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"This is where I spent many a day," Pamela Madsen tells me as she looks out her car window at a blue awning on the corner of Park Avenue and 102nd Street in New York City. "I could get here in the dark if I had to." Two decades ago, Madsen opened the door under that awning and walked into a fertility clinic that, today, no longer exists. She had her blood drawn, her hormones measured, her follicles counted. After treatment, she and her best friend and fellow patient would go to Sarabeth's Kitchen on Madison Avenue, where they'd inhale pumpkin waffles, bacon, and scones. Then they'd compare estrogen levels. "We joked that we were eating for 27 because we were making so many eggs," says Madsen.
Well known in the fertility world as a gutsy, outspoken and opinionated activist, Madsen has spent most of her adult life navigating the ins and outs of reproductive health. In 1999 she founded the American Fertility Association, a leading advocacy group; she left in 2008, launched a blog called The Fertility Advocate, and, in May, joined a New York fertility clinic as director of education. Last spring, after President Obama overturned Bush-era barriers to federally funded embryonic-stem-cell research, I called Madsen to get her professional take on the fate of some 400,000 frozen embryos stored in fertility clinics nationwide. Her musings quickly became personal. Madsen's own embryos had been on ice for more than 15 years, and though she'd been talking publicly about donating them to stem-cell science, she had yet to make the move.
Madsen's personal quest is fueling a newly invigorated field. In December the National Institutes of Health approved 40 human embryonic-stem-cell lines for use by researchers with government money for the first time since George W. Bush limited federal funding in 2001. Donated embryos—fertilized eggs at the earliest stages of development—are the source for these cells, which have the potential to unravel the mysteries of disease development and treat illnesses like diabetes and Parkinson's. The federally approved lines, which are self-replicating batches of cells, met a checklist for responsible research (no cash for embryos, for one thing) and were deemed "ethically above reproach," in the words of NIH Director Dr. Francis Collins. Close to 100 additional lines are pending review and the institute has OK'd funding for 31 embryonic-stem-cell research projects so far, totaling about $21 million. "This is a real change in the landscape," said Collins.
For years, scientists, ethicists, politicians, and religious groups have held very public debates about the moral status of embryos (when does life begin?) and their ultimate destiny. But the decision about what to do with them after baby making is done is exceedingly private and can prove far more vexing, both emotionally and practically, than ever anticipated. Once couples become parents, their leftover embryos often take on more significance. Discarding embryos can feel hollow and wrenching when that frozen cluster of cells has the potential to become a beloved son or daughter. Donating to research raises its own quandaries. Couples soon discover that many clinics don't offer the option and it is no easy task for patients to figure out how to proceed on their own. Even when they do, the phone calls and consent paperwork can become too burdensome or provoke too many questions or regrets. Storing frozen embryos indefinitely at IVF clinics can cost hundreds of dollars a year. Still, despite—or because of—the emotional entanglements, many couples do nothing.
Pamela's journey started when she met her husband, Kai, in 1977. She was 17, he was 21. Early on, they had trouble conceiving—she was diagnosed with "hostile cervical mucus"—and decided to get help. It was 1988, a decade into the IVF revolution, when doctors merged Madsen's eggs with her husband's sperm in a lab dish to create embryos. Several were transferred into Madsen's womb. One implanted and developed into the couple's first baby, Tyler, now a 21-year-old college student and Web-site designer. No. 2 wasn't so easy. A "fresh" transfer didn't take, so the couple had to resort to a batch of eight frozen embryos. Four were thawed, three were transferred, one implanted successfully. Now 17, Spencer hopes to study criminal justice. The four leftover embryos? Chilling in liquid nitrogen.
The Madsens' first challenge was simply locating the embryos. The couple had been treated at Mount Sinai Medical Center's Assisted Reproductive Technologies Program, which closed in 1996. At the time, officials contacted patients about what they wanted to do with their frozen embryos, but Madsen, who had always taken the lead in the couple's reproductive decisions, put the letters of inquiry aside. She was torn and confused. The avoidance embarrasses her even today. "I'm supposed to be a role model," she says. "But as educated and sophisticated around this stuff as I am, I was sticking my head in the sand."
It was for a good reason. Pamela longed for more children during those early years; Kai did not. "I'd say, 'I want to have another baby,' " and he'd say, 'With what man?' " she says. "I didn't want to go through the baby thing again," says Kai. "I was very happy with the two boys I had." Then one day, when her youngest was 6, Pamela, then 38, found herself passing a mommy milestone. "I'd see people with Cheerios and bananas flying in the diner, and I knew I was finished."
In April, Pamela contacted her former doctors, who had to track down the lab director in charge of her embryos at Mount Sinai. Several weeks went by. Pamela told me that the letters she received years back threatened to destroy any unclaimed embryos. But that was unlikely. Fearing lawsuits, clinics are reluctant to do this until they have clear orders from their patients. Even then, getting rid of them is risky. One month after Pamela's request, an e-mail from Mount Sinai provided the good news: "We have located your embryos and are happy to facilitate the transfer."
For the Madsens, who celebrated their 27th anniversary in August, the intangible suddenly became tangible. The embryos held a different meaning for each of them. For Pamela, they represented the possibility of life. Maybe the little girl she had always dreamed about. This is not somebody from whom I expected sentimentality. She's a self-assured, homegrown New Yorker who wears black cowboy boots and turquoise jewelry. She has always been exceedingly open about issues that make others squirm—she still jokes about that "hostile cervical mucus"—and she's now blogging provocatively about fertility, sexuality, and the depths of female desire. She's rabidly pro-choice. But at 49, Pamela finds herself surprisingly melancholy, even teary, about what it means to give up her embryos: an acceptance, once and for all, that she'll never have any more children. "There's a piece of me that says, 'Am I really going to let my embryos go?' "
Kai is far less conflicted. He has always seen the embryos as a kind of reproductive insurance—if the IVF round that produced Spencer hadn't worked, the Madsens could have tried again. After his two boys were born, Kai felt enormously grateful to have them, and the stored embryos became moot. "I have no emotional bond to them at all," he says. "When Spencer came, I was done. My family was complete."
