The reproductive potential of uterus transplantation: future prospects

The reproductive potential of uterus transplantation: future prospects


  • Giuseppe Gullo a:1:{s:5:"en_US";s:115:"Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy";}
  • Andrea Etrusco Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy
  • Manuela Fabio Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy
  • Gaspare Cucinella Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy
  • Claudio Rossi Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy
  • Valentina Billone Department of Obstetrics and Gynecology, Villa Sofia Cervello Hospital, University of Palermo, 90146 Palermo, Italy


Absolute uterine factor infertility (AUFI), Uterus transplantation (UTx), Ethical quandaries, tissue bioengineering


Background and aim:Absolute uterine factor infertility (AUFI) is a form of infertility whereby conception and/or maintenance of pregnancy is impossible as a result of uterine absence or its completed dysfunction. It affects 1/500 women of reproductive age while the incidence is about 8% of infertile couples. Uterus transplantation (UTx) has been gaining ground as a viable option to enable women with AUFI to have biological children and as an alternative to surrogacy, a highly controversial practice still banned in many countries.
Methods:The authors have set out to strike a reasonable balance between UTx benefits and the still numerous risks, whether clinical or ethical, associated with such an innovative form of transplant, which is not life-saving, requires immunosuppression throughout pregnancy and the organ to be removed right after childbirth.
Results: While still far from achieving mainstream status, considerable strides have been made in UTx outcomes, with many live births already recorded. Procedures from living donor are reportedly more effective in terms of success rates. Organ tissue engineering has been explored and developed with promising results.
Conclusions: UTx entails various risks and ethical quandaries which have to do with reproductive autonomy and rights. New human attempts and clinical trials of UTx should be performed to further optimize the procedure in relation to safety and effectiveness. Techniques such as tissue engineering could lead in the medium-long term to a wholly bioengineered uterus to be used for transplantation, relying on scaffolds from decellularized organs or tissues that can be recellularized by several types of autologous somatic/stem cells. Such advances hold promise in terms of solving UTx-related complications and organ supply difficulties.


Benjamin P Jones, Niccole Ranaei‐Zamani, Saaliha Vali et al. Options for acquiring motherhood in absolute uterine factor infertility; adoption, surrogacy and uterine transplantation Obstet Gynaecol 2021; 23: 138–147.

Capozzi VA, Rosati A, Rumolo V, et al. Novelties of ultrasound imaging for endometrial cancer preoperative workup. Minerva Med 2021; 112: 3-11.

Cavaliere AF, Perelli F, Zaami S, et al. Fertility Sparing Treatments in Endometrial Cancer Patients: The Potential Role of the New Molecular Classification. Int J Mol Sci 2021; 22: 12248.

Gullo G, Etrusco A, Cucinella G, et al. Fertility-Sparing Approach in Women Affected by Stage I and Low-Grade Endometrial Carcinoma: An Updated Overview. Int J Mol Sci 2021; 22: 11825.

Malvasi A, Zaami S, Tinelli A, et al. Kristeller maneuvers or fundal pressure and maternal/neonatal morbidity: obstetric and judicial literature review. J Matern Fetal Neonatal Med 2019; 32: 2598-2607

Hofmeyr GJ, Vogel JP, Cuthbert A, Singata M. Fundal pressure during the second stage of labour. Cochrane Database Syst Rev 2017; 3: CD006067.

Zaami S, Montanari Vergallo G, Malvasi A, et al. Uterine rupture during induced labor after myomectomy and risk of lawsuits. Eur Rev Med Pharmacol Sci 2019; 23:1379-1381

Habeš D, Střecha M, Kalousek I, Kestřánek J. Uterine rupture during pregnancy. Ceska Gynekol 2019; 84: 345-350.

Zaami S, Montanari Vergallo G, Napoletano S, et al. The issue of delivery room infections in the Italian law. A brief comparative study with English and French jurisprudence. J Matern Fetal Neonatal Med 2018; 31: 223-227

Mahmood A, Fazal ur Rehman, Chughtai F. A survey of infection control practices in the delivery room and nursery to investigate and control the high rate of neonatal sepsis: an experience at a secondary care hospital. J Pak Med Assoc 2008; 58: 237-40.

Frati P, Foldes-Papp Z, Zaami S, et al. Amniotic fluid embolism: what level of scientific evidence can be drawn? A systematic review. Curr Pharm Biotechnol 2014; 14:1157- 62

Montanari Vergallo G, Zaami S. Guidelines and best practices: remarks on the Gelli-Bianco law. Clin Ter 2018; 169: e82-e85.

Malvasi A, Marinelli E, Ghi T, Zaami S. ISUOG Practice Guidelines for intrapartum ultrasound: application in obstetric practice and medicolegal issues. Ultrasound Obstet Gynecol 2019; 54: 421.

Papatheodorou A, Vanderzwalmen P, Panagiotidis Y, et al. How does closed system vitrification of human oocytes affect the clinical outcome? A prospective, observational, cohort, noninferiority trial in an oocyte donation program. Fertil Steril 2016; 106: 1348-1355.

Gullo G, Petousis S, Papatheodorou A, et al. Closed vs. Open Oocyte Vitrification Methods Are Equally Effective for Blastocyst Embryo Transfers: Prospective Study from a Sibling Oocyte Donation Program. Gynecol Obstet Invest 2020; 85: 206-212.

Zaami S, Busardò FP. Elective egg freezing: can you really turn back the clock? Eur Rev Med Pharmacol Sci 2015; 19: 3537-3538.

