J Reconstr Microsurg 2022; 38(06): 429-440
DOI: 10.1055/s-0041-1735261
Original Article

Evolution and Transformation of Uterine Transplantation: A Systematic Review of Surgical Techniques and Outcomes

1   Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
,
2   Division of Plastic and Reconstructive Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
,
Eric Santamaría
3   Department of Plastic and Reconstructive Surgery, Hospital General Dr. Manuel Gea Gonzalez, National Cancer Institute, Mexico City, Mexico
,
Howard N. Langstein
1   Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
,
Pedro Ciudad
4   Department of Plastic, Reconstructive and Burn Surgery, Arzobispo Loayza National Hospital, Lima, Peru
,
Roberto Hernandez-Alejandro
5   Department of Surgery and Division of Abdominal Transplantation and Hepatobiliary Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
,
Richard G. Moore
6   Department of Obstetrics and Gynecology, Strong Memorial Hospital, University of Rochester Medical Center, New York
,
Jonathan I. Leckenby
1   Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
,
Oscar J. Manrique
1   Division of Plastic and Reconstructive Surgery, Strong Memorial Hospital, University of Rochester Medical Center, New York
› Author Affiliations

Abstract

Background Uterine transplantation (UTx) is acknowledged to be on the second (2A) of five steps of development in accordance with the staging system for the evaluation of surgical innovations. Accordingly, we aimed to systematically review the available evidence of the surgical techniques and outcomes of UTx in terms of graft survival.

Methods A comprehensive search was conducted across PubMed Medline, Cochrane-EBMR, Scopus, Web of Science, and CENTRAL through November 2020.

Results Forty studies, reporting 64 recipients and 64 donors, satisfied inclusion criteria. The surgical time and the estimated blood loss were 515 minutes and 679 mL for graft procurement via laparotomy, 210 minutes and 100 mL for laparoscopic-assisted graft harvest, and 660 minutes and 173 mL for robotic-assisted procedures, respectively. Urinary tract infections (n = 8) and injury to the urinary system (n = 6) were the most common donor complications. Using the donor's internal iliac system, two arterial anastomoses were performed in all cases. Venous outflow was accomplished through the uterine veins (UVs) in 13 cases, a combination of the UVs and the ovarian/uteroovarian veins (OVs/UOVs) in 36 cases, and solely through the OVs/UOVs in 13 cases. Ischemia time was 161 and 258 minutes when using living donors (LD) and deceased donors (DD), respectively. Forty-eight uteri were successfully transplanted or fulfilled the purpose of transplantation, 41 from LDs and 7 from DDs. Twenty-five and four live childbirths from LDs and DDs have been reported, respectively.

Conclusion UTx is still experimental. Further series are required to recommend specific surgical techniques that best yield a successful transplant and reduce complications for donors and recipients.

Authors' Contributions

(1) Conception and design: O.J.M., H.N.L., and J.M.E.; (2) administrative support: O.J.M. and H.N.L.; (3) provision of study materials or patients: O.J.M. and J.M.E.; (4) collection and assembly of data: V.P.B., J.M.E.; (5) data analysis and interpretation: O.J.M., J.M.E., and V.P.B.; (6) manuscript writing: all authors; and (7) final approval of manuscript: all authors.


Supplementary Material



Publication History

Received: 07 April 2021

Accepted: 19 July 2021

Article published online:
17 September 2021

© 2021. Thieme. All rights reserved.

