To the Editor:
We read with great interest the paper “Current status of uterus transplantation in primates and issues for clinical application” by Kisu et al. (1). In that paper, the authors address the present status of experimental and clinical uterus transplantation research and potential medical, social, and ethical issues related to it.
Uterine factor infertility (UFI), congenital or acquired, affects 3% to 5% of the general population (1, 2). At present, UFI patients have no option for having a genetically linked child other than with gestational surrogacy, which is illegal in many countries (1). Experimental studies carried out in the last decades have shown pregnancy and delivery in some allograft animal models (1). End to site anastomoses of two arteries and two veins in appropriate length and thickness to the recipients’ relevant external iliac vessels are defined as the best technique for vascular anastomoses based on experimental and clinical data (1-3). Warm ischemia time (WIT) both involves the ischemia during organ retrieval, from the time of cross clamping until cold perfusion is sustained, and the ischemia time starting with removal of the organ from ice until reperfusion (4) (35 minutes in our case). Cold ischemia time (CIT) starts when the organ is put in ice and cooled with a cold perfusion solution after organ procurement surgery, and ends after the tissue reaches physiological temperature during the transplantation procedure. Decreasing the length of CIT as well as WIT are important factors in improving graft survival in transplantation (4, 5).
Present data show that the kidney and liver seem to tolerate the extended warm ischemic period that takes place between circulatory arrest and organ procurement after cardiac death. There are limited data on the effects of warm ischemia on the uterus (5). Hemodynamic stability and electrolyte balance are the primary components of multiorgan donor care and are fundamental to graft survival.
We agree that more basic data and discussion on medical, ethical, social, and legal issues are needed before clinical application.
Although clinical pregnancy in a human was recently reported following uterus transplantation (2), the proof of success would be the delivery of a healthy baby.
Munire Erman Akar, M.D.
Department of Obstetrics and Gynecology, Akdeniz University, Antalya, Turkey
Okan Erdogan, M.D.
Department of General Surgery, Akdeniz University, Antalya, Turkey
1. Kisu I, Banno K, Mihara M, Suganuma N, Aoki D. Current status of uterus transplantation in primates and issues for clinical application. Fertil Steril 2013;100(1):280-94.
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. Johannesson L, Diaz-Garcia C, Leonhardt H, Dahm-Kähler P, Marcickiewicz J, Olausson M, et al. Vascular pedicle lengths after hysterectomy: toward future human uterus transplantation. Obstet Gynecol 2012 Jun;119(6):1219-25.
4. Halazun KJ, Al-Mukhtar A, Aldouri A, Willis S, Ahmad N. Warm ischemia in transplantation: search for a consensus definition. Transplant Proc. 2007 Jun;39(5):1329-31.
5. Del Priore G, Schlatt S, Malanowska-Stega J. Uterus transplant techniques in primates: 10 years’ experience. Exp Clin Transplant 2008;6(1):87-94.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.08.047
The authors respond:
Reply: Future uterine transplantation as a new organ transplantation
We deeply appreciate your interest and comments on our article on uterine transplantation. We agree with most of the points made by Dr. Akar in her letter (1). In addition, the report on clinical pregnancy after uterine transplantation by Akar et al. (2) is extremely important for the next steps in this field, since it shows that uterine transplantation can be successful as a basis for the implantation phase of pregnancy.
As Dr. Akar suggested, surgical techniques for transplantation are being established based on experimental and clinical data, but data on the allowable ischemia time for the uterus are still limited (1). Clarification of the effects of the ischemic period will be key to future performance of human uterine transplantation. The success of the method will also depend on establishment of a protocol for immunosuppressant drugs, diagnosis of rejection, the relationship between HLA matching and rejection, hemodynamic stability in the pregnant uterus, and outcome of the pregnancy and perinatal periods.
Uterine transplantation has started to be applied clinically in Turkey and Sweden, and many other countries are ready to use the method. Differences in social, ethical, and religious backgrounds among countries make it important to examine whether clinical use of uterine transplantation is desirable in each society. For this purpose, it may be beneficial to establish an environment for discussion of the introduction of uterine transplantation as a new assisted reproductive technology, with promotion of educational activities, opinion surveys, and establishment of study groups (Society).
Current experimental and clinical data show that uterine transplantation is possible from a technical viewpoint. However, the procedure has many medical, ethical, and social problems that require discussion prior to clinical application. Bioethical questions and the social needs for reproductive technology should be included in this discussion (3). Bioethical views may change with time and technical developments, and thus unforeseen ethical problems and social situations may arise when a new medical technology is introduced without extensive discussion of ethical issues.
The objective of uterine transplantation is the birth of a healthy baby, but the endpoint of the procedure should be to ensure both successful delivery and happy lives for the recipient, donor, baby, and other concerned persons, with minimal risks and burdens. In this context, the study of uterine transplantation has just started. Despite the many issues to be resolved, uterine transplantation can be an option for infertile women with uterus problems to have their own baby. This new organ transplantation technology will provide new hope for these women and further development of the technology is important for future reproductive medicine.
Iori Kisu, M.D., Ph.D., Kouji Banno, M.D., Ph.D.
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan
Mihara Makoto, M.D.
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
1. Akar ME, Erdogan O. [letter] Uterus transplantation. Fertil Steril 2013.
2. Akar ME, Ozkan O, Aydinuraz B, Dirican K, Cincik M, Mendilcioglu I, et al. Clinical pregnancy after uterus transplantation. Fertil Steril 2013; doi:pii:S0015-0282(13)00727-9.
3. Kisu I, Banno K, Mihara M, Suganuma N, Aoki D. Current status of uterus transplantation in primates and issues for clinical application. Fertil Steril 2013;100:280-294.
Published online in Fertility and Sterility doi:10.1016/j.fertnstert.2013.08.048