La Rosa VL, Valenti G, Sapia F, Gullo G, Rapisarda MCR. Psychological impact of gynecological diseases: the importance of a multidisciplinary approach. It J Gynaecol Obstet 2018; 30: 2.

Phillips AM, Magann EF, Whittington JR, Whitcombe DD, Sandlin AT. Surrogacy and Pregnancy. Obstet Gynecol Surv 2019; 74: 539-545.

Piersanti V, Consalvo F, Signore F, Del Rio A, Zaami S. Surrogacy and "Procreative Tourism". What Does the Future Hold from the Ethical and Legal Perspectives? Medicina (Kaunas) 2021; 57: 47.

Prapas Y, Ravanos K, Petousis S, et al. GnRH antagonist administered twice the day before hCG trigger combined with a step-down protocol may prevent OHSS in IVF/ICSI antagonist cycles at risk for OHSS without affecting the reproductive outcomes: a prospective randomized control trial. J Assist Reprod Genet. 2017; 34: 1537-1545.

Matoba Y, Kisu I, Sera A, Yanokura M, Banno K, Aoki D. Current status of uterine regenerative medicine for absolute uterine factor infertility. Biomed Rep 2019; 10: 79-86.

Johannesson L, Dahm-Kähler P, Eklind S, Brännström M. The future of human uterus transplantation. Womens Health (Lond) 2014; 10: 455-467.

Lefkowitz A, Edwards M, Balayla J. Ethical considerations in the era of the uterine transplant: an update of the Montreal Criteria for the Ethical Feasibility of Uterine Transplantation. Fertil Steril 2013; 100: 924-926.

Brännström M. Uterus transplantation and beyond. J Mater Sci Mater Med 2017; 28: 70.

Zaami S, Marinelli E, di Luca NM, Montanari Vergallo G. Ethical and medico-legal remarks on uterus transplantation: may it solve uterine factor infertility? Eur Rev Med Pharmacol Sci 2017; 21: 5290-5296.

Bruno B, Arora KS. Uterus Transplantation: The Ethics of Using Deceased Versus Living Donors. Am J Bioeth 2018; 18: 6-15.

Umani Ronchi F, Napoletano G. Uterus Transplantation and the redefinition of core bioethics precepts. Acta Biomed 2021; 92: e2021435.

Zaami S, Di Luca A, Marinelli E. Advancements in uterus transplant: new scenarios and future implications. Eur Rev Med Pharmacol Sci 2019; 23: 892-902.

Jones BP, Saso S, Yazbek J, et al. Uterine Transplantation: Scientific Impact Paper No. 65 April 2021. BJOG 2021; 128: e51-e66.

Ejzenberg D, Andraus W, Baratelli Carelli Mendes LR, et al Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility. Lancet 2019; 392: 2697-2704.

Brännström M, Johannesson L, Dahm-Kähler P, et al. First clinical uterus transplantation trial: a six-month report. Fertil Steril 2014; 101: 1228-1236.

Brännström M, Belfort MA, Ayoubi JM. Uterus transplantation worldwide: clinical activities and outcomes. Curr Opin Organ Transplant 2021; 26: 616-626.

Ratajczak JM, Hladun T, Orchel G. Iatrogenic ureterovaginal fistula after laparoscopic hysterectomy: a case report. Prz Menopauzalny 2021; 20: 48-51.

Del Rio A, Negro F, Piersanti V, Tini A. Uterus transplant update: innovative fertility solutions and the widening horizons of bioengineering. Eur Rev Med Pharmacol Sci 2021; 25: 3405-3410.

Hellström M, Bandstein S, Brännström M. Uterine Tissue Engineering and the Future of Uterus Transplantation. Ann Biomed Eng 2017; 45: 1718-1730.

Iske J, Elkhal A, Tullius SG. The Fetal-Maternal Immune Interface in Uterus Transplantation. Trends Immunol 2020; 41: 213-224.

Ding L, Li X, Sun H, et al. Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus. Biomaterials 2014; 35: 4888-48900.

Young RC, Goloman G. Allo- and xeno-reassembly of human and rat myometrium from cells and scaffolds. Tissue Eng Part A 2013; 19: 2112-9.

Gullo G, Carlomagno G, Unfer V, D'Anna R. Myo-inositol: from induction of ovulation to menopausal disorder management. Minerva Ginecol 2015; 67: 485-486.

Bezerra Espinola MS, Laganà AS, Bilotta G, Gullo G, Aragona C, Unfer V. D-chiro-inositol Induces Ovulation in Non-Polycystic Ovary Syndrome (PCOS), Non-Insulin-Resistant Young Women, Likely by Modulating Aromatase Expression: A Report of 2 Cases. Am J Case Rep 2021; 22: e932722.

D'Anna R, Corrado F, Loddo S, Gullo G, Giunta L, Di Benedetto A. Myoinositol plus α-lactalbumin supplementation, insulin resistance and birth outcomes in women with gestational diabetes mellitus: a randomized, controlled study. Sci Rep. 2021; 11: 8866.

D'Anna R, Santamaria A, Giorgianni G, et al. Myo-inositol and melatonin in the menopausal transition. Gynecol Endocrinol 2017; 33: 279-282.

Gullo G, Cucinella G, Perino A, et al. The Gender Gap in the Diagnostic-Therapeutic Journey of the Infertile Couple. Int J Environ Res Public Health 2021; 18: 6184.







How to Cite

Gullo G, Etrusco A, Fabio M, Cucinella G, Rossi C, Billone V. The reproductive potential of uterus transplantation: future prospects. Acta Biomed [Internet]. 2022 May 11 [cited 2024 Jul. 20];93(2):e2022138. Available from: