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• W2340509341 abstract "Despite all the advances achieved in reproductive medicine during the past three decades, the absolute uterine factor infertility (AUFI) still has no treatment. AUFI can be caused either by the absence of the uterus (congenital or acquired) or the lack of functionality [1, 2]. According to estimations based in the United Kingdom population, there are about 12,000 to 15,000 women of reproductive age with AUFI in the country [3]. There are no calculations for our geographical context, but extrapolating the above-mentioned figures to the Spanish population, it is estimated that there are 2000 to 3000 women of reproductive age with no chance to achieve motherhood by themselves.Up to date, the only options for genetic motherhood in women with AUFI are adoption or surrogacy. The latter allows acquiring genetic motherhood although, as in the former, it requires an administrative procedure to achieve the legal parenthood. Gestational surrogacy is only allowed in specific countries and it usually involves ethical, religious, social and legal issues in terms of autonomy, payment, physical and mental health of the surrogate [4, 5]. In any case, this option is illegal in Spain.It has been suggested that uterine transplantation (UTX) could be an alternative to surrogacy to achieve genetic parenthood. UTX should not be seen as a life-saving transplantation but as transplantation aiming to enhance the quality of life of the patient by supplying the function of a missing organ. This is the case of other type of transplantations such as limbs or face transplants [6]. Herein, the final aim of uterus transplantation is to treat infertility, which has been recognized as one of the most quality of live impairing condition [7].When the experiments of this thesis were designed, the available evidence regarding fertility after allogeneic UTX and immunosuppression was limited. There were neither study on the feasibility of the procedure nor about the effects on the offspring.There were conflicting data regarding the effect of transplantation of solid organs on fertility: while some studies found an improvement in pregnancy rates after solid organ transplantation, others found higher rates of spontaneous abortion and adverse perinatal outcomes.Therefore, the different studies presented in this thesis aim to build a core of pre-clinical knowledge on fertility after allogeneic UTX that can be used as the base of a future clinical trial, according to the recommendations of the IDEAL guidelines [8]. In this thesis, 6 studies published in 9 papers will be described. These studies explore the effect of UTX and the different immunosuppressive regimens on ovulation, implantation, development of pregnancy and offspring phenotype. A population-based study evaluating the effect of solid organ transplantation on the perinatal outcome will also be presented. In this study two unique registries were linked to provide more than 2,500,000 control births and over 2,000 births from mothers transplanted with solid organs. Lastly, this thesis also describes the first UTX case series in humans, conducted by our group, resulting in a live birth.The main findings of the above-mentioned studies were:-The calcineurin inhibitor cyclosporine A, but not tacrolimus, decreases ovulation and implantation rates in murine experimental models.-The offspring born from mothers who underwent allogeneic UTX were phenotypically normal. -Transplantation and immunosuppression have moderate or no effect on the incidence of adverse perinatal outcomes, especially when confounding factors linked to the basal health status of the mother are controlled.-UTX is a feasible treatment for AUFI, as it was proven by the first live birth after allogeneic UTX in the human. In summary, the findings of this thesis allow to open a new door to genetic motherhood for women suffering from AUFI, especially in socio-geographical contexts where surrogacy is not allowed. The studies included in this thesis also provide relevant clinical information that can be taken into account in the management of fertility issues of patients transplanted with solid organs in general." @default.
• W2340509341 created "2016-06-24" @default.
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• W2340509341 date "2015-01-01" @default.
• W2340509341 modified "2023-09-27" @default.
• W2340509341 title "Fertility and immunosuppression in allogeneic uterus transplantation" @default.
• W2340509341 hasPublicationYear "2015" @default.
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