Section 11-c

Uterus Transplantation

Wafa Fageeh, Giovanna Lucchini

Introduction have left these women to hope for the possibility of uterine transplant. Transplantation Uterine transplant is at a crossroads. It is possi- of the would relieve the anguish of bly the best solution for approximately 4% of women who greatly desire to conceive a child infertile women who undergo the frustration of and allow them hope for an opportunity to being unable to conceive due to the absence of a become pregnant. uterus. In some cases, this absence is due to con- A clinical milestone was made by Dr. Wafa genital abnormality (e.g. Rokitansky’s syn- Fageeh and her team when they successfully drome). In other cases, it is due to surgical transplanted a human uterus in Saudi Arabia in removal of the uterus at a relatively young age the year 2000 although the transplant lasted only due to clinical emergencies, such as obstetric 99 days [1]. The furor that followed this partial uterine rupture. success reveals the range of views of the scientif- Until recently, only life and death situations ic community and the public at large. Of course, warranted . Nonvital the concerned women were enthusiastic and transplantation simply to fulfill a patient’s wish- delighted at the potential for progress in this es or goals was not considered justified. It can be technique. Sceptical scientists raised the ques- argued, however, that this distinction is not tion as to whether this “non-life-saving trans- morally significant. Patients with kidney failure, plant” was necessary at all? Only further for example, can be kept alive by dialysis, but progress in transplant science can shed more their quality of life can be greatly enhanced by light on the answer to this critical question. kidney transplant, which is thus considered a Antirejection drugs are nonetheless becoming justified procedure. So a spectrum of rationales safer, and patients with cardiac and renal trans- may justify transplantation. Therefore, the only plants have had successful . Thus, in chance for women without a uterus to have the progress of the development of nonessential babies was by resorting to surrogate gestation. In human transplants, the uterus seems to be lead- many countries, this procedure is prohibited by ing the way because of the successful, if only the law. In some other countries, surrogate temporary, transplant in 2000. The three men- mothers are registered as legal mothers of babies strual cycles that followed indicated functionali- born through surrogacy. Another problem that ty of the uterine but the unfortu- parents may face if they decide to try surrogacy nate incident of thrombus was a drawback. is that they have no control over the course, care While other organ transplant donations most or outcome of such . These and other often come from cadavers and less often from ethical, moral and religious issues surrounding living donors (kidney or partial liver), the donor 410 W. Fageeh, G. Lucchini source for a uterus may be an otherwise healthy conditions, a transplant could provide their only living patient who requires uterus removal as a hope for experiencing a pregnancy of their own. care procedure. Furthermore, it should be At present, they can choose IVF, in which their mandatory to remove the transplanted uterus own egg and their partner’s sperm can be used from the recipient after successful pregnancies for gestational surrogacy. Technically, this is so the patient need not be subjected to lifelong straightforward, but it may not always be suit- antirejection medications. able for many couples. Uterine transplants could Since animal uterus transplantation has been help up to 47% of infertile women. The surgery done successfully, human uterine transplanta- would be comparable to a kidney transplant and tion could be considered for select cases. would offer advantages over surrogacy, especial- The interest in uterine transplantation has ly in countries where it is not allowed. been increasing in the scientific community With a uterine transplant, any health risk of since the mid-twentieth century, with the aim of pregnancy, such as high blood pressure, are overcoming problems linked to uter- taken by the genetic mother, which makes it ine absence or uncorrectable anomalies. It has acceptable from an ethical point of view. There is been stated that 5–10% of cases of infertility are also no financial consideration, a situation often caused by either congenital or acquired uterine criticised with surrogacy. It also clears up com- disorders, among which are Müllerian agenesis, plications regarding who is the legal mother. In Mayer-Rokitansky-Kuster-Hauser syndrome, some countries, the legal mother is the woman leiomyomas, Asherman’s syndrome and hys- who gives birth regardless of who is the biologi- terectomy are the most common [2]. New repro- cal mother. With transplantation, the biological ductive