The Costs of Human Uterus Transplantation

A Study Based on the Nine Cases of the Initial Swedish Live Donor Trial

Thomas Davidson; Jana Ekberg; Lars Sandman; Mats Brännström

Disclosures

Hum Reprod. 2021;36(2):358-366. 

In This Article

Discussion

Absolute uterine factor infertility was until recently the last major group of untreatable female infertility. The first birth after UTx in 2014 (Brannstrom et al., 2015) was the proof-of-concept of UTx as a new fertility treatment. This birth was within the first clinical UTx trial (Brannstrom et al., 2014) including nine procedures, which is also the focus of the present study. Concerning live donor procedures with the traditional laparotomy technique, as used in the present study, there exist very limited data. In 2016, the second UTx trial started and that was in the Czech Republic, with the aim to include ten each of live donor and deceased donor UTx-procedures (Chmel et al., 2019). Results have been presented concerning surgery and outcome for 6–24 months of five live-donor UTx procedures of this trial. There also exist presentations on recipient and donor outcome for some months after live donor procedures in two trials initiated in 2017, one in Germany with two procedures presented (Brucker et al., 2018) and one in USA with five procedures presented (Testa et al., 2017). No cost analyses have been performed in any of these trials. Thus, there is a need for health economic studies in this new area of infertility treatment and in transplantation surgery. In the latter field, it is a quality-of-life enhancing/life producing transplantation, rather than a life-saving transplantation, as for most solid organ transplants. Concerning, quality-of-life and psychological outcome of the uterus recipients of the present study, one report on 3-year outcome showed negative deviations in the mental component of health-related quality of life in some women and their partners, possibly related to the fact that live birth had not yet been achieved (Jarvholm et al., 2020a). However, a qualitative study of all recipients of the present study and covering the 5-year period after transplantation, showed that their self-image was in general positively affected, regardless of whether they had given birth or not (Jarvholm et al., 2020b). Taken together, the UTx procedure seems to be enhancing quality-of-life in the events of live birth(s) but may also have some smaller positive effect, even among those that do not achieve the ultimate goal of live birth.

We calculated the total cost to €74 564 per clinical UTx (Table II). The recipient had somewhat higher costs than the donor, but in terms of costs, they should be considered as an entity. The largest component was the cost of sick leave (€19 164), thereafter the cost of postoperative hospitalization and surgery cost. Hence, if a health care perspective is used (not considering the cost of sick-leaves) the cost per clinical UTx would account to €55 400.

There was a wide variation in costs between individual cases, with the largest difference being associated with postoperative hospitalization, which are costs when the patient is taken into the hospital for treatment that needs the resources of the hospital. The most common cause of re-hospitalization was rejection episodes that needed treatment with i.v. corticosteroids (Molne et al., 2017). All treatments were successful, and rejection could be reversed. Procedure No. 2 was associated with 64% of the costs of postoperative hospitalization, with the causes being described in detail (Brannstrom et al., 2014). Briefly, they were related to treatments of a persistent intra-uterine infection in the recipient and in the donor of a ureteric-vaginal fistula, including investigations and temporary treatment with a percutaneous nephrostomy. Surgery for ureteral re-implantation was performed 4 months after UTx and is not included in the present study, The calculated costs of surgery and hospitalization in connection with ureteral re-implantation is around €6000. Of note is that there was a wide variation, between approximately €50 000 and €100 000, in total costs when comparing a procedure with the lowest costs for all major sub-items and a procedure with greatest costs for all sub-items. The costs would naturally be even higher if postoperative care or complication of any patient would need management in an intensive care unit, with the associated very high costs.

There is a lack of studies to compare our results with. The most common live donor transplantation procedure is kidney transplantation, where typically a close family member will be the donor. A study from the USA (Lebovitz et al., 2020) found that the total societal net gain of compatible live donor renal transplant is positive ($1.1 million), when considering avoidance of haemodialysis, quality of life and sick leave. In a study from Canada, with a similar public health system as in Sweden, a detailed analysis of kidney donor-associated costs, including pre-operative examination, surgery and postoperative follow-up found the costs of the donor procedure, excluding costs for sick-leave, to be just below €10 000 (Habbous et al., 2018).

