Uterus transplantation: Medical breakthrough or surgical folly?
Although uterus transplantation has been proven to be feasible, is it practical or ethical?
Case: Patient asks for transplantation referral
During an annual ObGyn visit, a 28-year-old G0 with congenital absence of the uterus excitedly tells you about the news report of the first birth following uterus transplantation. She always has dreamed of becoming pregnant, and this medical breakthrough has spurred her imagination of what might be. You ask if she would consider adoption or a gestational carrier. Responding that she prefers to carry her own pregnancy, she asks you to refer her to a uterus transplantation program. You promise to look into this option for her. As she opens the door to leave your office, she mentions that her mother has volunteered to be the uterus donor.
Later, you have misgivings about making a referral for uterus transplantation. You wonder: Is this procedure an appropriate use of health care resources? Do its risks outweigh the benefits?
In September 2014, a 36-year-old Swedish woman gave birth following uterus transplantation. A 61-year-old family friend donated the uterus for the procedure.1 Prior to this breakthrough, women without a uterus had 3 reproductive alternatives: remain childless, adopt a child, or use a gestational carrier to give birth to their child. In many countries and some religions there are prohibitions against the use of a gestational carrier, leaving adoption as the only option to parenthood.
The first successful uterus transplantation did not occur by serendipity; a decade of careful work led to this breakthrough.2–4 Remarkably, it is now proven that this type of transplantation can result in the successful birth of a baby—but at what cost?
The Brännström Uterus Transplantation Program: A medical breakthrough
Dr. Mats Brännström at the University of Gothenburg, Sweden, is the leader of the courageous and innovative team that developed the world’s first successful uterus transplantation program. The team required a broad range of expertise and skills and included physicians, scientists, and support staff from Sahlgrenska University Hospital and Stockholm IVF in Sweden; University of Valencia, Spain; Griffith University, Australia; and the Cleveland Clinic, Florida. Two recent publications report on the outcomes of the first 9 uterus transplants.5,6
The successful protocol. The first step in the program is an exhaustive medical and psychosocial evaluation of the prospective uterus donor and recipient. Among the first 9 uterus recipients, 8 women had congenital absence of the uterus and 1 woman had a hysterectomy for cervical cancer. The uterus donors were mothers (in 5 cases), a mother-in-law, a sister, an aunt, and a friend.
After the recipient is approved for uterus transplantation, she undergoes in vitro fertilization (IVF) with cryopreservation of all embryos. IVF is recommended because it may not be possible to include the fallopian tubes in the uterus transplant or the tubes may not function properly following transplantation. The donor organ is harvested, using a modified radical hysterectomy with extended vascular pedicles, and transplanted into the pelvis of the recipient.
Following transplantation, immunosuppressive medications are prescribed daily to reduce the risk of organ rejection. The recipient is followed on a regular basis with physical examination and cervical biopsy to identify histologic markers of organ rejection. Episodes of rejection are treated with glucocorticoids and adjustment in the dose of immunosuppression medications. Fertility treatment with the recipient’s previously cryopreserved embryo begins 1 year following transplantation.
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.
