Reproductive, obstetric, and long-term health outcome after uterus transplantation: results of the first clinical trial.

OBJECTIVE: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). DESIGN: Prospective. SETTING: University hospital. PATIENT(S): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. INTERVENTION(S): In vitro fertilization was performed with embryo transfer (ET) of day 2 or day 5 embryos in natural cycles. Pregnancies and growth trajectory of the children born were observed. Health-related quality of life, psychosocial outcome, and medical health of donors and recipients were evaluated by questionnaires. MAIN OUTCOME MEASURE(S): The results of in vitro fertilization, pregnancies, growth of children, and long-term health of patients were reported. RESULT(S): Six women delivered nine infants, with three women giving birth twice (cumulative birth rates of 86% and 67% in surgically successful and performed transplants, respectively). The overall clinical pregnancy rate (CPR) and live birth rate (LBR) per ET were 32.6% and 19.6%, respectively. For day 2 embryos, the CPR and LBR per ET were 12.5% and 8.6%, respectively. For day 5 embryos, the CPR and LBR per ET were 81.8% and 45.4%, respectively. Fetal growth and blood flow were normal in all pregnancies. Time of delivery (median in full pregnancy weeks + days [ranges]) by cesarean section and weight deviations was 35 + 3 (31 + 6 to 38 + 0) and -1% (-13% to 23%), respectively. Three women developed preeclampsia and four neonates acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. Measures of long-term health in both donors and recipients were noted to be favorable. When UTx resulted in a birth, scores for anxiety, depression, and relationship satisfaction were reassuring for both the donors and recipients. CONCLUSION(S): The results of this first complete UTx trial show that this is an effective infertility treatment, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for donors and recipients. CLINICAL TRIAL REGISTRATION NUMBER: NCT02987023.

Striving for motherhood after uterus transplantation: a qualitative study concerning pregnancy attempts, and the first years of parenthood after transplantation.

STUDY QUESTION: How do women experience attempts to become pregnant, and the first years of motherhood, after uterus transplantation (UTx)? SUMMARY ANSWER: Women who try to become pregnant after UTx experience the general strains typically associated with infertility and childlessness, such as failure of embryo transfer (ET), and specific worries about graft survival but when they become mothers they essentially feel like other mothers, with the associated rewards and stresses. WHAT IS KNOWN ALREADY: UTx has proven to be a successful treatment for absolute uterine factor infertility (AUFI). Although UTx seems to have a positive effect on self-image there is a lack of knowledge about how women who have received uterine grafts experience pregnancy attempts, pregnancy itself and the first years of motherhood. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included the seven participants in the first UTx trial who had experienced surgically successful grafts. Pregnancy was attempted using ET 12 months after transplantation. Structured interviews were performed once a year for 5 years after transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Six of the seven participants (mean age 29.3 years at UTx) had AUFI owing to the congenital absence of the uterus, while the seventh woman had undergone a hysterectomy. Post-transplantation, yearly interviews (2013-2018) were performed, comprising a total of 34 interviews. Interview data were analysed thematically. MAIN RESULTS AND THE ROLE OF CHANCE: All seven participants achieved pregnancy during the study period and six became mothers. Experiencing the previously unimaginable was classed as an overarching theme with the following underlying themes: The yoke of childlessness; Going through the impossible and Motherhood as surreal and normal. The results showed that the women who try to achieve motherhood after UTx generally describe their situation as manageable and present strains comparable to other women undergoing infertility treatments. LIMITATIONS, REASONS FOR CAUTION: The fact that all participants came from one centre is a limitation. WIDER IMPLICATIONS OF THE FINDINGS: There are real psychological strains in motherhood after UTx, such as the concern the women expressed relating to health of the child and the effects of immunosuppressants. These findings are in line with those of other women who became pregnant after transplantation of organs other than the uterus. The results show that extra psychological support and attention should be given to those with repeated pregnancy failures or unsuccessful outcomes. In the cases where women became mothers, attention needs to be given to the possible worries connected to the UTx, but in other respects, they should be treated like any mother-to-be. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from the Jane and Dan Olsson Foundation for Science; Knut and Alice Wallenberg Foundation. A.L.F. grant from the Swedish state under an agreement between the government and the county councils; Swedish Research Council. The authors have no competing interests. TRIAL REGISTRATION NUMBER: NCT01844362.

