Houston, Texas, USA : Eleven babies have been born through uterine transplants of live donors, but no births had occurred from a uterus of a deceased donor. The mother became pregnant seven months after the transplant surgery.
A 32-year-old woman in Brazil who received a uterus transplant from a deceased donor successfully carried out a pregnancy and gave birth to a healthy baby, researchers reported on Wednesday. The case was announced in a published research paper by The Lancet medical journal.
Performed in 2016 in Brazil, the transplant could provide new hope to thousands of women who are unable to have children due to uterine problems. Currently, only 10 known cases of uterus transplants from deceased donors exist, but all had failed to produce a live birth.
The recipient was born without a uterus, due to a condition called Mayer-Rokitansky-Küster-Hauser syndrome. The donor was 45-years-old and had borne three children in her lifetime before dying of a stroke.
In a transplant surgery that lasted more than ten hours, doctors had to connect the donor’s uterus with the veins, arteries, ligaments, and vaginal canal of the recipient.
The woman was given five different drugs, along with antimicrobials, anti-blood clotting treatments and aspirin, to prevent her body from rejecting the new organ.
Five months after the surgery, the medical team observed no signs of rejection, noting that ultrasound scans were normal and the recipient experienced regular menstruation. The woman then became pregnant through in vitro fertilization with her own eggs, which she had previously frozen.
A baby girl was born, delivered via caesarean section, at 35 weeks and three days, weighing 2,550 grams (nearly 6 lbs), the case study reported.
When the report was submitted to The Lancet journal, the baby was seven months and 20 days old, continuing to breastfeed and weighed 7.2 kg.
Hope for women with uterine disorders
Dani Ejzenberg, the transplant team’s lead doctor at the University Of Sao Paulo School Of Medicine described the procedure as a “medical milestone.”
“Our results provide a proof-of-concept for a new option for women with uterine infertility,” Ejzenberg said.
“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,” he added.
Scientists have so far reported some 39 uterus transplants, which have resulted in 11 live births. The first baby born after one of these procedures was in Sweden in 2013, as part of an experimental study led by Swedish doctor Mats Brannstrom.
It is estimated that between 10 to 15 percent of couples of reproductive age worldwide are affected by infertility. The causes vary, but for one in 500 women, uterine problems are the cause.
Even if reproductive medicine has been remarkably successful during the past few decades, with the introduction of in vitro fertilization in the late 1970s and intracytoplasmic sperm injection in the early 1990s, it has been repeatedly mocked by infertility due to an absolute uterine factor. No treatment has been available for the women suffering from an absent or dysfunctional uterus, in terms of carrying a pregnancy.
Approximately one in 500 women suffer from absolute uterine infertility, and the option so far to become a mother has been to either adopt or utilize gestational surrogacy. As of today, a total of eleven cases of human uterus transplantations have been reported worldwide, conducted in three different countries. The results of these initial experimental cases far exceed what might be expected of a novel surgical method. Many more uterus transplantations are to be expected in the near future, as other research teams’ preparations are being ready to be put into clinical practice.
Future prospects of uterus transplantation
The future of uterus transplantation is prone to hold modifications of the procedure. New methods to evaluate the recipients, donors, and organs, like angiographic mapping of vessels, preoperative or even perioperative, will possibly simplify the procedure and improve the outcome. There will certainly also be other surgical options, such as laparoscopic and robotic-assisted methods, giving the possibility to reduce the surgical duration and concurrent risks for both recipients and live donors. Extensive efforts are currently made in the area of bioengineered organs for transplantation purpose, the uterus not being an exception.
The organ-engineering technology, being still in its infancy, pursues two ways of solution: the first involves donated organs, not suitable for transplantation, that is decellularized and the second alternative involves a synthetic matrix. The two different types of matrices would then after a recellularization process by the recipients own stem cells to be transplanted and in theory, function as good as any transplanted organ with the major benefit that no immunosuppression would be needed.
