COMMENTARY

Top Ob/Gyn Literature From 2014

Peter Kovacs, MD, PhD

Disclosures

December 11, 2014

An Important Transplant Surgery Achievement

Livebirth After Uterus Transplantation

Brannstrom M, Johannesson L, Bokstrom H, et al
Lancet. 2014 Oct 6. [Epub ahead of print]

One of the biggest gynecologic surgical achievements of 2014 was published by Brannstrom and colleagues. After over a decade of preliminary animal and human research, they have finally reported a successful live birth after uterine transplantation.

Uterine factor infertility affects about 5% of infertile women. It is the result of either the congenital absence of the uterus or an acquired problem (severe Asherman syndrome or after hysterectomy). Up until now, the only option for these women was surrogacy. The success achieved by this Swedish group opens up another opportunity for these women. It's not surprising that Prof Brannstrom's lecture at this year's American Society for Reproductive Medicine meeting received a standing ovation.

The patient described in the case report was a 35-year-old woman who underwent uterus transplantation in 2013. The recipient was diagnosed with congenital absence of a uterus. The donor was a 61-year-old close family friend. The donor underwent a hysterectomy with extensive vascular dissection to allow proper length vascular pedicles for anastomosis formation in the recipient. Her surgery lasted for over 10 hours. The recipient's procedure lasted half as long and involved proper vascular anastomosis formation and fixation of the uterus. Postoperatively, the recipient was placed on the required immunosuppression. She was monitored closely, including regular checks for infection or rejection. A month and a half after the surgery, the first spontaneous menstruation was noted, and then monthly periods followed. Mild rejection episodes were successfully managed by corticosteroids.

A year after the transplantation, the patient underwent a frozen embryo transfer involving the transfer of a single embryo. The in vitro fertilization (IVF) procedure with elective embryo cryopreservation had been performed before the transplantation procedure. The frozen embryo transfer was successful and resulted in a singleton intrauterine pregnancy. At 31 weeks and 5 days of gestation, the patient was admitted to the hospital due to severe preeclampsia and underwent cesarean section. A healthy newborn was delivered weighing 1775 g. Mild rejection episodes were treated by steroids during pregnancy. Both the mother and the newborn had an uneventful postnatal period.

Viewpoint

The Swedish surgical team is not the only group that has experimented with uterine transplantation. The first such report was published in 2002. In that case, the transplanted uterus had to be removed due to necrosis 3 months after the transplant surgery.[8] In the second report of uterine transplantation, the procedure was successful, and pregnancy was achieved through IVF, but the patient suffered a miscarriage.[9]

It took over 10 years for this Swedish group to finally achieve success. They started out with experimentation in various animal models, including primates, to develop the proper surgical technique and immunosuppressive protocols. In addition, they only recruited participants for their clinical trial once adequate information was gathered from preliminary experiments. This strict methodologic approach had to be one key factor in their success.

The possibility of uterine transplantation raises several medical and ethical questions, however. It seems obvious who could benefit most from the procedure: women with absolute uterine factor infertility. Besides surrogacy not being legal in many countries, a pregnancy after successful transplantation gives these women the chance to experience a pregnancy and delivery themselves. It is important to assess the potential candidate's ovarian function prior to staring the whole process. The recipient will first undergo an IVF procedure with elective embryo cryopreservation, and the transplantation will only be performed once an adequate number of quality embryos have been stored.

A live or deceased donor can be considered. The ideal donor would be a relative with the highest chance for adequate HLA match. A live donor, however, exposes herself to a long (in the current case, over 10 hours) and radical surgery. A deceased donor would be more ideal, but one has to worry about the impact of ischemia on the function of the transplanted organ.

Even if the surgery is successful, one still has to worry about immune rejection. To minimize this risk long-term, immunosuppressive therapy is needed, and regular evaluation should be offered.

In addition, the risks-benefits affecting the three parties have to be considered. The donor exposes herself to the surgical risks, the recipient exposes herself to the surgical risks and the adverse effects of long-term immunosuppression, and the fetus is exposed to the potentially teratogenic immunosuppressive agents.[10]

Despite these concerns, the researchers should be congratulated on their persistence over the course of a decade of experiments. Their success opens up a whole new area of treatment options for more specific types of infertility. Their results also underline how important it is to have properly trained physicians do these interventions as well as having gynecologic and transplant surgeons, internists, and infertility specialists work together to minimize risks and maximize success rates.

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