Guest post Medicine

The first uterus transplant, or how Lancet apologised to Saudis

A guest post by the science writer Martin Endara-Coll.

This is a guest post by the science writer Martin Endara Coll. It is the true story of the once much celebrated first ever uterus transplant performed by Wafa’a Fageeh in Saudi Arabia over two decades ago, and how The Lancet erased the truth to replace it with a grovelling apology to an oppressive regime.

Fageeh’s work was celebrated as breakthrough when it was published in 2002 and fell into obscurity right after, surrounded by accusations of gross ethics breaches and other misconduct. The next breakthrough in uterus transplantation, this time from a deceased donor, was reported in 2020 in Gothenburg, by a Swedish medical team led by Mats Brännström. Also this one was celebrated throughout the media, also in this case little is known about the long-term outcome.

As it happens, Brännström used to be a close collaborator of regenerative medicine researchers Michael Olausson and (at some point) also of Suchitra Sumitran-Holgersson, who both were found guilty of scientific misconduct and medical ethics breaches. They all tried to design a decellurised uterus for “stem cell” recellurisation and transplantation (Hellström et al 2014), a scientifically untenable and dangerous idea founded on Sumitran-Holgersson’s (and Paolo Macchiarini‘s!) fraud. Brännström informed me in this regard:

We have only carried out studies on de-recellularized uteri in rats and sheep. Some are published and some are in writing.

Whatever those papers may proclaim, these regmed experiments could only have worked in Suchitra’s fantasy. Poor sheep and rats. But one reason why Fageeh is still celebrated despite allegations of malpractice, is that live donor uterus transplants to work very well, even if hers didn’t.

In 2014, Brännström, Olausson and Suchitra’s husband Jan Holgersson (whose company markets his wife’s fraudulent medical technology) announced the results of a “First clinical uterus transplantation trial” using organs from live donors (Brännström et al 2014), later on Brännström and Olausson followed up with reports of successful live births (e.g, Brännström et al 2021). As Brännström told me, Olausson “was the senior transplant surgeon on the human transplants performed 2012-2013” and that he is “not collaborating with MO on any further studies“. About Suchitra’s husband, Brännström told me:

Jan Holgersson is the immunologist in the human uterus transplant project. We are working on some follow-up projects on immunology of the human transplantation trials.

Turned out Brännström didn’t know about Holgersson’s company Verigraft. My advice he double-checks all results provided by such collaborators.

Regarding his 2020 breakthrough of a dead donor uterus transplant, it seems this was less of a success, as Brännström admitted:

We are in the process of writing up a research article about our first deceased donor transplant. The uterus had to be removed before childbirth, but I can not give anymore specific information until the article is published. The patient is in good health.

And now, the Fageeh story by Martin Endara Coll:

The first uterus transplant, or how Lancet apologised to Saudis

By Martin Endara Coll

In the year 2000, a medical team led by the Saudi Arabian obstetrician Wafa’a Fageeh attempted the first womb transplant in the world. This womb transplant became a celebrated achievement in medical history and part of textbooks ever since. 

The news came as a surprise, not just because of her own perceived lack of expertise, but because the research on uterine transplantation was in its early stages everywhere.

In the case of Dr Fageeh, soon after the success story made the news, an article in The Lancet accused the doctors of taking the womb from a donor without her consent. While the strict opacity of Saudi Arabia didn’t allow for independent  investigations, we know for sure that the news article was erased without a trace by The Lancet, replaced instead with a bizarre apology to the medical team, and a version of the story provided by the Saudi government.  

Transplantation of the human uterus, Fageeh et al.  

In 2014, the world met the first baby born from a transplanted uterus. This  medical feat happened in Gothenburg, Sweden, where the team of Mats  Brännström had spent the previous decade doing animal research. They  started in small rodents, climbing up to primates, before finally operating on  humans. The case of Dr. Wafa’a Fageeh, on the other hand, was not preceded  by years of animal experimentation. At the time, she had only published two  papers, neither of them about transplants. Nothing suggests that she had experience in animal research or experimental surgeries. And yet, she found  herself leading the team that performed the first womb transplant in the world.  

