– Opening a new era of reproductive medicine
By Mimmi Mononen
Contraception and in-vitro fertilization have reformed reproductive medicine and currently benefit families, women and men all around the world by addressing their predicaments concerning family planning and childlessness. Approval of the first contraceptive pill dates back to 1960 following the discovery of synthetic progesterone a decade earlier. Two decades later, in 1978, an article published in The Lancet reported about the first baby that was born after in vitro fertilization, IVF. Another milestone was met this year, as Members of the Parliament in UK voted to allow mitochondrial donation, opening the possibility of three-parent-babies.
Five and half decades after the first contraceptive pill was launched, advances in reproductive research now can give hope for women with a diseased or even lacking a uterus to give birth to their own children with help of a uterine transplant. The first successful birth of a child following uterus transplantation was carried out at Sahlgrenska University Hospital in Gothenburg on September, as reported in The Lancet by Mats Brännström and colleagues.
…the Parliament in UK voted to allow mitochondrial donation…
The story begins in University of Gothenburg, where uterus transplantation has been studied since 1999. Goal of the research is to give women lacking a functional uterus, as a result of cancer operation or other defect, the possibility to give birth to their own children. In total nine women were transplanted in Gothenburg during 2013 with uteri received from living donors. In most cases the donor was mother of the patient, but even a relative or close family friend could act as a donor in some of the cases. Two out of nine transplantations lead to rejection shortly after the operation. The seven remaining women with successful transplantation started in 2014 with IVF treatments, in which a cryopreserved embryo was implanted in the transplanted uteri.
Last spring, a year after the transplantations, first pregnancy within the patient group was reported and the baby was delivered on September with help of Caesarean section. The transplant recipient was a 35-year-old woman lacking uterus due to Rokitansky syndrome, a congenital defect of the reproductive system, and the uterus was donated by a 61-year-old woman with no family connection to the patient. The 35-year-old thereby became the first in the world with a successful childbirth after uterus transplantation.
Applying to any novel medical procedure, the arising clinical and ethical considerations after a successful uterus transplantation cannot be disregarded. Regarding uterus transplantation, women’s health and issues related to reproduction call for careful case-by-case consideration.
Underlining the importance of informed consent, all the donors must understand both the benefits and possible risks of removal of the uterus. The previously reported complications of the transplant donors include bleeding, infection, and organ injury, along with subsequent fistula development. Uterus transplantation also requires longer time than other organ transplantation procedures, which increases the risks related to the operation time and anesthesia. In addition to the risks related to the procedure itself, considerations regarding the age and childbearing of the donor must be taken into account. In the reported case the donor was a 61-year-old menopausal woman, and the decision was made for her to use combined oral contraceptives beforehand to ensure optimal uterine vasculature. The success rate of the transplantation is significantly increased by the contraceptive treatment, but it also elevates the risks for the donor to suffer from thromboembolic events.
…considerations regarding the age and childbearing of the donor must be taken into account.
Also the transplant recipients need to be aware of the risks of the operation. As mentioned above, two out of nine recipients suffered from rejection of the transplanted organ causing a life-threatening condition requiring immediate actions. The complications were caused by thrombosis and intrauterine infection, and both the patients underwent removal of the transplanted uterus. Moreover, pregnancy of the reported case did not proceed without complications as the mother suffered three events of rejection of the transplanted organ. In the case of the 35-year-old, the rejections could be kept under control by immunosuppressant drugs. In addition, her Caesarean section was performed earlier than planned, at week 32, as she was suffering from preeclampsia, a pregnancy complication characterized by high blood pressure and damage to kidneys or other organ systems.
Lastly, Brännström and colleagues state in their report that the plan after successful childbirth is to eventually remove the transplanted uterus in order to avoid risks connected to prolonged usage of immunosuppressant drugs. However, this procedure has to be voluntary decision made by the transplant recipient herself, which arises yet another set of ethical considerations addressing the will of the patient and her partner, and the judgement of the medical doctor responsible for the procedure.
The successful childbirth after uterus transplantation is unavoidably accompanied by several clinical and ethical issues that need consideration. Despite this, the experiment carried out in University of Gothenburg indicates that the impossible is possible, as the scientific proof for successful uterus transplantation now exists. Both the mother and the child are currently healthy, and the newborn baby boy develops normally, which brings hope for women and their families suffering from childlessness.
…the impossible is possible, as the scientific proof for successful uterus transplantation now exists.
A short history of uterus transplantation
The first successful childbirth after uterus transplantation was reported last October in The Lancet, starting a new chapter in the history of reproductive medicine. However, the first documentation of successful uterus transplantation dates back to as early as 1966, when American scientists published a study reporting the first autotransplantation on a dog, subsequently followed by pregnancy and delivery. The first ovarian transplantation on a rabbit was carried out even earlier, 1896, in Austria.
The history of experimental uterus transplantations on humans is nearly as long as that of the animal trials. One of the most fascinating examples is the case of Lili Elbe, a Danish transgender pioneer born as Einar Mogens Wegener, also being the first documented recipient of sex reassignment surgery.
During the first two years of 1930s, she received a series of five operations in Germany, being well aware that the procedure was experimental with no guarantees of success. Within the timespan of two years, surgeries were performed to remove the testicles and penis, and to transplant ovaries taken from a 26-year-old woman. The transplantation lead to rejection, and due to the severe complications the transplants were removed. Despite the drawbacks, Lili was determined of being able to become a mother, and in 1931 she had her fifth and last surgery to transplant a uterus. The operation was followed by another rejection leading to Lili’s death shortly after the transplantation.
The life of Lili Elbe has inspired several authors, and a film version of The Danish Girl, an international bestseller from 2001, is being developed. Eddie Redmayne, the Oscar-winning actor of The Theory of Everything, has been announced to play the role of Lili Elbe.