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15 pages, 575 KiB

Open AccessArticle

Human Uterus Transplantation from Living and Deceased Donors: The Interim Results of the First 10 Cases of the Czech Trial

by Jiri Fronek, Jakub Kristek, Jaroslav Chlupac, Libor Janousek and Michael Olausson

J. Clin. Med. 2021, 10(4), 586; https://doi.org/10.3390/jcm10040586 - 04 Feb 2021

Cited by 36 | Viewed by 4903

Abstract

Introduction: Uterus transplantation (UTx) is a rapidly evolving treatment of uterine-factor infertility. We report the results of the first 10 UTx procedures performed at our institution. Methods: The program started in April 2016 as a two-arm study comparing the efficacy of UTx from [...] Read more.

Introduction: Uterus transplantation (UTx) is a rapidly evolving treatment of uterine-factor infertility. We report the results of the first 10 UTx procedures performed at our institution. Methods: The program started in April 2016 as a two-arm study comparing the efficacy of UTx from live donors (LD) and deceased donors (DD). Results: Between April 2016 and April 2018, we performed five DD UTx and five LD UTx. Two grafts had to be removed early due to thrombosis. One graft was removed due to chronic rejection and previous herpes simplex infection at month 7. Graft survival is 70% at one year. Recipient survival is 100% at two years. Live donor survival is 100% at three years. Three live-births have been achieved, two from a LD and one from a graft from a nulliparous DD. Vaginal anastomotic stenosis occurred in 63% (5/8) of grafts. Self-expanding stents have shown preliminary suitability for the treatment of vaginal stenosis. Three recipients developed severe acute rejection. Conclusion: The interim results of our study demonstrate mid-term viability in 70% of grafts. The LD UTx produced two live births and the DD UTx produced one live birth. Nulliparous donors should be considered for donation. Full article

(This article belongs to the Special Issue Uterus Transplantation)

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23 pages, 6493 KiB

Open AccessArticle

First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques

by Iori Kisu, Yojiro Kato, Yohei Masugi, Hirohito Ishigaki, Yohei Yamada, Kentaro Matsubara, Hideaki Obara, Katsura Emoto, Yusuke Matoba, Masataka Adachi, Kouji Banno, Yoko Saiki, Takako Sasamura, Iori Itagaki, Ikuo Kawamoto, Chizuru Iwatani, Takahiro Nakagawa, Mitsuru Murase, Hideaki Tsuchiya, Hiroyuki Urano, Masatsugu Ema, Kazumasa Ogasawara, Daisuke Aoki, Kenshi Nakagawa and Takashi Shiina Show full author list Hide full author list

J. Clin. Med. 2020, 9(11), 3694; https://doi.org/10.3390/jcm9113694 - 17 Nov 2020

Cited by 7 | Viewed by 3119

Abstract

Delivery following uterus transplantation (UTx)—an approach for treating uterine factor infertility—has not been reported in nonhuman primate models. Here, six female major histocompatibility complex (MHC)-defined cynomolgus macaques that underwent allogeneic UTx were evaluated. Antithymocyte globulin and rituximab were administered to induce immunosuppression and [...] Read more.

Delivery following uterus transplantation (UTx)—an approach for treating uterine factor infertility—has not been reported in nonhuman primate models. Here, six female major histocompatibility complex (MHC)-defined cynomolgus macaques that underwent allogeneic UTx were evaluated. Antithymocyte globulin and rituximab were administered to induce immunosuppression and a triple maintenance regimen was used. Menstruation resumed in all animals with long-term survival, except one, which was euthanized due to infusion associated adverse reaction to antithymocyte globulin. Donor-specific antibodies (DSA) were detected in cases 2, 4, and 5, while humoral rejection occurred in cases 4 and 5. Post-transplant lymphoproliferative disorder (PTLD) developed in cases 2 and 3. Pregnancy was attempted in cases 1, 2, and 3 but was achieved only in case 2, which had haploidentical donor and recipient MHCs. Pregnancy was achieved in case 2 after recovery from graft rejection coincident with DSA and PTLD. A cesarean section was performed at full-term. This is the first report of a successful livebirth following allogeneic UTx in nonhuman primates, although the delivery was achieved via UTx between a pair carrying haploidentical MHCs. Experimental data from nonhuman primates may provide important scientific knowledge needed to resolve unsolved clinical issues in UTx. Full article

