Is it possible to perform allogeneic uterus transplantation (UTx) with a donation from a live don... more Is it possible to perform allogeneic uterus transplantation (UTx) with a donation from a live donor in a non-human primate species and what immunosuppression is needed to prevent rejection? summary answer: Allogeneic UTx in the baboon is a donor-and recipient-safe surgical procedure; immunosuppression with induction therapy and a triple protocol should be used. what is known already: UTx may become a treatment for absolute uterine factor infertility. Autologous UTx models have been developed in non-human primates with reports on long-term survival of the uterine grafts. study design, size and duration: This experimental study included 18 female baboons as uterus donors and 18 female baboons as uterus recipients. The follow-up time was 5-8 weeks. participants/materials, setting and methods: Uterus retrieval was performed with extended hysterectomy including bilateral uterine and internal iliac arteries and ovarian veins. After UTx, with vascular anastomoses unilateral to the internal iliac artery and the external iliac vein, the uterus recipients received one of the following: no immunosuppression (n ¼ 4); monotherapy (oral slow release tacrolimus) (n ¼ 4) or induction therapy (antithymocyte globulin) followed by triple therapy (tacrolimus, mycophenolate, corticosteroids; n ¼ 10). Surgical parameters, survival, immunosuppression and rejection patterns were evaluated. main results and the role of chance: The durations of uterus retrieval and recipient surgery were around 3 and 3.5 h, respectively. The total ischemic time was around 3 h. All the recipients and the donors survived the surgery. All the recipients presented rejection to some extent within the first weeks following UTx. In one recipient, the uterus was of normal appearance at the end of the study period. In spite of occasional high (.60 ng/ml) blood levels of tacrolimus, there was no evidence of nephrotoxicity. limitations and reasons for caution: This initial non-human primate allogeneic UTx study indicates that further research is needed to optimize immunosuppression protocols in order to avoid uterine rejection. wider implications of the findings: The findings suggest that allogeneic UTx in primate species is feasible but continued work on this issue is needed.
background: Uterus transplantation (UTx) may provide the first available treatment for women affe... more background: Uterus transplantation (UTx) may provide the first available treatment for women affected by uterine infertility. The present study aimed to further develop a surgical technique for autologous UTx in a non-human primate species and to assess long-term function. methods: Female baboons (n ¼ 16) underwent autologous transplantation of the uterus with the Fallopian tubes and ovaries, performed with a previously published surgical technique (n ¼ 6, Group 1) or using a modified technique (n ¼ 10; Group 2). The uterine arteries were dissected to the proximal end of the anterior branch (Group 1) or the entire (Group 2) internal iliac artery, and the ovarian veins were dissected to the crossing over the ureter (Group 1) or further cranially to include greater lengths and patches of the cava/renal vein (Group 2). Back-table preparation created common venous and arterial ends with arterial anastomosis either end-to-side to the left external iliac artery (Group 1) or end-to-end to the left internal iliac artery (Group 2). results: Overall short-time survival of the animals was 88% (66% in Group 1 and 100% in Group 2). Of all the operated animals, 75% (66% in Group 1 and 80% in Group 2) resumed ovarian cyclicity. Regular menstruation after UTx was demonstrated only in Group 2 (60%). Menstruating animals (n ¼ 6) were each exposed to timed mating for ≥5 menstrual cycles, but pregnancy did not occur. Adhesions and tubal blockage were seen in post-mortem analysis. conclusions: The modified UTx model of Group 2 is a safe procedure and shows resumed long-term uterine function in a majority of the animals, although pregnancy could not be demonstrated.
background: Transplantation of the uterus has been suggested as a treatment of uterine factor inf... more background: Transplantation of the uterus has been suggested as a treatment of uterine factor infertility. This study investigates whether the sheep uterus can resume its capacity to harbour normal pregnancies after autotransplantation by vascular anastomosis. methods: From 14 ewes, the uterus, excluding one uterine horn, was isolated along with its oviduct and ovary and preserved ex vivo and then transplanted back with end-to-side anastomosis of the vessels of the graft to the external iliac vessels. After recovery, the ewes underwent surgical examination and serum progesterone measurements to ascertain healing and ovarian activity. Afterwards, five autotransplanted and five control ewes were placed with a ram for mating. Caesarean sections were performed before the estimated term of pregnancy and data on fetal measures were compared. results: Of the 14 ewes, seven survived surgery with ovarian activity intact and grafts showing normal appearance. Mating occurred in four of five transplanted ewes and in five out of five controls, and three transplanted animals and five control animals conceived. In one transplanted ewe, torsion of the uterus was observed after spontaneous initiation of labour. Foeti from transplanted mothers were comparable in size to those of controls. conclusions: Despite the encountered complications, this is the first report to demonstrate fertility and pregnancies going to term after autotransplantation of the uterus in an animal of a comparable size to the human.
