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Uterus Transplantation: Potential Patients, Fertility in Animal Models and Ethics Díaz-García C, Brännström M J

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Uterus Transplantation: Potential Patients, Fertility in Animal Models and Ethics Díaz-García C, Brännström M J Journal für Reproduktionsmedizin und Endokrinologie – Journal of Reproductive Medicine and Endocrinology – Andrologie • Embryologie & Biologie • Endokrinologie • Ethik & Recht • Genetik Gynäkologie • Kontrazeption • Psychosomatik • Reproduktionsmedizin • Urologie Uterus Transplantation: Potential Patients, Fertility in Animal Models and Ethics Díaz-García C, Brännström M J. Reproduktionsmed. Endokrinol 2013; 10 (Sonderheft 1), 72-81 www.kup.at/repromedizin Online-Datenbank mit Autoren- und Stichwortsuche Offizielles Organ: AGRBM, BRZ, DVR, DGA, DGGEF, DGRM, D·I·R, EFA, OEGRM, SRBM/DGE Indexed in EMBASE/Excerpta Medica/Scopus Krause & Pachernegg GmbH, Verlag für Medizin und Wirtschaft, A-3003 Gablitz FERRING-Symposium digitaler DVR 2021 Mission possible – personalisierte Medizin in der Reproduktionsmedizin Was kann die personalisierte Kinderwunschbehandlung in der Praxis leisten? Freuen Sie sich auf eine spannende Diskussion auf Basis aktueller Studiendaten. SAVE THE DATE 02.10.2021 Programm 12.30 – 13.20Uhr Chair: Prof. Dr. med. univ. Georg Griesinger, M.Sc. 12:30 Begrüßung Prof. Dr. med. univ. Georg Griesinger, M.Sc. & Dr. Thomas Leiers 12:35 Sind Sie bereit für die nächste Generation rFSH? Im Gespräch Prof. Dr. med. univ. Georg Griesinger, Dr. med. David S. Sauer, Dr. med. Annette Bachmann 13:05 Die smarte Erfolgsformel: Value Based Healthcare Bianca Koens 13:15 Verleihung Frederik Paulsen Preis 2021 Wir freuen uns auf Sie! Uterus Transplantation Uterus Transplantation: Potential Patients, Fertility in Animal Models and Ethics C. Díaz-García1, 2, M. Brännström1, 3 Uterus transplantation (UTx) has been suggested as an alternative to surrogacy to achieve genetic motherhood. Extensive experimental research must be done before any kind of transplantation moves to the clinical field in order to guarantee its safety and effectiveness. Since the final aim of this kind of transplantation is to accomplish motherhood, the success of UTx should be evaluated not only in terms of organ/patient survival but also in terms of functionality, which means that full-term pregnancies with healthy offspring should be considered as the measure of success. In this review we summarize the experimental studies accomplished during the last decade, using fertility as the main outcome, which we consider as the base for further development of UTx towards a clinical setting. Characteristics of potential patients and ethical concerns are also discussed. J Reproduktionsmed Endokrinol 2013; 10 (Special Issue 1): 72–81. Key words: uterus, transplantation, infertility, pregnancy, ethics Introduction essential aspect of the quality-of-life [5] that may benefit from UTx and also to of a woman and her partner. Uterine in- cover the animal-based UTx research During the last 2–3 decades the clinical fertile patients can today attain genetic that has tested the fertility potential of a fields of transplantation surgery and re- parenthood by use of gestational surro- transplanted uterus (Tab. 1). Addition- productive medicine have been the birth- gacy, which is permitted in some coun- ally, the central ethical aspects of UTx places of several clinical innovations, tries although most societies disapprove will be discussed. which have had profound positive con- of its use because of ethical, religious or sequences for large patient groups. Sev- legal reasons [6]. Uterine Infertility eral of the novel treatments have as well affected the society at large and resulted The research field of UTx has advanced Several groups of patients can be classi- in active media debate, in particular considerably during the last decade, re- fied as infertile due to absence of the from the ethics perspective. search with activities and interest aug- uterus or presence of a type of uterine mented by the human UTx case, which dysfunction that cannot be corrected by In reproductive medicine, the introduc- was performed in Saudi Arabia in 2000 surgery or hormonal/pharmacological tion of gonadotropin stimulation, in [7]. The human UTx effort was partly treatment. This uterine infertility can vitro fertilisation, intracytoplasmic successful since the surgery, involving a either be acquired or occur as a conse- sperm injection and oocyte donation living donor and a 26-year old recipient, quence of a congenital malformation have led to that most types of female and went uneventful. The uterus did not and include causes with no uterus present male infertility now can be effectively reject but had to be removed 3 months and those with a malfunctioning uterus treated. The groups of infertile women after