Friday, July 20, 2007

Transplantation of the Human Uterus

In the present-time, when the media talks only about Surrogacy & Gestational Carriers, there is a new & brave breed of scientists hard at work exploring new frontiers. We must doff our hats to the team from Saudi Arabia who have charted a completely new course in Reproductive Medicine. The work of Fageeh et al from the Multiorgan Transplant Unit, King Fahad Hospital and Research Center, Jeddah, Saudi Arabia was published in the Int J Gynaecol Obstet (2002 Mar;76(3):245-51).
Human uterine transplantation was performed on 6 April 2000 on a 26-year-old female who lost her uterus 6 years earlier due to post-partum hemorrhage. The donor, a 46-year-old patient with multiloculated ovarian cysts, underwent a hysterectomy modified to preserve tissue and vascular integrity. The donor uterus was connected in the orthotopic position to the recipient's vaginal vault and additional fixation was achieved by shortening the uterosacral ligament. The uterine arteries and veins were extended using reversed segments of the great saphenous vein, then connected to the external iliac arteries and veins, respectively. Immunosuppression was maintained by oral cyclosporine A (4 mg/kg/body wt.), azathioprine (1 mg/kg/body wt.) and prednisolone (0.2 mg/kg/body wt.). Allograft rejection was monitored by Echo--Doppler studies, magnetic resonance imaging (MRI), and measurement of the CD4/CD8 ratio in peripheral blood by fluorescence activated cell sorter (FACS scan). An episode of acute rejection was treated and controlled on the ninth day with anti-thymocytic globulin (ATG). The transplanted uterus responded well to combined estrogen--progesterone therapy, with endometrial proliferation up to 18 mm. The patient had two episodes of withdrawal bleeding upon cessation of the hormonal therapy. Unfortunately, she developed acute vascular thrombosis 99 days after transplantation, and hysterectomy was necessary. Macro- and microscopic histopathological examination revealed acute thrombosis in the vessels of the uterine body, with resulting infarction. Both fallopian tubes remained viable, however, with no evidence of rejection. The acute vascular occlusion appeared to be caused by inadequate uterine structure support, which led to probable tension, torsion, or kinking of the connected vascular uterine grafts.

Doctors at Hammersmith Hospital, London, aim to carry out the first successful womb transplant within two years, reported the Evening Standard recently. Doctors say that the womb would be taken from a dead donor and will only remain in the recipient for two or three years, or until a baby is born. Richard Smith, a surgeon at Hammersmith Hospital, working with teams in Budapest and New York, announced that animal trials have been successful; 'We have had stunningly good results in the laboratory with good blood supply to the organ', he said. The team now wishes to move on to clinical trials in humans. This procedure may bring hope to women whose own wombs have been rendered useless by disease or surgery, or who were born without one, for whom IVF is not an option, and for women who have come to the end of the line of IVF with no success. There are currently 15,000 women in Britain who have no uterus, of which about 200 have turned to surrogacy. The procedure would provide an alternative to surrogacy, where problems include difficulties in finding someone to carry the baby and fears that the surrogate mother will refuse to hand over the child once born. There are also risks for the surrogate mother herself. In 2004, Natasha Caltabiano died after given birth for another couple. However, womb transplantation may carry associated risks as well. The mother would have to give birth by Caesarean and would have to undergo a course of immunosuppressant drugs. For this reason the transplanted womb would only be in for two or three years and would be removed once a child is born. Mr Smith highlighted that women have already given birth to healthy children after kidney transplants, which required them to take immunosuppressant courses to prevent rejection. Women who undergo a womb transplant would also be offered psychological counselling. Mr Smith said that the hospital, which is currently funded by charitable donations, would need £250,000 a year in funding to perform the transplants. It is estimated that each transplant would cost about £50,000. Womb transplantation has provoked a mixed response from the authorities and the public. Infertility organisations have welcomed the news but have warned women not to raise their hopes until the procedure has undergone successful human trials. Professor Lord Robert Winston, however, warned that 'this is not a road we should be going down. It is a dangerous procedure which could cost a woman her life'. Dr Patrick O'Brien, spokesman for the Royal College of Obstetricians and Gynaecologists, called the procedure 'fascinating' and said that women would chose to undergo the transplant but added that it was a 'separate question, for the Human Embryology Authority and the public to consider'. Public discussion boards have revealed concerns over 'Frankenstein' procedures and some have preferred the alternative of adoption. Whilst issues of safety may be overcome by Mr Smith and his team, the ethical objection to such a procedure may remain.

Work is in progress in at least 5 different countries presently on Human Uteri Transplantation. Would love to have new information or links to similar work anywhere in the world. Please go ahead and blog.