The Key Role of Warm and Cold Ischemia in Uterus Transplantation: A Review

Abstract

Introduction: Uterus transplantation (UTx) is a promising treatment for uterine infertility that has resulted in several births since 2014. Ischemia is a key step in organ transplantation because it may lead to changes jeopardizing graft viability. Method: We performed a systematic review of animal and human studies relating to uterine ischemia. Results: We retained 64 studies published since 2000. There were 35 studies in animals, 24 in humans, and five literature reviews. Modest preliminary results in large animals and humans are limited but encouraging. In small animals, pregnancies have been reported to occur after 24 h of cold ischemia (CI). In ewes, uterine contractions have been detected after 24 h of CI. Furthermore, it has been shown in animals that uterine tolerance to CI and to warm ischemia (WI) can be increased by pharmacological products. In women, mean CI time in studies of births from uteri obtained from live donors was between 2 h 47 min and 6 h 20 min from a deceased donor; with only one birth in this case. Muscle contractions have also been demonstrated in myometrial samples from women, after six or more hours of CI. Conclusion: The uterus seems to be able to tolerate a prolonged period of CI, of at least six hours. Studies of the ischemia tolerance of the uterus and ways to improve it are essential for the development of UTx, particularly for procedures using grafts from deceased donors.

Deceased Donation Uterus Transplantation: A Review

“…Cold ischaemic time (CIT) is thought to affect the functionality of the graft in the short and long term [34]. The viability and functionality of the uterus after prolonged ischaemia has been frequently discussed in published literature.…”

“…The viability and functionality of the uterus after prolonged ischaemia has been frequently discussed in published literature. Animal studies show that uteri have good tolerance to an extended period of cold ischaemia, up to 24 h [34], but this is yet to be thoroughly investigated in human studies. Although a shorter CIT of 1 hour 50 minutes is achievable [6] and resulted in a livebirth, longer CITs of 6 hours 20 minutes [5] and 9 hours 9 minutes [8] did not appear to affect graft functionality as both achieved livebirths.…”

Morphologic assessment of hypertonic citrate adenine, histidine–tryptophan–ketoglutarate, and university of Wisconsin solutions for hypothermic uterus preservation in rats

“…However, rare studies focused on the cold ischemia time of uterus, 22 previous research in the mouse model showed that the mouse uterus can still carry pregnancies after 24 h of cold ischemic preservation in UW 15 . As for large animals, a study revealed that the uterus in sheep can tolerant up to 24 h of cold ischemic storage before transplantation with more severe inflammation compared with the 3 h group using Celsior solution 9 .…”

Custodiol-N Is Superior to Custodiol® Solution in Experimental Rat Uterus Preservation

“…In separate experiments, the uterus graft was proven to be resistant to both warm and cold ischemia [11,12]. To date, several different preservation solutions, such as IGL-1 ® [13], Celsior ® [14][15][16], University of Wisconsin [17,18], NaCl [17], Ringer's acetate [18], Perfadex ® [18], and Custodiol ® [19][20][21][22][23][24][25], were used in experimental and clinical practice of UTx. Based on literature, modulation of the solution used for uterus graft static cold storage (SCS) could prevent ROS formation with resulting in reduced cell damage [17].…”

“…To date, several different preservation solutions, such as IGL-1 ® [13], Celsior ® [14][15][16], University of Wisconsin [17,18], NaCl [17], Ringer's acetate [18], Perfadex ® [18], and Custodiol ® [19][20][21][22][23][24][25], were used in experimental and clinical practice of UTx. Based on literature, modulation of the solution used for uterus graft static cold storage (SCS) could prevent ROS formation with resulting in reduced cell damage [17]. On the basis of Custodiol ® solution, the novel Custodiol-N solution was developed and supplemented with glycine and alanine to inhibit formation of hypoxia-induced plasma membrane pores and fortified with iron chelators, including deferoxamine and LK-614, to inhibit cold-induced cell injury as well as L-arginine to decrease microcirculatory disturbances [26,27].…”