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333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Farrell RM, Johannesson L, Flyckt R. et al. Evolving ethical issues with advances in uterus transplantation. Am J Obstet Gynecol 2020; 222 (06) 584.e1-584.e5
  • 2 Chmel R, Pastor Z, Matecha J, Janousek L, Novackova M, Fronek J. Uterine transplantation in an era of successful childbirths from living and deceased donor uteri: Current challenges. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2020; 164 (01) 115-120
  • 3 Brännström M, Dahm Kähler P, Greite R, Mölne J, Díaz-García C, Tullius SG. Uterus transplantation: a rapidly expanding field. Transplantation 2018; 102 (04) 569-577
  • 4 Ayoubi JM, Carbonnel M, Pirtea P, Kvarnström N, Brännström M, Dahm-Kähler P. Laparotomy or minimal invasive surgery in uterus transplantation: a comparison. Fertil Steril 2019; 112 (01) 11-18
  • 5 Saso S, Clarke A, Bracewell-Milnes T. et al. Psychological issues associated with absolute uterine factor infertility and attitudes of patients toward uterine transplantation. Prog Transplant 2016; 26 (01) 28-39
  • 6 Wennberg AL, Rodriguez-Wallberg KA, Milsom I, Brännström M. Attitudes towards new assisted reproductive technologies in Sweden: a survey in women 30-39 years of age. Acta Obstet Gynecol Scand 2016; 95 (01) 38-44
  • 7 Kisu I, Banno K, Soeda E. et al. Survey of attitudes toward uterus transplantation among Japanese women of reproductive age: a cross-sectional study. PLoS One 2016; 11 (05) e0156179
  • 8 O'Donovan L, Williams NJ, Wilkinson S. Ethical and policy issues raised by uterus transplants. Br Med Bull 2019; 131 (01) 19-28
  • 9 Diaz-Garcia C, Pellicer A. Uterus transplantation from a deceased donor. Lancet 2019; 392 (10165): 2657-2658
  • 10 McCulloch P, Altman DG, Campbell WB. et al; Balliol Collaboration. No surgical innovation without evaluation: the IDEAL recommendations. Lancet 2009; 374 (9695): 1105-1112
  • 11 Shamseer L, Moher D, Clarke M. et al; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 2015; 350: g7647
  • 12 Moher D, Shamseer L, Clarke M. et al; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4 (01) 1
  • 13 Wells G, Shea B, O'Connell D. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. Accessed November 30, 2020 at: http//www.ohri.ca/programs/clinical_epidemiology/oxford.asp
  • 14 Dekkers OM, Egger M, Altman DG, Vandenbroucke JP. Distinguishing case series from cohort studies. Ann Intern Med 2012; 156 (1, pt 1): 37-40
  • 15 Murad MH, Sultan S, Haffar S, Bazerbachi F. Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med 2018; 23 (02) 60-63
  • 16 Oxford Centre for Evidence-Based Medicine.. OCEBM Levels of Evidence. Accessed November 30, 2020 at: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence
  • 17 Brucker SY, Brännström M, Taran FA. et al. Selecting living donors for uterus transplantation: lessons learned from two transplantations resulting in menstrual functionality and another attempt, aborted after organ retrieval. Arch Gynecol Obstet 2018; 297 (03) 675-684
  • 18 Djordjevic M, Milenkovic M, Dahm-Kähler P. et al. PD25–12 monozygotic twin uterus transplantation. J Urol 2018; 199 (4s): e551
  • 19 Fageeh W, Raffa H, Jabbad H, Marzouki A. Transplantation of the human uterus. Int J Gynaecol Obstet 2002; 76 (03) 245-251
  • 20 Brännström M, Johannesson L, Bokström H. et al. Livebirth after uterus transplantation. Lancet 2015; 385 (9968): 607-616
  • 21 Ejzenberg D, Andraus W, Mendes LRBC. et al. Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility. Lancet 2019; 392 (10165): 2697-2704
