Uterus transplantation

The uterine transplant is the surgical procedure whereby a healthy uterus is transplanted into a organism of which the uterus is absent or diseased. As part of normal mammalian sexual reproduction, a diseased or absent uterus does not allow normal embryonic implantation, effectively rendering the female infertile. This phenomenon is known as absolute uterine factor infertility (AUFI). Uterine transplant is a potential treatment for this form of infertility.

History

Studies

In 1896 Emil Knauer, a 29-year-old Austrian working in one of Vienna's gynecological clinics, published the first study of ovarian autotransplantation documenting normal function in a rabbit. This led to the investigation of uterine transplantation in 1918.[1][2] In 1964 and 1966, Eraslan, Hamernik and Hardy, at the University of Mississippi Medical Center in Jackson, Mississippi, were the first to perform an animal (dog) autotransplantation of the uterus and subsequently deliver a pregnancy from that uterus.[3] In 2010 Diaz-Garcia and co-workers, at Department of Obstetrics and Gynecology, University of Gothenburg in Sweden, demonstrated the world's first successful allogenic uterus transplantation, in a rat, with healthy offspring.[4]

Cases

Transplants

In 1931 in Germany, Lili Elbe, a Danish transgender woman, died from organ rejection three months after receiving one of the world's earliest uterine transplants.[5] With the availability of in vitro fertilization in 1978, uterine transplantation research was deferred.[6]

In Saudi Arabia in 2000, a uterine transplant was performed by Dr. Wafa Fagee, from a 46-year-old hysterectomy patient into a 26-year-old recipient.[7] whose own uterus had hemorrhaged after childbirth. The transplanted uterus functioned for 99 days, but ultimately needed to be removed after failure due to blood clotting. Within the medical community there was some debate as to whether or not the transplant could truly be considered to have been successful.[8] Post-operatively, the patient had two spontaneous menstrual cycles, followed by amenorrhoea; exploratory laparotomy confirmed uterine necrosis. The procedure has raised some moral and ethical concerns, which have been addressed in the literature.[9]

In Turkey, on 9 August 2011, the world's first uterus transplant from a deceased donor was conducted by a team of doctors at Akdeniz University Hospital in Antalya.[10][11][12][13][14][15][16] The 21-year-old Turkish woman, Derya Sert, who had been born without a uterus, was the first woman in history to receive a womb from a deceased donor. The operation, performed by Dr. Ömer Özkan, Dr. Munire Erman Akar and their team, was the world's first uterus transplant surgery gaining long-term function, as evident by the fact that Ms. Sert has had six menstrual periods post-surgery and is said to have a fully functioning uterus. The Turkish medical team who performed the delicate surgery, however, is still cautious about declaring the operation a complete success. "The surgery was a success. But we will be successful when she has her baby", Ozkan said. "For now, we are happy that the tissue is living".[17] On 12 April 2013, Akdeniz University announced that Derya Sert was pregnant.[18][19][20] The statement made by the university hospital also added that Ms Sert would give birth by C-section to prevent any complications. On 14 May 2013, it was announced that Ms Sert had terminated her pregnancy in its 8th week following a routine examination where doctors failed to detect a fetal heartbeat.[21]

In Sweden in 2012, the first mother-to-daughter[22] womb transplant was done by Swedish doctors at Sahlgrenska University Hospital at Gothenburg University led by Mats Brännström.[22][23][24]

The first uterine transplant performed in the United States took place on 24 February 2016 at the Cleveland Clinic.[25] The transplant failed due to a complication on 8 March and the uterus was removed.[26] In April it was disclosed that a yeast infection by Candida albicans had caused damage to the local artery compromising the blood support of the uterus and necessitating its removal.[27]

First successful pregnancy

In October 2014 it was announced that, for the first time, a healthy baby had been born to a uterine transplant recipient, at an undisclosed location in Sweden. The British medical journal The Lancet reported that the baby boy had been born in September, weighing 1.8 kg (3.9 lb) and that the father had said his son was "amazing". The baby had been delivered prematurely at about 32 weeks, by cesarean section, after the mother had developed pre-eclampsia. The Swedish woman, aged 36, had received a uterus in 2013, from a live 61-year-old donor, in an operation led by Dr. Brännström, Professor of Obstetrics and Gynaecology at the University of Gothenburg.[28][29]