Evolution of surgical steps in robotics-assisted donor surgery for uterus transplantation: results of the eight cases in the Swedish trial.

OBJECTIVE: To perform a stepwise development of the surgical method for robotics-assisted laparoscopy in donor hysterectomy for uterus transplantation (UTx), a unique treatment for absolute uterine-factor infertility. DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Eight donors, aged 38-62 years, underwent surgery for retrieval of the uterus and vasculature. INTERVENTION(S): Robotics-assisted laparoscopy was performed in donors for 6-7 h with video recording. Conversion to laparotomy was performed for last parts of retrieval surgery. MAIN OUTCOME MEASURE(S): Description, evaluation, and timing of 12 specific surgical steps, as well as surgical outcomes and complications. RESULT(S): There was a progression during the course of eight surgeries. In the initial two cases, seven and six items were completed with robotics compared with all 12 items in the last three procedures. The passive surgical time decreased from ∼20% in the first four cases to ∼8% in the last three procedures. The estimated median (range) blood loss, total surgical time, and length of hospital stay were, respectively, 125 mL (100-600), 11.25 h (10-13), and 5.5 days (5-6). Two reversible complications occurred: One patient acquired pressure alopecia, and one developed pyelonephritis. CONCLUSION(S): The study demonstrates a clear evolution of a strategy toward fully robotic donor surgery in UTx. This is likely to become the main approach in donor surgery of live UTx donors. CLINICAL TRIAL REGISTRATION NUMBER: NCT02987023.

Outcome of Recipient Surgery and 6-Month Follow-Up of the Swedish Live Donor Robotic Uterus Transplantation Trial.

Uterus transplantation has proved to be a feasible treatment for uterine factor infertility. Herein, we report on recipient outcome in the robotic uterus transplantation trial of 2017-2019. The eight recipients had congenital uterine aplasia. The donors were six mothers, one sister, and one family friend. Donor surgery was by robotic-assisted laparoscopy. Recipient surgery was by laparotomy and vascular anastomoses to the external iliacs. The duration (median (ranges)) of recipient surgery, blood loss, measured (left/right) uterine artery blood flow after reperfusion, and length of hospital stay were 5.15 h (4.5-6.6), 300 mL (150-600), 43.5 mL/min (20-125)/37.5 mL/min (10-98), and 6 days (5-9), respectively. Postoperative uterine perfusion evaluated by color Doppler showed open anastomoses but restricted blood distribution in two cases. Repeated cervical biopsies in these two cases initially showed ischemia and, later, necrosis. Endometrial growth was not seen, and hysterectomy was later performed, with pathology showing partly viable myometrium and fibrosis but necrosis towards the cavity. The other six patients acquired regular menstrual cyclicity. Surgery was performed in two patients to correct vaginal stenosis. Reversible rejection episodes were seen in two patients. In conclusion, the rate of viable uterine grafts during the initial 6-months of the present study (75%) leaves room for improvement in the inclusion/exclusion criteria of donors and in surgical techniques. Initial low blood flow may indicate subsequent graft failure.

Uterus transplantation: joys and frustrations of becoming a 'complete' woman-a qualitative study regarding self-image in the 5-year period after transplantation.

