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LETTER TO EDITOR
Proposing a Novel Organ Allocating System for Uterus Transplantation: Implications and Issues

Dear Editor:

Following the first uterus transplant (UTx) clinical trial in 2012, this field has grown rapidly with greater than 70 reported cases and over 23 live births. Although in most institutions UTx is still considered an “experimental treatment,” operating under institutional review board (IRB) guidelines, groups with more experience have recently begun to offer UTx as a “clinical option.” With increasing UTx demand, leaders in the field have raised several potential concerns, one of which is the lack of an organ allocation system (OAS)1 or prioritization criteria (PC) specific to UTx. In the United States, the underlying ethical considerations that govern organ prioritization are utility, justice, and respect for persons.2 Utility is the maximization of net benefits to the community and is focused on the best outcomes for organ transplant. Justice is fairness in the distribution of the burdens and benefits of organ procurement and allocation. Justice considers material principles for distribution, including urgency, waiting time, and age. Respect for persons is the respect for individual decision making (for example, accepting a donated organ).

Creation of a UTx PC is ethically complex because determining thresholds for utility in a life-enhancing transplant is more difficult than in a life-saving transplant. In the latter, graft survival and patient survival are measured and justice considerations about ranking are more clearly defined. For example, urgency is the primary distributive justice principle in prioritization of patients who can be categorized by illness severity (for example, those with heart and lung disease). Waiting time is the primary distributive justice principle for organs in which patients on wait lists have roughly equivalent severity of illness (for example, those with kidney disease). For UTx, ethical distributive principles are less obvious. Allocation guidelines for UTx have been proposed; however, no comprehensive ranking system has been described.3,4 Here, we propose a novel and flexible preliminary OAS that aims to accomplish the goal of fair uterus allocation for all patients while avoiding directed uterus graft donations to a specific group.

Organ allocation should be conceptualized as 2 separate events: listing and prioritization (Table 1 and Figure 1). Each UTx center has specific listing criteria (LC) and screening tests for UTx recipients that should ideally account for patient characteristics (age, comorbidities, extent of infertility treatment required, psychological stability, socioeconomic status, parenthood status), motivation, and patient pre­ferences (living vs deceased donor, donor age, parity).

Patient desires and motivations may play one of the largest roles in an OAS for UTx listing. The life-enhancing aspects of UTx require interested patients to seek out care that is not required. Therefore, those who most desire to carry and give birth to a child and are undergoing UTx with these specific motivations should be given high priority (expedited listing). Women should not undergo UTx solely to restore physiologic normality.3,4 Decisions regarding UTx candidacy should be determined at the center level.

After patients are listed for UTx, national level prioritization ensues via consideration of PC (Figure 2). A match run for each potential donor includes all patients with blood type and immunologic compatibility.5 Prioritization is the determination of how to rank all compatible patients based on objective criteria. Because UTx is a “quality of life” transplant, we believe that the primary distributive justice principle to consider should be waiting time. The definition of waiting time must be clarified (for example, time from diagnosis of infertility, time from embryo creation, or time from being placed on a wait list for transplant). The process of matching recipients to donors is rigorous and includes evaluations of medical compatibility based on blood typing, tissue typing, and cross-matching.5 Use of the proposed matching algorithm may influence the duration that a patient stays on a wait list or the odds of receiving their most closely matched organ. A patient with a low panel reactive antibody or more common blood and HLA types is expected to find a matched organ faster and as such should be ranked lower or receive a lower priority for UTx (principle of justice). Prioritization should be given to patients with high panel reactive antibody (that is, those with >98% or 0 antigen mismatch; perfect immunologic match).