  • 22 Ejzenberg D, Andraus W, Baratelli Carelli Mendes LR. et al. Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility. Lancet 2019;22;392(10165):2697–2704. Doi: 10.1016/S0140-6736(18)31766-5. Epub 2018 Dec 4. PMID: 30527853
  • 23 Akouri R, Maalouf G, Abboud J. et al. First live birth after uterus transplantation in the Middle East. Middle East Fertil Soc J 2020; 25 (30) 1-7
  • 24 Brännström M, Bokström H, Dahm-Kähler P. et al. One uterus bridging three generations: first live birth after mother-to-daughter uterus transplantation. Fertil Steril 2016; 106 (02) 261-266
  • 25 Testa G, McKenna GJ, Gunby Jr. RT. et al. First live birth after uterus transplantation in the United States. Am J Transplant 2018; 18 (05) 1270-1274
  • 26 Brännström M, Dahm-Kähler P, Kvarnström N. et al. Live birth after robotic-assisted live donor uterus transplantation. Acta Obstet Gynecol Scand 2020; 99 (09) 1222-1229
  • 27 Chmel R, Pastor Z, Novackova M, Matecha J, Cekal M, Fronek J. Clinical pregnancy after deceased donor uterus transplantation: Lessons learned and future perspectives. J Obstet Gynaecol Res 2019; 45 (08) 1458-1465
  • 28 Kristek J, Johannesson L, Novotny R, Kachlik D, Fronek J. Human uterine vasculature with respect to uterus transplantation: a comprehensive review. J Obstet Gynaecol Res 2020; 46 (11) 2199-2220
  • 29 Flyckt R, Falcone T, Quintini C. et al. First birth from a deceased donor uterus in the United States: from severe graft rejection to successful cesarean delivery. Am J Obstet Gynecol 2020; 223 (02) 143-151
  • 30 Flyckt RL, Farrell RM, Perni UC, Tzakis AG, Falcone T. Deceased donor uterine transplantation: innovation and adaptation. Obstet Gynecol 2016; 128 (04) 837-842
  • 31 Brännström M, Johannesson L, Dahm-Kähler P. et al. First clinical uterus transplantation trial: a six-month report. Fertil Steril 2014; 101 (05) 1228-1236
  • 32 Johannesson L, Kvarnström N, Mölne J. et al. Uterus transplantation trial: 1-year outcome. Fertil Steril 2015; 103 (01) 199-204
  • 33 Richards EG, Flyckt R, Tzakis A, Falcone T. Uterus transplantation: organ procurement in a deceased donor model. Fertil Steril 2018; 110 (01) 183
  • 34 Brännström M, Kvarnström N, Groth K. et al. Evolution of surgical steps in robotics-assisted donor surgery for uterus transplantation: results of the eight cases in the Swedish trial. Fertil Steril 2020; 114 (05) 1097-1107
  • 35 Chmel R, Cekal M, Pastor Z. et al. Assisted reproductive techniques and pregnancy results in women with Mayer-Rokitansky-Küster-Hauser syndrome undergoing uterus transplantation: the Czech experience. J Pediatr Adolesc Gynecol 2020; 33 (04) 410-414
  • 36 Johannesson L, Koon EC, Bayer J. et al. Dallas UtErus transplant study: early outcomes and complications of robot-assisted hysterectomy for living uterus donors. Transplantation 2021; 105 (01) 225-230
  • 37 Testa G, Koon EC, Johannesson L. et al. Living donor uterus transplantation: a single center's observations and lessons learned from early setbacks to technical success. Am J Transplant 2017; 17 (11) 2901-2910
  • 38 Testa G, Anthony T, McKenna GJ. et al. Deceased donor uterus retrieval: a novel technique and workflow. Am J Transplant 2018; 18 (03) 679-683
  • 39 Chmel R, Novackova M, Janousek L. et al. Revaluation and lessons learned from the first 9 cases of a Czech uterus transplantation trial: four deceased donor and 5 living donor uterus transplantations. Am J Transplant 2019; 19 (03) 855-864
  • 40 Ozkan O, Akar ME, Ozkan O. et al. Preliminary results of the first human uterus transplantation from a multiorgan donor. Fertil Steril 2013; 99 (02) 470-476
