A new bicornuate model of rat uterus transplantation

Abstract

Introduction: Uterus transplantation has revolutionized reproductive medicine for women with absolute uterine factor infertility, resulting in more than 40 reported successful live births worldwide to date. Small animal models are pivotal to refine this surgical and immunological challenging procedure aiming to enhance safety for both the mother and the child.

Material and methods: We established a syngeneic bicornuate uterus transplantation model in young female Lewis rats. All surgical procedures were conducted by an experienced and skilled microsurgeon who organized the learning process into multiple structured steps. Animals underwent meticulous preoperative preparation and postoperative care. Transplant success was monitored by sequential biopsies, monitoring graft viability and documenting histological changes long-term.

Results: Bicornuate uterus transplantation were successfully established achieving an over 70% graft survival rate with the passage of time. The bicornuate model demonstrated safety and feasibility, yielding outcomes comparable to the unicornuate model in terms of ischemia times and complications. Longitudinal biopsies were well-tolerated, enabling comprehensive monitoring throughout the study.

Conclusions: Our novel bicornuate rat uterus transplantation model provides a distinctive opportunity for sequential biopsies at various intervals after transplantation and, therefore, comprehensive monitoring of graft health, viability, and identification of potential signs of rejection. Furthermore, this model allows for different interventions in each horn for comparative studies without interobserver differences contrary to the established unicornuate model. By closely replicating the clinical setting, this model stands as a valuable tool for ongoing research in the field of uterus transplantation, promoting further innovation and deeper insights into the intricacies of the uterus transplant procedure.

Keywords: bicornuate uterus; rat; uterus transplantation.

FIGURE 1

(A, B) Schematic presentation of bicornuate uterine graft procurement and transplantation model. The right side shows the area where potential biopsies can be gathered. (C) Intraoperative view of a successful bicornuate uterine transplantation.

FIGURE 2

Learning curve and surgical times of one microsurgeon for uterine transplantation over an 18‐month period. Linear correlation calculated with the Pearson correlation coefficient. Comparison of unicornuate and bicornuate models (A) Procurement time for uterine transplant significantly reduced over time, (B) Transplantation time reduced by more than half an hour during the learning curve. (C) Bicornuate uterine procurement time slightly longer. (D) Transplantation time identical between groups.

FIGURE 3

Intraoperative sample images of biopsy procedure. (A) V‐shaped incision, (B) Uterus after biopsy, (C) Sutured biopsy site with a running suture with 7‐0 (Z1701 PDS II Ethicon Inc., Bridgewater, USA).

FIGURE 4

Hematoxylin and Eosin staining of bicornuate uterus transplant model. Scale bar in lower right of images reflects 100 μm. Top row 5× magnification, bottom row 20× magnification. (A, D) Biopsy 14 days after transplantation. (B, E) 50 days after transplantation. (C, F) 70 days after transplantation.