April 28, 2011
by Nancy Hass
The wallet-size case, cleverly designed by the drug company to fit the hypodermic needles and the tiny vials of hormones, sits on her kitchen counter, the only thing Leah really sees when she makes her morning coffee. The path she’ll start down in three days is scary, lonely, and a bit embarrassing—she had to ask a girlfriend to come over every morning to plunge a needle into her buttock—but also exciting. And she is sustained by an astonishing thought: I am freeing myself from the tyranny of the expiration date.
Leah, a willowy 35-year-old media-company executive, is accustomed to taking chances; that’s how she came to rise so high professionally at her age. But this one is big. She’s about to join the vanguard of what may be the most significant social change since the advent of the Pill, taking a technological step that in just the past year has emerged as a real option for women. She will spend at least $15,000—perhaps twice that—to freeze as many eggs as science can help her produce in a month or two and keep them in a cryogenic vat indefinitely. No one is officially tracking the numbers yet, but fertility experts say she is among the several thousand American women this year who are expected to opt for egg freezing, known technically as oocyte cryopreservation. “The science of egg freezing is finally at a place where it’s making a real difference in people’s lives and futures,” says Jamie Grifo, M.D., program director of the Fertility Center at New York University. “We’ve been working toward this point for years, and sometimes it’s hard to believe we’re here.”
Leah never thought she’d need to do this. The plan was to be married by now. But her on-and-off boyfriend, a gourmet-food importer, just isn’t headed in the same direction as she. He’s adorable but not serious. He smokes too much pot. Her boss at her last job had brought up egg freezing a couple of years before, after he and his wife, in their late 30s, had had trouble conceiving, and he urged her to look into anything that would spare her the pain they’d gone through. The idea had floated back to her in recent months. She knew she was coming dangerously close to the age when eligible men might search her eyes for desperation, that unseemly my-clock-is-ticking vibe. “Freezing my eggs is my little secret,” she says. “I want to feel there’s a backup plan. I don’t want to waste the next few years in a state of panic, or feel terrible every time I hear that one of my married friends is pregnant.”
Stopping the biological clock through egg freezing has long been the ultimate feminist fantasy. The Pill was the first step, enabling women to delay childbearing, a revolution that profoundly altered society. But over the past five decades, the price we’ve paid has been age-related infertility, on an epic scale. Many young women blithely believe they can wait until their 40s to have kids, but that is wishful thinking. At age 40, more than half will not be able to conceive without help, and by 44, even with IVF, that number plummets below 5 percent. No matter how nutritious your diet or strenuous your workout, your eggs still get old, still betray you.
Unlike embryos, which scientists have been able to freeze since the early 1980s (about 16 percent of successful IVF procedures are now done with embryos that have been frozen and thawed), eggs were, until recently, thought too delicate to survive the process. Made up of a single cell, they contain a large amount of liquid, and using the slow-freezing method that was successful for cryopreserving embryos created ice crystals that destroyed the eggs. In the past decade, increasing numbers of clinics have offered oocyte freezing to cancer patients undergoing radiation, but with scant success rates, the suggestion was more of a palliative comfort than a real option.
In 2006, however, embryologists started experimenting with new twists on cryopreservation, including a flash-freezing process known as vitrification, to chill the eggs to minus-196° C in a fraction of a second. The work was first done in Europe, mostly in Italy and Spain, where religious concerns made IVF patients uncomfortable keeping their excess embryos in the freezer indefinitely; they felt that unfertilized eggs would be easier to discard later on, if necessary.
In the past two years several published peer-reviewed studies, including one by the NYU clinic where Leah is being treated, have shown remarkable results. Prior to 2007, there were only a handful of reported births from frozen eggs; since then, more than 1,500 babies have been born around the world by this method. According to the studies, the birthrate in IVF procedures with frozen eggs extracted from women under 36 is now close to 50 percent—comparable to that of “fresh” eggs from women of that age. In a recently published study by NYU researchers, out of 23 cycles with frozen eggs, thirteen babies were born.