STUDY QUESTION: How is a women's self-image affected by uterus transplantation (UTx)? SUMMARY ANSWER: Women experienced receiving a uterus in both positive and negative ways, but in general, their self-image was positively affected; regardless of whether they have given birth to a child or not, recipients describe themselves as being 'back to normal' after the hysterectomy to remove the transplanted uterus. WHAT IS KNOWN ALREADY: UTx has repeatedly proved to be a successful treatment for absolute uterine factor infertility. However, there has been no previous qualitative long-term research into the self-image of women undergoing UTx. STUDY DESIGN, SIZE, DURATION: This complete, prospective cohort study included the nine recipients of the first UTxs performed in Sweden mostly in 2013. Interviews took place in the 5 years following surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eight out of the nine recipients had congenital absence of the uterus, a characteristic of Mayer-Rokitansky-Küster-Hauser syndrome, and one recipient lacked a uterus after a radical hysterectomy due to cervical cancer. The mean age of participants was 31.5 years at inclusion and at this time they all lived in stable marital relationships. Post-transplantation, interviews were performed annually for 5 years, comprising a total of 43 interviews. The interview followed a semi-structured guide. All interviews (median duration of around 25 minutes) were recorded, transcribed verbatim and then analysed by thematic approach. MAIN RESULTS AND THE ROLE OF CHANCE: The joys and frustrations of becoming a 'complete' woman are seen as a master theme, which influences the three underlying subthemes, a changed self-perception, a changed body and a changed sexuality. Each of these subthemes have three underlying categories. LIMITATIONS, REASONS FOR CAUTION: The small sample size is a limitation. WIDER IMPLICATIONS OF THE FINDINGS: The results provide information that will be helpful in pre-operative screening procedures and in the psychological support offered both to women who experienced successful and unsuccessful outcomes following UTx. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from the Jane and Dan Olsson Foundation for Science; the Knut and Alice Wallenberg Foundation; an ALF grant from the Swedish state under an agreement between the government and the county councils; the Swedish Research Council; a Ferring Pharmaceuticals scholarship in memory of Robert Edwards; and the Iris Jonzén-Sandblom and Greta Jonzén Foundation. The authors have no competing interests. TRIAL REGISTRATION NUMBER: NCT01844362.

Live birth after robotic-assisted live donor uterus transplantation.

INTRODUCTION: The proof-of-concept of uterus transplantation, as a treatment for absolute uterine factor infertility, came with the first live birth after uterus transplantation, which took place in Sweden in 2014. This was after a live donor procedure, with laparotomy in both donor and recipient. In our second, ongoing trial we introduced a robotic-assisted laparoscopic surgery of the donor to develop minimal invasive surgery for this procedure. Here, we report the surgery and pregnancy behind the first live birth from that trial. MATERIAL AND METHODS: In the present study, within a prospective observational study, a 62-year-old mother was the uterus donor and her 33-year-old daughter with uterine absence as part of the Mayer-Rokitansky-Küster-Hauser syndrome, was the recipient. Donor surgery was mainly done by robotic-assisted laparoscopy, involving dissections of the utero-vaginal fossa, arteries and ureters. The last part of surgery was by laparotomy. Recipient laparotomy included vascular anastomoses to the external iliac vessels. Data relating to in vitro fertilization, surgery, follow up, obstetrics and postnatal growth are presented. RESULTS: Three in vitro fertilization cycles prior to transplantation gave 12 cryopreserved embryos. The surgical time of the donor in the robot was 360 minutes, according to protocol. The durations for robotic surgery for dissections of the utero-vaginal fossa, arteries and ureters were 30, 160 and 84 minutes, respectively. The remainder of donor surgery was by laparotomy. Recipient surgery included preparations of the vaginal vault, three end-to-side anastomoses (one arterial, two venous) on each side to the external iliacs and fixation of the uterus. Ten months after transplantation, one blastocyst was transferred and resulted in pregnancy, which proceeded uneventfully until elective cesarean section in week 36+1 . A healthy boy (Apgar 9-10-10) was delivered. Follow up of child has been uneventful for 12 months. CONCLUSIONS: This is the first report of a live birth after use of robotic-assisted laparoscopy in uterus transplantation and is thereby a proof-of-concept of use of minimal invasive surgery in this new type of transplantation.

Live versus deceased donor in uterus transplantation.

Uterus transplantation to treat absolute uterine factor infertility is a rapidly evolving field still at its early clinical experimental stage. Most human uterus transplantation attempts and live births have been after transplantation with uteri from live donors, who, in most cases, are closely related to the recipient. However, successful transplant with live births after uterus transplantation from deceased donors has also been reported. This article discusses the pros and cons in relation to live and deceased donors for uterus transplantation.

Global results of human uterus transplantation and strategies for pre-transplantation screening of donors.

