Uterus transplantation: Medical breakthrough or surgical folly?

A unique feature of uterus transplantation is that the organ can be removed after childbearing is complete, thereby limiting lifetime exposure to immunosuppressive medications.

Uterus transplantation: Surgical folly?
Transplantation of a uterus involves major surgery. The inescapable reality is that the procedure will cause complications in some donors and recipients.

Specific complications faced. In the Brännström series, 1 uterus donor developed a postoperative ureterovaginal fistula, likely caused by extensive dissection of her ureters. This donor needed an additional operation to repair the fistula. Two of the 9 uterus transplants failed. One uterus was removed from the recipient 3 days after transplantation due to vascular occlusion and 1 uterus was removed 105 days after transplantation due to chronic infection resistant to antibiotic treatment. Seven of the transplants were successful and functioning in situ 12 months after transplantation as evidenced by regular menstrual bleeding. Five of the 7 recipients had rejection episodes, as demonstrated by the histology of cervix biopsies. Two of the recipients had 3 episodes of rejection. The rejection episodes were treated successfully with glucocorticoids and adjustment of immunosuppression medications.

Pregnancy in women with uterus transplantation is high risk because of the complications caused by immunosuppressive drugs and the high blood flow through the vascular grafts. ^7–9 In the Brännström series, the agents utilized for immunosuppression included mycophenolate mofetil, azathioprine, tacrolimus, and glucocorticoids. Mycophenolate mofetil is a potent teratogen and routinely is discontinued prior to initiating attempts at pregnancy. Azathioprine is associated with an increased rate of congenital anomalies, but the benefits of this immunosuppressive are believed to outweigh the risks for most pregnant women with an organ transplant. Tacrolimus increases the risk of developing hypertension, preeclampsia, and intrauterine growth restriction during pregnancy.

In the Brännström case report, the woman who became pregnant following uterus transplantation took tacrolimus and azathioprine to prevent organ rejection both before and during her pregnancy. Not unexpectedly, she developed preeclampsia with severe features at 31 weeks and 5 days. After admission to the hospital, a worrisome fetal heart rate pattern developed and a cesarean delivery was performed. The newborn male weighed 1,775 g, and no congenital anomalies were observed. During pregnancy, blood flow to the uterus is in the range of 500 mL/min, the equivalent of 1 unit of whole blood per minute. ¹⁰ This torrential pulsating flow may increase the risk of a vascular catastrophe such as the rupture of a major artery at one of the graft anastomoses, potentially causing the death of the fetus or mother. Much more experience will be needed to fully characterize the pattern of pregnancy complications that occurs following uterus transplantation.

The cost issue. Uterus transplantation is an extremely expensive medical procedure. In the United States each transplantation is likely to cost hundreds of thousands of dollars. Health care resources used to support uterus transplantation are not available for other pressing medical needs. Given that it is an experimental procedure, it is unlikely that health insurance will reimburse the costs of the medical care. Transplantation programs will need to seek major donors to support the costs, as was done in the Brännström program, or identify patients capable of paying for the transplant. If programs plan to have most patients pay for the procedure, bioethical concerns of equitable access and fair selection of recipients will need to be addressed.