The early spring day is unusually balmy, and Leah has on only a light cashmere sweater as she steps from the taxi into the lobby of the clinic on Manhattan’s East Side. She comes here every morning to get blood drawn. Doctors check how she is responding to the medications, in case the dose needs adjusting. In about twelve days, if her hormone levels look good and the ultrasounds show that she has plenty of follicles with eggs developing in them, she will be put under anesthesia so her doctor, Fred Licciardi, M.D., can extract the oocytes for freezing.
“Today I’m feeling strong,” she says as she sits down in the chair. Around her, in cubicles, are a half-dozen other women also there for daily blood work. Most are older by five or ten years, and all seem to be on a different emotional plane from Leah; they are going through IVF, hoping for a pregnancy that has thus far eluded them. They are working hard to control their panic; you can see it on their faces as they clutch their designer handbags or adjust the straps of their shoes with a combustible mix of anxiety and hope.
Not that Leah doesn’t have her worries, including whether the drugs will make her edgy and tearful, a particular concern since she recently started a demanding new job. She also can’t help wondering if hyperstimulating her ovaries like this will diminish her ability to have kids the natural way (doctors say the risk is no greater than with a cycle of IVF). And she tries not to think about the money she’s spending—her bonus for the year, plus some. “Hey, this is what people spend on breast implants,” she says, forcing a grin.
The nurse smiles and tells her she can go. Leah doesn’t know if that means her numbers are OK, but she figures the doctor will call if there’s a problem. “I’m just powering through, trying not to obsess about the details,” she says as she hails a cab at the corner. “I keep reminding myself that someday I’ll be grateful for having made myself do this.”
Leah is the only one of her social circle to plunge into egg freezing (her friends’ reactions have ranged from gung-ho support to insistence that she’s too young to worry about such things), but that may change in the next year or two. IVF is already a multibillion-dollar business, but some experts expect “fertility preservation,” as egg freezing is euphemistically referred to on the Web sites of many clinics, to eclipse that. And over the next decade, as the procedure becomes more common, the need for age-related IVF treatments, as well as the demand for egg donation, will, theoretically, recede tremendously.
With 30 million women in the United States between the ages of 20 and 34, the market for egg freezing is enormous, a truth that has not eluded those in the business of helping make babies. “There is already the potential for eight times the demand for egg freezing as there is for IVF procedures, just based on population numbers,” says Geoffrey Sher, M.D., a Las Vegas–based fertility doctor who claims to have started the first private IVF clinic in the United States in 1982 and now has seven IVF programs across the country. Sher, an active proponent of egg freezing whose bold self-promotion and early adoption of new methods makes him a controversial figure in the fertility world, expects that for now, at least, most women will opt to freeze eggs at between 30 and 36—the age at which they become aware that time is passing. But he hopes that one day it will become commonplace among much younger women, too. At 24, most women can easily produce enough healthy eggs to virtually guarantee they will one day be able to have their own genetic children (after 35, with fertility starting to wane, fewer of the eggs women freeze are likely to be viable). “You’re in a generation of people that has witnessed the pain of infertility,” he said. “If you’re a parent, do you want to give your child a new Honda when they graduate from college or a chance to have both a career and a family?”
For the foreseeable future, though, the main demographic for egg freezing is women like one I’ll call Rachel, since she does not want to be identified. Rachel is now 39 and froze her eggs in 2009. That was the year that her ex-husband—they split in 2004—had a baby with another woman. It was a wake-up call; Rachel, a public-relations executive, realized she wasn’t as young as she felt. Her relationship with her former husband was civil, so she called to ask him if he would pick up the tab. She wasn’t blaming him for her situation—she had married him in her late 20s and concedes that children hadn’t been on either of their minds. “We figured we’d have kids one day, and then things just fell apart with us,” she said. Her ex, who is quite wealthy, was happy to pay for the procedure. “He thought it was a great idea,” she said.
