The High-Tech Future of the Uterus

Following the recent success of the world's first uterus transplant, scientists are pursuing the new frontier of the bioengineered womb.

Danish Siddiqui / Reuters

When I suffered my third consecutive miscarriage this past May, my mom said she wanted to help me out however she could, even if it meant being my surrogate. I laughed it off—a 60-year-old surrogate?—but it turned out that, as always, Mom had been on to something.

In 2011, Kristine Casey, 61, gave birth to her own grandchild after being surrogate for her daughter, Sara, who had delivered stillborn twins and then suffered a miscarriage after years of infertility treatment. Surrogacy isn’t typically allowed in post-menopausal women because of the need for hormone supplements and the associated health risks—but occasionally, doctors make exceptions, especially for relatives, and Casey is the oldest of an increasingly large roster of women who have birthed their own grandchildren. And in just the past year, post-menopausal surrogacy has become a seemingly mundane mode of reproduction when compared to the new frontier of infertility solutions: living donor-uterus transplants and bioengineered wombs.

In September, a 36-year-old Swedish woman gave birth to a baby boy in the first-ever birth from a transplanted uterus. The woman, whose identity remains anonymous, was born without a uterus but with functioning ovaries. She is one of nine women to participate in a transplant study led by Mats Brännström, a professor of obstetrics and gynecology at the University of Gothenburg in Sweden. The uterus was donated by the woman’s 61-year-old friend, and conception was achieved by in-vitro fertilization, after which the embryo was implanted in the woman’s newly transplanted uterus.

This unprecedented achievement was observed with keen interest by transplant surgeons and fertility experts the world over, who hope that transplants might soon become a viable option for women who lose a uterus to cancer, are born without a uterus, or who are unable to conceive or carry due to uterine defects or anomalies. While surrogacy is the more well-known method of helping women with infertility have biological children, it has drawbacks. The most obvious one is that a woman doesn’t gestate her own child, but surrogacy also carries an array of legal and ethical dilemmas, including the concerns that poor surrogates might enter the arrangement solely because of the financial incentive, or that a surrogate might become attached to the baby. Surrogacy is illegal in some European countries, including Germany and France; other countries, like Australia and Canada, permit “altruistic surrogacy,” a legal framework that permits surrogacy but prohibits payment.

“A surrogate takes a large risk by going through a pregnancy for someone else, because pregnancy can cause various adverse medical conditions,” says Mats Hellström, an assistant professor at the Laboratory for Transplantation and Regenerative Medicine at the University of Gothenburg, and a member of the research group that achieved the birth via transplant. “The whole ethical part of surrogate motherhood is why many countries don’t permit it. The successful uterus transplants have shown that there is an alternative to surrogacy.”

Now that the hurdle of the transplanted uterus has been overcome, researchers have turned to a technology borrowed straight from sci-fi: a bioengineered uterus. Doctors in the burgeoning field of regenerative medicine produce organs and parts of organs in a few different ways. One is by taking a small number of stem cells from a patient’s blood or bone marrow, and then amplifying and shaping the growth of those cells. Another involves taking a moderate number of the patient’s own uterine cells, and then de-differentiating them, meaning that they are converted from highly specialized uterine cells back into less specialized cells to allow cellular growth (called “cellular amplification”) in the lab. The cells are then applied to a uterus-shaped scaffold. When transplanted, they re-differentiate back into specialized uterine cells.

“Once you get the correct cell numbers, you place them on the correct scaffold, and at that point you have tissue that is not immunologically different from the host,” says Dr. Roger C. Young, professor of obstetrics and gynecology and director of biomedical innovation at the University of Tennessee Health-Science Center. “This is the beginning of the era of regenerative medicine, which will, at least in some part, replace organ transplants.”

Bioengineered organs have a number of practical advantages over donor transplants, including the fact that recipients wouldn’t need to take immunosuppressants for the rest of their lives, as transplant recipients typically do to prevent their bodies from rejecting the new organ. “A bio-regenerated uterus allows you to avoid immunosuppression, and you get rid of the risks of surgery for the person donating the uterus,” says Dr. Arthur Caplan, director of the Division of Medical Ethics at the NYU Langone Medical Center. “The failure rates of transplanted organs are high, and we don’t have enough organs. Bioengineered organs are definitely the long-term solution.”

But the bioengineered uterus is years, if not decades, away. Hellström’s research group at the University of Gothenburg is on the cutting edge with their recent experiments in rat-uterus decellularization, a process that involves removing cells from tissue, leaving behind only the extracellular matrix (ECM), which then serves as a 3-D scaffold for introducing new cells. Yet Hellström laughed at my suggestion that artificial-uterus transplants might be available within 10 years: “Look at how long it took my colleague [Mäts Brannström] to develop the live-donor uterus transplant: 15 years of nonstop work. Now I have the same journey to make, the only difference being that my colleagues started with perfect material to transplant. I’m constructing the material as well.”

Years ago, the theoretical possibility of an artificial uterus gave rise to the idea of gestating a baby outside the mother’s body rather than transplanting the organ. This came to be called “Baby in a Box” after journalist Natalie Angier’s widely-read 1999 New York Times Magazine article of the same title. Angier predicted that the artificial uterus was “coming, if not in 10 years, then in 15 or 50.” The introduction to a 2006 anthology of bioethics essays, titled Ectogenesis: Artificial-Womb Technology and the Future of Human Reproduction, predicted that “we might soon see the day when a woman’s contribution to the birth of a live baby will be similar to that of a man, namely, both will only need to provide or donate gametes.”

