uterus transplantation
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A uterine transplant is a surgical procedure whereby a healthy
uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...
is
transplanted ''A.N.T. Farm'' is a Disney Channel original series that follows Chyna Parks (China Anne McClain) and her two best friends, Olive Doyle (Sierra McCormick) and Fletcher Quimby (Jake Short), who are in the "Advanced Natural Talents" (A.N.T.) program ...
into an organism of which the uterus is
absent Absence may refer to: Employment * Leave of absence, a period of time away from a job * Absenteeism, the habitual pattern of absence from work or duty * Absence rate, the ratio of workers with absences to total employees Sciences and philosophy ...
or diseased. As part of normal mammalian sexual reproduction, a diseased or absent uterus does not allow normal embryonic implantation, effectively rendering the female
infertile Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
. This phenomenon is known as absolute uterine factor
infertility Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
(AUFI). Uterine transplant is a potential treatment for this form of infertility.


History


Studies

In 1896, Emil Knauer, a 29-year-old Austrian working in one of
Vienna en, Viennese , iso_code = AT-9 , registration_plate = W , postal_code_type = Postal code , postal_code = , timezone = CET , utc_offset = +1 , timezone_DST ...
's gynecological clinics, published the first study of ovarian autotransplantation documenting normal function in a
rabbit Rabbits, also known as bunnies or bunny rabbits, are small mammals in the family Leporidae (which also contains the hares) of the order Lagomorpha (which also contains the pikas). ''Oryctolagus cuniculus'' includes the European rabbit speci ...
. This led to the investigation of uterine transplantation in 1918. In 1964 and 1966, Eraslan, Hamernik and Hardy, at the
University of Mississippi The University of Mississippi (byname Ole Miss) is a public research university that is located adjacent to Oxford, Mississippi, and has a medical center in Jackson. It is Mississippi's oldest public university and its largest by enrollment. ...
Medical Center in
Jackson, Mississippi Jackson, officially the City of Jackson, is the Capital city, capital of and the List of municipalities in Mississippi, most populous city in the U.S. state of Mississippi. The city is also one of two county seats of Hinds County, Mississippi, ...
, were the first to perform an animal (dog) autotransplantation of the uterus and subsequently deliver a pregnancy from that uterus. In 2010 Diaz-Garcia and co-workers, at Department of Obstetrics and Gynecology,
University of Gothenburg The University of Gothenburg ( sv, Göteborgs universitet) is a university in Sweden's second largest city, Gothenburg. Founded in 1891, the university is the third-oldest of the current Swedish universities and with 37,000 students and 6000 st ...
in
Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...
, demonstrated the world's first successful
allogenic In ecology, allogenic succession is succession driven by the abiotic components of an ecosystem. In contrast, autogenic succession is driven by the biotic components of the ecosystem. An allogenic succession can be brought about in a number of ways ...
uterus transplantation, in a rat, with healthy offspring.


Notable cases


Germany

Except perhaps in rare cases of
intersex Intersex people are individuals born with any of several sex characteristics including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical bina ...
individuals,
transgender women A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and som ...
are born with a male reproductive system. While
sex reassignment surgery Gender-affirming surgery (GAS) is a surgical procedure, or series of procedures, that alters a transgender or transsexual person's physical appearance and sexual characteristics to resemble those associated with their identified gender, and alle ...
can create a
vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...
for these women, the option of a uterus is currently unavailable to them, meaning they cannot carry a pregnancy and would need to take other routes to parenthood, whether it be a more traditional approach involving
coitus Sexual intercourse (or coitus or copulation) is a sexual activity typically involving the insertion and thrusting of the penis into the vagina for sexual pleasure or reproduction.Sexual intercourse most commonly means penile–vaginal penetr ...
or an alternative one such as
adoption Adoption is a process whereby a person assumes the parenting of another, usually a child, from that person's biological or legal parent or parents. Legal adoptions permanently transfer all rights and responsibilities, along with filiation, from ...
,
egg donation Egg donation is the process by which a woman donates eggs to enable another woman to conceive as part of an assisted reproduction treatment or for biomedical research. For assisted reproduction purposes, egg donation typically involves in vitro fe ...
, or a gestational carrier. General interest in uterine transplants for
transgender A transgender (often abbreviated as trans) person is someone whose gender identity or gender expression does not correspond with their sex assigned at birth. Many transgender people experience dysphoria, which they seek to alleviate through tr ...
women has waned in recent decades, due to the success and subsequent widespread availability of
assisted reproductive technology Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes o ...
, and being transgender has become virtually synonymous with being
infertile Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
. Nonetheless, at least one uterine transplant for a trans woman occurred, for the Danish artist
Lili Elbe Lili Ilse Elvenes (28 December 1882 – 13 September 1931), better known as Lili Elbe, was a Danish painter and transgender woman, and among the early recipients of sex reassignment surgery. She was a successful painter under her birth name Ein ...
(1882–1931), in one of the medical field's first attempts to treat the needs of transgender patients. Hoping to have children with her fiancé, she underwent a uterine transplant in 1931, in conjunction with
vaginoplasty Vaginoplasty is any surgical procedure that results in the construction or reconstruction of the vagina. It is a type of genitoplasty. Pelvic organ prolapse is often treated with one or more surgeries to repair the vagina. Sometimes a vaginoplas ...
, in Germany at the age of 48. However, she developed an postsurgical infection and died from
cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possib ...
just three months later.