Uterus transplantation (UTx) is the only available treatment for absolute uterine factor infertil... more Uterus transplantation (UTx) is the only available treatment for absolute uterine factor infertility (AUFI), which is caused by either absence (congenital or after hysterectomy) or presence of a non-functioning uterus. Uterus transplantation became a clinical reality after more than 10 years of structured animalbased research. Aside from gestational surrogacy, this procedure is the only alternative for women with AUFI to attain genetic motherhood. In the Middle East, North Africa and Turkey (MENAT) region, out of a population of around 470 million, more than 100,000 women of fertile age are estimated to suffer from AUFI. Introduction of UTx as an infertility treatment in this region will certainly differ in specific countries from ethical, religious and legal standpoints depending on culture and religion. The MENAT region is the cradle of three religions and the geographic area encompasses a variety of cultures and religions with different views on assisted reproduction. In light of these issues, the aim of this article is to give an overview of the research-based development of UTx and its clinical results up until today as well as to explore how UTx would fit into current infertility treatments in the MENAT region, with its existing multifaceted religious perspectives.
BACKGROUND-Twin birth is associated with a higher risk of adverse perinatal outcomes than singlet... more BACKGROUND-Twin birth is associated with a higher risk of adverse perinatal outcomes than singleton birth. It is unclear whether planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy. METHODS-We randomly assigned women between 32 weeks 0 days and 38 weeks 6 days of gestation with twin pregnancy and with the first twin in the cephalic presentation to planned cesarean section or planned vaginal delivery with cesarean only if indicated. Elective delivery was planned between 37 weeks 5 days and 38 weeks 6 days of gestation. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity, with the fetus or infant as the unit of analysis for the statistical comparison. RESULTS-A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. Women in the planned-cesarean-delivery group delivered earlier than did those in the
Objective: To report the 6-month results of the first clinical uterus transplantation (UTx) trial... more 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.
Uterus transplantation research has been conducted toward its introduction in the human as a trea... more Uterus transplantation research has been conducted toward its introduction in the human as a treatment of absolute uterine-factor infertility, which is considered to be the last frontier to conquer for infertility research. In this review we describe the patient populations that may benefit from uterus transplantation. The animal research on uterus transplantation conducted during the past two decades is summarized, and we describe our views regarding a future research-based human attempt. (Fertil Steril Ò 2012;97:1269-76. Ó2012 by American Society for Reproductive Medicine.
Australian and New Zealand Journal of Obstetrics and Gynaecology, 2011
Uterine transplantation (UTx) aims to treat unconditional uterine factor infertility by replacing... more Uterine transplantation (UTx) aims to treat unconditional uterine factor infertility by replacing a non-functioning or nonexisting uterus. After one attempt of UTx in the human 10 years ago, intensive research has been performed. The results of these specific studies on surgical technique, ischaemia-reperfusion injury, immunosuppression and fertility are discussed.
The Australian and New Zealand Journal of Obstetrics and Gynaecology, 1997
The twin reversed-arterial-perfusion (TRAP) sequence found in monozygotic twins is a consequence ... more The twin reversed-arterial-perfusion (TRAP) sequence found in monozygotic twins is a consequence of primary or secondary cardiac development disruption and direct arterioarterial and venovenous placental anastomoses.
The Australian and New Zealand Journal of Obstetrics and Gynaecology, 1997
Described is a case of Schwannoma (neurilemmoma) presenting as Bartholin's duct abscess. Case rep... more Described is a case of Schwannoma (neurilemmoma) presenting as Bartholin's duct abscess. Case report A 59-year-old. gravida 0, para 0, Aboriginal menopausal female was referred for evaluation with a presumed Bartholin's duct abscess. She reported that she noticed a small lump in her left vulvar region 2 years prior lo admission. In the week prior to her presentation. she reported pain, tenderness. and redness in the area. Physical examination revealed a red, tender and fluctuant mass approximately 5 cm in diameter in the left Bartholin's gland area. With the diagnosis of a Bartholin's duct abscess, a simple excision was performed under general anaesthesia without complications. Putholofp Figwe I. Histological section of Bartholin's gland showing cell nuclei with Smooth bodem and Uniform chromatin density. I. Registrar. 2. Resident.
Background Uterus transplantation is the fi rst available treatment for absolute uterine infertil... more Background Uterus transplantation is the fi rst 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 fi rst 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 fi rst 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 fl ows 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 fi rst 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.