The deed took place in the King Fahad Hospital and Research Center, in the  Saudi city of Jeddah, in April of the year 2000. But it wasn’t until two years later that the doctors reported the case in the International Journal of Gynecology  and Obstetrics:

W Fageeh, H Raffa, H Jabbad, A Marzouki, Transplantation of the human uterus Int J Gynecology & Obstetrics (2002) doi: 10.1016/S0020-7292(01)00597-5

The donor was ”a 46-year-old female who presented with bilateral multiloculated ovarian cysts […], this patient agreed to donate her uterus”. The recipient was “a 26-year-old female who had undergone a hysterectomy in 1994 because of massive bleeding following a cesarean section”. The paper has many flaws and it’s hard to understand how it passed peer review, as it’s hard to understand how a revolutionary organ transplant that had never been reported before was published only in such a specialized journal with an impact factor of 3.6. 

The general view was that this case was not preceded by proper research studies and team preparations.” 

The quote comes from none other than Mats Brännström, in the 2020 book he edited, describing Fageeh’s womb transplant from 20 years ago. 

Wafa’a Fageeh (Image. ResearchGate)

It’s easy to see how the general view could be so harsh after reading the “Experimental animal studies” section of the paper. The research is sloppy and insufficient, the results are not published and the sources are outdated. For reasons that are not explained, Dr. Fageeh chose to experiment on 16 baboons and 2 goats. The authors write that “the first eight animals underwent end-to-end uterine vascular anastomosis”, but it’s up to the reader to guess if those 8 animals were all baboons or a combination of baboons and goats. Nothing in the text suggests that the surgeons used a different technique for baboons than for goats, or whether the procedure yielded different results in each species. It would seem that the authors only needed 2 goats to feel confident enough to switch to primates, and only 16 primates to operate on humans. The knowledge they gained from each model is not included in the paper, and, as far as we know, not published anywhere else. The only result reported from the animal research  is that there were complications in 75% of the anastomoses in those initial 8 animals, and that in the other 8 it was reduced to 10%. 

The conclusion was that 

 “After reviewing the earlier reported experimental work by other researchers  and our satisfactory results, we decided to prepare for a human trial.”  

Incidentally, the earlier experimental work they used to prepare for the surgery is a study in dogs from 1966. The extreme confidence of the medical team goes beyond their secrecy with the results or the seemingly random selection of animal models. The surgery performed in “the animals” was autologous reimplantation of the uterus. That is, each animal got the womb removed and then re-implanted, which is very different from transplanting it to a different animal. The operation on the human patients was the first womb transplant Dr. Fageeh had ever done, a medical experiment she hadn’t dared to perform on animals.  

After the flimsy description of their preliminary research, the paper goes on to describe the donor and the recipient in a few words each. No medical history is mentioned, besides their hysterectomies, and while they tell us that the recipient was evaluated and found eligible for the transplant, the conditions for eligibility or the evaluation are not disclosed.  

After the procedure, the recipient was kept in observation while monitored for  several biomarkers, but none of these values are reported:

The recipient made an uneventful recovery with good wound healing. White blood count, cyclosporine level, and creatinine phosphokinase enzyme levels were checked twice a week.“

The lymphocyte CD4/CD8 cell ratio is only mentioned in the text, “found to be reversed to 3.4”. There are no tables, plots, or any other data from either of the patients. The figures in the paper are: an  illustration of the anastomoses they used, an ultrasound of the recipient, where we can see her full name (sic!), and a black-and-white histological picture with no arrows or description. There are pictures of the transplant which appeared in a book chapter in 2007, titled “Uterus Transplantation”, written by Wafa Fageeh and Giovanna Lucchini. For the initial transplant report, the authors considered that images, data and figures wasn’t something their research manuscript needed, and the editor agreed.  

