RAMB - Julho 2016

terus

transplant

: A

this

reality

ssoc

ras

2016; 62(4):295-296

295

EDITORIAL

Uterus transplant: Are we close to this reality?

ransplante

uterino

estamos

perto

desta

realidade

ani

jzenberg

, J

osé

aria

oares

únior

, E

dmund

C. B

aracat

Division of Gynecology, Department of Obstetrics and Gynecology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, SP, Brazil

http://dx.doi.org/10.1590/1806-9282.62.04.295

Some cases of

infertile couples are such insuperable chal-

lenges that they become dramatic, especially when wom-

en cannot become pregnant due to a congenitally absent

uterus (Mayer Rokitansky Küster Hauser – MRKH syn-

drome), or because it has been removed unexpectedly be-

fore childbearing. This may occur after hysterectomy for

treatment of cervical or endometrial cancer, uterine leio-

myoma, or postpartum hemorrhage.

It is estimated that the uterine factor represents 3 to

5% of cases of infertility.

This abnormality may have great

impact on the psychic sphere of many women, because

the options that remain are adoption or use of a replace-

ment uterus. Both alternatives present difficulties. In the

first case, the slowness and bureaucracy involved, while

the second includes the need for a relative or friend will-

ing to risk a pregnancy and the emotional ties that could

develop in relation to this baby. Moreover, the latter op-

tion is not allowed in many countries such as Japan and

Sweden. Then, the only option left for patients who want

to use their gametes is the possibility of uterine trans-

plant,

even if experimental.

Early research using animal models for uterus trans-

plant occurred in the 1960s and 1970s. It involved dogs,

sheep and primates. The initial idea was to transplant the

uterus along with the fallopian tubes to solve tubal fac-

tor infertility.

In the first experiments, two main issues

were raised: How to provide appropriate vascular support

to the transplanted organ; and how to prevent rejection

with the use of non-teratogenic substances. These chal-

lenges were not fully resolved at the time and are still con-

cerns of researchers.

4,5

The advent of

in vitro

fertilization,

which was successful in humans at the end of the 1970s,

reduced massively interest in uterus transplantation re-

search in animal models such as mice,

rats,

rabbits,

sheep

and monkeys

for many years. However, it did not

solve the problem of women with MRKH.

In 2000, the first uterine transplant in women was car-

ried out when a patient, who had lost her womb giving

birth, received the uterus of a living donor in Saudi Arabia.

However, this case progressed to graft loss and hysterecto-

my after three months of transplantation.

This created

frustration at that time and many researchers were skep-

tical about the success of the uterus transplants.

The second transplant was performed in 2011 in Tur-

key, with a report of two pregnancies in the transplanted

uterus, even though both ended in abortion.

More re-

cently, in 2014, the first birth of a series of nine patients

undergoing uterine transplantation occurred in Sweden.

Some researchers believe that this event was a milestone

in reproductive medicine, allowing pregnancy in a wom-

an aged 35 years with congenital uterine agenesis (MRKH

syndrome) who received the uterus from a 61-year-old

donor that became menopausal seven years earlier.

Sub-

sequently, three more births were successfully described,

and others may result from this series of cases.

14-16

There-

fore, a new frontier is opening up with these reports in

the field of human reproduction.

Uterus transplant, even with the very small number of

successful cases to date, is a major breakthrough in repro-

ductive medicine enabling pregnancy in women who did

not have a uterus. It is noted that the development of this

technique was possible only after great efforts in the field

of microsurgical techniques; extensive training in animal

models; research developed with transplantation of other

organs; and advances in human reproduction, such as em-

bryo cryopreservation and embryo biopsy; as well as the en-

hancement of drugs to prevent rejection of the uterus.

13-19

The evolution of immunosuppressants greatly dimin-

ished the fear of teratogenicity and raised the expectation

of success, especially after the reports of the Swedish

group.

However, training in other centers is necessary

both regarding the technical aspect of transplants and

management of immunosuppressive therapy.

18,19

We all know that there are still major challenges for the

improvement of the technique, selection of potential do-

nors, and the preservation of the organ to be transplanted.

Another highlight of this therapeutic modality

will be con-

taining the expectation of success within the community

in face of a learning curve required to implement any pro-

cedure. Finally, uterus transplant can be considered as a

therapeutic hope for women who were born without a uter-

us or lost it unexpectedly during their reproductive life.