Uterus transplantation research at the cutting edge?

13 09 2013

To the Editor:

We appreciate Dr. Donnez’s interest in our recent manuscript and his insightful remarks on uterus transplantation (1).

Uterine factor infertility affects 3% to 5% of the population (2). Uterus transplantation aims to increase the quality of life in uterine factor infertility patients facing psychological and social problems related to the loss of female identity. Gestational surrogacy offers the only current option for being a genetic parent, with limited availability and potential ethical and psychological problems (3).

Research experience in animals is essential prior to the introduction and attainment of the clinical application of a new surgical innovation. This is especially important when the indication is not life-threatening. Dr. Brannstrom’s group remains the leading team in uterus transplantation research (4). His group has described the basic techniques for uterus transplantation and reported the first pregnancy following uterus transplantation in an experimental animal model.

Due to limitations in postoperative care, assisted reproductive technology (ART), poor control of serum immunosuppressive levels, and financial issues, animal models have not been able to give sufficient information regarding its feasibility and role in acquirement of fertility potential.

Following the first human case of uterus transplantation performed in Saudi Arabia, technical problems have been better identified and solved with more experimental data (1). Results obtained from these animal models in the last decade encouraged us to work on cadaver models and use our transplantation center’s experience to perform the first uterus transplantation procedure from a deceased donor under an ethically approved strict research protocol. The use of deceased donor organs has disadvantages like inadequate time for presurgical tests and less chance of selection of a candidate with human leukocyte antigen match, but it has zero risk to the donor with the availability of a longer vascular graft.

Clinical pregnancy resulting in miscarriage occurred 18 months after the uterus transplantation. Although it is a great step forward, many questions remain to be answered before achieving a healthy near-term delivery. The causes of the miscarriage have been carefully and repeatedly reviewed. The major causes of miscarriage as cytogenetic, coagulation, endocrinologic, or anatomic factors have been investigated and ruled out. In the first clinical pregnancy we observed the retarded development of the gestational sac size compared with the embryo size. The reason might be uterine fibrosis related to immunosuppressive therapy or inflammation related to the intestinal secretions from the neovagina reaching the uterus. Although pregnancy and delivery have been achieved in a number of cervicovaginal agenesis patients in whom McIndoe vaginoplasty was performed, no pregnancy has been reported to date in cervicovaginal agenesis patients treated with intestinal vaginoplasty (5). The effect of intestinal secretions on pregnancy, the use of IV immunoglobulin, anti-tumor necrosis factor, sildenafil, glucocorticoids, or cellular therapies in case of recurrent miscarriage are other important factors to be investigated (2).

Brannstrom’s team has already performed two uterus transplantation surgeries from a live donor. They are planning to complete a series of up to 10 cases. The outcomes of these cases as well as our case will provide very important information for the future of uterine factor infertility.

Munire Erman Akar, M.D.
Department of Obstetrics and Gynecology, Akdeniz University, Antalya, Turkey

References

1. Donnez J. Live birth after uterine transplantation remains challenging. Fertil Steril 2013, in press.

2. Erman Akar M, Ozkan O, Aydinuraz B, Dirican K, Cincik M, Mendilcioglu I, et al. Clinical pregnancy following uterus transplantation. Fertil Steril 2013; doi:pii: S0015-0282(13)00727-9.

3. Ethics Committee of the American Society for Reproductive Medicine. Consideration of the gestational carrier: a committee opinion. Fertil Steril 2013;99:1838-41.

4. Brännström M, Diaz-Garcia C, Hanafy A, Olausson M, Tzakis A. Uterus transplantation: animal research and human possibilities. Fertil Steril 2012;97:1269-76.

5. Acién P, Acién MI, Quereda F, Santoyo T. Cervicovaginal agenesis: spontaneous gestation at term after previous reimplantation of the uterine corpus in a neovagina: case report. Hum Reprod 2008 Mar;23:548-53.

Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.09.022

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