Availability of deceased uterus donor: Is it a real case scenario in Spain?

The authors confirm contribution to the paper as follows: study conception and design: FC, MR, MC; data collection: MC, MR, JT; analysis and interpretation of results: MC, MR, FC, BDF; draft manuscript preparation: MC, MR, FC. All authors reviewed the results and approved the final version of the manuscript.

Ethical approval was waived by the Organización Catalana de Transplantes (OCATT), as the data were anonymized and retrospective.

From January 1st, 2015, to December 31st, 2019, 201 women aged from 18 to 50 were included in a multiorgan donation program after circulatory and brain death in Catalonia. Among these, 45 (22.4%) were donors after circulatory death and were excluded, leaving 156 (77.6%) donors after brain death. Donors were further considered valid if the donation was accepted by the family or previously agreed upon by the patient, resulting in the exclusion of 51 donors. Figure  1 shows the flowchart of potential deceased donors for uterus transplantation after applying exclusion criteria. Flowchart of potential deceased donors for uterine transplantation. The figure illustrates the flowchart of potential deceased donor candidates of uterus transplantation during the entire period (5 years) after applying exclusion criteria. We considered major abdominal surgery patients who had undergone two or more C‐sections, bowel resection, or myomectomy. Other abdominal surgeries such as appendectomy, cholecystectomy, and unilateral oophorectomy were not classified as major surgery. After applying exclusion criteria, 48 deceased donors were eligible, accounting for 23.9% of the total. When applying the SDM criteria, 14 deceased donors met inclusion criteria, whereas when EDM criteria were applied, 48 deceased donors met inclusion criteria (Figure  2 ). Both models applied to the same donor pool. Classification into standard donor model and extended donor model. The mean population in Catalonia from 2015 to 2019 was 7.57 million. Using SDM criteria, 1.8 potential DD PMP in the studied period were eligible (0.4 PMP per year). Using EDM criteria, 6.3 potential deceased donors PMP in the entire period were eligible (1.3 PMP per year).