Sarah Brokaw, a 41-year-old psychotherapist in Beverly Hills whose father is the former NBC news anchor Tom Brokaw, had a similar epiphany. When she was 37, her sister, two years older with a couple of kids, mentioned that many of her friends were having trouble conceiving. Brokaw’s doctor showed her a chart tracing the decline of fertility between 35 and 37. It was alarming. Deciding to freeze her eggs became a pivotal point of reference in Brokaw’s recently published book Fortytude, a self-help guide offering life strategies for women in middle age. “Freezing my eggs was part of me feeling like I was taking control of my future,” she says. “There’s a generation of women who now will have chances that no women before them have ever had.”
Hype aside, the number of women who avail themselves of the procedure would likely increase much faster if not for a thorny debate within the fertility establishment. The American Society for Reproductive Medicine (ASRM) deemed egg freezing “experimental” in 2006 and has stuck with that label despite the recent studies. In vitro fertilization itself never carried that designation, nor did newer technologies like intra-cytoplasmic sperm injection ICSI, the now-routine process of cracking open oocytes during the IVF process to help the sperm gain access to the egg.
“If the ASRM had slapped the experimental label on IVF 20 years ago, I never would have had my kids,” says Pamela Madsen, a longtime patient advocate who had two children through IVF and founded the American Fertility Association. “I’m sad to think that women in their mid-30s, the ones who should be thinking about this, won’t at least explore it. It might save them some heartache on the other side.”
Officials at the ASRM say that the experimental designation isn’t meant to scare women away from the procedure or suggest they believe it is dangerous. “Look, at this point we aren’t discouraging women from doing it,” said Samantha Pfeifer, M.D., a University of Pennsylvania–based reproductive endocrinologist who heads the ASRM’s committee on reproductive-medicine guidelines. “It may be an amazing chance for women to have control over their reproductive future. We just don’t think there are yet sufficient studies. We want to err on the side of caution.”
The new work on cryopreserved oocytes is indeed “really exciting, really encouraging,” she said, but the number of live births is still too small, and many were not monitored in a proper research environment. With the time lapse between freezing and thawing—frozen embryos are usually thawed and implanted within months, but women aren’t likely to need their frozen eggs for five years or more—not enough children born of a frozen egg have reached maturity, so the long-term repercussions are unknown. (No abnormalities have yet been reported.) There is also no data on how long eggs can be frozen, she adds. Preliminary studies suggest that frozen oocytes may last ten years; some researchers believe their shelf life may be much longer than that.
Pfeifer worries that some doctors may be giving patients a false sense of security. Even for a woman in her mid-30s, it takes about 20 frozen eggs to be reasonably sure of a single pregnancy—women of all ages produce many eggs that are unusable, and the percentage climbs as we grow older. That can mean two or more cycles of injecting hormones to stimulate the release of multiple oocytes, but there is still no guarantee of viable embryos. While the eggs retrieved can be looked at under a microscope to eliminate those that are obviously flawed, it’s not until the oocytes are combined with sperm that their viability is truly tested. Even then there’s no way to assure that a healthy-seeming embryo will implant and result in a baby. And at 50 percent success rates per cycle, half the women who believe their frozen eggs will ensure a baby will be disappointed each time they try. Embryologists are studying new chromosomal tests to show which eggs are most likely to make a normal embryo and are therefore worth freezing, an advance that is expected to increase overall birth rates, but that is still a few years off.
Pfeifer also points out that all clinics are not created equal. About 85 percent participate in ASRM’s reporting-and-monitoring system (IVF and donor-egg success rates per clinic are available on the group’s Web site; there is no national reporting on frozen eggs), but that leaves 15 percent that don’t. Some, she fears, may provide inadequate information about the procedure or about an older woman’s chance of conceiving. “We want people to choose carefully, to ask the right questions.”
