The Future Of Birth

Today's fertility treatments fail more often than they succeed, but assisted reproduction is still a young science, and researchers insist it's a hopeful one. "We've seen, huge changes in the past 10 years,' says Dr. Mark Sauer, a fertility specialist at the University of Southern California. It's hard to imagine where we might be in another 10." The fact that scientists are devising new techniques doesn't mean patients will benefit. Exciting innovations often prove worthless or harmful in the long run. But if several emerging technologies fulfill their promise, they could help couples conquer such knotty problems as advanced age, poor sperm quality and the body's rejection of healthy embryos.

It's no secret that the eggs in a woman's ovaries deteriorate as she ages. Procedures like in vitro fertilization (IVF) are only a third as successful in women older than 40 as they are in younger patients. Yet when older women "borrow" fresh eggs from younger donors, they enjoy younger women's success rates. Suppose a 20-year-old woman could have eggs removed from her own ovaries and frozen for safekeeping. When she was ready to conceive, a doctor would simply thaw them and use her partner's sperm to create implantable embryos.

The trouble is, eggs don't freeze well. Unlike embryos, which survive for years in cold storage, unfertilized eggs are extremely fragile. More than half of those frozen in any given experiment disintegrate when they're thawed. And even though the survivors are easily fertilized, the resulting embryos rarely develop properly. They're less likely than fresh-egg embryos to "implant," or take root in the womb, and they're more likely to be aborted as they gestate.

Fortunately, cyropreservation techniques are improving. Researchers have found that eggs are more likely to survive freezing if they're cooled very rapidly, or treated with chemicals such as DMSO (dimethylsulfoxide), which protect cellular membranes. When an egg survives the freezing process, says embryologist Patrick Quinn of California's Encino-Tarzana Regional Medical Center, it should last at least 400 years. Getting preserved eggs to develop properly after they're thawed and fertilized is still a challenge, but placing them in culture with tissue from fallopian tubes seems to help. Several teams have now succeeded at turning frozen eggs into healthy infants. Though the process is still too costly and inefficient to use in clinical practice, egg banking could be commonplace within decades.

A perfect egg doesn't count for much without some healthy sperm to match. In nearly half of all infertile couples, the male partner produces so few sperm, or such lethargic ones, that conception never occurs. Some clinics now offer such couples an experimental procedure called ICSI (intracytoplasmic sperm injection). To perform IICSII, the specialist first captures individual sperm cell with an ultrafine pipette (if thelman has no semen, the cells can sometimes be extracted surgically from his testicles). The healthiest-looking sperm are then injected, through a fine needle; into eggs that have been harvested from the mother.

ICSI is still very expensive, raising the cost of IVF by some $1,500 per try. But some clinics claim anecdotally that it produces 20 to 30 percent pregnancy rates in couples who had virtually no chance of conceiving through traditional IVF. And though no one has subjected the procedure to large clinical trials to see whether all that manipulation of the egg causes birth defects, there is so far no indication that it does. "This procedure occurs at such an early stage that if an injury occurred, it would be lethal," says Dr. G. David Adamson. a reproductive endocrinologist in Palo Alto, Calif.

Even when they manage to conceive--naturally or in test tubes--some couples suffer one miscarriage after another because the woman's immune system rejects healthy embryos as foreign tissue. A developing embryo is biologically foreign to the mother's body, for its cells bear the father's molecular signature as well as her own. The appearance of foreign molecules on the placenta normally prompts the mother's body to produce "blocking antibodies," which effectively hide the baby from her immune system. But as Dr. Alan Beer of the Chicago Medical School has shown, similarities in a couple's cell types can suppress the production of blocking antibodies, leaving the mom's immune system on full alert. Dr. Carolyn Coulam of the Genetics and IVF Institute in Fairfax, Va., estimates that 30 percent of recurrent miscarriages involve these immunological mixups.

Researchers are attacking the problem from various angles. Several teams have reported that injecting women with immunoglobulins (which seem to trigger production of blocking antibodies) can improve pregnancy and birthrates. In one recent study, Coulam's team gave imrnunoglobulin shots to 16 women who, despite producing fertile eggs, had failed at least two earlier rounds of IVF. The odds of succeeding at IVF on the third try are normally just 7 percent--yet nine of the 16 patients did just that.

In San Francisco, Dr. Geoffrey Sher and his colleagues at the Pacific Fertility Medical Center are experimenting with related treatments. In a 1994 study, Sher reported that low doses of aspirin and heparin, a blood thinner, raised pregnancy rates in women whose immune systems produced a suspected embryo killer called APA (anti-phospholipid antibody). In Sher's study, 49 percent of the women taking the remedy (82 out of 169) had embryos successfully implanted on their first IVF cycle. Only 16 percent of the women receiving a placebo (4 out of 25) managed that feat.

Few experts are ready to embrace the heparin-and-aspirin regimen until it's tested more thoroughly. Sher's study didn't firmly establish that APA had caused his patients' problems, or that his treatment acted specifically against APA. His buoyant assertion that "the long-awaited breakthrough. . . may finally have arrived" seems premature at best, considering the baby industry's history of unmet promises. Childless couples should be as wary as ever of big claims based on small experiments; none of the emerging technologies has been proven effective in large trials. But there's no question that the frontiers of fertility are expanding.

Trying Again



According a 1992 study, chances of getting pregnant with IVF

decease with each attempt.



ATTEMPT    PERCENT CHANCE



  1st           13.0%

  2d            10.7%

  3d             6.9%

  4th            4.3%



Source: KAPLAN