Moving the womb.
Transplantation always involves serious risks for recipients, stemming both from the solid organ transplant surgery itself and from the immunosuppressive drugs that transplant recipients will have to take for the rest of their lives. These risks, however, have been generally viewed as acceptable by surgeons, third-party payers, government regulators, and patients because the success rate is high and the benefit of receiving a heart, kidney, lung, or liver--continued life--is self-evident.
The point of a uterus transplant would not be to save a life, however. Uterus transplants would be attempted only to improve the recipient's quality of life: they would allow her to give birth. This very different risk-benefit calculation raises many ethical questions that should be thoroughly aired and understood before the procedure is attempted.
Thousands of women in the United States cannot bear children. Disease, accidents, complications from earlier pregnancies, and congenital malformations can impair a woman's uterine function, and some women simply do not have a uterus at all. But not all women who cannot bear children are flatly barred from parenthood. In some states in the United States and in other nations, there has been for many years an active market in surrogate mothers--women who will "rent" their wombs for a fee to other women so they may bear children. Gestational surrogacy is not an option for all women who do not have a functioning uterus, however. It is illegal in some states and in some countries, and, even in states where it is legal, many ethical and legal uncertainties surround the practice. Some religions, including Islam, have specific prohibitions against surrogacy. It can also be very expensive, yet it may not even satisfy a woman's need to have her own baby. Many women wish to bear their children themselves as part of the parenting experience. Various cases of older women who have utilized donor embryos or donor sperm and egg to become pregnant, despite great risks to themselves and their potential children, show how strong this desire can be. (2)
Women who want to experience pregnancy and those for whom gestational surrogacy is out of reach (whether for religious or financial reasons) form a group who are willing, even eager, to subject themselves to experimental uterine surgery. Their eagerness puts these women--and those seeking to recruit them--at risk of the "therapeutic misconception": they need to be frequently and emphatically reminded that the women who first receive uterus transplants are subjects in a research study, not patients getting a new treatment. It is unlikely that they will benefit by delivering a baby. Their motivation for participating ought to be that they will shed light on the safety and practicality of uterus transplants.
The Experience So Far
Only one known uterus transplant using a living donor has been attempted in humans. Physicians at the King Fahd Hospital in Saudi Arabia performed the operation in 2002. The donor was a forty-six-year-old woman, and the recipient was a twenty-six-year-old who had undergone a hysterectomy. Doctors had to remove the transplanted uterus after three months due to circulatory problems. (3)
A number of attempts have also been made with different kinds of animals. The team of transplant researchers at New York Downtown Hospital has been experimenting with uterus transplants in pigs and rats for five years. The transplanted uteri reportedly survived and functioned for several months in the pigs, producing normal menstrual cycles. (4) However, none of the animals were able to become pregnant, and the researchers do not know why. A few attempts have been made to transplant uteri in sheep and monkeys, but no pregnancies have resulted. A Swedish team that has been working with mice for many years has achieved one pregnancy that produced a birth. (5)
This work is not enough. There are significant differences between the reproductive anatomy of humans and that of rodents, pigs, and sheep. The fact that so few experiments--much less successful ones--have been carried out in primates should generate considerable concern about the wisdom of moving to human trials any time soon.
The New York team wants to obtain a uterus for transplant from a deceased donor, yet it makes more sense biologically to use a donor uterus from a tissue-matched sibling or relative. Such a donor would be able to consent to the donation knowing the risks and benefits. Living donation might also improve the quality of the organ to be transplanted, and close tissue matching might prolong its lifespan in the recipient, thereby decreasing the dose of immunosuppressive medications necessary to prevent rejection.
Obtaining the uterus from a deceased donor raises some unique ethical issues. The doctors in New York say they will use someone who has signed a donor card and whose family has no objection to uterus donation. But is this really enough? Few, if any, American women ever thought that the uterus might be one of the organs considered for donation when they signed a donor card. A woman might not prove as willing to donate her uterus as she would be to donate her heart or liver. The transplant team would be on firmer moral ground if they used a donated uterus from a woman who had explicitly consented to donate that organ prior to her death, and who made it very clear that she and her family renounced any and all claims to a relationship with any child that might result.
However, while using a close relative or sibling may seem to be the better choice, it also increases the risk of coercion. There could also be potential problems if a family member initially consents to being a uterus donor and then changes her mind--a possibility that a transplant team considering living donors must be prepared to manage.
Surgeons proposing uterus transplant have tended to dismiss concerns about risk to the prospective recipient by noting that, since the uterus is not a life-preserving organ, it can simply be removed if complications arise. But what if that uterus contains a fetus? What if the mother decides she is willing to die to try to give birth? What if the father or the mother decides they want the uterus removed even if it contains a fetus or an embryo? The surgical team has not said as much as they need to about their "exit" strategy if the experiment does not go as planned.
The New York surgical team says that risks to fetuses are not at issue because women who have had other types of transplants have given birth. This is not exactly true. Women have given birth following solid organ and bone marrow transplantation, which require the use of immunosuppressive agents during pregnancy. A national transplantation pregnancy registry provides some data as to the effects of immunosuppressive drugs on offspring. (6) The power of that data is limited, however, by the relatively small number of pregnancies tracked to date. There is no reliable data yet on the long-term health of children born posttransplant. When a woman has received a solid organ transplant, doctors usually recommend postponing pregnancy for two years to ensure that the graft survives. No one knows what guidelines to recommend concerning pregnancy after uterus transplantation.
