First Live Birth After Uterus Transplant From Deceased Donor

A woman in Brazil has become the first person in the world to have a baby following a uterus transplant from a deceased donor. The event is considered a milestone in a field where live uterus donors are in very short supply.






"The use of deceased donors could greatly broaden access to this treatment, and our results provide proof-of-concept for a new option for women with uterine infertility," said lead author Dani Ejzenberg, PhD, department of Obstetrics and Gynecology, Hospital das Clínicas, Faculty Of Medicine, University of São Paulo, in a press statement from The Lancet, which published details of the case this week.

Ejzenberg and colleagues report that the successful live birth, which took place a year ago at the Hospital das Clínicas, was to a 32-year-old woman who was born without a uterus as the result of congenital uterine agenesis, or Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, which affects 1 in 4500 women.

The uterus donor was a woman who died at the age of 45 of subarachnoid hemorrhage who had had three previous vaginal deliveries.

At the time of writing of the manuscript, the healthy baby girl had reached the age of 7 months and 20 days, weighed 7.2 kg (15 lbs, 14 oz), and was continuing to breastfeed. "[The baby], along with the mother, remains healthy and developing normally 7 months postpartum," the authors report.

As many as 10 previous tries at live births following uterus transplants from deceased donors have been attempted but none have succeeded.

"In a context in which the scarcity of human data is still the norm, [the report] reveals a breakthrough in the field of uterus transplantation," say Cesar Diaz-Garcia, MD, Nuffield Department of Women's and Reproductive Health, University of Oxford, UK, and Antonio Pellicer, MD, PhD, Department of Pediatrics, Obstetrics and Gynecology, University of Valencia, Spain, in an accompanying editorial.

Developments in Uterus Transplantation Are Recent

The concept of any kind of uterus transplant is relatively new, with the first transplant from a living donor conducted in Gothenburg, Sweden, in 2013, and the first live birth resulting from a living donor transplant taking place in 2015.

Since then, there have been 39 procedures resulting in 11 live births. But uteri from living donors are currently only typically available from women who are relatives of, or close to, the recipient, substantially limiting options for many infertile women.

"The need for a live donor is a major limitation as donors are rare, typically being willing and eligible family members or close friends," Ejzenberg and colleagues report.

"The numbers of people willing and committed to donate organs upon their own deaths are far larger than those of live donors, offering a much wider potential donor population," they add.

And, said Ejzenberg in an interview with Medscape's Portuguese site, there is potential to grow the pool of likely donors further by increasing the age limit at which uteri can be donated.

"We are thinking of raising the donor's maximum age to 50 years," he told Medscape.

"In the first successful case, in Sweden, the [living] donor was 61 years old; the literature reports cases of gestation in uteri of women up to 70 years."

"Apparently, age does not do much damage to the organ as long as the patient is not a smoker or has no underlying diseases that may compromise the vessels...Uterine function remains adequate," Ejzenberg explained.

The Breakthrough Case: IVF Followed by Successful Delivery

In the current case, the recipient, at 4 months prior to transplant, underwent one cycle of in vitro fertilization (IVF), which produced eight fertilized eggs that were then frozen.

The donor uterus was then transplanted in a 10.5-hour surgery, a complex process during which the uterus was attached to the recipient's veins, ligaments, and vaginal canal.

There was a loss of 1200 mL of blood during surgery, mostly from the transplanted organ. The observed bleeding was high but manageable and the uterus had good perfusion.

Post-surgery, the recipient spent 2 days in intensive care followed by 6 days in a specialized transplant ward.

During recovery, an intensive regimen of five immunosuppression drugs were started with prednisolone and thymoglobulin, and continued with tacrolimus and mycophenolate mofetil (MMF) until 5 months' post-transplantation, when MMF was replaced with azathioprine to prepare for embryo transfer.

At this time point, the uterus showed no signs of rejection and the recipient experienced regular menstruation.

A single embryo was transferred at 7 months post-transplantation, which the authors note was significantly earlier than in previous uterus transplants using deceased donors, where embryo transfers were performed at about 12 months.

The researchers had, in fact, planned to implant the embryo at 6 months, but the endometrium was not thick enough at that stage, so the procedure was postponed for 1 month.

Ten days after embryo transfer, the pregnancy was confirmed and proceeded without incident, aside from a kidney infection at 32 weeks treated with antibiotics in hospital.