Absolute uterine factor infertility, due to absence or non-function of the uterus, is one of the few major subgroups of infertility that has remained without any treatment. Uterus transplantation has now been proposed as treatment for this type of infertility. The first attempt of human uterus transplantation was in 2000. This was a live donor case, but due to suboptimal surgical solutions it resulted in a necrotic uterus being removed after 99 days. This first human case, although a failure, inspired several research groups around the globe to initiate animal-based studies to investigate uterus transplantation in relation to surgery, immunosuppression, rejection and pregnancy outcome. The research was carried out in several animal species and advanced the field substantially. In 2011, the second uterus transplantation attempt was performed, and this involved a deceased donor procedure. Although the case was surgically successful, with resumed menstruations, clinical pregnancy with live birth could not be achieved. The first clinical trial of uterus transplantation was initiated in Sweden in 2013 and involved nine live donor procedures. The world's first live birth was reported from that trial in September 2014 and this was followed by two more births within that trial in November 2014. Births after uterus transplantation has since been reported from Sweden and other centers in Europe, North America, Latin America, and Asia. Thirty human uterus transplantation procedures have been reported in the scientific literature so far but by our personal knowledge the double number of procedures have been performed. The published cases will be reviewed in detail, and we will also describe the pregnancies of the live births that have been published. A small number of graft failures have occurred. These may in part be linked to suboptimal selection of donors, specifically concerning the quality of the uterine arteries. Consequently, we will also address the issue of strategies for pre-surgical screening of donors.

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

OBJECTIVE: Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. DESIGN: Prospective comparative study. SETTING: General and cardiothoracic ICUs. PATIENTS: Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. CONCLUSIONS: In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

One uterus bridging three generations: first live birth after mother-to-daughter uterus transplantation.

OBJECTIVE: To determine whether a uterus from the mother of a woman with absolute uterine factor infertility can be transplanted to daughter and carry a pregnancy with delivery of a healthy child. DESIGN: Part of an observational study. SETTING: University teaching hospital. PATIENT(S): Twenty eight-year-old woman with uterine agenesis, her male partner, and her 50-year-old mother. INTERVENTION(S): In vitro fertilization with embryo cryopreservation before live donor uterus transplantation (UTx). Induction immunosuppression. Embryo transfer 12 months after UTx, pregnancy controls, delivery, and hysterectomy. MAIN OUTCOME MEASURE(S): Results of IVF-ET, parameters of pregnancy/birth, and surgical data of transplantation/cesarean section/hysterectomy. RESULT(S): Two IVF cycles before UTx resulted in 10 cryopreserved embryos. Donor surgery included hysterectomy with vascular pedicles of uterine vessels and proximal vessels up to and including parts of internal iliacs. Recipient surgery was by bilateral vascular connections to external iliacs, vaginal-vaginal anastomosis, and uterine fixation. Pregnancy occurred at the first single ET, and the pregnancy proceeded uneventfully until gestational week 34, when the patient developed cholestasis with intense pruritus. Cesarean section was performed at 34+6, with delivery of a healthy boy (weight 2,335 g). Hysterectomy was performed 3.5 months after delivery. The weight of the healthy child at 12 months was 9.3 kg. Grandmother (uterus donor) and mother are in good health 3 years after UTx. CONCLUSION(S): This is the first report of a live birth after mother-to-daughter UTx, and it also represents the second birth ever after human UTx. CLINICAL TRIAL REGISTRATION: NCT01844362.

Uterus transplantation trial: 1-year outcome.

OBJECTIVE: To report the 12-month outcome of seven patients with viable uteri after uterus transplantation (UTx). DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Seven patients with absolute uterine infertility and viable uteri for 12 months after live-donor UTx. INTERVENTION(S): Predetermined immunosuppression was with tacrolimus and mychophenolate mofetil (MMF) during 6 months, whereupon MMF should be withdrawn. Frequent ultrasound examinations were performed to assess uterine appearance and uterine artery blood flow. Cervical biopsies (for histological detection of rejection) were obtained at preset time points, with temporary adjustments of immunosuppression if there were signs of rejection. Menstruations were systematically recorded. MAIN OUTCOME MEASURE(S): Menstruation, uterine artery blood flow, histology of cervical biopsies, and blood levels of tacrolimus. RESULT(S): All patients showed regular menses after 1-2 months. Uterine artery blood flow was unchanged, with a median pulsatility index of 1.9 (range, 0.5-5.4). Blood levels of tacrolimus were approximately 10, 9, and 8 (µg/L) during months 2, 9, and 12, respectively. Four recipients showed mild inflammation in biopsies after MMF withdrawal and were treated with corticosteroids and azathioprine during the remainder of the 12 months. Subclinical rejection episodes were detected on ectocervical biopsies in five recipients. Histology showed apoptotic bodies and occasional spongiosis in the squamous epithelium. Moderate infiltration of lymphocytes and neutrophils was seen in the epithelial/stromal interface. All rejection episodes were successfully treated for 2 weeks with corticosteroids or dose increments of tacrolimus. CONCLUSION(S): We demonstrate long-term uterine viability after UTx, with continued menstruation and unaltered uterine artery blood flow. Subclinical rejection episodes were effectively reversed by temporary increase of immunosuppression. CLINICAL TRIAL REGISTRATION NUMBER: NCT01844362.

