A new surgical technique of uterine auto-transplantation in cynomolgus monkey: preliminary report about two cases

Iori Kisu, Makoto Mihara, Kouji Banno, Hisako Hara, Takumi Yamamoto, Jun Araki, Takuya Iida, Yohei Hayashi, Hisashi Moriguchi, Daisuke Aoki, Iori Kisu, Makoto Mihara, Kouji Banno, Hisako Hara, Takumi Yamamoto, Jun Araki, Takuya Iida, Yohei Hayashi, Hisashi Moriguchi, Daisuke Aoki

Abstract

Objective: Uterine transplantation experiments have been performed in various animal species for future clinical applications of uterine transplantation for permanent uterine factor infertility in humans. The aim of this study was to confirm the feasibility of uterine auto-transplantation in cynomolgus monkeys by developing new surgical techniques.

Methods: Two female cynomolgus monkeys underwent surgery under general anesthesia. The uterus with vascular grafts and the vaginal wall was removed, and back-table preparation was performed using heparinized saline. The uterus with vascular grafts and the vaginal wall was anastomosed with the vaginal stump and blood vessels in the pelvis, respectively. The auto-transplant uterine function was evaluated by confirming engraftment of the uterus by laparotomy, endometrial proliferation by transabdominal ultrasonography and periodical menstruation.

Results: The first animal died due to acute renal failure 2 days after the operation. Second-look laparotomy in the second animal at 40 days after the operation indicated there was no congestion in the uterus, and the uterus showed the typical red color of a normal uterus. Thereafter, endometrial proliferation was observed by transabdominal ultrasonography and periodical menstruation was confirmed, indicating re-established uterine function.

Conclusion: This is the preliminary report of uterine auto-transplantation in cynomolgus monkeys. This study demonstrates the feasibility of uterine auto-transplantation by using new surgical technique in cynomolgus monkeys. Accumulation of basic experimental data in non-human primates is required prior to performing the procedure in humans.

Figures

Fig. 1
Fig. 1
Anatomical characteristics of the inner genital organs of cynomolgus monkey. The uterus, ovaries, fallopian tubes, round ligament, and urinary bladder are shown (a). The anatomical characteristics of the inner genital organs are almost the same as those in humans. The ureter crosses the uterine artery and vein on the dorsal side, as in humans (b)
Fig. 2
Fig. 2
Relationship between the uterus and uterine blood vessels. The main uterine artery branches from the internal iliac artery (IIA) and divides into the ascending and descending branches. The ascending branch feeds the uterine body and joins the ovarian artery. The descending branch extends to the paracolpium. The superficial uterine vein (SUV) is located along the uterine artery (UA). The deep uterine vein (DUV) connects to the external iliac vein (EIV) in the cynomolgus monkey. The ureter is located along the uterine artery on the dorsal side and reaches the urinary bladder
Fig. 3
Fig. 3
Uterus excised with the vaginal wall. Uterus was connected only via the bilateral uterine arteries and superficial uterine veins in Case 1 (a). The front side of the uterus excised with the vascular pedicles and the vaginal wall (11 mm anterior and 14 mm posterior) in Case 2 (b). UC uterine cervix
Fig. 4
Fig. 4
The uterus before (a) and after (b) perfusion with heparinized saline via the uterine artery on the back-table. Blood components were washed out and the whole uterus became whitish in color
Fig. 5
Fig. 5
A suction tube was inserted via the vagina; the vaginal stump was identified in the abdominal cavity and opened (a). The vaginal wall and stump were sutured using four or five stitches each in the anterior and posterior regions using 4-0 PDS (b)
Fig. 6
Fig. 6
The right deep uterine vein (RDUV) was end-to-side anastomosed with the right external iliac vein (REIV) (a). Illustration of uterine auto-transplantation in a cynomolgus monkey (b). SUV superficial uterine vein, UA uterine artery, DUV deep uterine vein, EIAV external iliac artery and vein
Fig. 7
Fig. 7
The uterine color recovered after vascular anastomosis, but uterine congestion was noted in Case 1 (a) in comparison to the uterus in Case 2 (b)
Fig. 8
Fig. 8
Second-look laparotomy inspection in Case 2. There was no congestion in the uterus, and it had the characteristic red color of a normal uterus. Ut uterus

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