The woman had healthy ovaries but was born without a uterus, a condition that affects about one in 4,500 women. The procedure used an embryo from a laboratory, created using the woman's ovum and her husband's sperm, which was then implanted into the transplanted uterus. The uterus may have been damaged in the course of the caesarian delivery and it may or may not be suitable for future pregnancies. A regimen of triple immuno-suppression was used with tacrolimus, azathioprine, and corticosteroids. Three mild rejection episodes occurred, one during the pregnancy, but were all successfully suppressed with medication. Some other women were also reported to be pregnant at that time using transplanted uteri. The unnamed mother, who received a donated womb from a friend, said that she hoped the treatment would be refined to help others in the future.[30]

The transplant is intended to be temporary – the recipient will undergo a hysterectomy after one or two successful pregnancies. This is to avoid the need for her to take immunosuppressive drugs for life with a consequent increased risk of infection.[31]

The uterus transplantation research project at the University of Gothenburg, which started in 1999, has been evaluated in over 40 scientific articles.[32] The procedure remains the last resort – it is expensive and not likely to be covered by insurance and, unlike other methods of fertility assistance and treatment, is a relatively new and somewhat experimental procedure, performed only by certain specialist surgeons in select centres, in which the attendant risks of a relatively invasive organ transplant operation, including infection and organ rejection. Some ethics specialists regard the risks to a live donor, as opposed to a post-mortem donor, as being too great, and some find the entire procedure ethically questionable, especially since the transplant is not a life-saving procedure.[33][34][35]

Description

Procedures

Uterine transplantation starts with the uterus retrieval surgery on the donor. Working techniques for this exist for animals, including primates and more recently humans.[36][37][38][39][40][41] The recovered uterus may need to be stored, for example for transportation to the location of the recipient. Studies on cold-ischemia/eperfusion indicate an ischemic tolerance of more than 24 hours.[37]

The recipient has to look at potentially three major surgeries. First of all, there is the transplantation surgery. If a pregnancy is established and carried to viability a cesarean section is performed. As the recipient is treated with immuno-suppressive therapy, eventually, after completion of childbearing, a hysterectomy needs to be done so that the immuno-suppressive therapy can be terminated.

Ethics

Montreal Criteria

Aside from considerations of costs uterine transplantation involves complex ethical issues. The principle of autonomy supports the procedure, while the principle of non-maleficence argues against it. In regard to the principles of beneficence and justice the procedure appears equivocal.[9] To address this dilemma the "Montreal Criteria for the Ethical Feasibility of Uterine Transplantation" were developed at McGill University and published in Transplant International in 2012.[9] The Montreal Criteria are a set of criteria deemed to be required for the ethical execution of the uterine transplant in humans. These findings were presented at the International Federation of Gynecology and Obstetrics' 20th World Congress in Rome in October 2012.[42] In 2013 an update to "The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation" was published in Fertility and Sterility and has been proposed as the international standard for the ethical execution of the procedure.[43]

The criteria set conditions for the recipient, the donor, and the health care team, specifically:

  1. The recipient is a genetic female with no medical contraindications to transplantation, has uterine absence that has failed other therapy, has "a personal or legal contraindication" to other options (surrogacy, adoption). It is asked that she wants a child, is suitable for motherhood, psychologically fit, likely to be compliant with treatment, and understand the risks of the procedure.
  2. The donor is a female of reproductive age with no contraindication to the procedure who has concluded her childbearing or consented donating her uterus after her death. It is asked that there is no coercion and the donor is responsible and sound to make informed decisions.
  3. The health care team belongs to an institution that meets Moore's third criterion[44] regarding institutional stability and has provided informed consent to both parties. It is asked that there is no conflict of interests, and anonymity can be protected unless recipient or donor waive this right.

See also

References

  1. ↑ Knauer, Emil (1896). "Einige Versuche über Ovarientransplantation bei Kaninchen" [An attempt at ovary transplantation in rabbits]. Zentralblatt für Gynäkologie (in German) 20: 524–8.
  2. ↑ Nugent, D.; Meirow, D.; Brook, P. F.; Aubard, Y.; Gosden, R. G. (1997). "Transplantation in reproductive medicine: Previous experience, present knowledge and future prospects". Human Reproduction Update 3 (3): 267–80. doi:10.1093/humupd/3.3.267. PMID 9322102.
  3. ↑ Eraslan, S.; Hamernik, R. J.; Hardy, J. D. (1966). "Replantation of uterus and ovaries in dogs, with successful pregnancy". Archives of surgery 92 (1): 9–12. doi:10.1001/archsurg.1966.01320190011002. PMID 5948103.
  4. ↑ Díaz-García, César; Akhi, Shamima N.; Wallin, Ann; Pellicer, Antonio; Brännström, Mats. "First report on fertility after allogeneic uterus transplantation". Acta Obstetricia et Gynecologica Scandinavica 89 (11): 1491–1494. doi:10.3109/00016349.2010.520688.
  5. ↑ "Nicole Kidman as the world's first reported woman with surgically corrected Harry Benjamin Syndrome". Shb-info.org. Retrieved 2012-11-20.
  6. ↑ Confino E., Vermesh M., Thomas W., Gleicher N. (1986). "Unilateral rabbit uterus transplantation model". Int J Obstet Gynaecol 24: 321–325.
  7. ↑ Nair, Anjana; Stega, Jeanetta; Smith, J. Richard; Del Priore, Giuseppe (2008). "Uterus Transplant". Annals of the New York Academy of Sciences 1127: 83–91. doi:10.1196/annals.1434.003. PMID 18443334.
  8. ↑ Grady, Denise (March 7, 2002). "Medical First: A Transplant Of a Uterus". The New York Times.
  9. 1 2 3 Lefkowitz, Ariel; Edwards, Marcel; Balayla, Jacques (2012). "The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation". Transplant International 25 (4): 439–47. doi:10.1111/j.1432-2277.2012.01438.x. PMID 22356169.
  10. ↑ "Turkish woman has world's first womb transplant". timesofmalta.com. Retrieved 2012-11-21.
  11. ↑ "Revolutionary ‘Womb Transplant’ performed in Turkey - World’s First". Allvoices.com. Retrieved 2012-11-21.
  12. ↑ "World’s first successful uterus transplant performed in Turkey — RT". Rt.com. Retrieved 2012-11-21.
  13. ↑ "World’s first womb transplant in Turkey promises hope for women". Alarabiya.net. 2011-10-01. Retrieved 2012-11-21.
  14. ↑ "HEALTH - Doctors hopeful for uterus transplant". Hurriyetdailynews.com. 2011-09-13. Retrieved 2012-11-21.
  15. ↑ "World's first uterus transplant performed in Turkey/TRT-English". Trt-world.com. 2012-02-27. Retrieved 2012-11-21.
  16. ↑ "Turkish surgeons perform world's first uterus transplant | Family & Health". World Bulletin. Retrieved 2012-11-21.
  17. ↑ "World's first successful uterus transplant performed in Turkey". Rt.com. October 2011. Retrieved 2012-11-20.
  18. ↑ "Womb transplant recipient Derya Sert pregnant". AAP. 2013-04-13.
  19. ↑ "Yahoo Health". Retrieved 5 October 2014.
  20. ↑ "World’s first woman with uterus transplant gets pregnant - HEALTH". Retrieved 5 October 2014.
  21. ↑ Derya Sert'in gebeliği sonlandırıldı. CNNTurk.com. (Turkish)
  22. 1 2 Brännström, Mats; Johannesson, Liza; Dahm-Kähler, Pernilla; Enskog, Anders; Mölne, Johan; Kvarnström, Niclas; Diaz-Garcia, Cesar; Hanafy, Ash; Lundmark, Cecilia; Marcickiewicz, Janusz; Gäbel, Markus; Groth, Klaus; Akouri, Randa; Eklind, Saskia; Holgersson, Jan; Tzakis, Andreas; Olausson, Michael. "First clinical uterus transplantation trial: a six-month report". Fertility and Sterility 101 (5): 1228–1236. doi:10.1016/j.fertnstert.2014.02.024.
  23. ↑ Brännström, Mats; Diaz-Garcia, Cesar; Hanafy, Ash; Olausson, Michael; Tzakis, Andreas. "Uterus transplantation: animal research and human possibilities". Fertility and Sterility 97 (6): 1269–1276. doi:10.1016/j.fertnstert.2012.04.001.
  24. ↑ Brännström, M.; Wranning, C. A.; Altchek, A. (7 November 2009). "Experimental uterus transplantation". Human Reproduction Update 16 (3): 329–345. doi:10.1093/humupd/dmp049. PMID 19897849.
