 1993, IVF had an average 18.3 percent success rate nationwide. GIFT had a27.7 percent success rate. But those averages mask wildly divergent clinic-to-clinic differences. Dr. John Stangel of the fertility clinic IVF America calls GIFT "a promise that has not delivered." The Mayo Clinic is abandoning GIFT, says reproductive endocrinologist Daniel Dumesic, because it gets better results with IVF.
ZIFT is equally confusing. Ob-Gyn professor John Collins of McMaster University in Ontario recently wrote, "Why was this incompletely evaluated therapy [ZIFT] so popular?" The answer: the information about successful trials gets out to the public, the public demands it, and the doctors agree. But in March, a study of 40 women from the University of Iowa found that ZIFT achieved pregnancies in 58 percent of cases, compared with 19 percent with IVF.
No wonder couples are reeling. A 32-year-old software engineer in Boston has had seven failed IVFs, the last half dozen with ICSI (sperm injected directly into the egg). "The thought of giving up my dream is devastating," she says. "I'll ride any bandwagon, try any experiment." But which bandwagon? She's considered clinics that focus on immunological approaches, and on proteins that help the embryo latch onto the uterus. "But my clinic says they're experimental. Though they say there's a doctor in Boston who is a firm believer in embryo toxicity factors as the wave of the future," she says wearily. "Who knows?"
No one, until there are many more studies in which omen are randomly assigned to IVF, GIFT, ZIFT or another technique, says ark Hornstein, director of the in vitro program at Brigham and Women's Hospital in Boston. Until then, the infertility industry will continue to engage in a medical form of product segmentation, offering superficially different products, like laundry detergents with different fragrances, in order to create an aura of science and drum up repeat business. "I don't know flit was incompetence as much as arrogance," says Judy Posusney, an industrial hygienist in Philadelphia who tried IVF once before adopting this year. "New methods would be coming out and they would say 'Why don't you try this' or 'Yesterday they did a study, so why don't you try this'." Sherry Burns, 39, a poet in Kansas, went on fertility drugs for several years but drew the line at assisted reproduction. "I came to feel that the doctors were extremely anxious to have us try the high-tech procedures," she says. "They seemed upset when we told them we simply were not interested. In the end, I felt I could have just taken a match to a few thousand dollars and gotten the same results at less emotional cost."
One reason couples find themselves on an endless infertility roller coaster is misdiagnosis. A Boston couple saw six specialists when the husband was found to have a low sperm count. "Not one of them agreed on what the [cause] was or how to fix it," says the wife, 33. A New Hampshire software engineer, 38, spent two years with a reproductive endocrinologist who put her through a barrage of tests but didn't notice that her uterus had a rigid mass inside-and thus could never sustain a pregnancy. Nor did doctors catch her husband's prostate infection, which kept him from making viable sperm. So she went through five cycles of the fertility drug Clomid (taken orally) and one of Pergonal (injected), suffering such common side effects as moodiness and bloatedness. After each cycle she underwent intrauterine insemination of (ineffectual) sperm. "Both doctors came highly recommended but turned out to be idiots," she says. "They wasted two years of our [lives] through misdiagnoses." With her uterus repaired and her husband's prostate treated, she's now on her fourth IVF.
An accurate diagnosis is only the first hurdle. Doctors do not know which types of infertility are highly unlikely to yield to technology. "What is disturbing is: that the information is not being collected so that we could stop doing [IVF] for certain indications," says Dr. Patricia Baird, a geneticist and pediatrician who headed a 1993 Canadian Royal Commission that reviewed hundreds of reports on assisted reproduction worldwide. "If IVF does not work for certain indications, it is unethical and uncaring to continue to offer it." By 1996 the American Society for Reproductive Medicine expects to have guidelines to help determine which procedures are best for certain infertility conditions, says executive director Robert Visscher. "It will clarify an awful lot."
Nowhere is the experimental nature of this field starker than in its high rates of miscarriages. Clinics seem to have mastered retrieving eggs, fertilizing them and returning them. But in a high percentage of women-clinics won't give out the numbers-the pregnancy fails to take. Infertile women have a higher rate of miscarriage than other women, probably for reasons related to their infertility. Dr. Jonathan Van Blerkom of Denver's Reproductive Genetics In Vitro clinic blames low levels of oxygen in women's follicles, which can be caused by either age or drug-induced ovulation. Low oxygen levels toter an egg s metabolism, making the contents more acidic. Acidity can scatter the chromosomes; the body senses this abnormality and rejects the embryo. Says Dr. G. David Adamson, a reproductive endocrinologist and director of the Fertility and Reproductive Health Institute in San Jose, Calif., "If the eggs aren't as good, the miscarriage rate will be higher." Mark and Miranda Edelstein of Park Ridge, III., know about miscarriages. Miranda, 37, has suffered two, both after IUIs; her doctors suspect an immune-system problem. "We've been through lots of pain, emotionally and physically," says Mark, 35. "But the fact that there may be a glimmer of hope is enough to keep us going. Because all we have is hope."
The trouble is, it's so hard to distinguish false hope from the real thing, for the advice of yesterday fades as quickly as dietary advice on oat bran. Just a few years ago "experts" advised infertile men to have tiny varicose veins removed from their testicles (the veins, carrying blood, were thought to make the testes too hot to produce viable sperm). Others advised women to have tiny endometrial lesions removed. Now many of those same experts say those procedures aren't good for much beyond financing the doctor's country-club dues. "When you make your money off couples who say 'Do what's possible,' there's quite an incentive to encourage patients to do more," says medical ethicist Michelle Oberman, an assistant professor of law at DePaul University. "The whole system is based on trying and experimenting."