procedures are of no help in these situa- mother would be the legal, social and gestation- tions. The only chance for women affected by al mother. these problems to give birth is to rely on gesta- Since a uterine problem is a factor in 3–4% of tional surrogacy, which consists of using infertile women, there would probably be no gametes of a genetic couple to produce embryos shortage of women willing to try the technique that are then transferred to the womb of a because according to Dr. Mats Brännström of the woman who agrees to act as a host for the preg- Sahlgrenska Academy at Göteborg University in nancy [3]. The technique is legally approved in , he has received hundreds of enquiries Canada, UK, Brazil, South Africa, Israel, from women who have read about his pregnancy Hungary, the Netherlands, Australia and some success with uterine transplants in mice. Several states in the USA. Other countries have no spe- volunteers contacted Fageeh’s team to be donors, cific legislation on the practice of surrogacy and several others as would be recipients, indi- (Greece, Argentina, Belgium, Finland and India). cating that there is definitely a demand for this In most Muslim countries and some Asian terri- procedure even though the numbers may be tories, it is strictly forbidden on the basis of reli- small. gious or ethical grounds. Even in nations that have accepted this procedure by law, scattered incidences of resistance based on ethical, psy- chological, religious and economical issues have Landmarks in Organ and Uterine been reported [4, 5]. Transplantation Around 15% of all couples are infertile. Most resistant cases have been helped by assisted The advent of organ transplants began with that reproductive technologies, such as in vitro fertil- of the kidney in the early 1960s. Inspired by the isation (IVF) and intracellular sperm injection success, transplantations of other vital organs, (ICSI). However, for women who have healthy such as liver, heart, lung and pancreas, followed. but have had a or serious In the beginning, (Imuran) and uterine problems due to injury or congenital prednisone were the only available immunosup- Uterus Transplantation 411 pressive agents. In 1980, with the introduction of led to the development of different techniques to cyclospine therapy, the prognosis for transplant- obtain good viability of the transplanted organ. ed organs became better. Progress in safer and Among these, omentopexy has been commonly more easily tolerated immunosuppressive thera- used to obtain a milieu that supports sponta- py has opened the doors for the transplant of neous revascularisation, fixation of the uterus to nonvital organs, such as the uterus. the broad ligament has been tested with good The first study of ovarian transplantation was results and the more classical vascular anasto- published as early as 1896 by Knauer. However, mosis has been improved to the point of becom- attempts at uterine did not ing the most efficient surgical option. All these begin until 1918 [6]. Autotransplant of a uterus studies proved the surgical feasibility of the in a dog by Eraslan, Hamernik and Hardy in transplantation and even attempted to recreate 1964 and 1966 was the first to end in a successful the function of the normal uterus by producing delivery [7]. Confino, Vermesh and Gleicher some examples of pregnancies and deliveries in introduced the use of cyclosporine therapy for the grafted animals. From an immunological uterine in rabbits in 1986 [8]. point of view, experimental models using aza- In 2000, a human uterine transplant was per- thioprine and prednisolone were tested but formed in Saudi Arabia by Fageeh et al. [1]. never achieved outstanding results in avoiding Postoperatively, the patient had three sponta- rejection and because close monitoring of serum neous menstrual cycles followed by amenorrhea. drug levels was not easily carried out. Exploratory laparotomy confirmed uterine More recent epidemiologic and experimental necrosis due to vascular thrombosis. There was studies have underlined the effect of some no evidence of rejection. The attempt, however, immunosuppressive drugs on the foetus. raised discussions on many moral and ethical Azathioprine has proven to be mildly teratogenic issues. The scientific community, although on rats whereas seem to be deeply divided, consider this as the only refer- linked to a general augmented risk of cleft palate ence to a human success. Recently, interest has development [15, 16]. Cyclosporine has shown to fallen on further exploring the feasibility of restrict foetal growth, resulting in low birth human uterine transplantation as a replacement weight. However, these data were collected in a for surrogate gestation. population of patients suffering from autoim- mune diseases, and therefore the role of these diseases on gestation is still to be clarified [17]. Fageeh performed 16 autologous orthotopic Work