Concerning the total expenses for live donor transplantation surgery, the cost for the procedure at the hospital of a standard live donor kidney transplantation in a US setting is between $90 000 to $100 000 (Axelrod et al., 2018). The cost for live donor liver transplantation in USA is well above the cost for live donor kidney transplantation (Lebovitz et al., 2020). Estimation from a UTx group in the US, have come to a price of a live donor UTx procedure of around $200 000 (Sifferlin, 2019). However, this estimate was not based on any detailed analysis and not published in a scientific journal. It should be emphasized that the live donor transplantation costs from studies out of USA, as referred to above, only include the perioperative costs, including surgery and post-surgery hospitalization. In the present study, these costs were around 45% of the total costs. Noteworthy, is that health costs in general are higher in the USA than in most European countries, including Sweden. Recently, a feasibility study for performing UTx in the Netherlands (Peters et al., 2020) estimated the total costs for screening, IVF and UTx of live donor procedure to be around €77 100. This estimation did not include costs for immunosuppressive treatment, rehospitalisation and sick leave, which were included in the calculation of the present study. The estimated costs were markedly higher than the actual costs of the present study. Noteworthy is that the generalizability of the results of the present study is limited, but the range of costs would apply to Nordic countries, with similar health care systems and general costs levels as Sweden.

Uterus transplantation can be performed either as a deceased donor or a live donor procedure. There is a great difference in potential costs of a deceased donor UTx procedure and a live donor UTx procedure, since the costs for preoperative tests and surgery are greatly reduced in deceased donor UTx and possibly shared by the costs included for transplantation of abdominal and thoracic organs from a multiorgan donor. In the present study, the costs for the donor in conjunction with surgery were markedly higher than for the recipient but costs for sick leave and rehospitalization marginally lower for the donor as compared with the recipient. Thus, the total costs for a deceased donor UTx procedure, in our setting, would be considerably lower than for a live donor UTx procedure.

In the present study, we only evaluated costs up to 2 months after surgery. This time period includes the largest costs, since it includes costly surgery and sick leave. During the subsequent time interval from 2 months until pregnancy is achieved by ET, costs related to multiple gynaecological examinations with cervical biopsies, blood tests, continued immunosuppression, rejection treatments and possibly repeated ETs will be added and the cost will vary according to number of rejection episodes, with associated hospitalization and increased immunosuppression, as well as numbers of ETs to achieve pregnancy. In the present cohort, seven of the nine patients initiated pregnancy attempts and with two of them becoming pregnant at their first ET attempts (Molne et al., 2017).

It is of importance to note that the costs of this case series of nine patients are within the first research study on this subject, and the preparations were meticulous. We consider the total estimate to be in the higher interval, because of the extensive research protocol. It is likely that the cost of live donor UTx will vary between countries and that the costs will be lower in a future clinical setting.

Many healthcare jurisdictions are struggling with resource constraints, and especially within publicly funded healthcare systems, it is an ongoing discussion what should be publicly reimbursed and what not. In this discussion, assisted reproductive technologies are constantly brought to the fore (Balayla and Dahdouh, 2016; Wilkinson and Williams, 2016; Brannstrom et al., 2016b; Blake, 2018; McTernan, 2018; Sandman, 2018) and could be viewed as 'borderline' cases of what should be reimbursed. Different healthcare jurisdictions make different choices as to this. In this perspective, UTx has raised a discussion for whether it should receive public funding or not. Priority setting, in many countries, will involve taking patient need, effect of treatment and also cost-effectiveness into account. Given that we accept infertility as a patient need that justifies public funding (to some extent) will provide prima facie reason to fund also UTx for consistency and equality reasons. Here cost and cost-effectiveness of UTx will be a central consideration for whether it meets reimbursement criteria (Sandman, 2018). In this perspective, this article will feed into important policy discussions and provide input to future cost-effectiveness analysis of UTx. Here UTx faces a challenge, since it is not fully established how infertility treatment should be assessed in a cost-benefit analysis. According to practice, it is the effects gained by the parent(s), which are assessed, and any effects gained by the child are ignored. This will obviously have a considerable impact on the outcome of the cost-effectiveness analysis, but we will return to this in future publications.

In conclusion, we present the first available data on the cost of human UTx. The present study demonstrates that it is a costly infertility treatment at this early stage. Future developments in surgery, including introduction of minimal invasive surgery, may decrease the costs related to hospitalization and sick leave substantially.

processing....