From Fageeh et al 2002

The lack of evidence in the 2002 paper spreads to the acknowledgements section and the list of references. The authors thank “H.R.H. Prince Naif Bin Abdul Aziz,  Minister of Interior Affairs, for his support and patronage of the First  International Symposium on Uterine Transplantation, which was held in Jeddah  on 21-22 June, 2000.” We haven’t been able to find any evidence that this symposium happened, at least internationally. There is evidence of a “First International Symposium on Uterine Transplantation” happening in Sweden in 2007. New Scientist and BBC mention it, as well as a patient of Dr. Brännström. Finally, the list of references in Fageeh’s 2002 paper is unusually short, citing only 11 articles, half of which are from before 1990.  

The paper spent 12 months in peer review, but there is no evidence it did it any good. In any case, the editors Louis Keith and Guiseppe Del Priore were pleased that the authors chose their journal, as they wrote in an editorial in the same issue: 

“Clinical practice in the latter half of the 20th century has been dramatically changed by many advances, not the least of which is organ transplantation. […] Public attention to the problems of transplantation reached a zenith when Dr Christian Barnard transplanted the first heart in a human. Dr Bernard, the patient and their African hospital received constant media attention, and the daily progress of the patient was duly reported. From the beginning, however, commentary was not always supportive; criticism came from within and from outside the medical profession. […]

The editors of the International Journal of Gynecology and Obstetrics are pleased that Drs Fageeh, Raffa, Jabbad and Marzouki have chosen our journal to present their report on the first human uterine transplantation.“

Obviously these editors didn’t read Fageeh’s paper. They go on to remark that “the text presents in detail a thorough discussion of the preparatory animal experimentation in which surgical techniques were refined”, referring to the experiments on dogs from the 1960ies and Fageeh’s unpublished observations from goats and baboons.  

As is often the case with science, once the headline reaches the press the content of the paper becomes irrelevant. A spokesman for the British Royal College of Obstetricians and Gynaecologists called it “a very, very exciting  development” in an article for The Guardian. It also appeared in The New York  Times, CNN, and CBS News

There are, however, other gaps in the story. The absence of the freedom of press in Saudi Arabia casts a shade over the inconsistencies of the reports. Dr.  Fageeh has been interviewed very few times, and on one of those rare occasions from May 2000, she said that she had been invited to give virtual seminars at Harvard and Johns Hopkins, although there’s no  information on whether these seminars ever happened. She never published  another paper about womb transplants, besides the book chapter mentioned above, and in her following publications she changed her signature from W. Fageeh to W. M. Fageeh. When western media reported her alleged success story in 2002, the quotes about the relevance of the surgery came from western medical experts, never from Fageeh, other members of her team, or other Saudi doctors. From a certain point of view, it’s as if the procedure was a fluke. There weren’t any prizes, fame, or follow-up work. And yet, most articles and books in the field cite Fageeh’s work as the first womb transplant in history.  

The Lancet apologises

Most media articles were unaware that the transplant was reported in a more prominent journal before, but for the wrong reasons. In September of the year 2000, only a few months after the transplant, The Lancet published a news article titled Uterine transplantation failure causes Saudi Arabian government  clampdown, (Lancet. 2000 Sep 2;356(9232):838), written by Peter Kandela. Its text can’t be found on Pubmed or Google Scholar. It doesn’t exist on the webpage of The Lancet, even though Kandela was a regular contributor. The original issue was digitalized, but the pages 833 to 840, where this article should have been, are conveniently missing. It seems as if the accusations made by Kandela were so severe that The Lancet chose to erase his report from the internet.

