Reproductive Retirement

A woman's reproductive machinery starts shutting down well before menopause. Although some doctors are investigating innovative techniques for preserving female fertility, others insist that society should encourage women to start their families before their eggs expire.

Maxine Lipner began trying to conceive when she turned 40. A year later a fertility specialist told her that her odds of success were bleak. "I was devastated," says Lipner, a medical writer in Nyack, New York. "I was angry with myself for waiting so long. But I thought I had more time."

Lipner is not alone. Twenty percent of women who give birth in the United States are doing so after age 35, when female fertility starts its precipitous decline. For women under 30, the chance of getting pregnant from well-timed intercourse is about 25% per cycle; after age 40, it drops to 5%. Part of the problem is that, as women age, a greater proportion of their sex cells are genetically defective. Although doctors can't rejuvenate these eggs, researchers are pursuing techniques that could help preserve female fertility. Until such treatments become widely available, however, experts say that society should support women who want to have babies while they're still in their reproductive prime.

Few women appreciate that their window of reproductive opportunity is so narrow. In 2002, researchers at the American Infertility Association (AIA) in New York City conducted a nationwide survey on fertility. Of more than 12,000 women who took the quiz, only one answered all 15 questions correctly. When it comes to fertility, AIA director Pamela Madsen says, "women just don't have a clue. It's not that they're stupid. It's just that women are not given the information they need about reproduction and aging." So they postpone having children to establish careers, attain financial security, or look for a life partner--only to find that they've run out of time. Even M.D.s can be uninformed. At Stanford University's fertility clinic, reproductive endocrinologist Lynn Westphal says that she treats "a lot of physicians who should know that fertility wanes with age--or who do know it but haven't personalized it."

The buzz about advanced fertility treatments lulls many women into a false sense of security. "We hear about all these fabulous technologies and think, 'Worse comes to worst, I'll just use those,' " says Lindsay Nohr, founder of Fertile Hope, an organization that educates cancer patients about preserving their fertility after chemotherapy. But high-end reproductive techniques such as in vitro fertilization (IVF) can't revive exhausted eggs, says Madsen. The drugs used in IVF and other fertility-enhancing treatments can boost the quantity of eggs produced per month, but they can't improve the quality.

Females are born with a stockpile of oocytes, the cells that give rise to mature eggs. Between puberty and menopause, these immature cells die in droves. A girl who carries 7 million oocytes as a fetus might have only 200,000 when she gets her first period. And the remaining oocytes become increasingly funky with age. "By the time a woman is in her 40s, perhaps half the eggs she ovulates are chromosomally abnormal," says Patricia Hunt, a cytogeneticist at Case Western Reserve University in Cleveland, Ohio. They wind up with the wrong number of chromosomes--a situation that usually leads to difficulty conceiving, miscarriage, or babies with conditions such as Down syndrome.

Some researchers think that the frequency of such chromosomal mishaps mounts over time because oocytes get their marching orders from hormones. And when a woman nears menopause, her hormone concentrations start to go haywire. The resulting garbled signals can trip up the molecular machinery that orchestrates the orderly distribution of chromosomes during egg development, says Hunt. Sperm tend to escape such anomalies in part because they have better quality control, self-destructing if they detect mismatched chromosomes.

But the egg story is still evolving. In a study that appeared in Nature in March, scientists challenged the dogma that females are born with a lifetime supply of eggs, presenting evidence suggesting that mouse ovaries produce oocytes after birth. "If you could generate new eggs into adulthood, that would be tremendous," says Hunt. But it's unclear whether these oocytes can mature, she says, and the data don't explain why women--and mice--go through menopause. So the "jury's still out" on that study.

In the meantime, physicians are working to help young women put babymaking on the back burner by putting their oocytes on ice. The procedure is used most often by cancer patients, such as Nohr, who freeze oocytes before undergoing chemotherapy, a treatment that can decimate a woman's ovarian stash. More than 100 babies have been born from frozen eggs, and Stanford is now offering the service to women who want to bank their oocytes while they chase careers--or mates. Other clinics are freezing pieces of ovarian tissue, again for cancer patients. Although no babies have yet been born from frozen ovaries, the transplanted tissue pumps out hormones and releases eggs once a month.

But these approaches are not likely to allow the average woman to hit the snooze button on her biological clock. Women would have to commit themselves when they're young--when they might not be able to afford the treatments and when "reproduction is not even on their radar screen," says Westphal. And the procedures come with risks, says Lubna Pal, a reproductive endocrinologist at Albert Einstein College of Medicine in New York City. Surgery to obtain ovarian tissue, for instance, can do damage that compromises future fertility. "Exposing healthy young women to medical procedures is not the solution," says Outi Hovatta, a professor of obstetrics and gynecology at the Karolinska Institute in Stockholm.

The solution, Madsen says, lies in social reform--more on-site daycare, for example--and in increasing the public's awareness of fertility issues. "We need to tell women that they can't wait until they're 43 and the company V.P.," she says. "And we need to make employers realize that taking time off to have a child is not a luxury, it's a biological necessity."

Lipner says she would have welcomed an earlier lesson in fertility. "I wish I'd known up front that there's so little that can be done for older eggs," she says. "I wish I'd known that the finish line was much closer than I thought." Recognizing that eggs have a limited shelf life could help women make better-informed decisions about when to start building their nests.

Karen Hopkin is a freelance writer and editor for SAGE Crossroads. After 10 months of trying at home, 5 months of trying with drugs, and one failed IVF attempt, she still hopes she can find a 40-year-old egg with enough spunk to get the job done.