Is it possible to perform allogeneic uterus transplantation (UTx) with a donation from a live don... more Is it possible to perform allogeneic uterus transplantation (UTx) with a donation from a live donor in a non-human primate species and what immunosuppression is needed to prevent rejection? summary answer: Allogeneic UTx in the baboon is a donor-and recipient-safe surgical procedure; immunosuppression with induction therapy and a triple protocol should be used. what is known already: UTx may become a treatment for absolute uterine factor infertility. Autologous UTx models have been developed in non-human primates with reports on long-term survival of the uterine grafts. study design, size and duration: This experimental study included 18 female baboons as uterus donors and 18 female baboons as uterus recipients. The follow-up time was 5-8 weeks. participants/materials, setting and methods: Uterus retrieval was performed with extended hysterectomy including bilateral uterine and internal iliac arteries and ovarian veins. After UTx, with vascular anastomoses unilateral to the internal iliac artery and the external iliac vein, the uterus recipients received one of the following: no immunosuppression (n ¼ 4); monotherapy (oral slow release tacrolimus) (n ¼ 4) or induction therapy (antithymocyte globulin) followed by triple therapy (tacrolimus, mycophenolate, corticosteroids; n ¼ 10). Surgical parameters, survival, immunosuppression and rejection patterns were evaluated. main results and the role of chance: The durations of uterus retrieval and recipient surgery were around 3 and 3.5 h, respectively. The total ischemic time was around 3 h. All the recipients and the donors survived the surgery. All the recipients presented rejection to some extent within the first weeks following UTx. In one recipient, the uterus was of normal appearance at the end of the study period. In spite of occasional high (.60 ng/ml) blood levels of tacrolimus, there was no evidence of nephrotoxicity. limitations and reasons for caution: This initial non-human primate allogeneic UTx study indicates that further research is needed to optimize immunosuppression protocols in order to avoid uterine rejection. wider implications of the findings: The findings suggest that allogeneic UTx in primate species is feasible but continued work on this issue is needed.
background: Uterus transplantation (UTx) may provide the first available treatment for women affe... more background: Uterus transplantation (UTx) may provide the first available treatment for women affected by uterine infertility. The present study aimed to further develop a surgical technique for autologous UTx in a non-human primate species and to assess long-term function. methods: Female baboons (n ¼ 16) underwent autologous transplantation of the uterus with the Fallopian tubes and ovaries, performed with a previously published surgical technique (n ¼ 6, Group 1) or using a modified technique (n ¼ 10; Group 2). The uterine arteries were dissected to the proximal end of the anterior branch (Group 1) or the entire (Group 2) internal iliac artery, and the ovarian veins were dissected to the crossing over the ureter (Group 1) or further cranially to include greater lengths and patches of the cava/renal vein (Group 2). Back-table preparation created common venous and arterial ends with arterial anastomosis either end-to-side to the left external iliac artery (Group 1) or end-to-end to the left internal iliac artery (Group 2). results: Overall short-time survival of the animals was 88% (66% in Group 1 and 100% in Group 2). Of all the operated animals, 75% (66% in Group 1 and 80% in Group 2) resumed ovarian cyclicity. Regular menstruation after UTx was demonstrated only in Group 2 (60%). Menstruating animals (n ¼ 6) were each exposed to timed mating for ≥5 menstrual cycles, but pregnancy did not occur. Adhesions and tubal blockage were seen in post-mortem analysis. conclusions: The modified UTx model of Group 2 is a safe procedure and shows resumed long-term uterine function in a majority of the animals, although pregnancy could not be demonstrated.
background: Transplantation of the uterus has been suggested as a treatment of uterine factor inf... more background: Transplantation of the uterus has been suggested as a treatment of uterine factor infertility. This study investigates whether the sheep uterus can resume its capacity to harbour normal pregnancies after autotransplantation by vascular anastomosis. methods: From 14 ewes, the uterus, excluding one uterine horn, was isolated along with its oviduct and ovary and preserved ex vivo and then transplanted back with end-to-side anastomosis of the vessels of the graft to the external iliac vessels. After recovery, the ewes underwent surgical examination and serum progesterone measurements to ascertain healing and ovarian activity. Afterwards, five autotransplanted and five control ewes were placed with a ram for mating. Caesarean sections were performed before the estimated term of pregnancy and data on fetal measures were compared. results: Of the 14 ewes, seven survived surgery with ovarian activity intact and grafts showing normal appearance. Mating occurred in four of five transplanted ewes and in five out of five controls, and three transplanted animals and five control animals conceived. In one transplanted ewe, torsion of the uterus was observed after spontaneous initiation of labour. Foeti from transplanted mothers were comparable in size to those of controls. conclusions: Despite the encountered complications, this is the first report to demonstrate fertility and pregnancies going to term after autotransplantation of the uterus in an animal of a comparable size to the human.