Saudi Arabia

The first modern day attempt at a uterine transplant occurred in 2000, in Saudi Arabia. Dr. Wafa Fageeh transplanted a uterus, taken from a 46-year-old patient, into a 26-year-old patient whose uterus had been damaged by
hemorrhaging Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
following
childbirth Childbirth, also known as labour and delivery, is the ending of pregnancy where one or more babies exits the internal environment of the mother via vaginal delivery or caesarean section. In 2019, there were about 140.11 million births globall ...
. Because the patient ultimately needed for the uterus to be removed after just 99 days, due to
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
, whether or not the case is considered successful is disputed, but the uterus did function for a time, with the patient experiencing two
menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eggs a ...
s. Members of the medical community have expressed concerns over the ethics of the procedure.


Turkey

The first incidence of a uterine transplant involving a deceased donor occurred in
Turkey Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a list of transcontinental countries, transcontinental country located mainly on the Anatolia, Anatolian Peninsula in Western Asia, with ...
on 9 August 2011; the surgery, performed by Dr. Ömer Özkan and Dr. Munire Erman Akar, at the
Akdeniz University Akdeniz University ( tr, Akdeniz Üniversitesi) is a public research university established in Antalya, Turkey. It has been chosen as the second most beautiful university in Turkey, after Boğaziçi University, with its campus having a wide and gr ...
Hospital in
Antalya Antalya () is the List of largest cities and towns in Turkey, fifth-most populous city in Turkey as well as the capital of Antalya Province. Located on Anatolia's southwest coast bordered by the Taurus Mountains, Antalya is the largest Turkish cit ...
, on Derya Sert, a 21-year-old patient who'd been born without a uterus. In this case, the patient enjoyed long-term success with the transplanted uterus, experiencing periods and, two years post-surgery, pregnancy. During that pregnancy, Sert underwent an
abortion Abortion is the termination of a pregnancy by removal or expulsion of an embryo or fetus. An abortion that occurs without intervention is known as a miscarriage or "spontaneous abortion"; these occur in approximately 30% to 40% of pregn ...
in her
first trimester Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...
, after her doctor was unable to detect a
fetal heartbeat Heart development, also known as cardiogenesis, refers to the prenatal development of the heart. This begins with the formation of two endocardial tubes which merge to form the tubular heart, also called the primitive heart tube. The heart is t ...
, but this is a common complication and may not have been related to the transplant. Following another pregnancy that was initiated with
in vitro fertilisation In vitro fertilisation (IVF) is a process of fertilisation where an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating an individual's ovulatory process, removing an ovum or ova (egg or eggs) ...
and sustained for 28 weeks, the patient finally delivered a baby on June 4, 2020.


Sweden

In
Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...
in 2012, the first mother-to-daughter womb transplant was done by Swedish doctors at
Sahlgrenska University Hospital The Sahlgrenska University Hospital ( Swedish: ''Sahlgrenska Universitetssjukhuset'') is a hospital network associated with the Sahlgrenska Academy at the University of Gothenburg in Gothenburg, Sweden. With 17,000 employees the hospital is the lar ...
at
Gothenburg University The University of Gothenburg ( sv, Göteborgs universitet) is a university in Sweden's second largest city, Gothenburg. Founded in 1891, the university is the third-oldest of the current Swedish universities and with 37,000 students and 6000 s ...
led by Mats Brännström. In October 2014, it was announced that, for the first time, a healthy baby had been born to a uterine transplant recipient, at an undisclosed location in
Sweden Sweden, formally the Kingdom of Sweden,The United Nations Group of Experts on Geographical Names states that the country's formal name is the Kingdom of SwedenUNGEGN World Geographical Names, Sweden./ref> is a Nordic country located on ...
. The British medical journal ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...
'' reported that the baby boy had been born in September, weighing 1.8 kg (3.9 lb) and that the father had said his son was "amazing". The baby had been delivered prematurely at about 32 weeks, by
cesarean section Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or ...
, after the mother had developed
pre-eclampsia Pre-eclampsia is a disorder of pregnancy characterized by the onset of high blood pressure and often a significant amount of protein in the urine. When it arises, the condition begins after 20 weeks of pregnancy. In severe cases of the disease ...
. The Swedish woman, aged 36, had received a uterus in 2013, from a live 61-year-old donor, in an operation led by Dr. Brännström, Professor of Obstetrics and Gynaecology at the
University of Gothenburg The University of Gothenburg ( sv, Göteborgs universitet) is a university in Sweden's second largest city, Gothenburg. Founded in 1891, the university is the third-oldest of the current Swedish universities and with 37,000 students and 6000 st ...
. The woman had healthy ovaries but was born without a uterus, a condition that affects about one in 4,500 women. The procedure used an embryo from a laboratory, created using the woman's ovum and her husband's sperm, which was then implanted into the transplanted uterus. The uterus may have been damaged in the course of the caesarian delivery and it may or may not be suitable for future pregnancies. A regimen of triple immuno-suppression was used with
tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...
,
azathioprine Azathioprine (AZA), sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus, ...
, and
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...
. Three mild rejection episodes occurred, one during the pregnancy, but were all successfully suppressed with medication. Some other women were also reported to be pregnant at that time using transplanted uteri.