on Animal Models uterine replantation on baboons and 2 on goats. After a midline abdominal incision, hysterecto- The story of experimental animal models used my was done so as to preserve tissue and vascu- for the purpose of uterine transplantation lar integrity. The uterus was then flushed with begins in the early 1960s [7–14]. Sheep, dogs, Euro-Collins solution and replanted in the same macaques, rabbits and rats were used in both animal with cervico-vaginal anastomosis. The autologous and homologous transplantations. first 8 animals had end to end uterine vascular The intention was to understand two main areas anastomosis but occlusion and vascular throm- of this technique: (1) recreation and stable vas- bosis was observed in 12 out of the 16 vascular cularisation of the uterus, with anatomical net- connections. It was therefore decided to change work of small vessels, and (2) modulation of to an end to side anastomosis between uterine immunosuppressive treatment in order to avoid vessels and internal iliac vessels, which offered rejection, prevent toxicity for the mother and better results (18 out of 20 vessels remained eliminate teratogenicity for the foetus. Vascular viable). After 6 to 12 weeks the animals under- support of the pelvic region was crucial to went abdominal exploration that showed sur- survival and was therefore the most studied ele- vival of the uterine graft and good vessels paten- ment in the first proposed animal models. This cy [1]. 412 W. Fageeh, G. Lucchini

To complete the history of experimental sur- would involve removing the existing organ com- gery in uterus transplantation we need to quote pletely and replacing it by the donor uterus. the most recent animal model of this kind. The researcher leading the work on mice, Dr. Mats Brännström of the Sahlgrenska Academy at Göteborg University in Sweden and his team The First Human Uterine proposed a mouse model for homologous uterus Transplant transplantation. They had seen pregnancies in mice with donor which resulted in The first human uterine transplant is reproduced healthy babies. The mice used were syngenic in its entirety here to shed clarity on this very (inbred strain) and the vascular technique used important landmark in uterine transplantation. was that of end to side anastomosis between donor uterine vessels and recipient inferior cava vein. The viability of the uterus was sequentially Introduction examined and proved to be good for 8 weeks post operatively. The function of the transplant- During the past three decades, scientists have ed uterus was evaluated inducing pregnancies made tremendous efforts to solve infertility with good results. This model is still under problems; indeed, the achievements and develop- development [18]. ments that have occurred in this field have had a In their original work, the team took a uterus considerable clinical impact [18]. Infertility due from a donor mouse and transplanted it along- to the absence of a uterus or to a congenitally side the recipient mouse's own uterus. This malformed uterus with normally functioning meant they could compare how both worked. ovaries, has remained an obstacle to pregnancy, The team led by Mats Brännström grafted however, especially in communities where surro- one arm of the V-shaped mouse uterus from a gate gestational carriers are approved by neither donor mouse into another's abdomen, alongside religious nor ethical authorities. its existing uterus. The implanted partial uterus Uterine transplantation could provide a solu- was connected to the mouse's blood supply. tion to this problem, but its feasibility, safety and Several days later, tests demonstrated that blood reproducibility remain to be proven. To evaluate flow in both organs was similar, the team says. the potential for safe, successful, uterine trans- Three fertilized embryos were then transplanted plantation in humans, we reviewed earlier ani- into each of the uterus. mal experiments and clinical trials. The main Their report, published in the Journal of difficulty was vascular anastomosis between Endocrinology (V 174, Pg 157), reveals that one uterine vessels of donor and recipient [20]. of the three in the donor organ, and all three in Unlike other organs where large vessels are the the mouse's native uterus, developed into healthy source of blood supply, in the uterus, the blood fetuses. The experiment was terminated after 13 supply and drainage occur through a net of tiny days, two-thirds of the way through the pregnan- vessels. Most earlier animal experiments were cies, due to ethical restrictions placed on the performed with avascular techniques that led to research. failure and the formation of pelvic abscesses [8]. The reason their experiment on mice worked Human trials were limited to transplantation of is because they connected the vascular system of endometrial tissue [21], and no documentation the implanted uterus directly