Uterus transplants--update

Reproductive options continue to grow... Here's an update on transplantation of the uterus.

Uterus Transplant in Women With Absolute Uterine-Factor Infertility, by Giuliano Testa, MD, MBA1; Greg J. McKenna, MD1; Anji Wall, MD, PhD1; et alJohanna Bayer, MD1; Anthony R. Gregg, MD2; Ann Marie Warren, PhD3,4; Seung Hee S. Lee, MD1; Eric Martinez, MD1; Amar Gupta, MD1; Robert Gunby, MD2; Liza Johannesson, MD, PhD1,5, JAMA. Published online August 15, 2024. doi:10.1001/jama.2024.11679

"Assisted reproductive technologies have provided millions of women with fertility options. However, absolute uterine infertility, affecting 1 in 500 women, remains a barrier in reproductive medicine. Absolute uterine infertility can be acquired or congenital and due to either a dysfunctional or an absent uterus. Affected women who want to have children traditionally choose between adoption or surrogacy where legally available. The development of uterus transplant offers an option for women with absolute uterine infertility to experience pregnancy and childbirth. Since the first successful uterus transplant in 2011,1 more than 100 uterus transplant procedures have been performed worldwide, using grafts from living or deceased donors. Although no registry exists that precisely reports the number of live births resulting from these procedures, it is estimated that there are more than 70 live births worldwide.2,3 As of May 1, 2024, there have been 48 uterus transplants and 33 live births in the US."

Uterus transplants considered in Japan

 Here's the story from the Asahi Shimbun, including some background. For the time being, only living-donor organs seem to be allowed under Japanese law:

Medical group allows for uterus transplants to give birth

"A Japanese Association of Medical Sciences committee released a report on July 14 clearing the way for uterus transplants, a rare procedure that faces obstacles. 

...

"The biggest issue facing the committee was that the transplant objective would be to allow the woman to give birth.

"That differs greatly from other transplants in which the main objective is to save the recipient’s life. In addition, committee members had to consider allowing a transplant operation that held major health risks for both the donor and recipient.

"According to a report, there have been 85 cases of uterus transplants in 16 nations overseas as of March and 40 have led to the delivery of a baby.

"In many of those cases, an in-vitro fertilized embryo is placed in the transplanted uterus. But the uterus is removed after childbirth because of the need to continue using immunosuppressant agents to prevent the body from rejecting the transplanted organ.

"In Japan, there are an estimated 60,000 to 70,000 women between the ages of 20 and 50 who were born without uteruses or have had their uteruses surgically removed due to tumors or other causes.

...

"There are also legal hurdles that have to be cleared.

"Japan’s organ transplant law does not include uteruses as an organ that can be removed for transplantation from a brain-dead individual.

"For that reason, the report allowed for transplants from live donors in only a very few cases to conduct clinical research.

"The report also called for revising the organ transplant law to allow for uterus transplants from brain-dead women.

"But even if the law was revised, organ donations from brain-dead individuals are still not widespread in Japan, meaning it would be almost impossible to plan for a uterus transplant operation.

"Experts were divided in their views about the latest report.

"Nobuhiko Suganuma, a professor of reproductive medicine at Nagoya University of Arts and Sciences who heads the Japan Society for Uterus Transplantation, said providing an alternative for women who want to give birth was a positive development.

"But Yukiko Saito, an associate professor of medical ethics at Kitasato University, raised concerns about approving an available technology just because there may be people who want to utilize it."

The demand for a uterus transplant among transgender women (a survey study)

 A couple of years ago I gave a Department of Surgery Grand Rounds (a dawn seminar) at Stanford. Much later in the day, at dinner with transplant surgeons and others, someone asked me what other kinds of work I did.  So I started to tell them about my work on repugnant transactions and controversial markets, and used surrogacy as my main example. I pointed out that Sweden, where surrogacy is illegal, had pioneered uterus transplantation as an alternative that worked for some. But I suggested it wouldn't work for same-sex male couples, who are among those who use the well established legal market for surrogates in California.  The conversation quickly turned to why I was wrong.  As I recall what they said, the uterus is just a muscle, so could be transplanted into a man. Ovaries would be a problem, so in-vitro fertilization (IVF) would be needed to start the pregnancy, and of course the baby would have to be delivered via a C-section...

Since then, uterus transplantation has become somewhat more widespread, from both living and deceased donors.  As far as I know, no one is actually proposing to transplant a uterus into a man--for one thing, the demand may not be there.  But that's not the case with another group of people born without a uterus, namely transgender women.

Here's a recent survey from JAMA on just that, which shows that in fact there are transgender women who are open to bearing a child through a uterus transplant:

Jones BP, Rajamanoharan A, Vali S, et al. Perceptions and Motivations for Uterus Transplant in Transgender Women. JAMA Netw Open. 2021;4(1):e2034561. doi:10.1001/jamanetworkopen.2020.34561

"Key Points

"Question  What are the perceptions and motivations of transgender women for uterus transplant?

