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The healthy 2,550-g infant girl was born in December 2017 via a planned cesarean delivery at about 36 weeks’ gestation. Her mother, the transplant recipient, has congenital absence of the uterus from Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Removal of the transplanted uterus at the time of delivery allowed the woman to stop taking the immunosuppressive medications that she’d been on since the transplantation, which had been performed less than a year and a half previously.
The uterus had been retrieved from a 45-year-old donor who experienced a subarachnoid hemorrhage and subsequent brain death. The donor had three vaginal deliveries, and no history of reproductive issues or sexually transmitted infection, wrote Dani Ejzenberg, MD, and his colleagues at the University of São Paolo, Brazil.
The retrieval and transplantation procedures were done at the university’s hospital, in accordance with a research protocol approved by the university, a Brazilian national ethics committee, and the country’s national transplantation system. Thorough psychological evaluation was part of the research protocol, and the patient and her partner had monthly psychological counseling from therapists with expertise in transplant and fertility, wrote Dr. Ejzenberg and his colleagues.
In preparation for the transplantation, which occurred when the recipient was 32 years old, she had in vitro fertilization several months before the procedure. Eight “good-quality” blastocysts were retrieved and cryopreserved, said Dr. Ejzenberg and his coauthors. The recipient’s menstrual cycle resumed 37 days after transplantation, and one of the cryopreserved embryos was transferred about 7 months after the uterine transplantation procedure, resulting in the pregnancy.
The donor and recipient were matched only by ABO blood type, with no further tissue typing being done, wrote Dr. Ejzenberg and his colleagues. The immunosuppressive regimen paralleled that used in previous successful uterine transplantations from live donors in Sweden, with induction via 1 g intraoperative methylprednisolone and 1.5 mg/kg of thymoglobulin. Thereafter, the recipient received tacrolimus titrated to a trough of 8-10 ng/mL, along with mycophenolate mofetil 720 mg twice daily. Five months after her transplantation, the mycophenolate mofetil was replaced with 100 mg azathioprine and 10 mg prednisone daily, a regimen that she stayed on until cesarean delivery.
Broad-spectrum antibiotics, antifungals, and anthelmintics were administered during the patient’s hospital stay. Prophylactic antibiotics were continued for 6 months, and antiviral medication was given prophylactically for 3 months. The recipient had one episode of vaginal discharge, treated with antifungal medication, and one episode of pyelonephritis during pregnancy, treated during a brief inpatient stay.
Enoxaparin and aspirin were used for inpatient venous thromboembolism prophylaxis, and heparin and aspirin thereafter. Aspirin was discontinued at 34 weeks, and heparin the day before delivery.
Swedish and American teams involved in uterine transplantation are working to develop standardization of surgical techniques, immunosuppression protocol, and methods to monitor rejection.
However, pointed out Dr. Ejzenberg and his coauthors, some technical aspects were unique to the deceased donor transplantation. These included managing total ischemic time for the donor tissue because heart, liver, and kidney retrieval all were given priority.
One downstream effect of this was longer-than-expected procedure and anesthesia time for the recipient, because coordinating donor uterus retrieval and preparation of the surgical bed in the live recipient was tricky; surgery time was about 10.5 hours. Also, there was prolonged warm-ischemia time because six small-vessel anastomoses needed to be performed, wrote the investigators.
After reperfusion of the implanted uterus, there was brisk bleeding from a number of small vessels that had not been ligated on retrieval because of concerns about ischemic time. These were identified and sutured or cauterized, but the total estimated blood loss during the procedures was 1,200 mL, with most of that coming from the uterus, said Dr. Ejzenberg and his coauthors.
The donor uterus had a total of almost 8 hours of ischemic time, exceeding the previously published live donor maximum uterine ischemic time of 3 hours, 25 minutes. This experience can inform surgical teams considering future uterine transplantations.
Dr. Ejzenberg and his colleagues also said that they cast a broad net with immunosuppression, erring on the side of caution. With more experience may come the ability to scale back immunosuppressive regimens, they noted.
