Women with absolute uterine-factor infertility (AUFI) had until recently only the opportunity to have children through adoption, foster parenting, or gestational surrogacy. However, for some women with AUFI, none of these options is possible because of religious, societal, personal, or other reasons. Uterus transplantation (UTx) has recently been introduced as a unique opportunity for both genetic and gestational motherhood. To date, most UTx were accomplished with uterus transplants procured from living donors. Although deceased donor (DD) UTx have been performed successfully, the overall experience remains rare. Notably, most (10/13) DD UTx have been performed by the teams in Dallas, TX and Prague, Czech Republic. Recently, the first baby was born to a recipient after DD UTx in São Paulo,1 demonstrating proof of concept for DD UTx.
DD UTx is desirable, as it avoids risks associated with complex live donor hysterectomies and (2) not every patient in need may have a qualifying living donor available.
Thus, it appears critical to analyze the potential of DD UTx. Several unknowns and limitations to this pursuit need to be addressed and include (1) the lack of standardized evaluation criteria of uterus DD (both standard and extended criteria), (2) information on the availability of potential uterus DDs, (3) assuring that potential donors will be identified by organ procurement organizations (OPOs), and (4) issues of consent beyond that taken for the procurement of solid organs for transplantation.
Here, we address those issues in a transatlantic approach with an analysis in the Czech Republic, Sweden, the United Kingdom, and the United States (Figure 1). We aimed to roughly approximate the volume of potential uterus donors, demand for transplantation linked to geographical region. Moreover, we suggest criteria allowing OPOs to identify uterus DD and introduce the experience at our institutions on getting consent.
Our analysis was based on data (collected from 2012 to 2016) provided directly from the respective national bodies dealing with organ allocation; that is, the Coordination Center of Transplantation (Czech Republic),2 Scandiatransplant (Sweden),3 National Health Service Blood and Transplant (United Kingdom),4 and the United Network for Organ Sharing (United States).5 Notably, data of the National Health Service are collected per fiscal years. To estimate the uterus DD population/country, data on total donor volume/y and female brain death [donation after brain death (DBD)] donors 20–45 years were collected. Data on overall population were provided by Eurostat (for the Czech Republic, Sweden, and the United Kingdom) and the World Bank (for the United States).6,7 Female DDs were calculated per million people (PMP) of the total population.
Additional information of relevance for uterus donation (gynecological history, malignancies, pap smears, parity, and gynecological surgery [particularly, cesarean section]) was requested by the OPOs. Moreover, we collected information whether the next of kin’s authorization to uterus recovery was requested and whether the question on authorization to uterus recovery is present in a DD registry.
DEMAND FOR UTX
It is estimated that absolute uterine-factor infertility affects 1%–5% of reproductive-aged infertile women.8 AUFI may be the result of congenital uterus malformations or agenesis, previous hysterectomies, or acquired uterus dysfunction, such as myoma or Asherman syndrome.8 The prevalence of AUFI due to congenital uterus agenesis is estimated at 1:4000 female live births, that is, 0.025% of the general female population, or 250 PMP.9 Certainly, not all women suffering from AUFI wish to have children while others seek adoption or surrogacy as alternatives, making the “real” demand for uterus transplantation difficult to assess.
DD POOL SIZE
Of all DBD donors, 41.8% were female and averaged 8.17 PMP (in all participating countries in the studied period). Of all female DBD donors, 27.9%, that is, 2.33 PMP, on average were 20–45 years old (Table 1). This is a rough approximation of the maximum number of potential uterus DD candidates based on a single criterion. In reality, the prevalence of potential donors may be lower because many further criteria may be relevant, including the absence of a history of (major) abdominal or pelvic surgery, uterus pathologies including abnormal pap smear, history of donor infertility/subfertility, human papillomavirus infection, or other relevant systemic disease (Table 2).
A rough comparison of the potential DD and recipient prevalence (2.33 PMP versus 250 PMP) clearly demonstrates the apparent lack of potential DD grafts to treat all potential patients (although some of them prefer other solutions than UTx to address AUFI).
