Since the birth of the world's first "test-tube" baby nearly 30 years ago, doctors have made remarkable strides in helping infertile couples achieve their dreams of having a family.
Overall, about a third of couples who seek infertility treatment today will bring home a bundle of joy (or two or three), though that number can fluctuate dramatically depending on the reason a couple can't conceive naturally and the woman's age.
But now, improvements in the "take-home-baby rate" have slowed or even plateaued at the nation's top infertility clinics. And reproductive specialists find themselves at a crossroads, searching for new ways to boost success.
"We're better at what we do but we can't reverse the effect of aging," says Dr. Eric Surrey, medical director of the Colorado Center for Reproductive Medicine in Englewood and a past president of the Society for Assisted Reproductive Technology.
As Dr. Richard Scott, director of reproductive endocrinology at the University of Medicine and Dentistry of New Jersey, puts it, "We’re up against the glass ceiling of reproductive aging.”
A woman's fertility begins to decline in her late 20s, drops off more sharply after 35 and plummets when she hits 40. In fact, after age 30, the probability of a woman getting pregnant naturally decreases 3 percent to 5 percent per year — and even faster when she hits 40, notes the American Fertility Association. Whereas a healthy 30-year-old woman has a 20 percent chance of getting pregnant in any given month, by age 40 those odds drop to 5 percent.
Through the use of fertility drugs to induce ovulation and techniques such as in vitro fertilization (IVF) — in which an egg and sperm are combined in a lab dish and any resulting embryos are transferred to a woman's uterus — doctors worldwide have helped thousands of couples to overcome fertility problems. In the United States alone, nearly 400,000 babies were born as a result of assisted reproductive technologies since 1985, when the American Society for Reproductive Medicine began collecting data, through 2004.
But doctors have had the least success in cases where women are over 40 because their eggs are deteriorating or dramatically declining in number. In a last-ditch effort to conceive, these women often have to turn to donor eggs or embryos.
Doctors have continued to improve upon their existing techniques, with incremental improvements in their ability to induce ovulation, grow embryos longer in the lab and more safely transfer them to the womb. They're trying to find ways to improve the process even further and make it more tolerable for women using simpler hormone regimens that produce fewer side effects. And they're hopeful that new developments on the horizon — particularly embryo evaluation and egg-freezing — will allow them to boost birth rates even more.
"The success rate will never be 100 percent," says Surrey. "But there is a gap in current knowledge base that I think will be filled in the next five to 10 years."
Selecting the cream of the crop
One of the biggest challenges with IVF is figuring out which embryos to transfer to a woman's uterus. "With IVF failures, most often the embryo produced doesn't have the genetic [capability] to develop beyond a certain stage," explains Dr. Steven Ory, president of the American Society for Reproductive Medicine who is in private practice in Margate, Fla.
Currently, doctors simply look at the embryos and try to tell which ones seem most likely to fully develop based on their shape and size. So researchers are experimenting with several approaches that would allow them to evaluate embryos and transfer only the healthiest ones that are most likely to take up residence in the uterus.
A technique already in use is called preimplantation genetic diagnosis (PGD). Doctors extract a cell from an embryo and test it for chromosomal abnormalities. PGD is good for screening for specific genetic disorders such as cystic fibrosis and Tay-Sachs disease, and also can be used to select gender. But it tests fewer than half of the chromosomes in an embryo, so it's not a perfect indicator of overall embryo health and it hasn't been all that useful for most women.
"It has not been shown to consistently improve the outcome," says Ory.
To do better, scientists are experimenting with methods that assess how an embryo functions when it's in the culture solution in the lab. What chemicals and proteins does it release into the solution it's being bathed in and what does that say about its viability?
Ideally, doctors would like to be able to identify a biochemical marker that they could measure in the culture medium that would accurately indicate the healthiest embryos.
Experts predict such an advance might be available in the next several years. "I don't think that's science fiction," says Ory.
Researchers also are working on a technique called comparative genomic hybridization that aims to improve upon PGD by allowing doctors to remove more than one cell from an embryo and examine all 23 chromosomes, says Surrey.
Freezing a woman's future?
Another hot area of fertility research is egg-freezing, which would allow young women to store healthy eggs and then thaw them out when they're ready to have kids — perhaps 10 or even 15 years down the line. It also could benefit women with cancer who are about to undergo treatment that would destroy their eggs.
The field has been plagued by problems though, because unlike sperm and even embryos, eggs are much more fragile and don't freeze well. But recent quick-freezing advances are allowing doctors to get better results, and an estimated couple hundred or more babies worldwide have been born from frozen eggs that have been thawed and fertilized. Experts predict egg-freezing will be a much more common — and successful — practice within the next decade, perhaps within the next several years.
"There are some encouraging experiments but to date not enough programs have reported on good enough experiments for us to endorse it as a standard technique," says Ory, "but I think that day is rapidly approaching."
For now, though, experts caution that women should view egg-freezing with their eyes very much wide open.
Scott says his fear is that 24-year-olds will come into his clinic, freeze their eggs and then return at 45 — an age when it's very unlikely they'll conceive on their own — and not be able to become pregnant with the frozen eggs either.
"Egg-freezing is a way to hedge your bet but it’s not an absolute guarantee,” he cautions.
Plus, pregnancies at older ages carry more dangers, including the development of gestational diabetes and hypertension. And no one knows whether the children born from frozen eggs might face increased health risks.
Uterine transplants are another approach being explored on the fertility front. Theoretically, they would allow women without a healthy womb, either due to disease or because she was born without one, to bear children. But the surgery would be a major undertaking that would require a woman to take anti-rejection drugs that could pose a risk to a fetus.
In 2000, doctors in Saudi Arabia announced they had performed a uterine transplant in a woman, but the organ had to be removed after three months because of blood-clotting problems. Earlier this year, doctors at New York Downtown Hospital said they are making plans to do the first uterine transplant in the United States. Experiments in rodents have shown that uterine transplants can yield offspring.
Also in the future, though probably still a long way off, doctors might one day use stem-cell technology to produce sperm and eggs in the lab, allowing a man or woman who otherwise can't reproduce their own biological children to do so. Experiments have shown that human egg and sperm can be artificially grown, though no babies have been created.
And as for all those lingering fears that doctors will one day produce babies by cloning their parents, it seems we're no more likely to see that scenario play out today than we were 10 years ago when Dolly the cloned sheep made her debut.
Mainstream scientists aren't going down this path because of all the health and ethical concerns involved.
"No one wants to do reproductive cloning," says Scott. "It is scary.”