The explantation of the uterus and associated blood vessels after delivery afforded the opportunity for pathological examination of the uterus and other tissues, which showed no signs of rejection. The uterine arteries did have mild intimal fibrous hyperplasia that was likely related to the age of the donor, said Dr. Ejzenberg and his coauthors.
This successful completion of a deceased-donor uterine transplantation demonstrates the feasibility of accessing “a much wider potential donor population, as the numbers of people willing and committed to donate organs upon their own deaths are far larger than those of potential live donors,” wrote Dr. Ejzenberg and his colleagues. “Further incidental but substantial benefits of the use of deceased donors include lower costs and avoidance of live donors’ surgical risks.”
In 2011, a uterine transplantation from a deceased donor resulted in pregnancy, but ended in miscarriage.
Funding was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo and the Hospital das Clínicas of University of São Paulo School of Medicine. Dr. Ejzenberg and his colleagues reported that they had no conflicts of interest.
SOURCE: Ejzenberg D. et al. Lancet. 2018 Dec. doi: 10.1015/S0140-6736(18)31766-5.
Among the advances seen in this deceased-donor uterus transplant is a demonstration that ischemic time of nearly 8 hours – four times the average seen in live donation – does not preclude a successful transplantation. 
Also, the timetable for transplantation seen here did not involve the year-long waiting period between transplantation and pregnancy that has been the norm in live uterine transplantation.
However, uterine transplantation, whether from a living or deceased donor, is still in its early stages. Among the many unsettled questions are whether live or deceased donor transplantations yield superior results. Additional technical aspects to be further studied include best surgical approach for the donor uterus, best anastomosis technique, and optimal immunosuppression and antimicrobial/antifungal/antiviral regimens.
Continued work needs to be done to standardize these and other aspects of the peri- and postoperative care of women undergoing uterine transplantation.
In addition, long-term tracking of children born from transplanted uteri is needed, so outcomes can be assessed over the lifespan.
Going forward, it could be that uterine transplantation may be offered to an expanded cohort of women, including those with bulky, nonoperable uterine fibroids, those who have received pelvic radiotherapy, and even those who have had multiple unexplained problems with implantation during fertility treatments. In all cases, researchers should work toward achieving the highest live birth rate at the lowest risk to donors and patients, while also working to make more organs available; establishing registries, and encouraging prospective registration and transparent reporting of uterus transplantation procedures.
Cesar Diaz-Garcia, MD, is medical director of IVI-London, and Antonio Pellicer, MD, is professor of obstetrics and gynecology at the University of Valencia, Spain. These remarks were drawn from their editorial accompanying the report by Ejzenberg et al. (Lancet. 2018 Dec. doi: 10.1016/50140-6736(18)32106-8).
Among the advances seen in this deceased-donor uterus transplant is a demonstration that ischemic time of nearly 8 hours – four times the average seen in live donation – does not preclude a successful transplantation.
Also, the timetable for transplantation seen here did not involve the year-long waiting period between transplantation and pregnancy that has been the norm in live uterine transplantation.
However, uterine transplantation, whether from a living or deceased donor, is still in its early stages. Among the many unsettled questions are whether live or deceased donor transplantations yield superior results. Additional technical aspects to be further studied include best surgical approach for the donor uterus, best anastomosis technique, and optimal immunosuppression and antimicrobial/antifungal/antiviral regimens.
Continued work needs to be done to standardize these and other aspects of the peri- and postoperative care of women undergoing uterine transplantation.
In addition, long-term tracking of children born from transplanted uteri is needed, so outcomes can be assessed over the lifespan.
Going forward, it could be that uterine transplantation may be offered to an expanded cohort of women, including those with bulky, nonoperable uterine fibroids, those who have received pelvic radiotherapy, and even those who have had multiple unexplained problems with implantation during fertility treatments. In all cases, researchers should work toward achieving the highest live birth rate at the lowest risk to donors and patients, while also working to make more organs available; establishing registries, and encouraging prospective registration and transparent reporting of uterus transplantation procedures.