The term “ectogenesis” was coined in 1924 by British geneticist J.B.S. Haldane to describe artificial uteruses that would forge a utopian future where only pre-selected, genetically “superior” sperm and eggs would be used for reproduction. Adopting the point of view of this imagined future, Haldane wrote, “Had it not been for ectogenesis, there can be little doubt that civilization would have collapsed within a measurable time owing to the greater fertility of the less desirable members of the population in almost all countries.”

Half a century later, feminists envisioned an entirely different type of future where women, freed from the barriers of pregnancy and childbirth, would finally be on equal social and economic footing with men. In 1970’s The Dialectic of Sex, feminist writer Shulamith Firestone argued that in-vitro fertilization and gestation would free women from the “tyranny of their reproductive biology.”

Despite these lofty imaginings, regenerative-medicine researchers are more focused on the immediate problem of infertility than they are on revolutionizing society. The optimism about ectogenesis in the late 90s and early 2000s had been bolstered by the research of Dr. Helen Liu, who today is director of the Reproductive Endocrinology Laboratory at Weill Cornell Medical College. In 2001, Liu grew a human embryo for 10 days in an artificial womb, then halted the experiment because of federal law prohibiting human embryo experimentation after 14 days post-conception. In 2003, she grew a mouse embryo in a bioengineered uterus, but the baby was born was deformed.

At that juncture, Liu realized that in vivo gestation (within a living animal) would show more promising results than growing a fetus entirely in vitro. So for the next experiment, Liu grew the mouse embryos in an artificial uterus for a week, then transferred them into the abdominal cavity—not the uterus—of the mother. These babies came out anatomically normal but small for their gestational age.

Soon thereafter, Liu halted her experiments. “There was a lot of pressure from the press,” Liu tells me. “Everyone was talking about it. The medical ethicists were against it. Pro-life people were against it, and pro-choice people too—both sides. This came as a surprise to me. When I started, I just wanted to help women who had implantation problems. But it turned out to have all of these social implications, and I didn’t want to deal with it.” Today, Liu instead works on improving methods of in-vitro maturation and cryopreservation.

Since Liu’s mouse experiments, the medical community has more or less abandoned in-vitro gestation. The past decade saw a renaissance in transplant technology, and advances in the burgeoning field of human prenatal epigenetics have rendered gestation outside a mother’s body a less plausible concept. Scientists are learning more about the interplay between fetal development and the mother’s whole body—not just her uterus.

“The fetus gets an advantage by developing within a maternal body,” says Janet DiPietro, associate dean for research at the Johns Hopkins Bloomberg School of Public Health. DiPietro oversees the Johns Hopkins Fetal-Development Project, a 20-year endeavor that tracks how physiological aspects of the maternal-fetal bond shape development. DiPietro told me that everything from a mother’s circadian rhythms to her posture sends cues to the growing fetus.

“The maternal voice is heard very well, which probably sensitizes the baby to the sounds of their own language. Amniotic fluid develops the odor of certain foods that women eat, and so there’s a notion that cultural likes and dislikes are transmitted to the fetus via the amniotic fluid,” she says, “So the maternal context provides an environment that goes far beyond the direct circulatory-system connection.”

DiPietro explains that in the future, an artificial-uterus transplant is “far, far more likely” than in-vitro gestation, in part because the placenta, which grows from the uterus after implantation, is “one of the most enigmatic organs that we have.” Scientists can’t understand it, let alone construct it from scratch. The complex interplay between the placenta—which grows from the fetus’s own cells—and the mother’s blood flow, immune system, and circulating oxygen has been so poorly researched that Alan Guttmacher, director of the National Institute of Child Health and Human Development, recently called it “the least-understood human organ.” But with a bioengineered uterus, the assumption is that if you get the uterus right, a placenta, amazingly, will grow on its own once the transplant recipient becomes pregnant.

Even if the technology exists, however, uterus transplants—whether living-donor or artificial—might never become widely available. Funding for research is limited because a uterus, unlike a kidney or a heart, is not necessary for life. “In Sweden, people can afford this,” Caplan says. “Here we have healthcare-access problems, and transplanting a uterus would be in the bottom quarter of my

priority list for what we need to spend money on. Does that mean only the rich would get it? Yes. And that’s just the reality of it.”

Young at the University of Tennessee explains that a living-donor uterus transplant requires up to three operations—taking the organ from the donor, implanting it in the recipient, and then the possible C-section should a baby be born—all for a condition (infertility) that isn’t life-threatening. “I don’t think it will be widely accepted in the United States, and I personally don’t consider it a realistic solution to the problem,” he says. Young’s work is connected but somewhat different: bioengineering uterine tissue to repair a damaged or malformed uterus.

“Especially with the C-section rate being 33 percent in the United States, there will be more and more women with uterine defects and problems,” Young says. “There are many more people that need repair of the uterus than need replacement.” Young recently had to tell a patient that she can’t have more children due to damage from two previous C-sections; he hopes that within just five years, bioengineered uterine patches will be available.

In the case of my own miscarriages, the problem turned out to be chemical rather than anatomical: A thyroid problem was triggering an immunological response that is linked to first-trimester miscarriages. I was prescribed the requisite hormones, and I’m currently pregnant and safely in my second trimester. For women with uterine-factor infertility, the solution is not so simple, and advancements in bioengineered organs might one day prove to be a panacea.

Young believes that even if a bioengineered uterus is many decades off, simpler fixes like uterine patches might help women within just a few years. “If we can take this step by step,” he says, “the steps allow you to climb the wall in a much more efficient manner.”