United States

The first uterine transplant performed in the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
took place on 24 February 2016 at the
Cleveland Clinic Cleveland Clinic is a nonprofit American academic medical center based in Cleveland, Ohio. Owned and operated by the Cleveland Clinic Foundation, an Ohio nonprofit corporation established in 1921, it runs a 170-acre (69 ha) campus in Cleveland, ...
. The team was lead by Dr Andreas Tzakis. The transplant failed due to an undisclosed complication on 8 March, and the uterus was removed. In April, they reported a
yeast infection Candidiasis is a fungal infection due to any type of '' Candida'' (a type of yeast). When it affects the mouth, in some countries it is commonly called thrush. Signs and symptoms include white patches on the tongue or other areas of the mouth ...
had spread to one of the arteries the surgeons had connected to provide blood flow to the transplanted uterus, which damaged the artery and caused blood clots to form. In November 2017, the first baby was born after a uterus transplantation in the US. The birth occurred at
Baylor University Medical Center Baylor University Medical Center (Baylor Dallas or BUMC), part of Baylor Scott & White Health, is a not-for-profit hospital in Dallas, Texas. It has 1,025 licensed beds and is one of the major centers for patient care, medical training and resea ...
in Dallas, Texas, by Drs Liza Johannesson and Giuliano Testa, after a uterus donation from a non-directed living donor. The first baby born after a deceased donor uterus transplant in the US was at the Cleveland Clinic in June 2019.


India

The first uterine transplant performed in
India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
took place on 18 May 2017 at the Galaxy Care Hospital in Pune, Maharashtra. The 26-year-old patient had been born without a uterus, and received her mother's womb in the transplant. India's first uterine transplant baby, weighing 1.45 kg, was delivered through a
Caesarean section Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or mo ...
at Galaxy Care Hospital in
Pune Pune (; ; also known as Poona, (List of renamed Indian cities and states#Maharashtra, the official name from 1818 until 1978) is one of the most important industrial and educational hubs of India, with an estimated population of 7.4 million ...
on Thursday. The surgery was performed by a team of doctors at Pune's Galaxy Care Hospital and led by the hospital's medical director, Dr. Shailesh Puntambekar.


Brazil

The first uterine transplant performed in Brazil took place on 2016 at the Hospital das Clínicas da USP in São Paulo. The 32-year-old patient had Mayer-Rokitansky-Küster-Hauser Syndrome, and therefore born without an uterus, and received a deceased donor's womb in the transplant. Brazil's first uterine transplant baby was delivered through a
Caesarean section Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or mo ...
at Hospital das Clínicas da USP on December 2017. The surgery was performed by a team of doctors at Hospital das Clínicas da USP and led by Dr. Dani Ejzenberg, the head of the Human Reproductive Center at the hospital. Results of this procedure, the first to be performed in Latin America, were published in the medical journal The Lancet, in December 2018.


Current status

The transplant is intended to be temporary – recipients will have to undergo a
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
after one or two successful pregnancies. This is done to avoid the need to take
immunosuppressive drug Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...
s for life with a consequent increased risk of infection. The procedure remains the last resort: it is a relatively new and somewhat experimental procedure, performed only by certain specialist surgeons in select centres, it is expensive and unlikely to be covered by insurance, and it involves risk of infection and organ rejection. Some
ethics Ethics or moral philosophy is a branch of philosophy that "involves systematizing, defending, and recommending concepts of right and wrong behavior".''Internet Encyclopedia of Philosophy'' The field of ethics, along with aesthetics, concerns m ...
specialists consider the risks to a live donor too great, and some find the entire procedure ethically questionable, especially since the transplant is not a life-saving procedure.