Cesar Diaz-Garcia, MD, is medical director of IVI-London, and Antonio Pellicer, MD, is professor of obstetrics and gynecology at the University of Valencia, Spain. These remarks were drawn from their editorial accompanying the report by Ejzenberg et al. (Lancet. 2018 Dec. doi: 10.1016/50140-6736(18)32106-8).
Among the advances seen in this deceased-donor uterus transplant is a demonstration that ischemic time of nearly 8 hours – four times the average seen in live donation – does not preclude a successful transplantation.
Also, the timetable for transplantation seen here did not involve the year-long waiting period between transplantation and pregnancy that has been the norm in live uterine transplantation.
However, uterine transplantation, whether from a living or deceased donor, is still in its early stages. Among the many unsettled questions are whether live or deceased donor transplantations yield superior results. Additional technical aspects to be further studied include best surgical approach for the donor uterus, best anastomosis technique, and optimal immunosuppression and antimicrobial/antifungal/antiviral regimens.
Continued work needs to be done to standardize these and other aspects of the peri- and postoperative care of women undergoing uterine transplantation.
In addition, long-term tracking of children born from transplanted uteri is needed, so outcomes can be assessed over the lifespan.
Going forward, it could be that uterine transplantation may be offered to an expanded cohort of women, including those with bulky, nonoperable uterine fibroids, those who have received pelvic radiotherapy, and even those who have had multiple unexplained problems with implantation during fertility treatments. In all cases, researchers should work toward achieving the highest live birth rate at the lowest risk to donors and patients, while also working to make more organs available; establishing registries, and encouraging prospective registration and transparent reporting of uterus transplantation procedures.
Cesar Diaz-Garcia, MD, is medical director of IVI-London, and Antonio Pellicer, MD, is professor of obstetrics and gynecology at the University of Valencia, Spain. These remarks were drawn from their editorial accompanying the report by Ejzenberg et al. (Lancet. 2018 Dec. doi: 10.1016/50140-6736(18)32106-8).
The healthy 2,550-g infant girl was born in December 2017 via a planned cesarean delivery at about 36 weeks’ gestation. Her mother, the transplant recipient, has congenital absence of the uterus from Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Removal of the transplanted uterus at the time of delivery allowed the woman to stop taking the immunosuppressive medications that she’d been on since the transplantation, which had been performed less than a year and a half previously.
The uterus had been retrieved from a 45-year-old donor who experienced a subarachnoid hemorrhage and subsequent brain death. The donor had three vaginal deliveries, and no history of reproductive issues or sexually transmitted infection, wrote Dani Ejzenberg, MD, and his colleagues at the University of São Paolo, Brazil.
The retrieval and transplantation procedures were done at the university’s hospital, in accordance with a research protocol approved by the university, a Brazilian national ethics committee, and the country’s national transplantation system. Thorough psychological evaluation was part of the research protocol, and the patient and her partner had monthly psychological counseling from therapists with expertise in transplant and fertility, wrote Dr. Ejzenberg and his colleagues.
In preparation for the transplantation, which occurred when the recipient was 32 years old, she had in vitro fertilization several months before the procedure. Eight “good-quality” blastocysts were retrieved and cryopreserved, said Dr. Ejzenberg and his coauthors. The recipient’s menstrual cycle resumed 37 days after transplantation, and one of the cryopreserved embryos was transferred about 7 months after the uterine transplantation procedure, resulting in the pregnancy.
The donor and recipient were matched only by ABO blood type, with no further tissue typing being done, wrote Dr. Ejzenberg and his colleagues. The immunosuppressive regimen paralleled that used in previous successful uterine transplantations from live donors in Sweden, with induction via 1 g intraoperative methylprednisolone and 1.5 mg/kg of thymoglobulin. Thereafter, the recipient received tacrolimus titrated to a trough of 8-10 ng/mL, along with mycophenolate mofetil 720 mg twice daily. Five months after her transplantation, the mycophenolate mofetil was replaced with 100 mg azathioprine and 10 mg prednisone daily, a regimen that she stayed on until cesarean delivery.
