Of course cryopreservation will not help those whose eggs are already sitting on the porch in little rocking chairs. But researchers have found ways to keep old eggs alive. Jon Tilly, the director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital in Boston, has been studying genetically altered mice to better understand the process of apoptosis, or natural cell death. Cells are programmed to die: Fifty or sixty genes, maybe more, regulate their expiration. One specifically involved in the death of immature eggs in the ovaries is known as the bax gene. When Tilly and his researchers studied mice that lacked the bax gene, they found that 24-month-old females—the equivalent of 80- to 100-year-old humans—still have functioning, estrogen-producing ovaries.
“We were pretty amazed,” says Tilly. “And the bax gene has a precise counterpart in humans that appears to be responsible for the decimation of eggs during menopause.” Silencing of one of the “cell death” genes may be the first step in finding treatments to help woman delay menopause or avoid the health problems—osteoporosis, heart disease—associated with the cessation of estrogen production. Tilly also believes that in the not-wildly-distant future the ability to suppress the bax gene in women’s ovaries may prolong their fertility too. He is quick to add, however, that even though the old female mice with newly viable eggs were allowed to cavort with young, studly mice, they did not produce offspring. This is because older mice lose the capacity to excrete adequate levels of two hormones: one that stimulates egg follicles to grow and mature and another that causes the ripened egg to be released from the ovary into the reproductive tract.
Another approach to ending infertility involves beating the numbers game. What if a woman had an unlimited number of eggs? This may someday be possible if researchers can get somatic cells—that is, cells from anywhere in the body—to act like sex cells. Normal cells are diploid, with 46 chromosomes—23 from one’s father and 23 from one’s mother. The gonads (testicles and ovaries) divide the chromosomes to create haploid cells, namely spermatozoa and eggs. As the eggs age, most suffer from aneuploidy, the uneven division of the chromosomes. Anything other than 23 sets of chromosomes makes the egg either entirely unviable, or viable but resulting in abnormalities like Down’s syndrome. It is not that the eggs, in their undeveloped state, are abnormal; it’s that something about the machinery of meiosis—the chromosomal division at ovulation—goes awry as women age. The key to fixing this problem is to make faux eggs—normal body cells that behave like eggs by undergoing meiosis. Thus, anyone 18 to 100 would have an unlimited supply of easily harvested “sex cells.”
This is exactly what Cohen and some other researchers are working on now. Bioethicists balk, because the process sounds like a kissing cousin to cloning. But it’s not. The resulting cell has half its mother’s chromosomes and, when united with sperm, could be expected to create a bona fide, half-his, half-hers human. The catch is that the parents could theoretically be 100 or more years old. “This is going to involve some major discussions about what’s clinically acceptable and what’s socially acceptable,” Cohen says.
Of course, even if they have all the financial resources in the world, most couples past the age of retirement probably won’t want to start raising children. “This won’t be some huge public policy issue,” says Arthur Caplan, director of the University of Pennsylvania’s Center for Bioethics. “It’s not like you’ll see all these people running from nursing homes to birthing centers.” But, Caplan adds, the very fact that 50-year-old mothers and fathers could become relatively commonplace raises another issue. “One of the ethical questions becomes: What’s in the best interest of the child? And the answer is simple: It’s good not to be an orphan. A good, loving environment requires one parent.
So if a father is 20 and a mother 80, that’s not a problem. If the father is 60 and the mother 40, well, one should think about the implications of depriving a child of grandparents. It’s not morally reprehensible, but it’s an issue. Now, if both parents are in their sixties”—as was the case in 1996 with Arceli Keh, the 63-year-old Filipino who gave birth after lying about her age to her fertility specialists in California—“that’s a problem.”
Contemplating their own untimely demise won’t deter truly determined older parent wanna-bes, like Eileen and Charles Volz of Millbury, Massachusetts. Eileen, a certified public accountant, was 42 and had just married Charles, a digital commerce executive, in 1992 when she was diagnosed with breast cancer. Radiation and chemotherapy put her into immediate menopause, but she overcame the cancer. Four years passed before she and her husband heard about egg donation. “People thought we were a little nuts,” says Charles Volz. “I mean, I already had three children, and she had survived breast cancer—why should we tempt fate?”
One look at their son, C.J., answers the question. On her first try at Machelle Seibel’s clinic, she got pregnant with a donor egg and had C.J. at 48. “I never for a moment felt he wasn’t mine,” Eileen says. “Genetics is the smallest part of being a mother.”
Eileen Volz is now 50; her husband is 48. They tried a second round of egg donation, which failed, but they are contemplating a third. Sure they’ll be collecting Social Security by the time C.J. is ready to head off to college. But Charles Volz speaks for older parents everywhere when he offers this Pollyannaish view of his midlife adventure: “It’s not a problem at all. Hey, I’m going to live forever.”
Perhaps the biggest question for science and society will not be answered for a number of years, until the first generation of children born to older parents through assisted reproductive technology enters their teenage years: What happens when children nature did not intend to create become adults? Already there are some troubling questions about the 20,000 children conceived throughout the world by intracytoplasmic sperm injection. Aggressively injecting a sperm into an egg manually has been found to change a whole sequence of molecular events in fertilization; for example, the dna packaged in the head of the sperm unravels more slowly than in normal fertilization, throwing off the timing of the process. Scientists worry that although there hasn’t been an obvious increase in birth defects so far, sex chromosome abnormalities may show up when the children reach puberty. One 1998 study in Belgium showed that of 1,082 prenatal tests on intracytoplasmic sperm injection pregnancies, one in 120 had sex chromosome abnormalities, as compared to a general population figure of one in 500 pregnancies.
“Fertility is a unique field in some respects,” says Massachusetts General’s Jon Tilly. “In most fields of scientific inquiry, most of the problems are worked out in animal models. But here, technology is moving so fast, and people are so desperate for answers, that work on humans is paralleling work on animals. That may be turn out to be good, because we are accelerating the application of our knowledge. But it may be bad, because we don’t know what’s safe. We don’t know about unforeseen problems. There may be reasons the body is not designed to be reproducing after its early forties.”