to the existing of successful uterine transplantation was avail- blood supplies, rather than using stents which able in the English literature. have caused other transplants to fail. The Islamic religious position on uterine As predicted by the Swedish researchers, the transplantation was clarified in March 1990, procedure conducted in mice would be easier to before initiation of this project, when the Islamic repeat in humans. In a woman, the procedure Jurisprudence Council approved the transplan- Uterus Transplantation 413 tation of reproductive organs that do not trans- vessels in an end-to-side fashion using monofil- fer genetic coding. ament, nonabsorbable polypropylene sutures. This modification was technically easier to accomplish. It also provided wider anastomotic Experimental Animal Studies stoma and a higher success rate in the remaining ten animals, with proven vascular patency in 18 The project conformed with the Guiding of 20 (90%) vascular connections. All animals Principles in the Care and Use of Laboratory underwent abdominal exploration after 6–12 Animals approved by the authorities of the King weeks to evaluate survival of the reimplanted Fahd Medical Research Center. Previous experi- uterus, and the following steps were taken: ments had proven the feasibility of uterine trans- - assessment of vascular patency by visualising plantation in animals, with successful pregnancy emptying and refilling of veins and pulsatili- [7]. As the main difficulties lay in uterine vascu- ty of arteries, and by palpation of the arteries lar connections, some researchers performed for presence or absence of thrill avascular uterine transplantation in the animals, assessment of uterine and viabili- which resulted in failure and in the formation of ty by evaluation of their color and texture pelvic abscesses. We, therefore, decided to con- - observation of bright red fresh bleeding from centrate our animal studies on uterine reimplan- the tissue on abrasion or puncture tation rather than transplantation.We focused on - determination of pelvic infection. the vascular surgical anatomy and its variations Our animal studies demonstrated survival of [22], the physiology of the uterine blood flow and the uterine graft and indicated that good mid- mastery of microvascular techniques of uterine and long-term vessel patency could be achieved arterial and venous anastomosis. using skillful microvascular techniques for uter- Autologous orthotopic uterine reimplanta- ine arterial and venous anastomosis in an end- tion was performed on 18 virgin female animals to-side fashion. (16 baboons and two goats). The baboons’ aver- After reviewing the earlier reported experi- age age, weight and height were 2–4 years, 15.6 mental work by other researchers [6] and our kg and 37 cm, respectively; the goats’ average satisfactory results, we decided to prepare for a age, weight and height were 2–3 years, 20–30 kg human trial. Protocols for human uterine trans- and 60–71 cm, respectively. Surgery was per- plantation were designed detailing indications, formed with the animals under general anaes- contraindications, selection criteria, surgical thesia without muscle relaxation. Prophylactic techniques, regimen and antibiotics (tetracycline, 20 mg/kg body weight) clinical follow-up. Detailed informed consent were given for 5 days. In each animal, a midline forms were prepared for the donor and recipient abdominal incision was made. Hysterectomy was according to the guidelines and regulations of modified to preserve tissue and vascular integri- the Food and Drug Administration (FDA). ty. The extirpated uterus was flushed in both the antegrade and retrograde manner with 60 cm3 of cold Euro-Collins solution then reimplanted Materials and Methods orthotopically in the same animal by doing cer- vicovaginal anastomosis. The first eight animals The potential recipient was a 26-year-old woman underwent end-to-end uterine vascular anasto- who had undergone a hysterectomy in 1994 mosis, but anastomotic occlusion and pelvic because of massive bleeding following a cesare- abscesses occurred due to graft failure and vas- an section. She had consulted us concerning the cular thrombosis in 12 of the 16 (75%) vascular possibility of uterine transplantation and after connections. Therefore, the technique was mod- thorough evaluation was found to be eligible. ified so that the anastomosis was performed The donor was a 46-year-old woman who pre- between the uterine vessel and the internal iliac sented with bilateral multiloculated ovarian 414 W. Fageeh, G. Lucchini cysts measuring 8×6 cm on the right side and were anastomosed to each uterine vein and 3×2 cm on the left side. Hysterectomy with bilat- artery, respectively, with 6×0 nonabsorbable eral salpingo- was planned, as this polypropylene suture (Prolene Ethicon) on a patient agreed to donate her uterus. ABO com- sterile side bench to extend the