Livebirth after uterus transplantation.

BACKGROUND: Uterus transplantation is the first available treatment for absolute uterine infertility, which is caused by absence of the uterus or the presence of a non-functional uterus. Eleven human uterus transplantation attempts have been done worldwide but no livebirth has yet been reported. METHODS: In 2013, a 35-year-old woman with congenital absence of the uterus (Rokitansky syndrome) underwent transplantation of the uterus in Sahlgrenska University Hospital, Gothenburg, Sweden. The uterus was donated from a living, 61-year-old, two-parous woman. In-vitro fertilisation treatment of the recipient and her partner had been done before transplantation, from which 11 embryos were cryopreserved. FINDINGS: The recipient and the donor had essentially uneventful postoperative recoveries. The recipient's first menstruation occurred 43 days after transplantation and she continued to menstruate at regular intervals of between 26 and 36 days (median 32 days). 1 year after transplantation, the recipient underwent her first single embryo transfer, which resulted in pregnancy. She was then given triple immunosuppression (tacrolimus, azathioprine, and corticosteroids), which was continued throughout pregnancy. She had three episodes of mild rejection, one of which occurred during pregnancy. These episodes were all reversed by corticosteroid treatment. Fetal growth parameters and blood flows of the uterine arteries and umbilical cord were normal throughout pregnancy. The patient was admitted with pre-eclampsia at 31 full weeks and 5 days, and 16 h later a caesarean section was done because of abnormal cardiotocography. A male baby with a normal birthweight for gestational age (1775 g) and with APGAR scores 9, 9, 10 was born. INTERPRETATION: We describe the first livebirth after uterus transplantation. This report is a proof-of-concept for uterus transplantation as a treatment for uterine factor infertility. Furthermore, the results show the feasibility of live uterus donation, even from a postmenopausal donor. FUNDING: Jane and Dan Olsson Foundation for Science.

Experimental uterus transplantation.

Today, most causes of infertility are successfully treated. Yet there is still a subgroup of female infertility affecting around 4%, which so far is untreatable because of an absolute uterine factor. To acquire motherhood, these women are today referred to either adoption or surrogacy. Research in the field of uterus transplantation has been evaluated in different animal models for decades and has presently reached a human clinical application as a possible treatment for absolute uterine factor infertility. Organ transplantation is no longer reserved to those with a life-threatening disease and neither is organ transplantation together with concurrent immunosuppression prohibiting pregnancy. Uterus transplantation involves four parties - recipient, donor, partner of recipient and future child - and is a subject of ethical controversies.

First clinical uterus transplantation trial: a six-month report.

OBJECTIVE: To report the 6-month results of the first clinical uterus transplantation (UTx) trial. This type of transplantation may become a treatment of absolute uterine-factor infertility (AUFI). DESIGN: Prospective observational study. SETTING: University hospital. PATIENT(S): Nine AUFI women and their live uterine donors, the majority being mothers. INTERVENTION(S): Live-donor UTx and low-dose induction immunosuppression. MAIN OUTCOME MEASURE(S): Data from preoperative investigations, surgery and follow-up for 6 months. RESULT(S): Durations of donor and recipient surgery ranged from 10 to 13 hours and from 4 to 6 hours, respectively. No immediate perioperative complications occurred in any of the recipients. After 6 months, seven uteri remained viable with regular menses. Mild rejection episodes occurred in four of these patients. These rejection episodes were effectively reversed by corticosteroid boluses. The two graft losses were because of acute bilateral thrombotic uterine artery occlusions and persistent intrauterine infection. CONCLUSION(S): The results demonstrate the feasibility of live-donor UTx with a low-dose immunosuppressive protocol. CLINICAL TRIAL REGISTRATION NUMBER: NCT01844362.

Prediction of ovarian hyperstimulation syndrome in women undergoing in vitro fertilization.