CONSENT FOR UTX
UTx is a life-giving, however not life-saving, procedure. Together with other nonvital organs, including face, extremities, penis, or larynx, UTx is considered a vascular composite allograft (VCA). Thus, being registered as an organ donor may not necessarily include the consent to uterus (or any other VCA) donation.10 According to the 2017 policy of the Organ Procurement and Transplantation Network, recovery of VCA for transplant purposes has to be explicitly authorized. Thus, a separate authorization to recover the uterus is obligatory in the United States and United Kingdom. Organ donation in the Czech Republic and Sweden presumes consent; however, there is no special legislation regarding VCAs; nevertheless, it has become common practice to get an authorization for uterus recovery. Although this approach is not necessarily mandatory, it is highly recommended to obtain an explicit consent for uterus donation for either research and transplant purposes.
CRITERIA FOR UTERUS DONATION
Uterus DD criteria need to be established and promoted. Table 2 lists criteria that have been used by the teams in Dallas and Prague. Although criteria for an “ideal” donor appear obvious, it is less clear on what donors may still be acceptable to meet the demand for uterus transplantation. Certainly “working” criteria will be useful that may be subject to change as more experience is gained.
Age limits are based on 2 potential risks associated with postmenopausal donors: (1) with increasing age microvascular disturbances may impair both blood flow and function11 and (2) assessing fertility in postmenopausal DD uteruses is challenging in the absence of hormonal stimulation. Thus, age limits of 18–45 years have been chosen somewhat arbitrarily, as microvascular changes are generally minimal in this age group with a functioning uterus. Thus, establishing histological criteria to grade these microvascular changes may be useful in expanding the donor pool as well as in ruling out uteri deemed otherwise adequate based on age criteria alone.
In our opinion, donation after circulatory death is currently not a viable option, because warm ischemia may potentially impair fertility.
Specific aspects of a potential donor’s surgical and oncological history, including cesarean section, hysterectomy, and gynecological malignancies, were usually available in all countries. In contrast, data on parity and pap smears are usually not available. Whenever a uterus DD had been identified, the next-of-kin had to be contacted for missing information. During working hours, the patient’s gynecologist was contacted by the coordinator. Notably, there was access to the patient’s gynecological records (if the patient’s data were present) in the National Patient Overview, a database with all patients’ charts in Sweden.
Based on our experience, we recommend that every graft be inspected (by colposcopy) for potential cervical dysplasia. In the experience of the Prague team, a graft had to be discarded due to cervical dysplasia that had not been documented in the provided gynecological history.
Despite its experimental status, UTx has advanced rapidly. The supply of living donors may be insufficient to meet the demand. Thus, the potential of DDs has to be explored. Defining and promoting uterus DD criteria are essential for proper evaluation and the success of DD uterus transplantation. The information provided on DDs and access to information that includes gynecological history is often incomplete. Improving access to gynecological and overall history may allow better donor allocation, offering the best possible outcome for recipients.
The authors thank Professor Stefan G. Tullius, MD, PhD, FACS, for his support in design and editing of the manuscript.
1. Ejzenberg D, Andraus W, Baratelli Carelli Mendes LR, et al. Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility.Lancet20193922697–2704
2. Koordinační Středisko Transplantací [Coordination Center Transplantation].2019Jak fungujemeAvailable at https://www.kst.cz/o-nas/jak-fungujeme/
. Accessed April 28, 2019
4. National Health ServiceNHS Blood and Transplant.2019Available at https://www.nhsbt.nhs.uk/
. Accessed April 28, 2019
5. United Network for Organ SharingWhat is UNOS?2019Available at https://unos.org/about
. Accessed April 28, 2019
7. The World BankPopulation, Total.2019Available at https://data.worldbank.org/indicator/SP.POP.TOTL?locations = US
. Accessed April 28, 2019
8. Practice Committee of the American Society for Reproductive MedicineAmerican Society for Reproductive Medicine position statement on uterus transplantation: a committee opinion.Fertil Steril2018110605–610
9. Oppelt P, Renner SP, Kellermann A, et al. Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for clinical diagnosis and staging.Hum Reprod200621792–797
10. Rahmel A. Vascularized composite allografts: procurement, allocation, and implementation.Curr Transplant Rep20141173–182
11. 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 Transplant2017172901–2910