Although LC and PC are distinct, some factors such as age may impact both. Two factors regarding recipient age must be considered in the context of LC: (1) what constitutes childbearing age and (2) how medical and surgical risks vary at different ages. If the recipient is not of an advanced maternal age, that is, not an age that may make a pregnancy “high risk,” the more important factor to consider is how old the “eggs” are at retrieval. The chance of a successful pregnancy is dependent on the quality of the “retrieved eggs.” In addition, ethical considerations such as the “fair inning argument” (everyone is entitled to a normal span of health) and the “prudential lifespan account” (resources should be invested across lifespans to make life go as well as possible) must be considered.3 In the context of PC and based on ethical arguments, it seems most fair to rank older patients higher than younger patients due to their faster approaching end to childbearing capacity. However, younger patients must not be unfairly overlooked. “Wait list time,” either from the date of infertility diagnosis, embryo creation, or UTx listing, should be a major determinant in PC or in an OAS.6,7 Wait list time also directly impacts recipient age, as recipients will grow older while they are waiting to receive an organ.

In UTx, success is gauged by a livebirth outcome. As such, the extent of required infertility treatment,3 urgency of organ need, and prediction of in vitro fertilization success are additional factors that must be considered in a fair and efficient OAS (however difficult it may be to rank based on these factors). However, the ranking of patients based on these complex factors (prioritization) may be extremely difficult, if not impossible. It may be more practical to consider these factors as LC by centers when recruiting patients for potential UTx. We suggest giving priority (expedited listing) to those in the most stable relationships (for example, married). Patients who have not been able to adopt, use surrogacy, or give birth to a child of their own should also be ranked higher in an allocation system. Although some women desire more than 1 child, all those desiring a child should be given a chance before a second chance is granted. With the consideration of all of these factors, our group has devised a ranking system for potential UTx recipients based on point values for the detailed variables. We suggest that this system will be useful in ethically allocating organs in the rapidly growing field of UTx.


References:

  1. Farrell RM, Johannesson L, Flyckt R, et al. Evolving ethical issues with advances in uterus transplantation. Am J Obstet Gynecol. 2020; 222(6):584.e1-584.e5. doi:10.1016/j.ajog.2020.01.032
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  2. US Department of Health and Human Services. https://optn.transplant.hrsa.gov/resources/ethics/ethical-principles-in-the-allocation-of-human-organs/
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  3. Bayefsky MJ, Berkman BE. The ethics of allocating uterine transplants. Camb Q Healthc Ethics. 2016;25(3):350-365. doi:10.1017/S0963180115000687
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  4. Bruno B, Arora KS. Uterus transplantation: the ethics of using deceased versus living donors. Am J Bioeth. 2018;18(7):6-15. doi:10.1080/15265161.2018.1478018
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  5. Jackson AM, Kraus E. Blood tests for kidney transplants. National Kidney Foundation. Accessed March 23, 2021. https://www.kidney.org/atoz/content/BloodTests-for-Transplant
    CrossRef - PubMed
  6. Wall A, Testa G. Living donation, listing, and prioritization in uterus transplant. Am J Bioeth. 2018;18(7):20-22. doi:10.1080/15265161.2018.1478026
    CrossRef - PubMed
  7. Johannesson L, Wall A, Tzakis A, et al. Life underneath the VCA umbrella: Perspectives from the US Uterus Transplant Consortium. Am J Transplant. 2021;21(5):1699-1704. doi:10.1111/ajt.16445
    CrossRef - PubMed


DOI : 10.6002/ect.2021.0260


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From the 1Plastic and Reconstructive Surgery Department, Rush University Medical Center, Chicago, Illinois; the 2Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, Texas; and the 3Department of Obstetrics and Gynecology, Baylor University Medical Center, Dallas, Texas, USA
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no declarations of potential conflicts of interest.
Corresponding author: Alireza Hamidian Jahromi, Department of Plastic and Reconstructive Surgery, Rush University Medical Center, 345 E Ohio Street, Number 2009, Chicago, IL 60611, USA
Phone: +1 318 518 4600
E-mail: Alirezahamidian@yahoo.com, alireza_hamidianjahromi@rush.edu