UNLABELLED: OBJECTIVE. Ovarian hyperstimulation syndrome (OHSS) is a severe side effect of in vitro fertilization (IVF). The aim of this study was to identify independent predictors which could be used to identify IVF patients at risk for OHSS. DESIGN: A prospective observational study. SETTING: University hospital. POPULATION: Six hundred and twenty-four consecutive patients treated with conventional IVF or intracytoplasmic sperm injection. METHODS: Observational clinical data were compared. MAIN OUTCOME MEASURES: Patients who developed OHSS were compared with patients who did not develop OHSS using univariate and multivariate analyses. RESULTS: Twenty-eight patients developed OHSS considered as severe and requiring hospitalization. Independent predictors of OHSS were number of follicles at oocyte aspiration, number of aspirated oocytes and total number of medium/large-sized follicles before hCG. When these variables were combined in a receiver operating characteristic (ROC) curve they showed a sensitivity of 82.1% and a specificity of 90% for OHSS. The only independent predictor of OHSS before the ovulatory dose of hCG was total number of medium/large-sized follicles before hCG. A corresponding ROC found a sensitivity of 82.1% and specificity of 79.4%. CONCLUSION: Prediction of OHSS that is of severity requiring hospitalization can be done with reasonable high sensitivity and specificity both before and after the ovulatory dose of hCG.

Transplantation of the uterus in sheep: methodology and early reperfusion events.

AIM: Uterine transplantation is developing into a clinical treatment for uterine factor infertility. An animal model with a similar uterus size and vessels to humans and with pregnancy extending over several months would be beneficial for research on uterine transplantation. The aim of this study was to develop and evaluate autotransplantation of the sheep uterus to an orthotopic position in the pelvis. METHODS: Female sheep (n=7) were subjected to laparotomy with the uterus and its vascular supply and drainage being surgically isolated. The excised uterus was kept ex vivo at +4 degrees C for 60 min and then autotransplanted with vascular end-to-side anastomoses to the external iliac vessels. The effects of uterine blood-reperfusion were assessed by measurements of pCO(2), pO(2), lactate and pH in uterine venous blood. Uterine contractility and histology was assessed after 3 h of reperfusion. RESULTS: Reperfusion of blood was observed in five out of seven transplanted uteri. The pCO(2)/pO(2)-ratio and the lactate level were initially elevated but decreased and became normal after 60 min. After 3 h of reperfusion there was a visible tissue blood flow and spontaneous uterine contractions were seen. Histological analysis revealed a mild inflammation, but no edema or stasis. CONCLUSIONS: This study demonstrates that the sheep uterus can successfully be autotransplanted to an orthotopic position with novel vascular connections. This model is suitable for future experiments studying long-term results concerning uterine viability and pregnancy using a transplanted uterus of similar size to the human uterus.

Transplantation of the uterus in the sheep: oxidative stress and reperfusion injury after short-time cold storage.

OBJECTIVE: To study the effects of cold ischemia and reperfusion after transplantation of the sheep uterus and to compare the preservation solution Perfadex (Vitrolife, Mölndal, Sweden) with Ringer's acetate. DESIGN: Experimental animal study. SETTING: University hospital. ANIMAL(S): Adult, female sheep. INTERVENTION(S): One uterine horn with the common uterine cavity and cervix of sexually mature ewes was auto-transplanted after 1 hour of cold ischemic storage in either Perfadex (n = 5) or Ringer's acetate (n = 5). During 3 hours of reperfusion, uterine venous blood was collected and analyzed for several parameters that were indicative of oxidative stress and reperfusion injury. A biopsy was taken for histological analysis at the end of the experiment. MAIN OUTCOME MEASURE(S): Lipid peroxidation and ascorbyl radicals in uterine venous blood during reperfusion. Light microscopy and quantification of neutrophils in tissue after 3 hours of reperfusion. RESULT(S): A decline in pH and a rise in lactate and pCO(2)-pO(2), as well as an elevation of antioxidant capacity, lipid peroxidation, and intensity of ascorbyl radical electron spin resonance signal, was found that was more prominent after storage in Ringer's acetate. The histological analysis revealed mild inflammation in both study groups. CONCLUSION(S): Short-time cold ischemic storage of the sheep uterus does not induce any severe reperfusion damage, but the use of the protective buffer Perfadex decreases oxidative stress and inflammation when compared with a more simple solution.