Researchers seek tick of women's biological clock

SEATTLE

Theresa Naluai-Cecchini's lab coat fluttered as she strode down the hallway of the University of Washington Medical Center.

Her left hand clutched a plastic container that looked very much like a toolbox, except for the orange "Biohazard" sticker affixed to it.

As Naluai-Cecchini pushed the elevator button, her attention seemed fixed on her mission rather than the social significance of her team's project, which could revolutionize the lives of women everywhere.

Soon their work could solve a riddle that even the most sophisticated science cannot unravel today: how many years a woman has left to get pregnant.

Researchers at the UW's Fertility and Endocrine Center, working with a $400,000 federal grant, are closing in on a solution to the fertility frustration.

They may not be able to extend childbearing years, but within three years they may be able to give a woman information that right now cannot be found anywhere in the world: how much longer she can reasonably expect to remain fertile.

No one had ever bothered to figure out how long women remain fertile because it had never been much of a concern. Most infertility problems in the past have been related to anatomical abnormalities.

"When I started 40 years ago in this business, you never saw a 40-year-old infertility patient," said Dr. Michael Soules, head of the fertility clinic and one of three doctors in charge of the project. "They started showing up about 10 years ago. They were delaying childbirth like no other generation."

For all the significance of the work, for all its breakthrough scientific potential, the core of the project's methods couldn't be simpler. In the end, it comes down to counting. Find a way to accurately count the eggs in enough ovaries and patterns begin to emerge.

"This is not rocket science," said Soules.

The counting is significant because of the possible relationship that exists among the different types of eggs in the ovaries. The researchers believe a typical baby girl is born with about 1 million eggs, 500,000 in each ovary. The eggs sit in small clusters just under the surface of the ovary and are known in this state as primordial follicles.

After puberty, some of these eggs begin to grow and move toward the center of the ovary. The layers of cells that surround these eggs also grow, secreting a liquid as they do. And in that liquid lies the hopes of the project.

The growing egg and surrounding cells are known as antral follicles, and the UW researchers believe there is a correlation between the number of them at any given time and the total number of eggs in the ovary. The more antral follicles, the more eggs remaining. What makes this so important is that the liquid in antral follicles shows up on sonograms.

Soon, doctors may be able to tell a woman how many eggs she has with a simple ultrasound.

The team wants to count another 100 or so ovaries before it draws any conclusions, but the researchers believe that a normal, fertile woman has between 20 and 25 antral follicles at any time. Women with 10 or fewer will have a hard time conceiving.

Though the researchers are confident of their findings so far, plenty of work remains. It may be that women are born with vastly different numbers of eggs, or that they lose them at different rates. And it may be that both of those possibilities are true. If that's the case, the researchers may never be able to predict how long a woman will remain fertile because they won't know whether her eggs are diminishing quickly or slowly.

But even then, the sonogram would provide a useful snapshot of a woman's fertility. If it showed she had, say, 15 antral follicles, and she wanted children, she would know to start thinking about getting pregnant fairly soon.

"Maybe you're planting a seed," said Dr. Nancy Klein, who heads the team along with Soules and Dr. Angela Thyer. "You can say, 'Hey, you're looking a little low.' Maybe she'll think about having children at 30 instead of waiting."