length of vascu- patibility, human leukocyte antigen (HLA) tissue lar pedicles (Fig. 3). The eight vascular grafts matching and negative cytotoxic antibodies in were flushed again with Euro-Collins solution to the recipient were confirmed. check for any anastomotic leaks. A small lacera- tion of the anterior wall of the donor’s left ureter The Procedure was found and was splinted with a double J tube The Donor and sutured by the urologist. On 6 April, 2000, uterine extirpation was carried out with the patient under general anesthesia. The Recipient The donor’s abdomen was opened through a A preoperative oral dose of cyclosporine (4 midline incision; bilateral en-block oophorecto- mg/kg body weight) was administered 6 h prior my was performed, and the ovaries were sent for to surgery, and methyl prednisolone (500 mg frozen section, which confirmed the benign i.v.) was administered to the patient at induction nature of the cysts. Uterine removal was accom- of anaesthesia. The recipient’s laparotomy was plished using a technique modified so as to started when donor uterine extirpation was maintain the vascular pedicle of the uterus as imminent. A midline subumbilical incision was long as possible and thus maintain tissue selected, and intra- and retroperitoneal adhe- integrity. The long vascular pedicle was main- sions were lysed. Internal and external iliac ves- tained by transecting the round ligaments as far sels were dissected bilaterally. The bladder and laterally as possible. Ureters were identified and rectum were dissected from the cervical stump, protected. Infundibulopelvic ligaments were and the latter was excised. The donor uterus was clamped, divided and sutured. Pararectal and placed in orthotopic position, and the was paravesical spaces were developed with care to then sutured to the recipient vaginal vault by avoid traumatising the numerous small veins in single, interrupted, nonabsorbable 2×0 Ti-Cron the broad ligaments and paravesical space. (Ethicon) sutures. Uterosacral shortening was Uterine arteries were then encircled with vessel accomplished using two nonabsorbable 2×0 Ti- loops. Uterosacral ligaments were serially divid- Cron sutures. The extended uterine veins and ed and sutured. The uterovesical peritoneum was arteries were then anastomosed to the external incised, and the bladder was separated from the iliac veins and arteries, respectively, with 6×0 cervix and . At that stage, methyl pred- Prolene. No ovarian arterial or venous anasto- nisolone (500 mg) and heparin (20,000 IU) mosis was performed. Five hundred milligrams were given IV. Uterine arteries were clamped 1 of methyl prednisolone was given IV on releas- in. away from the uterine body (Fig. 1). The vagi- ing the iliac clamps and reestablishing uterine na was entered by circumferential incision and perfusion. The abdomen was closed in layers the extirpated uterus immersed in cold saline for after complete homeostasis. The recipient made topical hypothermia. The graft was flushed with an uneventful recovery with good wound heal- modified, cold (4°C), Euro-Collins solution, ing. White blood count, cyclosporine level and antegrade through uterine arteries and retro- creatinine phosphokinase enzyme levels were grade through uterine veins, to ensure removal checked twice a week. Immunosuppression con- of all white blood cells and fibrin and to induce sisted of oral cyclosporine (4 mg/kg body central core cooling for tissue preservation dur- weight) divided into two doses to assure a serum ing the ischaemia period. The uterosalpingeal trough level of 200 ng%, azathioprine (Imuran) graft was additionally trimmed to ensure (1 mg/kg body weight) and prednisolone, with a removal of any remnants of unwanted tissue maintenance dose of 0.2 mg/kg body weight. (Fig. 2). A 6-cm-long segment of the great saphe- The adequacy of immunosuppression was moni- nous vein and an 8-cm-long reversed segment tored by measuring the lymphocyte subpopula- Uterus Transplantation 415

Fig. 1.Preparation of vascular pedicles

Fig. 2. Doppler ultrasound with excel- lent uterine artery filling

Fig. 3.Tubes with patency and no rejec- tion 416 W. Fageeh, G. Lucchini tion (CD4/CD8 = helper/suppressor) cell ratio by good blood perfusion and viability of the trans- cytoimmunological cytometer (FACS Scan) and planted uterus. Doppler ultrasound to study flow volume, pul- satility and resistance index [23]. On the ninth Removal of the Transplanted Uterus postoperative day, the patient complained of low abdominal and back pain, general fatigue, On the 99th day, the patient experienced a sud- malaise and body aches. She had minimal den feeling of heaviness, with a foul-smelling serosanguineous vaginal discharge, low-grade vaginal discharge on straining. Speculum exam- fever and tachycardia, indicating acute rejection. ination revealed a dusky-coloured cervix pro- The CD4/CD8 ratio was found to be reversed to lapsing