The couple is united, however, in a desire to donate their embryos to science, and their sons support their decision. Spencer is indifferent to the embryos, despite developing from a frozen one himself. "To me, life starts when you're a person and when you're alive," he says. He believes in stem-cell science. Tyler does, too. "I think it's a very noble thing to do," he says.
So do plenty of others. In a survey of patients at nine U.S. fertility clinics, Dr. Anne Lyerly, an ob-gyn and medical ethicist at Duke University, found that about 60 percent would be "somewhat" or "very likely" to donate to research—a much higher number than previously believed. Early on, the Madsens discussed other prospects. Neither one could imagine giving their embryos to another couple, an "adoption" option endorsed by pro-life groups. "I have this weird fantasy of my Jewish New York embryo waking up in Kansas wanting a bagel," says Pamela, who can't fathom having a biological child raised by somebody else. In the survey, 59 percent also said they'd be very unlikely to donate to others and 11 percent said they would be somewhat unlikely to do so. Lyerly says feelings often change as couples go through treatment. "What seemed like a good option to patients in the beginning emerges as something unthinkable after they've seen how embryos can become a baby," she says. At East Coast Fertility in Plainview, N.Y., where Madsen works, medical director Dr. David Kreiner and embryologist John Moschella say that a few patients have taken their embryos home with them, preserving them like ashes after cremation or burying them in a small ceremony. Women have even requested that the embryos be transferred back into their bodies at an infertile time so that they can die naturally. For the Madsens, destruction seemed futile if they could help humankind. Too much love went into creating their embryos, she says: "They should serve some divine purpose, not go down a drain."
At first, Pamela thought she'd like to donate her embryos directly to researchers studying breast cancer or ALS, illnesses that family and friends had battled. But few scientists work directly with embryos, the raw material for stem-cell lines. For one thing, deriving these lines requires special skills. And there are legal and financial hurdles. Despite the new NIH guidelines, a federal law against embryo destruction still stands. Any scientist who wants to create new embryonic-stem-cell lines needs private money to do so. It is only after those lines are created that they may be eligible for government dollars.
Which makes it challenging to find a place that wants your embryos—and can afford them. Some IVF clinics have partnered with stem-cell scientists or institutes, but Lyerly found that only four of the nine clinics she surveyed mentioned research donation as an option. WiCell, the nonprofit institute supporting the University of Wisconsin-Madison and the work of Dr. James Thompson, the pioneering researcher who isolated the first human embryonic stem cell, stopped recruiting embryos a couple of years ago. They've got almost 900 in stock and don't want to add on unnecessarily, says Jeff Jones, director of research services. "We feel like couples really agonize over the decision to donate to research," he says, "and we want to make sure we make good use of them." The University of California, San Francisco's IVF Tissue Bank, which has distributed 856 embryos to researchers since 2005, has had to limit the number of embryos it will accept because of cost, says director Dr. Elena Gates. Round-trip airfare for one tank, plus equipment and staff adds up to about $1,000 per embryo. "We'd like to continue accepting embryos," says Gates, but "we need to address how we're going to pay for them."
Last spring, Pamela called a number listed on the Harvard Stem Cell Institute’s (HSCI) Web site. The institute has few restrictions on donated embryos (lucky for the Madsens, embryo age doesn't matter). Since 2002, HSCI has received embryos from more than 1,000 couples in 26 states. This year's total: 450. The institute won't accept donations from states that prohibit embryo research, including Louisiana and North Dakota, but New York embryos qualify and HSCI told Pamela that they'd arrange transport and pay the costs. Bingo.
Before they signed the nine-page consent form, the Madsens were told that their donation would be permanent once the embryos were used in research, they would not be compensated, and they would not benefit either financially or medically from any scientific discoveries. They also learned that their embryos might be used to derive much-prized stem-cell lines, but they might also be used to help scientists perfect their derivation techniques. Their embryos would remain completely anonymous and they would never be placed in another woman's uterus. No matter what, the embryos themselves would ultimately be destroyed.
HSCI researchers, who are funded by private donors and disease groups, including the Juvenile Diabetes Research Foundation, plan to submit 82 lines to the NIH; 27 have been approved so far. Despite exciting advances in induced pluripotent cells—which are derived from adult cells and have embryonic-like properties—scientists say embryonic stem cells are still as relevant and critical as ever. "They really do have amazing properties of renewal and differentiation," says Dr. Doug Melton, HSCI's codirector, who has done pioneering work on type 1 diabetes. Every embryo HSCI receives, including each of the four donated by the Madsens, helps move the research forward, he says.
While Pamela and Kai are still steadfast in their desire to donate, there are things neither one of them fully appreciated when they started this journey. One is that if their embryos are used to create stem-cell lines, those cells could reproduce and live on for decades. Kai tells me he thought donating was a finite thing. Pamela is unnerved by the idea that her embryos may be used simply as teaching aids. "You have this fantasy that you're doing this great thing," she says. "It would be way better to know they're going to be used to develop a cure."
Then she pauses. And reassesses. "I have to think of it as part of a space project," she says. "A lot goes into the final launch." Even if the Madsen embryos don't provide the cells that save millions of lives, they may teach scientists how to get there. Late last summer, the Madsens signed their paperwork. If all goes according to plan, Harvard will ship a container to New York City sometime soon, pick up four tiny clusters of cells, and bring them back to its lab. The Madsen embryos claimed, at last.