  • 41 Ramani A, Testa G, Ghouri Y. et al. DUETS (Dallas UtErus transplant study): complete report of 6-month and initial 2-year outcomes following open donor hysterectomy. Clin Transplant 2020; 34 (01) e13757
  • 42 Brännström M, Dahm-Kähler P, Ekberg J. et al. Outcome of recipient surgery and 6-month follow-up of the Swedish live donor robotic uterus transplantation trial. J Clin Med 2020; 9 (08) 2338
  • 43 Brucker SY, Strowitzki T, Taran F-A. et al. Living-donor uterus transplantation: pre-, intra-, and postoperative parameters relevant to surgical success, pregnancy, and obstetrics with live births. J Clin Med 2020; 9 (08) 2485
  • 44 Froněk J, Janousek L, Chmel R. Deceased donor uterus retrieval - the first Czech experience. Rozhl Chir 2016; 95 (08) 312-316
  • 45 Brännström M, Dahm-Kähler P, Kvarnström N. Robotic-assisted surgery in live-donor uterus transplantation. Fertil Steril 2018; 109 (02) 256-257
  • 46 Brännström M, Enskog A, Kvarnström N, Ayoubi JM, Dahm-Kähler P. Global results of human uterus transplantation and strategies for pre-transplantation screening of donors. Fertil Steril 2019; 112 (01) 3-10
  • 47 Jones BP, Saso S, Bracewell-Milnes T. et al. Human uterine transplantation: a review of outcomes from the first 45 cases. BJOG 2019; 126 (11) 1310-1319
  • 48 Ozkan O, Dogan NU, Ozkan O. et al. Uterus transplantation: From animal models through the first heart beating pregnancy to the first human live birth. Womens Health (Lond) 2016; 12 (04) 442-449
  • 49 Daolio J, Palomba S, Paganelli S, Falbo A, Aguzzoli L. Uterine transplantation and IVF for congenital or acquired uterine factor infertility: a systematic review of safety and efficacy outcomes in the first 52 recipients. PLoS One 2020; 15 (04) e0232323
  • 50 Flyckt R, Kotlyar A, Arian S, Eghtesad B, Falcone T, Tzakis A. Deceased donor uterine transplantation. Fertil Steril 2017; 107 (03) e13
  • 51 Erman Akar M, Ozkan O, Aydinuraz B. et al. Clinical pregnancy after uterus transplantation. Fertil Steril 2013; 100 (05) 1358-1363
  • 52 Wei L, Xue T, Tao KS. et al. Modified human uterus transplantation using ovarian veins for venous drainage: the first report of surgically successful robotic-assisted uterus procurement and follow-up for 12 months. Fertil Steril 2017; 108 (02) 346-356.e1
  • 53 Huang Y, Ding X, Chen B. et al. Report of the first live birth after uterus transplantation in People's Republic of China. Fertil Steril 2020; 114 (05) 1108-1115
  • 54 Puntambekar S, Telang M, Kulkarni P. et al. Laparoscopic-assisted uterus retrieval from live organ donors for uterine transplant. J Minim Invasive Gynecol 2018; 25 (04) 571-572
  • 55 Puntambekar S, Telang M, Kulkarni P. et al. Laparoscopic-assisted uterus retrieval from live organ donors for uterine transplant: our experience of two patients. J Minim Invasive Gynecol 2018; 25 (04) 622-631
  • 56 Puntambekar S, Puntambekar S, Telang M. et al. Novel anastomotic technique for uterine transplant using utero-ovarian veins for venous drainage and internal iliac arteries for perfusion in two laparoscopically harvested uteri. J Minim Invasive Gynecol 2019; 26 (04) 628-635
  • 57 Ejzenberg D, Andraus W, Carelli Mendes LR B, Ducatti L, Song A, Tanigawa R, Baracat E.C.. Livebirth After Uterus Transplantation From a Deceased Donor in a Recipient With Uterine Infertility. Obstetric Anesthesia Digest 2019; 39 (03) 167 DOI: 10.1097/01.aoa.0000575292.34874.2f.
  • 58 Clavien PA, Barkun J, de Oliveira ML. et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg 2009; 250 (02) 187-196
  • 59 Maubon A, Hardeman S, Decroisette E. et al. RI-WS-8 Fertilite apres embolisation des arteres uterines pour hemorragie de la delivrance. J Radiol 2009; 90 (10) 1393