At the time when uterus transplantation will enter the clinical arena in a wider perspective, the participants will express a broader diversity, both medically and psychologically. It will be of utmost importance to continue to develop and improve protocols for psychology with thorough assessment and support in a systematic and structured way.
Uterus transplantation was a breakthrough in the field of reproductive medicine and has so far showed a remarkable successful outcome. Bearing this in mind, this procedure is still only proof of concept for uterus transplantation as a treatment for uterine factor infertility in a live related donor setting by laparotomic technique. Before introducing uterus transplantation in a wider general setting, several more carefully monitored pregnancies are required to evaluate major obstetrical risks, including miscarriage, preeclampsia, preterm birth, and fetal growth restriction. The concept of uterus transplantation will though surely be expanded to be demonstrated in other settings in the near future.
All the current successful cases have been performed at a single institution, after years of meticulous research in several animal models. The years of extensive collaboration between gynecological and transplant surgeons, pathologists, and anesthesiologists is the single most important factor in achieving such a remarkable good outcome of this novel procedure. With more cases being performed in the near future, by new surgical teams and centers, one can expect a wider and more extensive variety of different complications and this might come to affect the overall outcome.
Prior to the clinical introduction of uterus transplantation, it was debated whether it was ethically and morally defendable to perform the procedure. Now that it is proven to be successful in a controlled setting, the question might instead be whether it will be defendable or not to develop the uterus transplantation procedure further.
Previous Reported Cases of human uterus transplantation
A transplantation of a uterus, unlike any other organ transplantation, involves no less than four parties – recipient, donor, partner of the recipient, and the possible future child. All of them are exposed to potential risks if the surgery has to be performed. Uterus transplantation is a complex procedure and is surrounded by not only medical and psychological implications but also ethical, moral, and cultural concerns and expectations.
In 2014, the report of the first live birth following human uterus transplantation was published, showing that uterine factor infertility, even when considered absolute, is now treatable.This first birth has later been followed by three more births proving the outcome of uterus transplantation in this early stage of clinical implementation to be astonishing.
Worldwide, a total of eleven cases of human uterus transplantations have so far been reported, conducted in three different countries and cultural settings.
The first uterus transplantation was reported in 2002. A Saudi Arabian team then performed transplantation in a 26-year-old woman who lost her uterus due to peripartal bleeding 6 years earlier following a cesarean section. The graft was from a 46-year-old, previously healthy, woman who underwent hysterectomy when removing her ovaries due to benign bilateral multiloculated ovarian cysts. In order to prolong the short retrieved uterine vessels of the graft, patches from the great saphenous veins of the recipient were used and anastomosed to the external iliac vessels. During the first 3 months, cyclic hormonal therapy with estrogen and progesterone was given and two withdrawal bleedings occurred promptly after cessation of the hormones. Three months postoperatively, the uterus was found to be necrotic and was removed. The authors espoused inadequate tissue support of the graft, leading to tension and thrombosis of the supplying vessels, as a reason for this outcome.
The second human uterus transplantation was reported in 2011. A 23-year-old woman with MRKH syndrome and a previous jejunum-derived vaginal reconstruction was transplanted with a uterus from a deceased 21-year-old donor. The internal iliac artery and vein of the donor were anastomosed in an end-to-side fashion to the external iliac artery and vein of the recipient. After 20 days, the recipient had her first menstruation. Another two irregular menstrual cycles happened, and she was subsequently given cyclic hormonal therapy providing monthly withdrawal bleedings.
The first clinical series of uterus transplantation cases was performed in Sweden in 2012/2013. The trial involved nine transplantations with uteri from live donors. During the initial 4 months, two of the women had to undergo hysterectomy, in one case due to thrombosis of the uterine arteries and in another case due to a severe untreatable intrauterine infection. The remaining seven women started menstruating during the first 4–8 weeks post surgery, and the grafts remained viable with regular menstruations during the posttransplantation years.