"Findings  This survey study of 182 transgender women found that to more than 90% of the respondents indicated that uterus transplant may improve quality of life in transgender women, alleviate dysphoric symptoms, and enhance feelings of femininity.

"Meaning  This report on the desire and willingness of transgender women to undergo uterus transplant may support the need for further animal and cadaveric model research, which is necessary to assess the feasibility of performing this procedure in transgender women"

Are uterus transplants repugnant? And to whom? And why? (in the Irish Times)

Here's an article in the Irish Times on uterus transplants , that makes clear the view that the views of those not directly involved should play a large  and perhaps decisive role in public discussions of transactions that some may find repugnant. The author indicates that among his concerns is that the parentage of the baby might be in doubt (i.e. that a child conceived from the eggs and sperm of his genetic parents and carried to birth by his pregnant genetic mother might have to be regarded as the child of the donor of the uterus...). I wonder if even the author thinks this is a serious reason to ban uterus transplants; rather, I get the sense that he is throwing his net widely in the hope that different objections might resonate with different parts of his audience. Maybe his goal is simply to be controversial. [Just to be clear, I am not disagreeing that child welfare is an important concern when evaluating issues related to reproduction and childbirth...but this concern strikes me as particularly far-fetched.]

Are uterus transplants ethically acceptable?
Several infertile women worldwide have given birth with wombs received from either living or dead donors   by George Winter

"In September 2014, the first live birth following UTx was reported from Sweden by Prof Mats Brännström and colleagues. The recipient had Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome – she was born without a viable womb – and the donor was a 61-year-old friend. Since then, there have been at least 12 successful births worldwide following UTx.

"Recently, it was revealed that the first baby had been born following a womb transplant from a deceased donor. Ten previous attempts had been made in different countries to deliver a live baby following a uterus or womb transplant from a deceased donor, but this – performed by surgeons in Brazil – was the first with a successful outcome.

...

"The UTx procedure begins with in-vitro fertilisation, using the recipient’s egg and her partner’s sperm; the subsequent embryo is frozen; a uterus – from a living or dead donor – is transplanted; the embryo is thawed and implanted; and following pregnancy and delivery by Caesarean section, a hysterectomy is performed, obviating the need for lifelong immunosuppressive therapy."

...

"The “Ethical Considerations” section of the Womb Transplant UK website implies that any societal misgivings on the acceptability of UTx will be ignored: “Ultimately, the decision to go forward will depend on the judgment of the researchers, the participating institution, and most importantly, the patient to whom the transplant will be offered.”

"Hardly an unbiased trio.

"What ethical dilemmas might arise?

"If a transplanted uterus were to jeopardise a recipient’s life, it could be removed; but what if it contains a viable foetus? And there is debate over living versus deceased donation, with Spanish and Japanese teams favouring the Swedish “live” model, and French, Belgian and UK researchers preferring deceased donors. Writing in the journal Bioethics, Dr Nicola Williams cites the view of the International Federation of Gynaecology and Obstetrics that “the retrieval of a uterus from a living donor necessitates a relatively major surgery with its own risk of complications [and] constitutes reason enough to deem the procedure ethically inappropriate”.

"Also, how much would a child be entitled to know about the donor from whose uterus he or she issued, and – irrespective of whether the donor had been dead or alive – would the infant be the child of the donor or the recipient?"

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George Winter, the author of the piece, apparently writes often on ethical issues in medicine (although the above is the first article I had read by him). See e.g.  his recent related articles on The ethical considerations of face transplants and 
The brave new world of wombless gestation--Artificial womb technology poses many ethical questions – we need to debate them
(that article is about experimental technology about lamb embryos brought to term "in a plastic “biobag” – literally, a womb with a view ..."  I was relieved to note that, in considering the implications for humans, the author didn't raise the question above about the parentage--or in this case perhaps the humanity--of the baby (so maybe he was just kidding.)

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And see my related post from yesterday:
Friday, December 14, 2018  Successful birth in Brazil to a woman who received a uterus transplanted from a deceased donor

Successful birth in Brazil to a woman who received a uterus transplanted from a deceased donor

The Lancet reports the first known case of a live birth to a woman born without a uterus who received a transplanted uterus from a deceased donor.

Livebirth after uterus transplantation from a deceased donor in a recipient with uterine infertility

December 04, 2018 DOI:https://doi.org/10.1016/S0140-6736(18)31766-5

Background

Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centres and programmes worldwide. However, no case of livebirth via deceased donor uterus has, to our knowledge, been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischaemia.

Methods

In September, 2016, a 32-year-old woman with congenital uterine absence (Mayer-Rokitansky-Küster-Hauser [MRKH] syndrome) underwent uterine transplantation in Hospital das Clínicas, University of São Paulo, Brazil, from a donor who died of subarachnoid haemorrhage. The donor was 45 years old and had three previous vaginal deliveries. The recipient had one in-vitro fertilisation cycle 4 months before transplant, which yielded eight cryopreserved blastocysts.

Findings

The recipient showed satisfactory postoperative recovery and was discharged after 8 days' observation in hospital. 