Broad-spectrum antibiotics, antifungals, and anthelmintics were administered during the patient’s hospital stay. Prophylactic antibiotics were continued for 6 months, and antiviral medication was given prophylactically for 3 months. The recipient had one episode of vaginal discharge, treated with antifungal medication, and one episode of pyelonephritis during pregnancy, treated during a brief inpatient stay.
Enoxaparin and aspirin were used for inpatient venous thromboembolism prophylaxis, and heparin and aspirin thereafter. Aspirin was discontinued at 34 weeks, and heparin the day before delivery.
Swedish and American teams involved in uterine transplantation are working to develop standardization of surgical techniques, immunosuppression protocol, and methods to monitor rejection.
However, pointed out Dr. Ejzenberg and his coauthors, some technical aspects were unique to the deceased donor transplantation. These included managing total ischemic time for the donor tissue because heart, liver, and kidney retrieval all were given priority.
One downstream effect of this was longer-than-expected procedure and anesthesia time for the recipient, because coordinating donor uterus retrieval and preparation of the surgical bed in the live recipient was tricky; surgery time was about 10.5 hours. Also, there was prolonged warm-ischemia time because six small-vessel anastomoses needed to be performed, wrote the investigators.
After reperfusion of the implanted uterus, there was brisk bleeding from a number of small vessels that had not been ligated on retrieval because of concerns about ischemic time. These were identified and sutured or cauterized, but the total estimated blood loss during the procedures was 1,200 mL, with most of that coming from the uterus, said Dr. Ejzenberg and his coauthors.
The donor uterus had a total of almost 8 hours of ischemic time, exceeding the previously published live donor maximum uterine ischemic time of 3 hours, 25 minutes. This experience can inform surgical teams considering future uterine transplantations.
Dr. Ejzenberg and his colleagues also said that they cast a broad net with immunosuppression, erring on the side of caution. With more experience may come the ability to scale back immunosuppressive regimens, they noted.
The explantation of the uterus and associated blood vessels after delivery afforded the opportunity for pathological examination of the uterus and other tissues, which showed no signs of rejection. The uterine arteries did have mild intimal fibrous hyperplasia that was likely related to the age of the donor, said Dr. Ejzenberg and his coauthors.
This successful completion of a deceased-donor uterine transplantation demonstrates the feasibility of accessing “a much wider potential donor population, as the numbers of people willing and committed to donate organs upon their own deaths are far larger than those of potential live donors,” wrote Dr. Ejzenberg and his colleagues. “Further incidental but substantial benefits of the use of deceased donors include lower costs and avoidance of live donors’ surgical risks.”
In 2011, a uterine transplantation from a deceased donor resulted in pregnancy, but ended in miscarriage.
Funding was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo and the Hospital das Clínicas of University of São Paulo School of Medicine. Dr. Ejzenberg and his colleagues reported that they had no conflicts of interest.
SOURCE: Ejzenberg D. et al. Lancet. 2018 Dec. doi: 10.1015/S0140-6736(18)31766-5.
The healthy 2,550-g infant girl was born in December 2017 via a planned cesarean delivery at about 36 weeks’ gestation. Her mother, the transplant recipient, has congenital absence of the uterus from Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Removal of the transplanted uterus at the time of delivery allowed the woman to stop taking the immunosuppressive medications that she’d been on since the transplantation, which had been performed less than a year and a half previously.
The uterus had been retrieved from a 45-year-old donor who experienced a subarachnoid hemorrhage and subsequent brain death. The donor had three vaginal deliveries, and no history of reproductive issues or sexually transmitted infection, wrote Dani Ejzenberg, MD, and his colleagues at the University of São Paolo, Brazil.
The retrieval and transplantation procedures were done at the university’s hospital, in accordance with a research protocol approved by the university, a Brazilian national ethics committee, and the country’s national transplantation system. Thorough psychological evaluation was part of the research protocol, and the patient and her partner had monthly psychological counseling from therapists with expertise in transplant and fertility, wrote Dr. Ejzenberg and his colleagues.