into the vagina. Immediate Doppler 3.4. Abdominal Doppler ultrasound showed ultrasound confirmed cessation of uterine blood increased brightness due to myometrial oedema. flow. A diagnosis of mechanical occlusion of the The patient was treated by increasing the oral uterine vessels with resulting uterine infarction doses of cyclosporine and azathioprine and was made, and the need to perform a hysterecto- administering an intravenous pulse of methyl my became obvious. At surgery, the uterus was prednisolone. The rejection did not resolve, found to be infarcted, and the uterine arteries, however. Antithymocytic globulin (ATG) (2.5 veins and their supplying grafts were throm- mg/kg body weight) was given, controlling and bosed. Both fallopian tubes remained pink and resolving the rejection phenomenon. Cervical viable, however. Histopathologic microscopic inspection on the 12th day revealed good healing examination confirmed the above findings as of the cervicovaginal anastomosis, with some well as the viability of both tubes and absence of venostasis of the lower one third of the ecto- any rejection (Fig. 5). cervix. Biopsy was not attempted so as to avoid anastomotic disruption. The symptoms of rejec- tion disappeared after 2 days, and the CD4/CD8 Discussion ratio was 1.3. Doppler ultrasound revealed excel- lent bilateral uterine arterial perfusion, with low Advances in immunology make organ transplan- resistance indices (Fig. 4). Hormonal therapy tation for end-stage organ failure a clinical real- with oestrogen and progesterone (Progyluton) ity [24]. Advances in microvascular surgery and was given for the first 3 months to build up the tissue preservation as practiced in ovarian trans- atrophic endometrium. Two withdrawal bleed- plantation [25] provide support for major steps ings occurred promptly after cessation of hor- in the new era of the surgical management of monal therapy. These were considered to reflect infertility [26]. Such advances can be applied

Fig. 4. Irrigation of donor vessels Uterus Transplantation 417

Fig. 5. Preparation of donor uterus

successfully in uterine transplantation, and fine polypropylene monofilament, nonab- indeed, our experimental work with microvascu- sorbable sutures is required. Suspension of the lar uterine vessel anastomosis provides ample uterus to the anterior abdominal wall (ven- clinical evidence of good mid- and long-term trouteropexy) and by uterosacral shortening is vascular patency and graft survival. essential to avoid displacement of the uterus Simple noninvasive techniques, such as with consequent tension, torsion or kinking on Doppler ultrasound, to monitor and detect early the vascular pedicle and anastomosis, with rejection are essential. Cytoimmunological mon- obstruction of blood flow and vascular throm- itoring for activated lymphocyte subpopulation bosis. (CD3/CD4) cell ratio using monoclonal antibod- ies is a simple, noninvasive technique to monitor rejection, with sensitivity and specificity Conclusion approaching 96% and 88%, respectively [27]. Our clinical results with the first human uterine Punch biopsy from the endocervix to detect and transplantation confirm the surgical technical histopathologically grade rejection seen as feasibility and safety of this procedure in gynae- myocyte necrosis and perivascular infiltration of cologic, surgical and vascular terms. Acceptable lymphocytes is an invasive procedure that could short- and midterm outcomes were documented be associated with certain risks. It was, therefore, by good endometrial proliferation on hormonal not applied in our patient. therapy and the occurrence of two withdrawal Modification of the hysterectomy technique bleedings in the transplanted menopausal donor in the donor is essential to promote preservation uterus. of a longer vascular pedicle and application of a An understanding of the surgical vascular gentle, atraumatic technique to preserve the anatomy and physiology of uterine blood flow uterus and differs from conventional hysterecto- and the application of microvascular techniques my. Extension of the vascular pedicle for a in uterine vessel anastomosis solved the earlier required length using a conduit such as the great reported difficulties encountered in that aspect. saphenous vein or the radial artery may be Cytochemical and cytoimmunological noninva- advantageous in selected patients, and applica- sive techniques for monitoring graft rejection tion of microvascular techniques by an experi- are useful and reliable. Preservation of tissue enced vascular surgeon is mandatory. The use of and vascular integrity during uterine extirpation 418 W. Fageeh, G. Lucchini is essential. A vascular pedicle of good length children or a mother since the chance for a good with the possible use of an extension conduit, immune and blood type match would be high. It such as the radial artery or the great saphenous would be possible to carry