Commentary: Uterine Transplantation

Scientists have been exploring the possibility of uterine transplantation for a long time. A report of the first successful transplantation was published in 2002, but we had to wait for more than a decade to hear about the first successful delivery after uterine transplantation.^[1] Last week, Prof Brännström and colleagues^[2] reported the case of a successful delivery of a healthy male newborn at 31 weeks following uterine transplantation. It raises several important medical and ethical questions.

Candidates

First of all, who needs uterine transplantation? Of the reproductive-age population, 10%-15% is affected by infertility, and in up to 5% of these cases, a uterine factor plays the most important role.^[3] It may be the result of a congenital issue, such as absence or hypoplasia of the uterus, or an acquired problem following hysterectomy or postsurgical severe intrauterine adhesions. Up until now, couples affected by uterine factor infertility had two options: adoption or gestational surrogacy. Because of regulatory differences, these options are not available in all countries. Uterine transplantation, however, could be a third choice for these patients.

Women with congenital anomalies who desire a pregnancy are likely to be younger with adequate ovarian function. This is important because the ability to conceive decreases with age, and success rates are rather low over age 40. Those who become infertile following surgical intervention (eg, hysterectomy for fibroids) are likely to be older and have poor prognosis because of age-related factors. In such cases, it is important to assess ovarian reserve prior to considering transplantation. Couples will probably require assisted reproduction following the transplant surgery. The embryo for transfer should be obtained prior to the transplantation, for several reasons. Most important, the transplant surgery should not be performed if there are no viable embryos. In addition, the stimulation and retrieval are associated with more risks when the patient is taking immunosuppressive therapy and has distorted anatomy following the surgical transplantation.

Donors

Just as important as selecting the appropriate candidate is determining the ideal donor candidate. A relative would be preferred because with human leukocyte antigen (HLA) sharing, there is less risk for immunosuppression. However, if the donor is an older relative, such as a mother, there is a likelihood that a postmenopausal uterus may limit the success of reproduction. On the other hand, if the donor is of reproductive age, then she loses the ability to become pregnant again in the future. In addition, a live donor exposes herself to surgical risks that are greater than those of a simple hysterectomy, as the procedure is more radical in order to obtain adequate vascular pedicles. A deceased (brain-dead) donor, therefore, may be ideal. In this case, however, there already may be damage to the uterus that could affect its long-term survival.

Further research involving primate models is needed to improve the surgical techniques that will result in long-term survival and adequate function of the transplanted organ, as well as to work out the appropriate immunosuppressive protocols. The difficult issue that slows down research is how to assess function. Resumption of menstruation is not enough, as we can only determine proper function when the whole intervention has resulted in the delivery of a healthy newborn. In this regard, primate research has not always been encouraging.^[4]

Ethical Dilemmas

The process of uterine transplantation also raises several ethical questions. Uterine transplantation differs from lung, kidney, or heart transplantation because the uterus is not a vital organ. Still, a patient's life may feel less than full, because an important function, reproduction, is not possible without a properly functioning uterus. Therefore, we can look at uterine transplantation as a way to improve quality of life. Although surrogacy may allow couples to become parents of their own genetic children, the emotional and psychological link that develops during pregnancy and childbirth will be missing. In addition, the process of surrogacy may raise legal problems. Therefore, the availability of effective uterine transplantation should improve the recipient's quality of life. The risks and benefits affecting the three parties, however, have to be considered.

Medical Risks

Most important, the recipient has to understand the full procedure—the need for assisted reproduction, the need for immunosuppressive therapy, and the possibility of failure because of organ rejection or embryo rejection. Finally, we have to consider the risks affecting the fetus/newborn. Immunosuppressive therapy may have toxic effects, such as renal toxicity and hypertensive complications (although no teratogenic effects have been shown).^[4] There are also risks for miscarriage, intrauterine growth retardation, and preterm delivery. The pregnancy in the report by Prof Brännström and colleagues resulted in the birth of a healthy boy, but at 31 weeks and following a pregnancy affected by hypertensive complications.

A Step Forward

The study authors should be congratulated on their efforts to improve pregnancy opportunities and quality of life of those affected by uterine factor infertility. This case, however, raises important medical and ethical questions that need to be considered before a wider application becomes a reality. Much can be learned from this case, and the information should be used to further improve the surgical and medical technique of uterine transplantation.

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