Francisco M Sanchez Margallo, PhD1, B. Moreno, PhD1, M.c. Calles, PhD1, E. Abellan1, J. Mijares1, J.a. Dominguez, MD2, V. Garcia, PhD3, I.s. Alvarez, PhD3. 1Minimally Invasive Surgery Center Jesus Uson, 2Instituto Extremeño de Reproducción Asistida, 3University of Extremadura. School of Medicine
Introduction: Uterine infertility factors include congenital and acquired pathologies. Recently, the uterine transplant has become an alternative for infertile women. The aims of this study were to assess the feasibility and safety of an experimental uterine autotransplant model, including 3D laparoscopy and microsurgical techniques that may be suitable for human uterine transplants.
Material and methods: Ten ewes weighed 40-50kg underwent general anesthesia, basal angiography (Figure 1) and 3D laparoscopic ovariohysterectomy (Figure 2). After dissection manoeuvres heparin was administered (100UI) every hour until the transplant was completed. The uterus was removed and irrigated with a cold sterile heparin solution using a 21G intravenous catheter, to remove residual blood (Figure 3). Finally, the uterus was transplanted. End-to-end anastomosis technique with continuous suturing was used to approximate the veins and end-to-end anastomosis technique with non-continuous suturing was used to approximate the arteries (Figure 4). The cervix was sutured with a non-continuous suturing pattern and the uterus was fixed to the pelvic cavity to avoid rotation. Follow-ups were carried out 15 days, 1 month and 2 month after the surgery. The postoperative studies included ultrasonography, hysteroscopy, uterine angiography and exploratory laparoscopy. FSH, LH, progesterone and estradiol plasma levels were analyzed. After 3-months postuterine transplantation assisted reproduction techniques have been used in all animals.
Figure 1. Basal angiography study. The picture shows the distribution of the left uterine artery in the sheep model.
Figure 2. Vascular dissection maneuvers during laparoscopic ovariohysterectomy.
Figure 3. The uterus was irrigated with a cold sterile heparin solution.
Figure 4. End-to-end anastomosis in the uterine artery.
Results: All transplants were carried out successfully without complications. Complete tissue reperfusion of blood was achieved in all animals within 30 seconds after vascular anastomosis without evidence of arterial or venous thrombosis. The mean operative time for the hysterectomy was 117 minutes. The mean duration of the ischemia was 187 minutes. The mean total duration of the surgery was 374 minutes. At one-month follow-up, one animal showed a closed cervix at hysteroscopy and it was impossible to identify the uterine structures during the exploratory laparoscopy. In the rest of the ewes, the exploratory laparoscopy carried out 1 month after surgery showed abdominal adhesions but the uterine structures could be identified. One sheep have an aneurysm 4 weeks after the transplant. All animals have patent uterine arteries after 4, 8 and 12 months after the transplant. At 6-months postuterine transplantation six sheep (60%) become pregnant using assisted reproduction techniques.
Conclusions: We have developed a modified procedure combining 3D laparoscopy and microsurgery for the uterine extraction and vascular anastomosis that has allowed us to perform successful uterine transplants in the sheep model. We also demonstrate that pregnancy can be achieved after a successful uterine transplant. More studies were necessary in order to determine the possibilities of these approaches in a clinical setting.