(This article belongs to the Special Issue Uterus Transplantation)

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21 pages, 861 KiB

Open AccessArticle

Living-Donor Uterus Transplantation: Pre-, Intra-, and Postoperative Parameters Relevant to Surgical Success, Pregnancy, and Obstetrics with Live Births

by Sara Yvonne Brucker, Thomas Strowitzki, Florin-Andrei Taran, Katharina Rall, Dorit Schöller, Markus Hoopmann, Melanie Henes, Martina Guthoff, Nils Heyne, Stephan Zipfel, Norbert Schäffeler, Hans Bösmüller, Falko Fend, Peter Rosenberger, Eckhard Heim, Urban Wiesing, Konstantin Nikolaou, Sabrina Fleischer, Tamam Bakchoul, Christian F. Poets, Rangmar Goelz, Cornelia Wiechers, Karl-Oliver Kagan, Bernhard Krämer, Christl Reisenauer, Ernst Oberlechner, Stephanie Hübner, Harald Abele, Pernilla Dahm-Kähler, Niclas Kvarnström, Mats Brännström, Silvio Nadalin, Diethelm Wallwiener and Alfred Königsrainer Show full author list Hide full author list

J. Clin. Med. 2020, 9(8), 2485; https://doi.org/10.3390/jcm9082485 - 03 Aug 2020

Cited by 46 | Viewed by 4663

Abstract

Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS), a congenital disorder characterized by uterovaginal aplasia, but with functional ovaries. Based on our four successful living-donor transplantations and two resulting births, this analysis presents parameters relevant to [...] Read more.

Uterus transplantation (UTx) can provide a route to motherhood for women with Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS), a congenital disorder characterized by uterovaginal aplasia, but with functional ovaries. Based on our four successful living-donor transplantations and two resulting births, this analysis presents parameters relevant to standardizing recipient/donor selection, UTx surgery, and postoperative treatment, and their implementation in routine settings. We descriptively analyzed prospectively collected observational data from our four uterus recipients, all with MRKHS, their living donors, and the two newborns born to two recipients, including 1-year postnatal follow-ups. Analysis included only living-donor/recipient pairs with completed donor/recipient surgery. Two recipients, both requiring ovarian restimulation under immunosuppression after missed pregnancy loss in one case and no pregnancy in the other, each delivered a healthy boy by cesarean section. We conclude that parameters crucial to successful transplantation, pregnancy, and childbirth include careful selection of donor/recipient pairs, donor organ quality, meticulous surgical technique, a multidisciplinary team approach, and comprehensive follow-up. Surgery duration and blood vessel selection await further optimization, as do the choice and duration of immunosuppression, which are crucial to timing the first embryo transfer. Data need to be collected in an international registry due to the low prevalence of MRKHS. Full article

(This article belongs to the Special Issue Uterus Transplantation)

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13 pages, 2276 KiB

Open AccessArticle

Outcome of Recipient Surgery and 6-Month Follow-Up of the Swedish Live Donor Robotic Uterus Transplantation Trial

by Mats Brännström, Pernilla Dahm-Kähler, Jana Ekberg, Randa Akouri, Klaus Groth, Anders Enskog, Verena Broecker, Johan Mölne, Jean-Marc Ayoubi and Niclas Kvarnström

J. Clin. Med. 2020, 9(8), 2338; https://doi.org/10.3390/jcm9082338 - 22 Jul 2020

Cited by 37 | Viewed by 2206

Abstract

Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017–2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one [...] Read more.

Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017–2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one family friend. Donor surgery was by robotic-assisted laparoscopy. Recipient surgery was by laparotomy and vascular anastomoses to the external iliacs. The duration (median (ranges)) of recipient surgery, blood loss, measured (left/right) uterine artery blood flow after reperfusion, and length of hospital stay were 5.15 h (4.5–6.6), 300 mL (150–600), 43.5 mL/min (20–125)/37.5 mL/min (10–98), and 6 days (5–9), respectively. Postoperative uterine perfusion evaluated by color Doppler showed open anastomoses but restricted blood distribution in two cases. Repeated cervical biopsies in these two cases initially showed ischemia and, later, necrosis. Endometrial growth was not seen, and hysterectomy was later performed, with pathology showing partly viable myometrium and fibrosis but necrosis towards the cavity. The other six patients acquired regular menstrual cyclicity. Surgery was performed in two patients to correct vaginal stenosis. Reversible rejection episodes were seen in two patients. In conclusion, the rate of viable uterine grafts during the initial 6-months of the present study (75%) leaves room for improvement in the inclusion/exclusion criteria of donors and in surgical techniques. Initial low blood flow may indicate subsequent graft failure. Full article

(This article belongs to the Special Issue Uterus Transplantation)

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11 pages, 1033 KiB

Open AccessArticle

Uterus Transplantation with Live Donors: Screening Candidates in One French Center

by Marie Carbonnel, Aurelie Revaux, Elena Menzhulina, Lea Karpel, Renaud Snanoudj, Morgan Le Guen, Dominique De Ziegler and Jean Marc Ayoubi

J. Clin. Med. 2020, 9(6), 2001; https://doi.org/10.3390/jcm9062001 - 25 Jun 2020

Cited by 21 | Viewed by 2307

Abstract

We report our experience regarding the profile and screening process of potential recipients (R) and their live donors (D) in our Uterus transplantation (UTx) trial from 2014 to 2020. The initial screening was performed using medical questionnaires and consultations. The second step of [...] Read more.

We report our experience regarding the profile and screening process of potential recipients (R) and their live donors (D) in our Uterus transplantation (UTx) trial from 2014 to 2020. The initial screening was performed using medical questionnaires and consultations. The second step of the screening consisted of two individual interviews with an independent multidisciplinary committee. Then, a complete medical, biological and imaging assessment of the directed living D, the R, and her partner was performed over a two-day hospitalization. A total of 239 women contacted our department: 165 potentials R and 74 potentials D. During the first step of screening, 141 R and 45 D were excluded. Only 12 R/D pairs were pursued. During inclusion, 10 R/D pairs were excluded. One R/D pair is still under evaluation. Finally, only 1 R/D pair was definitively included (0.6%), which led us to perform the first French UTx in March 2019 with a successful graft. The primary limiting factors of inclusion were due to very strict criteria and difficulty of having a suitable directed living D. The International Society of UTx (ISUTx) guidelines based on worldwide results of trials can help ease our inclusion criteria in the future while remaining safe for patients. Full article

(This article belongs to the Special Issue Uterus Transplantation)

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19 pages, 5923 KiB

Open AccessArticle

Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques

by Iori Kisu, Hirohito Ishigaki, Katsura Emoto, Yojiro Kato, Yohei Yamada, Kentaro Matsubara, Hideaki Obara, Yohei Masugi, Yusuke Matoba, Masataka Adachi, Kouji Banno, Yoko Saiki, Iori Itagaki, Ikuo Kawamoto, Chizuru Iwatani, Takahiro Nakagawa, Hideaki Tsuchiya, Takako Sasamura, Hiroyuki Urano, Masatsugu Ema, Kazumasa Ogasawara, Daisuke Aoki, Kenshi Nakagawa and Takashi Shiina Show full author list Hide full author list

J. Clin. Med. 2019, 8(10), 1572; https://doi.org/10.3390/jcm8101572 - 01 Oct 2019

Cited by 11 | Viewed by 3345

Abstract

Uterus transplantation (UTx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. Therefore, allogeneic animal models of UTx are required for resolution of clinical issues. In this study, long-term outcomes were evaluated [...] Read more.

Uterus transplantation (UTx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. Therefore, allogeneic animal models of UTx are required for resolution of clinical issues. In this study, long-term outcomes were evaluated in four recipients (cases 1–4) after allogeneic UTx in cynomolgus macaques. Immunosuppression with antithymocyte globulin induction and a triple maintenance regimen was used. Postoperative ultrasonography and biopsy of the transplanted uterus and immunoserological examinations were performed. All four recipients survived for >3 months after surgery, but continuous menstruation did not resume, although temporary menstruation occurred (cases 1 and 2). All animals were euthanized due to irreversible rejection and no uterine blood flow (cases 1, 2 and 4) and post-transplant lymphoproliferative disorder (case 3). Donor-specific antibodies against MHC class I and II were detected in cases 1, 2 and 4, but not in case 3. Peripheral lymphocyte counts tended to elevate for CD3⁺, CD20⁺ and NK cells in conjunction with uterine rejection, and all animals had elevated stimulation indexes of mixed lymphocyte reaction after surgery. Establishment of allogeneic UTx in cynomolgus macaque requires further exploration of immunosuppression, but the clinicopathological features of uterine rejection are useful for development of human UTx. Full article

