Abstract

ObjectiveTo develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model.MethodsIn this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively.ResultsViable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis.ConclusionWe have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.

Highlights

  • Uterine-factor infertility includes cases of absence of the uterus or those with nonfunctional uterus in terms of pregnancy capability and occurs due to congenital or acquired causes such as uterine agenesis, hysterectomy, uterine hypoplasia, arcuate uterus and intrauterine adhesions [1]

  • Ewe 4 developed diarrhea, followed by severe vaginal and rectal infection 3 months after the transplantation; an exploratory laparotomy was performed to evaluate the status of the transplanted uterus in this sheep

  • We found small uterine veins deep down in the pelvis, which made their separation difficult; these veins were too short for subsequent anastomosis, which may have been a factor for the poor outcomes

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Summary

Introduction

Uterine-factor infertility includes cases of absence of the uterus or those with nonfunctional uterus in terms of pregnancy capability and occurs due to congenital or acquired causes such as uterine agenesis, hysterectomy, uterine hypoplasia, arcuate uterus and intrauterine adhesions [1]. Most women with uterine-factor infertility cannot become genetic mothers, except through the use of gestational surrogacy. Surrogacy and adoption are temporary solutions for uterine-factor infertility. Whether these services are valid options for reproduction or brokered commodities is much debated. Many argue that these techniques do not adequately meet the needs of infertile couples who wish to carry their own biological child to term [2]. The logical but radical treatment approach would be uterine transplantation, which could allow these women to become both genetic and gestational mothers [3]

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