Ultrasound scans showed no fetal anomalies, and the infant girl was delivered at around 36 weeks by caesarean section on December 15, 2017.

The baby weighed about 2.55 kg (6 pounds), and the transplanted uterus was also removed during delivery, with no anomalies observed.

"Looking ahead, we are not evaluating leaving the uterus in for the rest of [the patient's] life, but it may be possible to have more than one gestation," Ejzenberg explained to Medscape.

"It is quite acceptable to think about leaving the uterus with immunosuppression for years. In Sweden, they have had two pregnancies from an immunosuppressed patient with the same transplanted organ (from a living donor). Our patient's immunosuppression time was approximately 15 months and there were no problems," he said.


The Uterus Is a "Sturdy Organ"

The uterus was extracted from the deceased donor after the heart, liver, and kidneys, and coordination problems caused a longer ischemic time for the uterus than planned.

The duration of cold ischemia, between the clamping of the aorta until positioning of the organ, was 6 hours, 20 minutes, and warm ischemia time — between positioning the uterus in the cavity until vascular anastomosis — was 1 hour, 30 minutes.

This indicates that a human uterus from a deceased donor can remain functional after ischemia for around double the time (approximately 8 hours) previously described for organs from a living donor (around 3.5 hours).

"The uterus really is a sturdy organ," said surgeon Wellington Andraus, MD, PhD, coordinator, Digestive Organ Transplantation, Faculty Of Medicine, University of São Paulo.

And, Andraus told Medscape's Portuguese site, "With other organs such as the heart, kidney, and liver, perfusion pumps are used, [and this is] something that can probably be applied to the uterus later."


Possible Important Benefits From Deceased Donors

Although more time is needed to understand the long-term outcomes of delivery with uterus transplantation from a deceased donor, the authors note some potentially important advantages, in addition to the opening up of a vastly larger potential pool of donors.

"Further incidental but substantial benefits of the use of deceased donors include lower costs and avoidance of live donors' surgical risks," they explain.

Looking ahead, however, there are many unanswered questions that remain to be addressed, the editorialists point out.

These "range from surgical techniques, including open versus laparoscopic retrieval of the uterus and type of vessels used for anastomosis (internal iliac branches versus ovarian versus both), to immunosuppression protocols and adjuvant therapies before or after the procedure — and before or during pregnancy."

Ejzenberg and coauthors themselves suggest a modification in the number of venous anastomoses that can be used in the future to improve venous drainage.

The editorialists add that postoperative control should "be standardized" and external validity of the timing and scoring of rejection scales needs to be assessed.

And long-term outcomes of the offspring need to be recorded, they stress.

Once such issues are ironed out, uterus transplantation could feasibly be expanded to include more types of patients, including those with inoperable fibroids, those who have received pelvic radiotherapy, or those with unexplained implantation failures, Garcia and Pellicer suggest.

"All in all, the research to be done in this field (whether from alive or deceased donors) should maximize the live birth rate, minimize the risks for patients involved in the procedures (donor, recipient, and unborn child), and increase the availability of organs," they conclude.


Could Transgender Women Carry Children One Day?

In the interview with Medscape's Portuguese site, Andraus elaborated on some of the ethical issues that have emerged with uterus transplants.

"When you have contact with women who cannot get pregnant because they do not have a womb, you see how important it is to them, to the family, to the couple. They do not have the slightest doubt that they want to undergo transplantation."

And the desire to carry a child is not exclusive to those born female. The news about uterine transplants has already raised the interest of trans women (those born male but who have transitioned to female).

"Technically it could be developed for this group of people. Today it is not possible because there is no technique available for this. We do not know if a man's body would carry a pregnancy, if testosterone could be a problem. There are no studies yet," lead author Ejzenberg told Medscape.

Andraus said it is technically possible to transplant a uterus into a trans woman.

"At the last World Congress this issue was addressed, and it was agreed that for ethics and community acceptance no one would list such patients. But in people who have already had sex-change surgery it is technically possible to place a uterus."

"The patient has a neovagina, the pelvic vessels are similar, the pelvis may be a little narrower in man, but it is possible to make a connection with the neovagina of the transplant and implant in the vessels of the pelvis. There would be no technical impediment, but no group has yet asked for permission to study this," Ejzenberg concluded.

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