your own child in the vein, could be required. Strong fixation of the same womb [donated by mother] as you devel- transplanted uterus to the anterior abdominal oped during your growth as a foetus” [18]. wall and the sacral promontory is required, as Commenting on the work by Brännström and the uterus lacks the support of the uterosacral his team, Dr. John Mills, chairman of the British ligaments and could develop slow progressive or Fertility Society and a consultant obstetrician acute prolapse with consecutive thrombosis, and gynaecologist at Ninewells Hospital, infarction and loss of the uterus. Dundee, UK, said: “This paper has described Further clinical experience and additional successful pregnancies in the mouse, at least to development of the surgical techniques could the early pregnancy stage, and will obviously make uterine transplantation useful in the treat- give hope to those surgeons who are interested ment of infertility, especially in communities in carrying out a similar operation in humans. where the surrogate mother concept is unaccept- More evidence of success in other animals will able from a religious or ethical point of view. be required before it is justified to make such an attempt.” He said there was a huge difference between mice and humans, which meant much more work was needed. He also said the Swedish Controversies work and successful pregnancies in women who had taken immunosuppressant drugs after kid- ney or heart transplants showed that progress is Unlike other organs, which are supplied by large being made on the issue of reducing the rejec- blood vessels, the uterus receives its blood sup- tion of transplants. ply from a network of tiny vessels. This means US experts Dr. Louis Keith and Dr. Guiseppe that establishing a blood supply for the trans- Del Priore described transplantation of the planted organ is extremely complex and prone to reproductive organs as the “last frontier” in the problems. In addition, blood vessels supplying field of organ transplantation. To some individu- the uterus must be able to expand to three times als, childbearing is the greatest event of a life- their normal size during pregnancy if they are to time. To such persons, transplantation of organs support a developing foetus. of reproduction would not be considered frivo- lous or unnecessary even though these organs do not sustain life [31]. Further clinical experience and additional development of the surgical tech- The Future niques could make uterine transplantation use- ful in the treatment of infertility, especially in Uterine transplantation is still supported by communities where the surrogate mother con- gynaecologists who believe that advancement in cept is unacceptable from a religious or ethical microsurgery and immunology may allow the point of view. achievement of good results without major side- Dr. Richard Smith from the Chelsea and effects or risks for the transplanted mother and Westminster Hospital in London, who has been her foetus. Two frontiers clearly lie in the path of carrying out laboratory experiments to test the progress of further development in uterine feasibility of a uterus transplant, says that a simi- transplant. One is improving and optimising lar operation should be possible in the UK in 2 immunosuppression techniques. The second is years. According to him ,there is a small group of to develop an ideal vascular model for uterine women who are very keen to have children and transplant, its survival and functionality and who would be prepared to undergo that sort of subsequent pregnancy. surgery to achieve that end [31]. Peter Bowen- According to Brännström: “Suitable donors Simpkins, from the Royal College of Obstetricians could be either a sister after she has had her own and Gynaecologists, said he believed the develop- Uterus Transplantation 419 ment would eventually lead to women without a looking for venues to discuss their experiences uterus being able to give birth. “This shows it is and other cooperative efforts. In relation to uter- technically possible. The womb survived for more ine transplantation, these sites include: than two menstrual cycles, so the first crucial hur- - www.uterinetransplant.com dles have been passed” [31]. - www.uterinetransplant.net - www.uterinetransplant.org The latter two were under development at the time of publication of this material. Monitoring The Web to Assist the Progress of contemporary views and progress will continue this Procedure on www.uterinetransplant.net, which will also provide a platform for publications. Researchers Web and Internet-based activities have shown an and clients will use the forum available at ability to bring together persons keen on further www.uterinetransplant.org to continue exchang- development of techniques as well as clientele ing views and cooperate with each other.

References

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