Uterine allografts: A new era in reproduction

Surgeon

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November 18, 2019
Volume: 
64
Issue: 
11
Table 1
Table 1

Uterine transplantation (UTx) has rapidly moved from a theoretical construct to a clinical reality. Over just the past 5 years, the world has witnessed several notable milestones in this quickly-evolving field. With healthy live birth being the ultimate goal of a reproductive transplant, the 14 babies born to date following UTx for which reports exist and the additional ongoing pregnancies represent proof of concept for the viability of this experimental procedure. 

Options for AUFI
UTx represents the first and only treatment for women with absolute uterine factor infertility (AUFI). AUFI can be either congenital (e.g., Mayer Rokitansky Kuster Hauser syndrome) or acquired. Estimated to affect one in 500 women, AUFI has previously only been addressed using in vitro fertilization (IVF) with gestational carriers, fostering, adoption, or planning a life without children.1 For some women, these may be acceptable options, but for others, these alternatives may not be desired, often due to personal, social, cultural or religious beliefs. Choices for women with AUFI are especially limited in parts of the world where gestational carriers and even adoption may be socially unacceptable, highly restricted, or banned completely. Interviews of women with AUFI in a uterine transplant trial indicate that the diagnosis of AUFI can be a devastating and life-altering experience and that achieving reproductive autonomy is a key desire of women with this condition.2

AUFI Milestones
The advent and rapid ascent of UTx have been marked by innovation. Initial international attempts in humans performed outside of clinical trials were not successful, and technical success for the Swedish team was ultimately achieved following decades of preparatory work in small mammals and non-human primates. As with any new surgical procedure, the technical elements have quickly advanced and evolved (Table 1). 

In case you missed it: Uterine transplantation from deceased donor results in livebirth

Together with documented technical success and increased media attention has come improved public perception and enhanced physician awareness and support for the procedure. Sixty percent of American Association of Gynecologic Laparoscopists (AAGL) and American Society for Reproductive Medicine (ASRM) members support UTx as a treatment for AUFI.10 A 2018 study of public perception of UTx in the United States indicated that 78% of respondents supported UTx and 45% believed it should be covered by insurance.11 Another recent study indicated that 74% of women would donate their uterus for transplant.12 It is unclear what the cost of a uterine transplant will be, and how or whether insurance will cover this reproductive procedure. As the discussion evolves along with the science, questions regarding access, cost, and safety will be paramount. 

Slow initial acceptance of UTx may be due to the fact that, unlike other transplants, UTx is not a life-saving transplant. Like face, hand, and other vascularized composite allographs, the uterine transplant can be life-enhancing and indeed can be life-giving. Also distinct from other known organ transplants, UTx is an “ephemeral” transplant.13 This means that the uterus will be removed after one or two live births are achieved and is not intended to be a lifelong transplant. This means that women receiving a UTx will not be exposed to immunosuppression once the uterus has been removed after childbearing. 

Despite growing numbers of live births, UTx remains a significant undertaking for both recipients and living donors. The procedure for donor hysterectomy is similar to radical hysterectomy, and donor complications have been reported in the literature.14,15 Historically, donor surgeries have involved long operating room times (10-13 hours in the original Swedish series) and large incisions, although this may change as laparoscopic and robotic approaches are pioneered. Although a deceased donor model obviates this risk completely, most live births to date have been achieved with living donors. Deceased donor UTx represents a more ethical choice by eliminating donor risk, however, it has the limitations of organ availability, less convenient scheduling, and more restricted medical history on the donor.1 It is unknown how outcomes from deceased donor trials will compare with living donor trials and whether one approach will demonstrate superiority over the other or whether both approaches will coexist. Recent studies suggest no recipient preference for a living vs a deceased donor.2

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Disclosures: 

The authors report no potential conflicts of interest with regard to this article.

References: 
  1. Flyckt RL, Farrell RM, Perni UC, Tzakis AG, Falcone T. Deceased donor uterine transplantation: innovation and adaptation. Obstet Gynecol. 2016 Oct;128(4):837-42.
  2. Richards EG, Agatisa PK, Davis AC, et al. Framing the diagnosis and treatment of absolute uterine factor infertility: Insights from in-depth interviews with uterus transplant trial participants. AJOB Empir Bioeth. 2019 Jan-Mar;10(1):23-35.
  3. Brännström M, Johannesson L, Bokström H, et al. Live birth after uterus transplantation. Lancet. 2015 Feb 14;385(9968):607-616.
  4. Kuehn, B.M. 2017. US uterus transplant trials under way. JAMA. 317, no. 10 (March 14): 1005-1007.
  5. Brännström MP, Dahm Kähler R, Greite J, et al. Uterus transplantation: a rapidly expanding field. Transplantation. 2018;102(4): 569-577.
  6. Wei L, Xue T, Tao K-S, 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 Steri. 2017;108(2): 346-356.e1.
  7. 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(4):628-635.
  8. 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(4): 622-631.
  9. 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;392 (10165): 2697-2704.
  10. Hariton,E, Bortoletto P, Goldman RH, Farland LV, Ginsburg ES, Gargiulo AR. A survey of public opinion in the united states regarding uterine transplantation. J Minim Invasive Gynecol. 2018;25(6): 980-985.
  11. Bortoletto P, Hariton E, Farland LV, Goldman RH, Gargiulo AR. Uterine transplantation: a survey of perceptions and attitudes of american reproductive endocrinologists and gynecologic surgeons. J Minim Invasive Gynecol. 2018;25(6):974-979.
  12. Rodrigue JR, Tomich D, Fleishman A, Glazier AK. Vascularized composite allograft donation and transplantation: a survey of public attitudes in the United States. Am J Transplant. 2017 Oct;17(10):2687-2695.
  13. Flyckt R, Davis A, Farrell R, Zimberg S, Tzakis A, Falcone T. Uterine transplantation: surgical innovation in the treatment of uterine factor infertility. J Obstet Gynaecol Can. 2018 Jan;40(1):86-93.
  14. 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 Nov;17(11):2901-2910. 
  15.  Johannesson L, Kvarnström N, Mölne J, et al. Uterus transplantation trial: 1-year outcome. Fertil Steril. 2015;103(1):199-204.
  16. Practice Committee of the American Society for Reproductive Medicine. American Society for Reproductive Medicine position statement on uterus transplantation: a committee opinion. Fertil Steril. 2018 Sep;110(4):605-610.
  17. Flyckt R, Farrell RM, Falcone T. Advancing the science of uterine transplantation: minimizing living donor risk on a path to surgical innovation. J Minim Invasive Gynecol. 2019 May - Jun;26(4):577-579.
  18. Tummers P, Göker M, Dahm-Kahler P, et al. Meeting report: first state-of-the-art meeting on uterus transplantation. Transplantation. 2019 Mar;103(3):455-458.

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