A review of immunosuppressive therapy in the context of uterine VCA and pregnancy.

Uterine vascularized composite allotransplantation (VCA) represents one of the latest developments in the field of transplant surgery and treatment of uterine-factor infertility. Unlike other forms of VCA, uterine transplantation involves a temporary allograft, pregnancy-associated physiologic and pharmacokinetic changes, and complex maternal-fetal immunologic interactions, creating distinct challenges in immunosuppression management. Herein, we perform a comprehensive review of the latest and relevant literature on immunosuppressive strategies in the context of VCA and pregnancy, with particular emphasis on their relevance to uterine VCA. Evidence from solid organ transplantation, autoimmune disease, and reported uterine transplant protocols was synthesized to inform stage-specific management strategies. Available data support corticosteroids, calcineurin inhibitors, azathioprine, and hydroxychloroquine as pregnancy-compatible agents, whereas mycophenolate mofetil, methotrexate, and cyclophosphamide remain contraindicated due to teratogenicity. Pregnancy-related pharmacokinetic and pharmacodynamic changes significantly influence drug exposure and necessitate individualized dosing and close therapeutic monitoring. Emerging evidence suggests that pregnancy-associated immune modulation, including regulatory T-cell expansion and microchimerism, may reduce rejection risk, although this remains incompletely characterized. Based on best available evidence, we present a summary for immunosuppressive management spanning induction, preconception optimization, pregnancy, delivery, and postpartum graft removal. Future priorities include development of noninvasive rejection monitoring, precision pharmacokinetic modeling, and tolerance-inducing strategies to improve maternal, fetal, and allograft outcomes in uterine transplantation.