In preparation for the transplantation, which occurred when the recipient was 32 years old, she had in vitro fertilization several months before the procedure. Eight “good-quality” blastocysts were retrieved and cryopreserved, said Dr. Ejzenberg and his coauthors. The recipient’s menstrual cycle resumed 37 days after transplantation, and one of the cryopreserved embryos was transferred about 7 months after the uterine transplantation procedure, resulting in the pregnancy.
The donor and recipient were matched only by ABO blood type, with no further tissue typing being done, wrote Dr. Ejzenberg and his colleagues. The immunosuppressive regimen paralleled that used in previous successful uterine transplantations from live donors in Sweden, with induction via 1 g intraoperative methylprednisolone and 1.5 mg/kg of thymoglobulin. Thereafter, the recipient received tacrolimus titrated to a trough of 8-10 ng/mL, along with mycophenolate mofetil 720 mg twice daily. Five months after her transplantation, the mycophenolate mofetil was replaced with 100 mg azathioprine and 10 mg prednisone daily, a regimen that she stayed on until cesarean delivery.
Broad-spectrum antibiotics, antifungals, and anthelmintics were administered during the patient’s hospital stay. Prophylactic antibiotics were continued for 6 months, and antiviral medication was given prophylactically for 3 months. The recipient had one episode of vaginal discharge, treated with antifungal medication, and one episode of pyelonephritis during pregnancy, treated during a brief inpatient stay.
Enoxaparin and aspirin were used for inpatient venous thromboembolism prophylaxis, and heparin and aspirin thereafter. Aspirin was discontinued at 34 weeks, and heparin the day before delivery.
Swedish and American teams involved in uterine transplantation are working to develop standardization of surgical techniques, immunosuppression protocol, and methods to monitor rejection.
However, pointed out Dr. Ejzenberg and his coauthors, some technical aspects were unique to the deceased donor transplantation. These included managing total ischemic time for the donor tissue because heart, liver, and kidney retrieval all were given priority.
One downstream effect of this was longer-than-expected procedure and anesthesia time for the recipient, because coordinating donor uterus retrieval and preparation of the surgical bed in the live recipient was tricky; surgery time was about 10.5 hours. Also, there was prolonged warm-ischemia time because six small-vessel anastomoses needed to be performed, wrote the investigators.
After reperfusion of the implanted uterus, there was brisk bleeding from a number of small vessels that had not been ligated on retrieval because of concerns about ischemic time. These were identified and sutured or cauterized, but the total estimated blood loss during the procedures was 1,200 mL, with most of that coming from the uterus, said Dr. Ejzenberg and his coauthors.
The donor uterus had a total of almost 8 hours of ischemic time, exceeding the previously published live donor maximum uterine ischemic time of 3 hours, 25 minutes. This experience can inform surgical teams considering future uterine transplantations.
Dr. Ejzenberg and his colleagues also said that they cast a broad net with immunosuppression, erring on the side of caution. With more experience may come the ability to scale back immunosuppressive regimens, they noted.
The explantation of the uterus and associated blood vessels after delivery afforded the opportunity for pathological examination of the uterus and other tissues, which showed no signs of rejection. The uterine arteries did have mild intimal fibrous hyperplasia that was likely related to the age of the donor, said Dr. Ejzenberg and his coauthors.
This successful completion of a deceased-donor uterine transplantation demonstrates the feasibility of accessing “a much wider potential donor population, as the numbers of people willing and committed to donate organs upon their own deaths are far larger than those of potential live donors,” wrote Dr. Ejzenberg and his colleagues. “Further incidental but substantial benefits of the use of deceased donors include lower costs and avoidance of live donors’ surgical risks.”
In 2011, a uterine transplantation from a deceased donor resulted in pregnancy, but ended in miscarriage.
Funding was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo and the Hospital das Clínicas of University of São Paulo School of Medicine. Dr. Ejzenberg and his colleagues reported that they had no conflicts of interest.
SOURCE: Ejzenberg D. et al. Lancet. 2018 Dec. doi: 10.1015/S0140-6736(18)31766-5.
FROM THE LANCET