Uterine allotransplantation in a rabbit model using aorto-caval anastomosis

A long-term viability study

Srdjan Saso, Gemma Petts, Jayanta Chatterjee, Meen Yau Thum, Anna L. David, David Corless, Michael Boyd, David Noakes, Iain Lindsay, Giuseppe Del Priore, Sadaf Ghaem-Maghami, J. Richard Smith

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Objective Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model. Study design A longitudinal study involving uterine cross transplantations (n = 9 donors, n = 9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 μg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia. Results In this case series, long-term rabbit survival was 11% (n = 1). Surgical survival was 56% (n = 5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month. Conclusion Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalEuropean Journal of Obstetrics Gynecology and Reproductive Biology
Volume182
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Fingerprint

Venae Cavae
Rabbits
Transplants
Animal Models
Transplantation
Tissue Donors
Euthanasia
Inferior Vena Cava
Tacrolimus
Vagina
Graft Survival
Embolism
Hysterectomy
Hematoma
Immunosuppression
Infertility
Uterus
Allografts
Fertility
Blood Vessels

Keywords

  • Allogeneic
  • Fertility
  • Graft survival
  • Rabbit
  • Transplantation
  • Uterus

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Uterine allotransplantation in a rabbit model using aorto-caval anastomosis : A long-term viability study. / Saso, Srdjan; Petts, Gemma; Chatterjee, Jayanta; Thum, Meen Yau; David, Anna L.; Corless, David; Boyd, Michael; Noakes, David; Lindsay, Iain; Del Priore, Giuseppe; Ghaem-Maghami, Sadaf; Smith, J. Richard.

In: European Journal of Obstetrics Gynecology and Reproductive Biology, Vol. 182, 01.11.2014, p. 185-193.

Research output: Contribution to journalArticle

Saso, S, Petts, G, Chatterjee, J, Thum, MY, David, AL, Corless, D, Boyd, M, Noakes, D, Lindsay, I, Del Priore, G, Ghaem-Maghami, S & Smith, JR 2014, 'Uterine allotransplantation in a rabbit model using aorto-caval anastomosis: A long-term viability study', European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 182, pp. 185-193. https://doi.org/10.1016/j.ejogrb.2014.09.029
Saso, Srdjan ; Petts, Gemma ; Chatterjee, Jayanta ; Thum, Meen Yau ; David, Anna L. ; Corless, David ; Boyd, Michael ; Noakes, David ; Lindsay, Iain ; Del Priore, Giuseppe ; Ghaem-Maghami, Sadaf ; Smith, J. Richard. / Uterine allotransplantation in a rabbit model using aorto-caval anastomosis : A long-term viability study. In: European Journal of Obstetrics Gynecology and Reproductive Biology. 2014 ; Vol. 182. pp. 185-193.
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abstract = "Objective Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model. Study design A longitudinal study involving uterine cross transplantations (n = 9 donors, n = 9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 μg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia. Results In this case series, long-term rabbit survival was 11{\%} (n = 1). Surgical survival was 56{\%} (n = 5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month. Conclusion Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.",
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AU - Thum, Meen Yau

AU - David, Anna L.

AU - Corless, David

AU - Boyd, Michael

AU - Noakes, David

AU - Lindsay, Iain

AU - Del Priore, Giuseppe

AU - Ghaem-Maghami, Sadaf

AU - Smith, J. Richard

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N2 - Objective Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model. Study design A longitudinal study involving uterine cross transplantations (n = 9 donors, n = 9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 μg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia. Results In this case series, long-term rabbit survival was 11% (n = 1). Surgical survival was 56% (n = 5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month. Conclusion Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.

AB - Objective Uterine transplantation (UTx) has been proposed as a treatment option for women diagnosed with absolute uterine factor infertility. Allogeneic UTx has been attempted in a number of animal models, but achieving an adequate blood supply for the transplanted uterus still presents the biggest challenge. Microvascular re-anastomosis was unsuccessful in a number of animal models. The aim was to assess whether a large vessel aortic-caval vascular patch technique can bring about long-term graft survival after allogeneic UTx in a rabbit model. Study design A longitudinal study involving uterine cross transplantations (n = 9 donors, n = 9 recipients) was performed in New Zealand white rabbits using an aortic-caval macrovascular patch harvested as part of the uterine allograft. All rabbits were allogeneic and of proven fertility, with at least one previous litter each. The end result of the donor graft harvest was a total hysterectomy transecting across the vagina and the most lateral aspects of the uterine horns together with an aortic-caval macrovascular patch (aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). Tacrolimus (500 μg twice daily) was administered for immunosuppression post-transplant. The recipients were closely monitored until death or euthanasia. Results In this case series, long-term rabbit survival was 11% (n = 1). Surgical survival was 56% (n = 5). Three rabbits (UTx #3, #4 and #8) died intra-operatively as a result of blood aspiration, ventricular hematoma, and massive hemorrhage. Three does (#1, #2, #7 and #9) died within the first 24 h as a result of the veno-vena and anastomosis breakdown. Does #6 and #9 died secondary to pre-operative pneumonia and a pulmonary embolus, respectively. Only one rabbit survived longer than a month. Conclusion Our method used a macrovascular patch technique to ensure adequate blood supply to the donor uterine graft. We have demonstrated the feasibility of uterine allotransplantation using this technique in the rabbit, but were unable to demonstrate a higher long-term survival percentage because of issues related to using a rabbit model.

KW - Allogeneic

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