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

Materials and Methods

Patients and Procedure Map

The patients of the present study comprise the recipients and the donors of nine live-donor uterus transplantation procedures, taking place in Sweden in 2013 (Brannstrom et al., 2014, 2015). The patient material has been described in detail, in the initial publication of this trial, presenting results of surgery and 6-month follow-up (Brannstrom et al., 2014). Briefly, the recipients were eight women with uterine agenesis as part of the Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome as well as one woman that had undergone hysterectomy for cervical cancer. They were all in stable relationships and underwent IVF with their partners before transplantation. The donors were genetically linked in seven cases (5 mothers, one sister, one maternal aunt) and not in two cases (mother-in-law, friend). All patients went through psychological screening prior to transplantation (Jarvholm et al., 2015). The median (range) ages of recipients, recipients' partners and donors at the time of UTx were 34 (27–38), 34 (29–40) and 53 (37–62) years, respectively. Of importance for the present paper is that the outcome in two out of nine recipients did not follow a standard pattern. The recipient of UTx procedure No. 2 acquired an intrauterine infection and was re-hospitalized for treatments and the outcome was hysterectomy 3.5 months after UTx. The recipient of UTx procedure No. 9 had an early graft failure, caused by vascular thrombosis, and the uterus was removed within a week after transplantation.

The procedure map was decided prior to the study and according to the research protocol. In general, preoperative investigations were done in parallel to IVF, with cryopreservation of oocytes during a 6–12 months period. The reason to perform IVF before UTx, was to ascertain fertilization and embryo development within the couple and to avoid oocyte pick up in an immunosuppressed woman with altered pelvic anatomy. After surgery and recovery, the transplanted woman would be closely monitored for 12 months to detect and treat any rejections/infections as well as to establish stable levels of immunosuppressant. In the present cohort, the first embryo transfer (ET) took place 12 months after UTx.

Procedures Included

The timeframe for the study included the time from start of pre-operative investigations until the completion of the second postoperative month. The reason for choosing this timeframe is that it would include also costs for immediate postoperative complications as well as sick leave and that it would not include costs for ETs and investigative preparations for that, with wide variations in numbers necessary to achieve pregnancy and in disparate opinions concerning suitable time for first ET in relation to UTx, spanning from 3 months (Johannesson et al., 2019) to the 12 months of the present study.

The cost analysis performed relates to observed costs, rather than protocol-based costs. The pre-transplantation investigations that were included in the cost analysis included imaging, clinical examinations, assessments by specialists in several fields, microbiology/serology test, electrocardiography and general blood test. The tests are specified in our original publication on 6 months outcome of this cohort (Brannstrom et al., 2014) and further in Table I. Moreover, IVF, with the aim to cryopreserve at least eight embryos of good quality, typically necessitating two IVF stimulations, was performed prior to UTx. Surgery of UTx included donor surgery to harvest the uterus with vascular pedicles and recipient surgery to insert the uterus with vascular anastomoses to the external iliac vessels. The surgical duration of the donor (10.5–13 h) was markedly longer than the predicted maximum of around 6 h, which was around 2-fold greater than uterine harvesting in our non-human allogeneic UTx model (Johannesson et al., 2013). Recipient surgery had durations within the predicted range (4–6 h), but since we had anticipated a much shorter duration of donor surgery the first recipient had a very long anaesthesia time, waiting for the organ procurement to be completed. In procedures Nos. 2 and 3, we still assumed that we would have considerably shorter surgical durations in donors but later, from procedure No. 4, adjusted to the facts of very complex and time-consuming donor surgery. Postoperative care and hospital stays were according to local routines for patients undergoing major gynaecological surgery and organ transplantations. Outpatient visits were twice every week during the initial post-transplantation month and then weekly during the second month. Samples, for vaginal bacterial culture and cervical biopsy for rejection diagnosis, were taken weekly during the first month and then once a month. The durations of sick leave were according to Swedish standard routines for patients undergoing abdominal hysterectomy and transplantation, with modifications concerning recommended duration according to postoperative health and type of occupation.

Calculation of Costs

The data were treated according to per protocol analysis and the methodology of a cost analysis was used (Drummond et al., 2015). All costs were identified, quantified in physical units, and finally valued. A societal perspective was used for the analysis as recommended in Sweden (The Dental and Pharmaceutical Benefits Agency, 2003), which means that also costs such as productivity losses due to sick leaves were included. Resource use was valued according to its opportunity cost, that is, the best alternative use of the resources. Costs were calculated in Swedish Krona (SEK), in 2020-year values, and presented in Euros (€) using an exchange rate of €1 = SEK10.52 (18 June 2020).

The cost calculations included preparations, surgery and all costs up to 2 months after the surgery for both the recipient and the donor. Hence, costs of IVF were included, but no costs related to ET, pregnancy and delivery. In this context, it is of note that the first ET attempts would start 12 months after UTx, which is in accordance with recommendations for solid organ transplantation (Cabiddu et al., 2018) and is in order to stabilize organ function, minimize immunosuppression, and because a majority of rejection episodes after transplantation occur during the initial post-transplantation year.

Most costs of tests and clinical procedures are taken from the tariff list year 2020 of Sahlgrenska University Hospital, Göteborg, Sweden (Västra Sjukvårdsregionen, 2020), which is the hospital where the transplantations were performed. We used the most recent tariff list (rather than the list of year 2013 when the transplantations were performed) to be relevant for a decision maker of today. All unit costs are presented in Table I.

Time used by staff was calculated using average monthly salary plus 53% (payroll taxes and extra costs for vacation), divided in minutes, and then multiplied with the number of minutes they spend with the patient. Time used by donor and recipient during the preparation phase were not included, as this was assumed as non-working time.

The pre-transplantation investigations covered several meetings and diagnostic tests. Both the donor and the recipient had a first meeting with a gynaecologist for about 20 min, equalling a cost of about €200. Later, both the donor and the recipient had a longer meeting, for about 2 h, including more staff (gynaecologist, transplant surgeon, anaesthesiologist and psychiatrist), equalling a cost of about €1000. Several tests were taken, both of the donor and the recipient, including MRI (€531), computerized tomography (€349), and several blood tests concerning blood chemistry, haematology and virology, as specified in Table I.

The costs of the UTx surgery covered all resources used during the surgery and were calculated based on the time used for both the donor and the recipient. The cost per minute of anaesthesia was set at €5.60, and for surgery €7.50. Furthermore, a surgeon fee at €5.50 per minute was included, covering both gynaecologist and transplantation surgeon.

The cost of hospital care per day at the transplantation centre at Sahlgrenska University Hospital was €1043, which was used both for postoperative hospitalization and for re-hospitalization. Data concerning sick leave, expressed as number of days, was obtained from the Swedish Social Insurance Agency. The costs of sick leave were based on the expected productivity loss. Median monthly salary in Sweden in 2019 was €3013. Including fees and taxes (53%; covering payroll taxes and extra costs for vacation) this represents €4610. As the average is 21 working days per month, the cost of each day is estimated to €220. IVF, with no ET, but including embryo cryopreservation, is assumed to cost €3163, according to cost of privately funded IVF (Nordic IVF, 2020).

Drug costs are taken from official tariff lists in 2020 (Apoteket, 2020; Janusinfo, 2020); hence no potential discounts were calculated for.

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