  25. ↑ Zeltner, Brie (2016-03-07). "Cleveland Clinic introduces nation's first uterus transplant recipient". The Plain Dealer. Retrieved 2016-03-08.
  26. ↑ Zeltner, Brie (2016-03-09). "Nation's first uterus transplant, performed at the Cleveland Clinic, fails". The Plain Dealer. Retrieved 2016-03-10.
  27. ↑ Denise Grady (April 8, 2016). "Yeast Infection Led to Removal of Transplanted Uterus". The New York Times. Retrieved April 8, 2016.
  28. ↑ "Woman has healthy baby boy after womb transplant in Sweden". ABC News.
  29. ↑ Brännström, M.; Johannesson, L.; Bokström, H.; Kvarnström, N.; Mölne, J.; Dahm-Kähler, P.; Enskog, A.; Milenkovic, M.; Ekberg, J.; Diaz-Garcia, C.; Gäbel, M.; Hanafy, A.; Hagberg, H.; Olausson, M.; Nilsson, L. (2014). "Livebirth after uterus transplantation". The Lancet. doi:10.1016/S0140-6736(14)61728-1.
  30. ↑ "BBC News - Womb transplant couple 'had no doubt' of success". BBC News.
  31. ↑ Ossola, Alexandra (18 February 2014). "Everything You Need To Know About Uterus Transplants". Popular Science. Retrieved 10 October 2014.
  32. ↑ "World's first child born after uterus transplantation". ScienceDaily.
  33. ↑ "Medical first: Baby born to woman who got new womb". Journal Star (2006-2014 Gatehouse Media, Inc.). 4 October 2014. Retrieved 4 October 2014.
  34. ↑ "BBC News". BBC News. Retrieved 5 October 2014.
  35. ↑ "The Daily Telegraph". Telegraph.co.uk. 3 October 2014. Retrieved 5 October 2014.
  36. ↑ Johannesson, Liza; Diaz-Garcia, Cesar; Leonhardt, Henrik; Dahm-Kähler, Pernilla; Marcickiewicz, Janusz; Olausson, Michael; Brännström, Mats. "Vascular Pedicle Lengths After Hysterectomy". Obstetrics & Gynecology 119 (6): 1219–1225. doi:10.1097/AOG.0b013e318255006f.
  37. 1 2 Brännström, M.; Wranning, C. A.; Altchek, A. (2009). "Experimental uterus transplantation". Human Reproduction Update 16 (3): 329–45. doi:10.1093/humupd/dmp049. PMID 19897849.
  38. ↑ Wranning, C. A.; Akhi, S. N.; Diaz-Garcia, C.; Brännström, M. (15 December 2010). "Pregnancy after syngeneic uterus transplantation and spontaneous mating in the rat". Human Reproduction 26 (3): 553–558. doi:10.1093/humrep/deq358.
  39. ↑ Enskog, A.; Johannesson, L.; Chai, D. C.; Dahm-Kahler, P.; Marcickiewicz, J.; Nyachieo, A.; Mwenda, J. M.; Brännström, M. (2 June 2010). "Uterus transplantation in the baboon: methodology and long-term function after auto-transplantation". Human Reproduction 25 (8): 1980–1987. doi:10.1093/humrep/deq109.
  40. ↑ Dahm-Kähler, Pernilla; Wranning, Caiza; Lundmark, Cecilia; Enskog, Anders; Mölne, Johan; Marcickiewicz, Janusz; El-Akouri, Randa Racho; McCracken, John; et al. "Transplantation of the uterus in sheep: Methodology and early reperfusion events". Journal of Obstetrics and Gynaecology Research 34 (5): 784–793. doi:10.1111/j.1447-0756.2008.00854.x.
  41. ↑ Wranning, Caiza Almen; El-Akouri, Randa Racho; Lundmark, Cecilia; Dahm-Kahler, Pernilla; Molne, Johan; Enskog, Anders; Brännström, Mats. "Auto-transplantation of the uterus in the domestic pig (Sus scrofa): Surgical technique and early reperfusion events". Journal of Obstetrics and Gynaecology Research 32 (4): 358–367. doi:10.1111/j.1447-0756.2006.00426.x.
  42. ↑ Lefkowitz A., Edwards M., Balayla J. (2012). "O081 THE MONTREAL CRITERIA FOR THE ETHICAL FEASIBILITY OF UTERINE TRANSPLANTATION". International Journal of Gynecology & Obstetrics 119 (Supplement 3): S289. doi:10.1016/S0020-7292(12)60511-6.
  43. ↑ Ethical considerations in the era of the uterine transplant: an update of the Montreal Criteria for the Ethical Feasibility of Uterine Transplantation.A Lefkowitz, M Edwards, J Balayla - Fertility and Sterility, 2013. doi:10.1016/j.fertnstert.2013.05.026
  44. ↑ Moore FD (2000). "Ethical problems special to surgery: surgical teaching, surgical innovation, and the surgeon in managed care". Arch Surg 135: 14–16.

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