Description


Procedures

Uterine transplantation starts with the uterus retrieval surgery on the donor. Working techniques for this exist for animals, including primates and more recently humans. The recovered uterus may need to be stored, for example for transportation to the location of the recipient. Studies on cold-
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
reperfusion indicate an ischemic tolerance of more than 24 hours. The recipient has to look at potentially three major surgeries. First of all, there is the transplantation surgery. If a pregnancy is established and carried to viability a
cesarean section Caesarean section, also known as C-section or caesarean delivery, is the surgical procedure by which one or more babies are delivered through an incision in the mother's abdomen, often performed because vaginal delivery would put the baby or ...
is performed. As the recipient is treated with immuno-suppressive therapy, eventually, after completion of childbearing, a
hysterectomy Hysterectomy is the surgical removal of the uterus. It may also involve removal of the cervix, ovaries (oophorectomy), Fallopian tubes (salpingectomy), and other surrounding structures. Usually performed by a gynecologist, a hysterectomy may b ...
needs to be done so that the immuno-suppressive therapy can be terminated.


Ethics


Montreal criteria

Aside from considerations of costs, uterine transplantation involves complex
ethical issues Ethics or moral philosophy is a branch of philosophy that "involves systematizing, defending, and recommending concepts of right and wrong behavior".''Internet Encyclopedia of Philosophy'' The field of ethics, along with aesthetics, concerns ma ...
. The principle of
autonomy In developmental psychology and moral, political, and bioethical philosophy, autonomy, from , ''autonomos'', from αὐτο- ''auto-'' "self" and νόμος ''nomos'', "law", hence when combined understood to mean "one who gives oneself one's ...
supports the procedure, while the principle of
non-maleficence ' () is a Latin phrase that means "first, do no harm". The phrase is sometimes recorded as '. Non-maleficence, which is derived from the maxim, is one of the principal precepts of bioethics that all students in healthcare are taught in school a ...
argues against it. In regard to the principles of beneficence and justice the procedure appears equivocal. To address this dilemma the "Montreal Criteria for the Ethical Feasibility of Uterine Transplantation" were developed at
McGill University McGill University (french: link=no, Université McGill) is an English-language public research university located in Montreal, Quebec, Canada. Founded in 1821 by royal charter granted by King George IV,Frost, Stanley Brice. ''McGill Universit ...
and published in ''Transplant International'' in 2012. The Montreal Criteria are a set of criteria deemed to be required for the ethical execution of the uterine transplant in humans. These findings were presented at the International Federation of Gynecology and Obstetrics' 20th World Congress in Rome in October 2012. In 2013 an update to ''"The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation''" was published in ''
Fertility and Sterility The American Society for Reproductive Medicine (ASRM) is a nonprofit, multidisciplinary organization for advancement of the science and practice of reproductive medicine. The society has its headquarters in Washington, D.C and its administrati ...
'' and has been proposed as the international standard for the ethical execution of the procedure. The criteria set conditions for the recipient, the donor, and the health care team, specifically: # The recipient is a genetic female, with the ability to consent, with no medical contraindications to transplantation, has uterine disease that has failed other therapy, and has "a personal or legal contraindication" to other options (
surrogacy Surrogacy is an arrangement, often supported by a legal agreement, whereby a woman agrees to delivery/labour for another person or people, who will become the child's parent(s) after birth. People may seek a surrogacy arrangement when pregnan ...
,
adoption Adoption is a process whereby a person assumes the parenting of another, usually a child, from that person's biological or legal parent or parents. Legal adoptions permanently transfer all rights and responsibilities, along with filiation, from ...
). The recipient needs to be considered suitable for motherhood, deemed to be psychologically fit on evaluation, is likely to be compliant with treatment and the medical team, and understands the risks of the procedure. # The donor is a female of reproductive age with no contraindication to the procedure who has concluded her childbearing or consented donating her uterus after her death. There is no coercion and the donor is responsible and capable of making informed decisions. # The health care team belongs to an institution that meets Moore's third criterion regarding institutional stability and has provided informed consent to both parties. There is no conflict of interests, and anonymity can be protected unless recipient or donor waive this right.


See also

*
Male pregnancy Male pregnancy is the incubation of one or more embryos or fetuses by organisms of the male sex in some species. Most species that reproduce by sexual reproduction are heterogamous—females producing larger gametes (ova) and males producing sma ...
*
Transgender pregnancy Transgender pregnancy is the gestation of one or more embryos or fetuses by transgender people. Currently, the possibility is restricted to those born with female reproductive systems, and transition-related treatments may impact fertility. Trans ...
*
Transplantable organs and tissues Transplantable organs and tissues may refer to both organs and tissues that are relatively often transplanted (here "major organs and tissues"), as well as organs and tissues which are relatively seldom transplanted (here "non-major organs and tis ...


References


External links


Nine Swedish women undergo uterus transplants
{{Female genital procedures Obstetrical and gynaecological procedures Organ transplantation Uterus