  • 60 Racho El-Akouri R, Wranning CA, Mölne J, Kurlberg G, Brännström M. Pregnancy in transplanted mouse uterus after long-term cold ischaemic preservation. Hum Reprod 2003; 18 (10) 2024-2030
  • 61 Zitkute V, Kvietkauskas M, Leber B, Strupas K, Stiegler P, Schemmer P. Ischemia and reperfusion injury in uterus transplantation: A comprehensive review. Transplant Rev (Orlando) 2020; 34 (03) 100550
  • 62 Tardieu A, Dion L, Lavoué V. et al. The key role of warm and cold ischemia in uterus transplantation: a review. J Clin Med 2019; 8 (06) 760
  • 63 Latchana N, Peck JR, Whitson BA, Henry ML, Elkhammas EA, Black SM. Preservation solutions used during abdominal transplantation: current status and outcomes. World J Transplant 2015; 5 (04) 154-164
  • 64 Badet L, Eugène M, Hauet T, Barrou B. The use of preservation solutions in renal transplantation [in French]. Prog Urol 2006; 16 (01) 25-31
  • 65 Obimbo MM, Ogeng'o JA, Saidi H. Comparative regional morphometric changes in human uterine artery before and during pregnancy. Pan Afr Med J 2012; 13: 30
  • 66 Jiga LP, Lupu CM, Zoica BS, Ionac M. Experimental model of heterotopic uterus transplantation in the laboratory rat. Microsurgery 2003; 23 (03) 246-250
  • 67 Arnolds K, Gomez N, Berry A. et al. Assessment of an alternative to the uterine vein for venous drainage in human uterine transplantation: a case series following laparoscopic hysterectomy. Gynecol Obstet Invest 2016; 81 (05) 436-441
  • 68 Fujii S, Takakura K, Matsumura N. et al. Precise anatomy of the vesico-uterine ligament for radical hysterectomy. Gynecol Oncol 2007; 104 (01) 186-191
  • 69 Fornalik H, Fornalik N. Uterus transplantation: robotic surgeon perspective. J Minim Invasive Gynecol Fertil Steril 2018; 109 (02) 365
  • 70 Johannesson L, Järvholm S. Uterus transplantation: current progress and future prospects. Int J Womens Health 2016; 8: 43-51
  • 71 Chen GW, Liu XY, Cui ZY. et al. Surgical technique and outcomes of uteri retrieval from brain-dead multi-organ donors: a preclinical research of human uterine transplantation [in Chinese]. Zhonghua Yi Xue Za Zhi 2018; 98 (39) 3178-3182
  • 72 Johannesson L, Diaz-Garcia C, Leonhardt H. et al. Vascular pedicle lengths after hysterectomy: toward future human uterus transplantation. Obstet Gynecol 2012; 119 (06) 1219-1225
  • 73 Kisu I, Banno K, Matoba Y, Aoki D. Uterus transplantation: advantages and disadvantages of a deceased donor. Arch Gynecol Obstet 2019; 299 (05) 1213-1214
  • 74 Welman T, Villani V, Shanmugarajah K, Hettiaratchy S. From kidney transplants to vascularized composite allografts: the role of the plastic surgeon in transplantation. Vasc Compos Allotransplantation 2015; 2 (04) 71-74
  • 75 Karaca E, Hockenberger AS, Yildiz H. Investigating changes in mechanical properties and tissue reaction of silk, polyester, polyamide, and polypropylene sutures in vivo. Text Res J 2005; 75 (04) 297-303
  • 76 Feldman MK, Hunter SA, Perni UC. et al. New frontier: role of the radiologist in uterine transplantation. Radiographics 2020; 40 (01) 291-302
  • 77 Wong AK, Joanna Nguyen T, Peric M. et al. Analysis of risk factors associated with microvascular free flap failure using a multi-institutional database. Microsurgery 2015; 35 (01) 6-12
  • 78 Nicholson CJ, Sweeney M, Robson SC, Taggart MJ. Estrogenic vascular effects are diminished by chronological aging. Sci Rep 2017; 7 (01) 12153
  • 79 Mohammadbaigi H, Darvishi M, Moayeri A. Variations of anterior and posterior division of internal iliac artery: a systematic review and clinical implications. Biomed Res Ther 2019; 6 (05) 3189-3206