Hysterectomy after uterus transplantation and detailed analyses of graft failures

Abstract

Introduction The first live birth after uterus transplantation occurred in Sweden in 2014. Uterus transplantation has repeatedly, and at many centers worldwide, proven to be a feasible treatment for absolute uterine factor infertility. Hysterectomy in live donors and transplantation are well described in numerous reports. However, there are no reports of hysterectomy in the recipient after uterus transplantation, which will occur at either graft failure, after childbirth, or after numerous failed pregnancy attempts. We present the first report of hysterectomy in recipients after uterus transplantation with detailed analyses of findings in conjunction with graft failures. Material and Methods An analysis of recipient hysterectomies (n = 10), performed in 2012–2020, was conducted. Data from the international uterus transplantation registry (ISUTx registry) were extracted, and medical records were systematically reviewed, to collect and compile characteristics of recipients and donors, as well as pre‐, per‐, and postoperative data, including clinical course of graft failures. Results Hysterectomy in recipients was performed in conjunction with cesarean section (n = 3), 3–6 months after cesarean section (n = 3), or after failed pregnancy attempts (n = 1) or graft failure (n = 3). The durations of anesthesia (2 h 36 min to 7 h 35 min) and hysterectomy surgery (1 h 42 min to 5 h 52 min) ranged widely, with long perioperative interruptions for insertion of ureteral catheters in two cases. Adhesions to the uterus were abundant, the majority being mild. Three uteri that subsequently showed graft failure (hysterectomy at 1, 3, and 8 months post transplantation) showed histological signs of ischemia in biopsies taken 1‐week post‐transplant and early signs of central hypoperfusion by Doppler ultrasound. In these graft failure explants, there were no epithelial linings in the uterine cavity or in the cervix. The inner uterine wall was severely ischemic and/or necrotic, whereas outer parts were partly viable. There were signs of moderate atherosclerosis of uterine arteries but no rejection. Mild postoperative complications were frequent (6/10), with one supravaginal hematoma requiring surgical drainage. Conclusions Hysterectomy after uterus transplantation is a complex and time‐consuming procedure, and perioperative ureteral catheters may be helpful. Histopathology of early cervical biopsies showing ischemic signs may indicate subsequent irreversible damage, leading to graft failure.

Uterine allograft removal by total laparoscopic hysterectomy after successful cesarean delivery in a living-donor uterus recipient with uterovaginal agenesis (MRKHS)

“…This is possible since UTx is not a life-saving procedure and done to limit the duration of IS therapy and its detrimental side effects on the body [17][18][19], such as increased risk of infection, renal dysfunction due to nephrotoxicity, malignancy, and the costs of long-term immunosuppressive drug treatment [18]. Thus, initial general recommendation was that hysterectomy should be performed after a recipient graft time (RGT) of 7 years or less, after live birth(s) as the goal of successful UTx have occurred [5]. However, it may become necessary in individual cases to remove the uterine allograft even before a pregnancy occurs in order to prevent potential harm to the recipient, as extensively discussed by Ayoubi and colleagues [20].…”

“…However, as a nonvital organ, the uterus is dispensable and hence the allograft should be removed again after a maximum of 2 births to limit the health-damaging effects of long-term IS. Hitherto uterine allograft removal usually has been done by open laparotomy, either immediately after cesarean delivery or in a later procedure [ 5 ]. Laparotomy has been considered to best ensure the complete removal of donor tissue—an absolute prerequisite for terminating IS treatment—because from an open surgery perspective it seemed easier and the risk of organ injury seemed to be lower by removing all donor tissue via laparotomy, especially in the area of the vascular anastomoses, the ureters, and the bladder.…”

Considerations in performing hysterectomy secondary to uterus transplantation

“…In our experiments using cynomolgus macaques, the general conditions, including biochemical parameters, remained good in all animals when graft failures occurred because of ischemia and irreversible rejection. 3 , 4 In Karlsson et al’s study, 1 all three failed uterine grafts showed early ischemic signs, including reduced blood flow towards the inner uterine wall documented by Doppler studies. These cases eventually caused necrotic changes on uterine biopsy, leading to infectious episodes.…”

“…We read with great interest the recent publication by Karlsson et al 1 regarding the surgical outcomes of hysterectomy after uterus transplantation (UTx), with a detailed description of graft failures. These novel perspectives based on the Swedish team’s experiences are very significant because hysterectomy is predetermined as an elective procedure due to the existence of several possible scenarios after UTx.…”

“…These cases eventually caused necrotic changes on uterine biopsy, leading to infectious episodes. 1 In kidney transplantation, where hemodialysis can be introduced as an alternative life‐saving treatment, some controversial reports have opposed the removal of asymptomatic failed allografts due to the morbidity and mortality associated with post‐transplant nephrectomy. 5 However, the uterine cavity is in contact with the external environment via the vagina.…”