Part of ASRM’s caution may stem from the psychological hurdle that egg freezing poses for many infertility doctors, says Licciardi, Leah’s doctor at NYU. Treating a couple that has been struggling to get pregnant is one thing—they have fewer options, and the worst thing that can happen is that the IVF attempt fails—but suggesting that a young woman sock away frozen eggs is a new mind-set for reproductive endocrinologists. “You’re used to feeling that you’re a last-ditch effort, a savior, and this is very different because you’re intervening at a much earlier stage in their lives,” he tells Leah as he leads her to the door after a checkup. “Some doctors worry that young women might make life choices thinking they have this insurance. It’s hard, believe me. I think about that a lot. I want to give you options, and I want it all to work out for you.”
Of course, there are also larger questions at stake as a generation of women stands poised to embrace egg freezing as a lifestyle choice. With scores of over-40 parents already wheeling infants through the mall, it’s hard not to wonder: How old is too old to be a mother? Egg freezing isn’t going to make that question any easier to answer. Some women can easily carry a child until age 60 (with hormone treatments, doctors can ready the uteruses of even postmenopausal women). While many IVF clinics have an age limit for patients they will accept for their egg-donor programs—NYU’s is 50, with exceptions—if egg freezing becomes routine, it may make such cutoffs harder to enforce. If your uterus is able and you are fit, at what age does it become irresponsible to use eggs produced by your 35-year-old self to make a baby?
Clinicians don’t spend much time thinking about such things—they focus on getting women pregnant, period—but some concede that cutting-edge technologies can create new risks while alleviating old ones. “We know we’ll have to convince some women that it’s not a good idea to wait that long, for them or their baby,” said William Schoolcraft, M.D., founder and medical director of the Colorado Center for Reproductive Medicine in Denver, one of the clinics on the forefront of egg-freezing research and practice. “We know it’s very delicate territory.” The average age of egg-freezing patients in his practice is around 36, but he has frozen eggs of women who are 40, the sort of career-minded patients, he concedes, who might not decide till age 50 or so that it’s time to have a baby. When that happens, he will require such patients to see a high risk–pregnancy specialist to find out if their bodies can withstand a pregnancy. Women of 50 or 55 may look supple and dewy, but half of all pregnant women over 45 experience severe complications, including gestational diabetes, premature labor, and preeclampsia (hypertension). “Yes, women will be able to have biological children at advanced ages,” said Schoolcraft, “but we still aren’t entirely comfortable with it.”
On the eighth day of her hormone regimen, Leah has a routine ultrasound. She’s been feeling fine—much better than she’d expected considering the onslaught of hormones she’s been pumping into her system. But as the doctor runs the gel-covered sensor over her belly, she can tell from his face that there’s a problem. Instead of the ten or fifteen follicles she’d hoped would be readying to release eggs, there seem to be only five. Her vision gets blurry, and a sob rises in her throat. Later, in his office, Licciardi tells her gently that she might have to do another cycle in order to get enough eggs to make freezing worthwhile. That means another $15,000, another round of hormones, another month of anxiety. She had known all along that a significant percentage of women, even ones as young as she is, don’t respond well to the hormones. But she had put it out of her mind. “I’d begun to think I was one of the ones who’d sail through,” she says through tears in the taxi.
A day later, though still shaky, she has resolved to go on. Licciardi has explained that being less responsive to stimulating hormone can indicate difficulty getting pregnant at any age, so harvesting ten eggs in two cycles, while not optimal, will still increase her chances of having a baby down the road. Her dream of meeting the perfect man in a few years and effortlessly reproducing may never come true, but knowing now is better than living in a fantasy, she decides. Her mother has already said she will kick in for another cycle.
“I’m in this now, really in it,” Leah says, back in her office. A few hours ago she had injected the trigger medication that will release her eggs. Within 30 hours, she will be on a gurney under sedation, as the doctor extracts them and plunges the oocytes into the cryoprotectants. “Even if I have to do a third cycle, I will—when I get my bonus at the end of the year,” she says. “I’m determined to get enough eggs before it’s too late. It’s going to take more strength and more money than I thought, but I’ll make this work.”