transplantation due to uterine pro- (Fig. 1). The prevalence of uterine infer- that today, in spite of the developments lapse with thrombotic vessels. tility among patients of childbearing age in reproductive medicine, are untreat- is not exactly known but it is likely to be able are those that are irreversibly infer- The large amount of UTx research dur- significant, with a recent estimation of as tile due to uterine cause. ing recent years have used several ani- many as 12,000–15,000 uterine infertile mal models to study issues such as tech- patients in the United Kingdom [9]. This During the last decade, the discipline of niques for retrieval and transplantation estimation would indicate the presence transplantation surgery has introduced surgery, uterine tolerance to ischemia- of more than 150,000 uterine infertile several organs/tissues for transplanta- reperfusion, rejection mechanisms and patients in Europe, although obviously tion, which of would enhance the qual- tests of immunosuppressants to prevent only a portion of these would have the ity-of-life of a patient rather than being rejection [8]. The ultimate goal of UTx firm desire to carry a pregnancy through necessary for a continued life. Examples research is to develop techniques that UTx. of these novel types of procedures are can enable long-term survival of a uter- transplantations of the hand [1], the ab- ine graft with the potential to success- Numerically, the largest group of women dominal wall [2], the larynx [3], and the fully implant an embryo and to carry a with uterine infertility is that of women face [4]. Uterus transplantation (UTx) pregnancy to term. that have undergone hysterectomy dur- may provide a chance for uterine infer- ing fertile age. Each year in the United tile patients to experience pregnancy and The purpose of this review is to summa- States, around 600,000 women are hys- to give birth, which naturally is a very rize the groups of uterine infertile patient terectomized and a substantial propor- Received: July 11, 2012; accepted after revision: October 8, 2012 From the 1Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Sweden, and the 2Department of Obstetrics and Gynecology, La Fe University Hospital, University of Valencia, Spain Correspondence: Mats Brännström MD, PhD, Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, SE-41345 Sweden; e-mail: [email protected] 72 J Reproduktionsmed Endokrinol 2013; 10 (Special Issue 1) For personal use only. Not to be reproduced without permission of Krause & Pachernegg GmbH. Uterus Transplantation nal trachelectomy [18] should be per- Table 1. Results of the experimental models analyzing fertility after uterus trans- plantation. formed. Larger tumours have to be sur- gically removed by a radical hysterec- Degree of histo- Study Animal Position of Mode of Pregnancy tomy. In an analysis of cervical cancer compatibility model the graft conception rate (per surgery) patients who had undergone radical hys- terectomy at a major cancer centre in the Syn Racho 2002 [59] Mouse Heterotopic Embryo-transfer * United States, during a time-era before Racho 2003 [60] Mouse Heterotopic Embryo-transfer 100% introduction of the trachelectomy proce- Racho 2003 [62] Mouse Heterotopic Embryo-transfer 47.4% dure, it was found that more than 40% Wranning 2011 [63] Rat Orthotopic Natural mating 40.7% were of fertile age at the time of diagno- Auto Enskog 2010 [71] Baboon Orthotopic Natural mating 0% sis [15]. Out of these patients, about half Wranning 2010 [67] Sheep Orthotopic Natural mating 21.4% of them would today still be, recom- mended radical hysterectomy because of Allo Díaz-García 2010 [73] Rat Orthotopic Natural mating 62.5% a tumour size greater than 2 cm, in spite Ramírez 2011 [74] Sheep Orthotopic Embryo-transfer 25% of the availability of trachelectomy sur- * Only one animal underwent embryo-transfer as part of the graft evaluation protocol gery. These patients could in the future be candidates for UTx. Even if adjuvant radiotherapy over the pelvis or chemo- therapy, which both may be toxic to the ovaries, are given after cervical cancer surgery, future fertility for these patients would be possible by gonadotropin stimulation followed by oocyte cryo- preservation [19] or IVF and embryo cryopreservation prior to these adjuvant cancer therapies. More than 99% of cer- vical cancers are caused by an infection with an oncogenic strain of human papillomavirus [20] and it has to be en- Figure 1. Uterine infertile patients that may become treated by uterus transplantation. © M. Brännström sured that the virus is cleared from the epithelia of the upper vagina, before tion of these surgeries are performed in plasia [14]. Still, cervical cancer affects transplantation. Clearance of cervical patients below 40 years of age [10]. In an a large proportion of relatively young HPV infection usually occurs
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