Perhaps the chuelest form of false hope is the clinics' favorite number: of the healthy couples trying to conceive the old-fashioned way, 20 percent get pregnant each month. As IVF America's Stangel puts it, "We're taking the most difficult couples and giving them a pregnancy rate that is comparable to the fertile population." But in a full year of attempts. 90 percent of healthy couples will conceive. Of couples turning to assisted reproduction, however, a year of trying makes little difference. The success rate drops with each procedure, from 13 percent on the first IVF to 4.3 percent by the fourth, according to a 1992 study. The easy cases get pregnant on the first try, explains Stangel; each failure is a sign that the infertility is more intractable than doctors thought. "It suggests that perhaps the policy should be 'Don't encourage people to keep trying'," says Edward Kaplan of Yale University, who chronicled the declining success-per-try. (His wife made several IVF tries; last year they adopted a baby girl from Lithuania.) "It's like going to a casino. There is always going to be, in any few minutes, a winner. You hear the money clinking down. But what you don't hear are the losers."
Yet the couples keep trying. Some seem trapped in their own private Vietnams: having spent $10,000 and with nary a swollen abdomen to show for it, they can't quit until they have a victory--a baby. Valerie Hendy, 44, a New York publicist, echoes the gaming analogy: "You almost feel like you've got a bug for gambling. You say, 'What else is there to try, what else have you got?'" Infertility counselors attribute some of this persistence to recent adoption fiascoes in which biological parents wrest-ed away toddlers adopted as infants. "That's the scare," says Diane Aronson, director of RESOLVE, a nationwide education and support group for infertile couples. "People say, 'I'd rather stay in treatment. I feel like I could have some control'."
Of course, to many couples yearning for a biological child, even one-in-a-million odds would be acceptable. That is, and should remain, an individual's decision. Except that the decision is not always a fully informed one. No one knows whether paying $50,000 for a baby affects a couple's expectations of that child, and how they treat him or her. No one knows whether pumping a woman full of fertility drugs affects her long-term health. One report last year linked Clomid to ovarian cancer. No one knows what risks come with the surgeries for ZIFT and GIFT. "This is an anomaly in medical history: the experimental subjects are not the underprivileged but the elite of society," says reproductive endocrinologist James Simon of Georgetown University. "The wealthy are the guinea pigs and they are paying for it."
Seventeen years ago last month, Louise Brown, the world's first test-tube baby, was born in England. It was a delivery heard round the world, hailed as no less than a medical miracle and evidence that, whatever cards nature had dealt you, modern medicine could slip you an ace. "American society has a lot of faith in medicine and science, and people believe what they want to believe," says George Annas of Boston University. "Physicians doing IVF have not done much to discourage the belief that this is a miracle technology." Far from being a miracle, high-tech treatments for infertility are a little bit of science, a lot of art, and a great deal of luck.
Procedures Up
The total number of assisted-reproduction procedures is on the
rise.
YEAR IVF GIFT ZIFT
1985 3,921 56 --
1987 11,806 2,663 --
1989 18,211 4,372 1,048
1991 24,671 5,452 2,104
SOURCE: PANAK
State Laws
Only six states mandate insurance coverage of
assisted-reproduction technology
STATE DATE ENACTED
Arkansas 1987
Hawaii 1987
Illinois 1991
Maryland 1985
Massachusetts 1987
Rhode Island 1989
In the United States, about 2.8 million couples seek help for infertility every year. Of those, about 40,000 try high-tech assisted reproduction. The five most common techniques:
1 IN VITRO FERTILIZATION (IVF):
How it works: An egg and sperm are combined in a laboratory dish. If the egg is fertilized, the resulting embryo is transferred into the woman's uterus.
How common: 27,000 procedures each year
Success rate: 18.6 percent
Cost: $6,000 to $10,000 for single cycle of IVF
2 GAMETE INTRAFALLOPIAN TRANSFER (GIFT);
How it works: A doctor, using a laparoscope, inserts eggs and sperm directly into a woman's fallopian tube. Any resulting embryo floats into the uterus.
How common: 4,200 procedures initiated each year
Success rate: 28 percent
Cost: $6,000 to $10,000 per attempt
3 INTRAUTERINE INSEMINATION (IUI):
How it works: In this most common procedure, frozen sperm--that of the husband or an unknown donor--is shuttled by a catheter directly into the uterus, bypassing the cervix and upper vagina.
How common: 600,000 procedures with donor sperm
Success rate: 10 percent with donor sperm
Average cost: $300 with donor sperm
4 ZYGOTE INTRAFALLOPIAN TRANSFER (ZIFT):
How it works: In a two-step procedure, eggs are fertilized in the laboratory and any resulting zygotes (fertilized eggs) are transferred to a fallopian tube.
How common: 1,500 procedures each year
Success rate: 24 percent
Cost: $8,000 to $10.000 per attempt
5 INTRACYTOPLASMIC SPERM 5 INJECTION (ICSI):
How it works: A doctor, using a microscopic pipette, injects a single sperm from a man's ejaculate into an egg. The zygote is returned to the uterus.
How common: 1,000 procedures each year
Success rate: 24 percent
Cost: $10,000 to $12,000 per attempt