Absolute uterine factor infertility was historically untreatable until uterine transplantation became a viable option in multiple transplant centers worldwide. While most attempts and live births have been reported from LDs, successful transplantation from DDs has also been demonstrated, resulting in healthy births. 12 , 13 LDs offer several benefits over DDs, including better preoperative planning, standardized procedure, shorter ischemic times, and avoidance of interference with vital organ retrieval. On the other hand, the advantages of using a DD donor include eliminating surgical risks for the donor, the potential for younger donors, and the ability to obtain longer vascular pedicles. Additionally, DDs are a source of grafts that offer a potential solution to the shortage of organs compared to LDs, although data on the number of potential uterus donors and appropriate donor allocation criteria remain rare. Our study reveals that applying standard donor criteria could potentially yield 1.8 deceased donors PMP during the study period, while applying extended donor criteria could increase this to 6.3 PMP, translating to 0.4 and 1.3 PMP per year, respectively. However, whether these estimated numbers meet the actual demand for grafts cannot be conclusively determined, as there is scarce literature addressing donor availability as well as women's preferences toward UTx. 14 , 15 The estimated prevalence of historically untreatable uterine infertility is approximately 250 per million people. 9 However, accurately assessing true demand for deceased donor uterus transplants remains challenging for several reasons: first, not all women suffering this condition seek maternity, nor do all wishing to conceive have a potential living donor. Also, numbers could differ depending on the geographical region. In 2019, Kristek et al. 9 conducted a transatlantic analysis estimating 2.33 PMP potential deceased brain death donors of women aged 20–45 across the Czech Republic, Sweden, United Kingdom, and United States over a five‐year period, prior to applying specific donor criteria. The study also highlighted the need to standardize eligibility criteria, proposing both standard and expanded criteria as used by the teams in Prague and Dallas. To our knowledge, only three additional studies have also provided insights into potential DD numbers, conducted in France, 8 Australia, 16 and a letter to the editor analyzing the UK perspective. 17 In the study by Didon et al. in France, 8 they estimated a donor pool of 2.8, 3.8, and 8.6 PMP per year based on very ideal, ideal, and expanded donor criteria, respectively. Remarkably, the study by Pittman et al. in Australia, 16 did not calculate it by the PMP, but provided absolute numbers, showing 21 potential death brain donors per year meeting all eligibility criteria proposed by the teams in Sweden, the United States, and the Czech Republic. 18 , 19 , 20 They conclude that there could be enough DD to consider this model in Australia. However, it is of importance to highlight that no data regarding gynecological records (parity, menstrual status, gynecological diseases), body mass index (BMI), or serological status were available in the study population, likely increasing the number of potential donors compared to our results. Consistent with previous studies, they also emphasized the need to standardize donor criteria. The literature provides conflicting data regarding parity criteria for DD eligibility. Only one study addressing the potential pool of DD considers parity, including nulliparous women in the extended criteria group. 9 However, when reviewing the criteria of the teams currently performing DD UTx, some consider nulliparous women, such as the Czech group in the EDC, 6 and the Cleveland group in the USA, 5 stating that while they prefer multiparous donors, they consider nulliparous donors due to the scarcity of available DDs. In contrast, other teams only consider women who have had at least one normal pregnancy and childbirth. 18 Our study excluded women with BMI <35 kg/m 2 , while more restrictive criteria, such as BMI < 30 kg/m 2 , are employed by some groups. 5 Regarding donor age, accessing younger donors is advantageous as older age may impact uterine function and reproductive outcomes; it is thought that with increasing age, arteries from the uterus could have lower elasticity and higher stiffness, thus increasing the risk of preeclampsia and other adverse outcomes. 21 Menopausal status poses challenges in a DD program, as hormonal preparation with estrogen is not feasible unlike living donors, where the donor undergoes hormonal treatment; thus, it might potentially affect the graft success and live birth rates due to tissue atrophy. 5 We limited our study to women aged <50 years to mitigate these challenges. Age limits vary among different transplant teams: the Cleveland group from USA does not describe an age limit but only includes premenopausal women, 5 whilst other groups consider including women up to 60 (including those with menopausal status), such as the Czech group in the EDC. 9 It is known that age may impact uterine function and reproductive outcomes. With increasing age, arteries from the uterus could have lower elasticity and higher stiffness, thus increasing the risk of preeclampsia and other adverse outcomes. 21 While UTx from circulatory death donors is not currently considered, exploring this option could expand the donor pool, as it happens with other solid organ transplants such as kidney. 22 In our study, 22.4% of initial donors were excluded due to circulatory death, highlighting the need for further research into the impact of warm ischemia on uterine function and reproductive outcomes. 9 Access to complete medical records during organ procurement varies, often relying on information provided by family members. The next‐of‐kin could probably provide some information regarding the patient's parity and major gynecological history, but some information could be missing, such as the last PAP smear or other gynecological conditions. As previously proposed by Kristek et al., 9 we also consider that performing a colposcopy prior to graft removal could be appropriate to rule out cervical dysplasia. The Czech group also proposes additional assessments to enhance graft success, such as a back‐table hysteroscopy, gynecological ultrasound, and a computed tomography angiography for evaluation of arteries. 6 Ethical considerations in UTx involve ensuring that families are adequately informed that the uterus will be used solely for reproductive purposes, without transferring genetic material from the donor. Legislation and consent practices vary globally, influencing donor availability and program implementation. Organ donation law in Spain presumes consent such as it happens in France, Sweden and the Czech Republic, whereas in other countries (i.e., United States), donors' consent must be explicit. 8 This legal framework is part of a soft opt‐out model that, combined with a centralized national coordination system and active hospital‐based programs, positions Spain as a world leader in organ donation. 23 With a record figure of over 40 deceased donors per million population – higher than in any other country‐ Spain has a long‐standing and internationally recognized experience in deceased donation, particularly for solid organs such as kidney and liver. 24 This robust infrastructure supports the potential integration of DD uterus transplantation into existing transplant programs. Given the unique nature of UTx, however, additional considerations must be taken into account, as the organ is shared by two people (baby and mother), it is a temporary transplant, and the goal is to obtain a newborn and enhance the quality of life of both parents, but it is not live‐saving. We encountered limitations inherent to research using administrative datasets, as there is always a risk of inaccuracies due to the reliance on database's accuracy, which may have led to missing donor‐related data, coding errors in donor classification, and incomplete information regarding exclusion criteria. Another potential limitation is the fact that it was conducted in a small region of Spain. Nevertheless, Catalonia accounts for approximately 24% of transplants in Spain and has one of the highest rates of transplants in the world, with a mean of 176 procedures PMP. 11 , 25 Despite these limitations, our study has significant strengths. It is the first to address organ availability for UTx in Spain, representing initial steps toward implementing this model in a specific geographic region. Moreover, we assess and compare the potential number of donors depending on inclusion criteria.

