Uterine transplantation: a systematic review

Ejzenberg, Dani; Mendes, Luana Regina Baratelli Carelli; Haddad, Luciana Bertocco de Paiva; Baracat, Edmund Chada; D’Albuquerque, Luiz Augusto Carneiro; Andraus, Wellington

doi:10.6061/clinics/2016(11)10

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Sumário

REVIEW • Clinics 71 (11) • Nov 2016 • https://doi.org/10.6061/clinics/2016(11)10 copy

Uterine transplantation: a systematic review

Authorship SCIMAGO INSTITUTIONS RANKINGS

Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women.

Infertility; Pregnancy; Uterus; Transplantation; Human

Reference	Immunosuppression Scheme
Reference	Induction	Maintenance	Rejection Treatment
Fageeh W. et al., 2002 (¹¹11. Fageeh W, Raffa H, Jabbad H, Marzouki A. Transplantation of the human uterus. Int J Gynaecol Obstet. 2002;76(3):245-51, http://dx.doi.org/10.1016/S0020-7292(01)00597-5. http://dx.doi.org/10.1016/S0020-7292(01)... )	Cyclosporine 6 h prior to surgery and 500 mg IV methylprednisolone.	Cyclosporine, azathioprine and prednisolone.	Treated with cyclosporine, azathioprine, IV methylprednisolone and anti-thymocyte globulin.
Erman Akar M. et al., 2013 (¹²12. Erman Akar M, Ozkan O, Aydinuraz B, Dirican K, Cincik M, Mendilcioglu I, et al. Clinical pregnancy after uterus transplantation. Fertil Steril. 2013;100(5):1358-63, http://dx.doi.org/10.1016/j.fertnstert.2013.06.027. http://dx.doi.org/10.1016/j.fertnstert.2... )	Anti-thymocyte globulin and 1 mg prednisolone.	TAC^* * TAC = tacrolimus, , MMF^ MMF = mycophenolate mofetil and prednisolone for the first 12 months. Then discontinued MMF and replaced with azathioprine.	Doses of prednisone and azathioprine were adjusted.
Brännström M. et al., 2014 (¹⁹19. Brännström M, Johannesson L, Dahm-Kähler P, Enskog A, Mölne J, Kvarnström N, et al. First clinical uterus transplantation trial: a six-month report. Fertil Steril. 2014;101(5):1228-36, http://dx.doi.org/10.1016/j.fertnstert.2014.02.024. http://dx.doi.org/10.1016/j.fertnstert.2... )	1 g MMF, 500 mg methylprednisolone and anti-thymocyte globulin.	TAC, MMF and oral glucocorticosteroids once daily on the day of surgery and during the first 4 postoperative days.	Treated with corticosteroids.
Brännström M. et al., 2015 (¹³13. Brännström M, Johannesson L, Bokström H, Kvarnström N, Mölne J, Dahm-Kähler P, et al. Livebirth after uterus transplantation. Lancet. 2015;385(9968):607-16, http://dx.doi.org/10.1016/S0140-6736(14)61728-1. http://dx.doi.org/10.1016/S0140-6736(14)... )	IV anti-thymocyte globulin just before surgery and 12 h later and 500 mg methylprednisolone.	TAC and MMF during the first 6 months. Withdrawal of MMF after 6 months and addition of azathioprine and prednisolone.	Treated with corticosteroids.
Johannesson L. et al., 2015 (²³23. Johannesson L, Kvarnstrom N, Molne J, Dahm-Kahler P, Enskog A, Diaz-Garcia C, et al. Uterus transplantation trial: 1-year outcome. Fertility and Sterility. 2015;103(1):199-204, http://dx.doi.org/10.1016/j.fertnstert.2014.09.024. http://dx.doi.org/10.1016/j.fertnstert.2... )	IV anti-thymocyte just before surgery and 12 h later and 500 mg methylprednisolone.	TAC and MMF during the first 10 months post-surgery. Azathioprine instead of MMF after 10 months to avoid the potentially teratogenic effects of MMF.	Five milligrams daily of prednisolone and corticosteroids or dose increments of TAC.

	FDA Safety Classification	Observation
Steroids	B – No evidence of risk in humans	No evidence of teratogenicity for steroids.
Cyclosporine	C – Risks cannot be ruled out	Does not lead to an increased rate of malformations but is associated with low birth weight.
Tacrolimus	C – Risks cannot be ruled out	Preterm birth, transient hyperkalemia and renal impairment.
Everolimus/Sirolimus	C – Risks cannot be ruled out	Limited knowledge is available on the use of mTOR inhibitors in pregnant women.
Azathioprine	D – Positive evidence of risk	Prematurity and low birth weight have been observed in pregnancies with azathioprine medication.
MMF	D – Positive evidence of risk	Strictly contraindicated in pregnancy and associated with miscarriage and a wide spectrum of malformations in the fetus.

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