Precious cargo: Only one mature follicle releases an oocyte each month, making the egg the limiting factor in fertility research.

It is day seven of a young woman's menstrual cycle. More than a dozen small follicles in her ovaries respond to the surge of hormones, releasing estrogen, filling with blood and growing faster than any other structure in the body. Within a couple of days, one among them becomes dominant, growing even larger and protecting and nourishing the egg it carries. The others shrink rapidly, stop secreting estrogen and disappear.

But what if you could capture those young follicles before they shrink into oblivion? What if you could allow each to fulfill its destiny and release an egg capable of fertilization? This fall, scientists at three centers in the US will initiate a clinical trial to do just that. Stanford researcher Barry Behr and others plan to recruit young women with polycystic ovary syndrome—who have many more follicles than average—to collect their immature follicles and bathe the cells in a nourishing mixture of growth factors, proteins, vitamins and amino acids.

The technique, called in vitro maturation (IVM), has already been successful in some East Asian nations, in Australia and at McGill University in Canada. Nearly 200 babies have been born and, so far, all appear perfectly healthy.

IVM is one of many new advances in the booming field of assistive reproductive technology (ART), which burst into fame with the birth of the first 'test-tube' baby in 1978. Today, there are more than a million babies born by in vitro fertilization (IVF). In the US, despite the cost of IVF—treatment cycles average $12,000—35,000 IVF babies were born in 2000, accounting for nearly 1% of all babies born that year. Between 1988 and 2000, the success rate of IVF in women under 35 doubled to nearly 40%.

With a clinical pregnancy rate of 30%, IVM is less efficient than IVF. But the technique allows women to bypass hormone treatment and offers women with polycystic ovary syndrome a safe alternative to IVF, says Behr, director of the IVF and ART labs at Stanford University.

At recent fertility meetings, experts were heard proudly proclaiming that they would soon be able to help anyone. At the moment, however, there is little they can do to help women older than 40, who make up at least half of US fertility patients. The IVF success rate in those women drops to just 6%.

To help those who cannot be reached by available techniques, there are some bizarre technologies in the pipeline. Several groups are trying to create eggs and sperm in the test tube (Nature 424, 364; 2003). Others are freezing ovarian tissue from patients undergoing chemotherapy—but scientists do not yet know how to grow follicles from such an early stage. Because eggs are usually the limiting factor in ART, some groups are perfecting egg-freezing techniques.

Progress in the field is slow because eggs rarely become available, says Roger Gosden, scientific director of the Jones Institute for Reproductive Medicine in Virginia. “Most eggs left over from IVF are stale and faulty,” Gosden notes. Fertility research relies heavily on animal models, particularly farm animals, but the results do not always hold up in humans.

Even selecting embryos for implantation is more like a beauty contest than based on any meaningful markers of fitness, says Gosden. To more accurately judge their merit, embryos can be matured for an additional 24–48 hours in vitro—akin to guessing a marathon winner after the 21-mile mark, rather than the 2-mile mark. But doubts remain about that technique's safety.

Of mounting concern in the field is the fact that many such procedures are widely adopted before they are proven to be safe. Recent studies suggest that babies born by ART might be at greater risk of birth defects, low birth weight and genetic diseases (Nature 422, 656; 2003). But many in the fertility industry have derided those studies, citing a lack of adequate controls.

To find meaningful trends in the skimpy and contradictory literature, the Genetics and Public Policy Center at Johns Hopkins University has assembled a panel of experts, and expects to hold a public forum on the topic in November. The panel's report on ART risks is expected by the end of the year.

One of the most politically charged issues in ART is preimplantation genetic diagnosis (PGD). In use since 1988, PGD is used to screen for disorders such as cystic fibrosis and familial Alzheimer disease, and for gender selection. “[Soon] there will be no IVF without PGD,” predicts Yury Verlinsky, director of the Chicago-based Reproductive Genetics Institute.

Partly prompted by concerns about PGD, the President's Council on Bioethics is pondering legislative options for ART and is expected to announce its findings by the end of November. The US fertility industry is currently subject only to voluntary self-regulation. In most other countries, including the UK and Canada, the government funds and regulates ART.

Verlinsky is one of several researchers who have been vocal about keeping ART free of federal regulation. Others contend that without oversight, it is easy to lose sight of unsavory turns research may take. At a recent fertility conference in Madrid, for instance, Israeli scientists announced that they had succeeded in growing egg-producing follicles from aborted fetuses, and US researchers presented evidence of chimeric 'she-male' human embryos.

“Just look at what goes on out there,” says Jeffrey Kahn, director of the Center for Bioethics at the University of Minnesota. Self-regulation may be enough for other medical techniques, Kahn says, “but for something that has societal implications, that's not a good answer.”