Uterus transplantation (UTx) is the only available treatment for absolute uterine factor infertil... more Uterus transplantation (UTx) is the only available treatment for absolute uterine factor infertility (AUFI), which is caused by either absence (congenital or after hysterectomy) or presence of a non-functioning uterus. Uterus transplantation became a clinical reality after more than 10 years of structured animalbased research. Aside from gestational surrogacy, this procedure is the only alternative for women with AUFI to attain genetic motherhood. In the Middle East, North Africa and Turkey (MENAT) region, out of a population of around 470 million, more than 100,000 women of fertile age are estimated to suffer from AUFI. Introduction of UTx as an infertility treatment in this region will certainly differ in specific countries from ethical, religious and legal standpoints depending on culture and religion. The MENAT region is the cradle of three religions and the geographic area encompasses a variety of cultures and religions with different views on assisted reproduction. In light of these issues, the aim of this article is to give an overview of the research-based development of UTx and its clinical results up until today as well as to explore how UTx would fit into current infertility treatments in the MENAT region, with its existing multifaceted religious perspectives.
BACKGROUND-Twin birth is associated with a higher risk of adverse perinatal outcomes than singlet... more BACKGROUND-Twin birth is associated with a higher risk of adverse perinatal outcomes than singleton birth. It is unclear whether planned cesarean section results in a lower risk of adverse outcomes than planned vaginal delivery in twin pregnancy. METHODS-We randomly assigned women between 32 weeks 0 days and 38 weeks 6 days of gestation with twin pregnancy and with the first twin in the cephalic presentation to planned cesarean section or planned vaginal delivery with cesarean only if indicated. Elective delivery was planned between 37 weeks 5 days and 38 weeks 6 days of gestation. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity, with the fetus or infant as the unit of analysis for the statistical comparison. RESULTS-A total of 1398 women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406 women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal-delivery group. Women in the planned-cesarean-delivery group delivered earlier than did those in the
Objective: To report the 6-month results of the first clinical uterus transplantation (UTx) trial... more 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.
Uterus transplantation research has been conducted toward its introduction in the human as a trea... more Uterus transplantation research has been conducted toward its introduction in the human as a treatment of absolute uterine-factor infertility, which is considered to be the last frontier to conquer for infertility research. In this review we describe the patient populations that may benefit from uterus transplantation. The animal research on uterus transplantation conducted during the past two decades is summarized, and we describe our views regarding a future research-based human attempt. (Fertil Steril Ò 2012;97:1269-76. Ó2012 by American Society for Reproductive Medicine.
Australian and New Zealand Journal of Obstetrics and Gynaecology, 2011
Uterine transplantation (UTx) aims to treat unconditional uterine factor infertility by replacing... more Uterine transplantation (UTx) aims to treat unconditional uterine factor infertility by replacing a non-functioning or nonexisting uterus. After one attempt of UTx in the human 10 years ago, intensive research has been performed. The results of these specific studies on surgical technique, ischaemia-reperfusion injury, immunosuppression and fertility are discussed.
The Australian and New Zealand Journal of Obstetrics and Gynaecology, 1997
The twin reversed-arterial-perfusion (TRAP) sequence found in monozygotic twins is a consequence ... more The twin reversed-arterial-perfusion (TRAP) sequence found in monozygotic twins is a consequence of primary or secondary cardiac development disruption and direct arterioarterial and venovenous placental anastomoses.
The Australian and New Zealand Journal of Obstetrics and Gynaecology, 1997
Described is a case of Schwannoma (neurilemmoma) presenting as Bartholin's duct abscess. Case rep... more Described is a case of Schwannoma (neurilemmoma) presenting as Bartholin's duct abscess. Case report A 59-year-old. gravida 0, para 0, Aboriginal menopausal female was referred for evaluation with a presumed Bartholin's duct abscess. She reported that she noticed a small lump in her left vulvar region 2 years prior lo admission. In the week prior to her presentation. she reported pain, tenderness. and redness in the area. Physical examination revealed a red, tender and fluctuant mass approximately 5 cm in diameter in the left Bartholin's gland area. With the diagnosis of a Bartholin's duct abscess, a simple excision was performed under general anaesthesia without complications. Putholofp Figwe I. Histological section of Bartholin's gland showing cell nuclei with Smooth bodem and Uniform chromatin density. I. Registrar. 2. Resident.
Background Uterus transplantation is the fi rst available treatment for absolute uterine infertil... more Background Uterus transplantation is the fi rst 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 fi rst 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 fi rst 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 fl ows 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 fi rst 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.
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