While using LDs remains the more established option, including DDs in UTx programs is a reasonable consideration. This study highlights the critical need to expand inclusion criteria for deceased donors in uterus transplantation programs, particularly in countries with low donation rates. By demonstrating how the EDM significantly increases the potential donor pool, our findings underscore a pathway for regions with emerging transplantation programs to establish cadaveric donor‐based solutions. These approaches could mitigate the barriers posed by the lack of living donors and contribute to global equity in access to this innovative treatment. Additionally, our results provide a basis for developing standardized international guidelines for donor criteria without significantly increasing the risk of graft failure or adverse outcomes, a crucial step in ensuring consistency and fairness across programs. This is particularly relevant in settings where legislative or logistical challenges currently limit donor availability. By bridging gaps in existing literature and leveraging Spain's recognized leadership in organ donation, this study offers insights with potential applicability to diverse international contexts, extending the impact beyond our region.

Absolute uterine factor infertility, a term historically used to describe untreatable uterine absence or dysfunction, is now being redefined by the success of uterus transplantation (UTx), which enables both gestational and genetic motherhood. It is considered an emerging alternative to surrogacy and adoption. A uterus graft may be obtained from either a living donor (LD) or a deceased donor (DD). The first live birth after a LD graft was accomplished by Brännström's team in Sweden in 2014, 1 whereas the first live birth after a DD was reported in 2017 2 in São Paulo, Brazil, demonstrating the procedure's feasibility. To date, over 90 UTx procedures have been performed worldwide, 3 with approximately 22% using DDs, with these cases being reported in the USA, 4 , 5 Czech Republic, 6 Brazil 2 and Turkey. 7 Although most UTx procedures have used LDs, considering DDs seems reasonable due to the absence of surgical risks for the donor. Additionally, it could help address the shortage of potential living donors, which poses a barrier to UTx, and patients who do not have a qualifying living donor could also benefit from the procedure. Other advantages of using DDs are shorter graft procurement surgery and more extensive vascular dissection. 8 However, experience with DDs remains limited worldwide, and data on the potential number of available uterine grafts is scarce. 8 , 9 Interestingly, a significant challenge shared by groups performing the procedure is the limited number of living donors due to strict inclusion criteria and the necessity to develop strategies for diminishing donor risks. Therefore, the availability of deceased donors represents a key strategy to address the shortage of living donors, especially in regions with emerging uterine transplantation programs. Thus, the aim of this study is to explore the feasibility of a deceased donor program in Catalonia by analyzing the potential number of uterine grafts available for uterus transplantation in a deceased multiorgan donation program in our region of Spain, a country which has maintained global leadership in organ donation for decades, with the highest rate of 49.6 donors per million population (PMP), 10 , 11 offering a valuable perspective that could be adapted and applied internationally and providing insights that can be scaled to regions with similar challenges.

The authors of this manuscript have no conflicts of interest to disclose as described by the Acta Obstetricia et Gynecologica Scandinavica.

We retrospectively analyzed data reported in our Organ Procurement Organization, known as Organización Catalana de Transplantes (OCATT) regarding all females aged 18 to 50 years who were multiorgan donors. We included donors who experienced circulatory and brain death from January 1st, 2015, to December 31st, 2019, just prior to the COVID‐19 pandemic. Most clinical and gynecological variables were obtained from the OCATT donor record and its standardized procurement form. This structured form includes predefined fields capturing key medical history items – such as cause of death, eligibility, previous surgeries, hypertension or diabetes, smoking status, active infection, and use of drugs. When information was missing or unclear, or for the collection of variables such as gynecological history (often incomplete in the procurement form), we accessed additional data available to OCATT within the regional healthcare system. The inclusion and exclusion criteria were adapted based on pre‐defined models available in the literature, 8 , 9 as shown in Table  1 . We further divided potential donors into two categories: standard donor model (SDM) and extended donor model (EDM) as previously described by Kristek et al. 9 Donor numbers were compared between these two categories, and we calculated the number of grafts available for each category per million population in Catalonia, according to Eurostat data. Inclusion and exclusion criteria for deceased donors. Donors after circulatory death Age  50 Previous hysterectomy Active infection (i.e., seropositive for HIV, HBV, HCV, CMV) Major abdominal or gynecological surgery Systemic disease (including diabetes mellitus and high blood pressure) Current pelvic benign or malignant gynecological pathology (i.e., cancer, fibroids, polyps, severe endometriosis, uterine malformation and intrauterine adhesions) History of repeated abortions Active smoker BMI ≤35 (kg/m 2 ) Abbreviations: BMI, Body Mass Index; CMV, cytomegalovirus; HBC, Hepatitis C virus; HBV, Hepatitis B virus; HIV, human immunodeficiency virus.