(This article belongs to the Special Issue Uterus Transplantation)

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Review

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18 pages, 279 KiB

Open AccessReview

The Key Role of Warm and Cold Ischemia in Uterus Transplantation: A Review

by Antoine Tardieu, Ludivine Dion, Vincent Lavoué, Pauline Chazelas, Pierre Marquet, Pascal Piver, Camille Sallée, Yves Aubard, Chantal Barin-Le Guellec, Frederic Favreau and Tristan Gauthier

J. Clin. Med. 2019, 8(6), 760; https://doi.org/10.3390/jcm8060760 - 29 May 2019

Cited by 20 | Viewed by 2905

Abstract

Introduction: Uterus transplantation (UTx) is a promising treatment for uterine infertility that has resulted in several births since 2014. Ischemia is a key step in organ transplantation because it may lead to changes jeopardizing graft viability. Method: We performed a systematic [...] Read more.

Introduction: Uterus transplantation (UTx) is a promising treatment for uterine infertility that has resulted in several births since 2014. Ischemia is a key step in organ transplantation because it may lead to changes jeopardizing graft viability. Method: We performed a systematic review of animal and human studies relating to uterine ischemia. Results: We retained 64 studies published since 2000. There were 35 studies in animals, 24 in humans, and five literature reviews. Modest preliminary results in large animals and humans are limited but encouraging. In small animals, pregnancies have been reported to occur after 24 h of cold ischemia (CI). In ewes, uterine contractions have been detected after 24 h of CI. Furthermore, it has been shown in animals that uterine tolerance to CI and to warm ischemia (WI) can be increased by pharmacological products. In women, mean CI time in studies of births from uteri obtained from live donors was between 2 h 47 min and 6 h 20 min from a deceased donor; with only one birth in this case. Muscle contractions have also been demonstrated in myometrial samples from women, after six or more hours of CI. Conclusion: The uterus seems to be able to tolerate a prolonged period of CI, of at least six hours. Studies of the ischemia tolerance of the uterus and ways to improve it are essential for the development of UTx, particularly for procedures using grafts from deceased donors. Full article

(This article belongs to the Special Issue Uterus Transplantation)

13 pages, 422 KiB

Open AccessReview

Current Progress in Uterus Transplantation Research in Asia

by Iori Kisu, Yu Liu, Gaowen Chen, Min Jong Song, Cherry Yin-Yi Chang, Tan Hak Koon, Kouji Banno and Daisuke Aoki

J. Clin. Med. 2019, 8(2), 245; https://doi.org/10.3390/jcm8020245 - 14 Feb 2019

Cited by 17 | Viewed by 4472

Abstract

Uterus transplantation (UTx) is now a possible approach for women with absolute uterine factor infertility to deliver a child, following the first successful delivery by Brännström et al. in Sweden in September 2014. This remarkable achievement attracted major attention worldwide and caused many [...] Read more.

Uterus transplantation (UTx) is now a possible approach for women with absolute uterine factor infertility to deliver a child, following the first successful delivery by Brännström et al. in Sweden in September 2014. This remarkable achievement attracted major attention worldwide and caused many countries to prepare for UTx, including countries in Asia. To date, three groups have performed UTx in humans in Asia, and many others are aiming for the clinical application of UTx with accumulation of basic experimental data. Therefore, it is likely that UTx will expand rapidly in Asia in the near future, although this will depend on ethical, social and religious views in each country. With this background, herein we summarize the current progress of UTx in East, Southeast and South Asia, with the purpose of increasing understanding of the current status of basic and clinical UTx research in each country and sharing progress and knowledge to ensure future development of UTx research in Asia. Full article

(This article belongs to the Special Issue Uterus Transplantation)

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