Advancements made in reproductive research for human uterine transplants

Abstract

OBJECTIVE: The purpose of this project is three-fold: (1) to investigate in a sheep and goat model of uterine transplantation after utero-ovarian ligation and uterine vessel reanastomosis (2) assess tissue rejection and endometrial changes that occur by histological studies and (3) to determine a success rate of pregnancy after a successful uterine transplant.DESIGN: Pilot study.MATERIALS AND METHODS: Our research project explores feasibility of uterine transplantation by comparing vascular changes, uterine morphology and tissue viability in the uterine auto (n-4 goats) and allo-transplant model (n-10 sheep). The sheep and goat model were preferred since the anatomical land marks and vascular anatomy are comparable to human with the exception of a bicornuate uterus in the sub-primate model. The short-term effects of warm and cold tissue ischemia were quantified and uterine tissue reperfusion were analyzed after vascular reanastomosis. The goats were naturally mated with a buck and the sheep were synchronized with progesterone implants for the preparation of an embryo transfer. Our endpoint is delivery of healthy offspring from both the auto and allo-transplanted groups.RESULTS: Our results demonstrate vascular patency and complete tissue reperfusion of blood in our 14 animals within 30 seconds after vascular reanastomosis without evidence of arterial or venous thrombosis. At six months post-uterine transplantation, hysterectomies were performed documenting viable uterine tissue and vascular patency in six out of the ten uterine allo-transplants. The presence of functional ovarian tissue and fallopian tube patency was documented in two of the four transplanted goat models. One of our uterine auto-transplanted goats delivered two health offspring by natural mating.CONCLUSIONS: We have developed a modified surgical procedure that has allowed us to perform successful uterine transplants in the sub-primate model. Our pilot study demonstrates that the ewe and goat are excellent models for uterine transplant research. By exploring the different alternatives for uterine factor fertility such as adoption and surrogacy, the uterine transplant may be considered another alternative for infertility. OBJECTIVE: The purpose of this project is three-fold: (1) to investigate in a sheep and goat model of uterine transplantation after utero-ovarian ligation and uterine vessel reanastomosis (2) assess tissue rejection and endometrial changes that occur by histological studies and (3) to determine a success rate of pregnancy after a successful uterine transplant. DESIGN: Pilot study. MATERIALS AND METHODS: Our research project explores feasibility of uterine transplantation by comparing vascular changes, uterine morphology and tissue viability in the uterine auto (n-4 goats) and allo-transplant model (n-10 sheep). The sheep and goat model were preferred since the anatomical land marks and vascular anatomy are comparable to human with the exception of a bicornuate uterus in the sub-primate model. The short-term effects of warm and cold tissue ischemia were quantified and uterine tissue reperfusion were analyzed after vascular reanastomosis. The goats were naturally mated with a buck and the sheep were synchronized with progesterone implants for the preparation of an embryo transfer. Our endpoint is delivery of healthy offspring from both the auto and allo-transplanted groups. RESULTS: Our results demonstrate vascular patency and complete tissue reperfusion of blood in our 14 animals within 30 seconds after vascular reanastomosis without evidence of arterial or venous thrombosis. At six months post-uterine transplantation, hysterectomies were performed documenting viable uterine tissue and vascular patency in six out of the ten uterine allo-transplants. The presence of functional ovarian tissue and fallopian tube patency was documented in two of the four transplanted goat models. One of our uterine auto-transplanted goats delivered two health offspring by natural mating. CONCLUSIONS: We have developed a modified surgical procedure that has allowed us to perform successful uterine transplants in the sub-primate model. Our pilot study demonstrates that the ewe and goat are excellent models for uterine transplant research. By exploring the different alternatives for uterine factor fertility such as adoption and surrogacy, the uterine transplant may be considered another alternative for infertility.