...

The female baby weighed 2550 g at birth, appropriate for gestational age, with Apgar scores of 9 at 1 min, 10 at 5 min, and 10 at 10 min, and along with the mother remains healthy and developing normally 7 months post partum. The uterus was removed in the same surgical procedure as the livebirth and immunosuppressive therapy was suspended.

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In Brazil (where commercial surrogacy is apparently illegal, and legal surrogates must be family members of the intended mother), the urge to have one's own baby is nevertheless strong. 

See earlier post:

Wednesday, January 15, 2014

Womb transplants in Sweden (where surrogacy is illegal)

First Uterus Transplant in the U.S., at the Cleveland Clinic

Uterus transplants were pioneered in Sweden, where surrogacy is illegal. But there is also demand in the U.S.

The NY Times has the story: First Uterus Transplant in U.S. Bolsters Pregnancy Hopes of Many

"The procedure’s purpose is to enable women born without a uterus, or who had theirs removed, to become pregnant and give birth. The patient will have to wait a year before trying to become pregnant, letting her heal and giving doctors time to adjust the doses of medication she needs to prevent organ rejection.

Then she will need in vitro fertilization to become pregnant. Before the transplant, the patient had eggs removed surgically, fertilized with her husband’s sperm and frozen. The embryos will be transferred into her uterus.

The transplant will be temporary: The uterus will be removed after the recipient has had one or two babies, so she can stop taking anti-rejection drugs.

The Cleveland hospital’s ethics panel has given it permission to perform the procedure 10 times, as an experiment. Officials will then decide whether to continue, and whether to offer the operation as a standard procedure. The clinic is still screening women who may be candidates for the operation.

The leader of the surgical team is Dr. Andreas G. Tzakis, who has performed 4,000 to 5,000 transplants of kidneys, livers and other abdominal organs. To prepare for uterus transplants, he traveled to Sweden and worked with doctors at the University of Gothenburg, the only ones in the world to have performed the procedure successfully so far. Nine women have had the operation in Sweden, with the transplants taken from living donors. At least four recipients have had babies, who were born healthy though premature.

About 50,000 women in the United States are thought to be candidates for transplanted uteruses."

Womb transplants in Sweden (where surrogacy is illegal)

The NY Times has the story: Swedish Doctors Transplant Wombs Into 9 Women

 "STOCKHOLM — Nine women in Sweden have successfully received transplanted wombs donated from relatives in an experimental procedure that has raised some ethical concerns. The women will soon try to become pregnant with their new wombs, the doctor in charge of the pioneering project has revealed.

"The women were born without a uterus or had it removed because of cervical cancer. Most are in their 30s and are part of the first major experiment to test whether it's possible to transplant wombs into women so they can give birth to their own children.

"In many European countries, including Sweden, using a surrogate to carry a pregnancy isn't allowed.
...
"Some experts have raised concerns about whether it's ethical to use live donors for an experimental procedure that doesn't save lives. But John Harris, a bioethics expert at the University of Manchester, didn't see a problem with that as long as donors are fully informed. He said donating kidneys isn't necessarily life-saving, yet is widely promoted.

"Dialysis is available, but we have come to accept and to even encourage people to take risks to donate a kidney," he said.

"Brannstrom said the nine womb recipients are doing well. Many already had their periods six weeks after the transplants, an early sign that the wombs are healthy and functioning.
...
"None of the women who donated or received wombs has been identified. The transplants began in September 2012 and the donors include mothers and other relatives of the recipients.
...
"The transplant operations did not connect the women's uteruses to their fallopian tubes, so they are unable to get pregnant naturally. But all who received a womb have their own ovaries and can make eggs. Before the operation, they had some removed to create embryos through in-vitro fertilization. The embryos were then frozen and doctors plan to transfer them into the new wombs, allowing the women to carry their own biological children.
...
""If this had been possible when I was younger, no doubt I would have been interested," she said. Gimre, who has two foster children, said the only option for women like her to have biological children is via surrogacy, which is illegal in many European countries, including Norway and Sweden.
...
"The technique used in Sweden, using live donors, is somewhat controversial. In Britain, doctors are also planning to perform uterus transplants, but will only use wombs from dying or dead people. That was also the case in Turkey. Last year, Turkish doctors announced their patient got pregnant but the pregnancy failed after two months.

"Mats has done something amazing and we understand completely why he has taken this route, but we are wary of that approach," said Dr. Richard Smith, head of the U.K. charity Womb Transplant UK, which is trying to raise 500,000 pounds ($823,000) to carry out five operations in Britain.

"He said removing a womb for donation is like a radical hysterectomy but it requires taking a bigger chunk of the surrounding blood vessels to ensure adequate blood flow, raising the risk of complications for the donor. Smith said British officials don't consider it ethical to let donors take such chances for an operation that isn't considered life-saving.
...
"Doctors in Saudi Arabia performed the first womb transplant in 2000, using a live donor, but it had to be removed after three months because of a blood clot."