A woman who has a transplanted liver and later undertakes a pregnancy presents a very different case from a woman who subjects both herself and her potential offspring to these drugs purely for the purpose of carrying a pregnancy. Also, the potential risk to a fetus or fetuses from the procedure is not solely that of exposure to immunosuppressive drugs. There is a risk of structural failure caused by clotting and thrombosis of major arteries supplying oxygen to the transplanted uterus. This could have a negative effect on fetal development, increasing the possibility not only of fetal death, but of preterm delivery and developmental problems associated with poor circulation, infection, and loss of fluid.
For uterus transplantation, the risks seem to be justifiable only if clinical equipoise exists--that is, if the risk-benefit ratio of the experimental procedure can reasonably be assumed to be equal to existing alternatives. Uterus transplants fail the clinical equipoise test. We lack solid animal data on the impact of uterus transplant on maternal health and fetal well-being, so we don't really know the risks. In addition, most women have the safe alternatives of gestational surrogacy, adoption, and foster care to allow them to experience parenthood. The desire to experience a pregnancy, while certainly legitimate, cannot be considered separately from the ultimate goal of pregnancy--namely, a healthy child. The available evidence cannot yet assure that outcome.
Finally, aside from the physical risks, a child born from a uterus transplant could also face some unique psychological issues. The child or adult might seek contact with the survivors of the woman who had donated the uterus. Children born after sperm donation, adoption, or surrogacy sometimes go to great lengths to find information about their conception; surely children gestated in a dead woman's uterus would wonder about their origins. Provisions must be made for handling these issues prior to undertaking the first cadaver uterus transplants.
Many women who want a uterus transplant might not be candidates for one, but the selection process for identifying subjects has received very little discussion. Women born without a uterus or with certain congenital anomalies will not have the appropriate vascular connections for attachment. Women who had their uteri removed because of cancer--particularly cervical or childhood cancer--may not be candidates if the original cancer treatment involved radiation that led to scarring, which makes vascular reattachment difficult. And there are obvious questions that must be asked about the psychological stability and social support necessary to undergo an experimental transplant fraught with unknown risks.
The prospect of uterus transplant has also led to some discussion about the possibility of a male pregnancy. (7) While this idea may seem appealing to some, the physiological requirements for nourishing a uterus and maintaining a pregnancy make it exceedingly unlikely that a uterus transplant would work in a man. During a pregnancy, up to one-fifth of a woman's cardiac output goes to the pregnant uterus. Since the vascular connections for a uterus do not exist in males, they would have to be created. Hormonal supplementation would also be required, along with the immunosuppression. Obviously, the bodily incompatibilities are so daunting that to even try for a male pregnancy seems inappropriate. While it makes for some fascinating science fiction scenarios, the risks involved make the selection of a male subject for this experiment ethically dubious.
The Glory of Being First
There are transplant teams willing to undertake uterus transplants and women willing to undergo them. But this is an experiment that requires more than willingness. Multiple studies demonstrate the difficulty of achieving informed consent with desperate patients. The transplant team must manage conflicting roles and interests in order to ensure truly informed and voluntary consent from potential donors, donor families, and recipients. In the midst of all this, the prospect of being the first to successfully transplant a uterus--and win acclaim and publicity for the programs, doctors, and institutions involved in the effort--raises deep concerns about conflict of interest. The desire to be first could make it very difficult for the team to seriously consider whether sufficient evidence exists to support a favorable risk-benefit ratio for initiating a clinical trial. Society must be reassured that donation involving a cadaver donor will be done according to the highest standards of informed consent. The transplant team must be clear about how it will manage a pregnancy if the transplant goes wrong. And the risk to the fetus of being conceived and carried in a transplanted uterus must be carefully weighed against the woman's desire to have the experience of the gestational component of motherhood. Is that worth a lifetime of risk to a child? Until these questions are answered, it is not time to initiate experiments with uterus transplantation.
(1.) R. Stein, "First U.S. Uterus Transplant Planned," Washington Post, January 15, 2007.
(2.) A.L. Caplan, Smart Mice, Not So Smart People (Lanham, Md.: Rowman & Littlefield, 2006).
(3.) W. Fageeh et al., "Transplantation of the Human Uterus," International Journal of Gynecology & Obstetrics 76 (2002): 245-51.
(4.) Stein, "First U.S. Uterus Transplant Planned."
(5.) D. Kingsley, "Swedes Achieve World's First Womb Transplant," ABC.net, July 2, 2003, http://www.abc.net.au/science/news/stories/ s892281.htm.
(7.) B. Radford, "Male Pregnancy," Skeptical Inquirer 31, no. 2 (2007): 22-23.
Arthur L. Caplan, Constance Perry, Lauren A. Plante, Joseph Saloma, and Frances R. Batzer, "Moving the Womb," Hastings Center Report 37, no. 3 (2007): 18-20.
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|Author:||Caplan, Arthur L.; Perry, Constance; Plante, Lauren A.; Saloma, Joseph; Batzer, Frances R.|
|Publication:||The Hastings Center Report|
|Date:||May 1, 2007|
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