One year later, a couple of months before Fageeh’s paper was published, The Lancet issued an apology to her and her medical team: 

Apology to Dr Wafa Mohammed Khalil Fageeh, obstetrician and gynaecologist and assistant professor at King Abdilaziz University, and her medical team

In our September 2, 2000, issue we published a news item (Kandela P. Uterine  transplantation failure causes Saudi Arabian government clampdown. Lancet  2000; 356: 838) about a uterine transplant done in April, 2000, by a Saudi medical team led by Dr Wafa Fageeh. We wrote that the transplant had failed because the uterus was rejected by the recipient. This is incorrect; in fact, the recipient had two menstrual cycles after the operation but after 99 days, a vascular occlusion led to the removal of the transplanted uterus. 

We reported that the case had caused controversy because the family of the donor had lodged an official complaint against Dr Wafa Fageeh and her medical team because they said that the donor had not consented before surgery to the removal of her womb for transplantation. 

We also reported that the family had complained that the donor had suffered severe problems as a result of the surgery, including the severance of the left ureter. 

The Lancet now wishes to make it clear that the relevant Saudi authorities have inquired into the complaints of the donor and the family and have concluded that proper informed consent was given prior to the transplant operation. The Lancet also wishes to make it clear that during the operation the donor sustained only a small laceration to her left ureter which was treated during the operation and that as a result the donor has completely recovered. We are happy to set the record straight.”

Apologies are not a common thing in the scientific literature. The Lancet has issued 24 in all of its long history, more than half before the year 1900. The previous time that The Lancet published an apology letter was in 1965, making the one to Dr. Fageeh a very unusual oddity. Even odder is that the apology is signed by Dr. Fageeh herself, instead of Kandela or the editorial team. It’s worth mentioning that a year had passed between the publication of Kandela’s article and the apology letter that “set the record straight”, even though the Saudi  government only needed to check if the donor had consented to give her uterus and when it was removed from the recipient’s body. 

Peter Kandela (Photo:Twitter)

Kandela wasn’t the first one to suggest that the donor hadn’t agreed to donate her womb. Two articles published in the Saudi-owned newspaper Asharq Al Awsat, in August and September of the year 2000, accused Dr. Fageeh of similar charges. In her reply to these articles,  Fageeh admits that there was a formal complaint against her, but dismisses it  because the person who filed it wasn’t a guardian or a first-degree relative of  the patient. Already then, in September of 2000, she claimed to have legal  proof of informed consent. Dr. Fageeh was aware of the accusations against her by the time The Lancet published Kandela’s news article echoing them, and yet the apology wasn’t issued until September of 2001. It’s unlikely that Fageeh wasn’t aware of a leading medical publication reporting on her pioneering operation. On the other hand, if she was aware of the article, the delay to rebut it could have come from the communication between The Lancet and the Saudi government, suggesting that the evidence was not clear enough to “set the record straight”. Kandela also claims that the Saudi government had issued a ban on any experimental medical procedure, entrusting a committee to approve them case by case. This was reported in September 2000 as well, by an article in the Emirati newspaper Al-Bayan. While Fageeh admits that the ban is in place, she assures it’s not related to her case.  

In the 20 years that have passed since the transplant, the accusations against the medical team haven’t been properly investigated. There hasn’t been any updates about whether Dr. Fageeh or other doctors in Saudi Arabia have attempted new womb transplantations. In their apology, The Lancet  doesn’t mention the ban on experimental procedures imposed by the government. They also forget to mention that even Fageeh admits that a  complaint was filed against her by someone related to the donor. While the truth about the case may never come to light, the little information we have paints a gloomy picture. Instead of investigating the issue, a prominent medical journal erased one of their articles and replaced it with an apology dictated by an authoritarian government. The case report by Fageeh et al. about the uterine transplant was published despite its obvious deficiencies and even praised by the editors and media. It may not be surprising, but it’s still concerning that scientific journals give in to external pressure, especially when the pressure comes from one of the most repressive dictatorships in the world and a doctor is accused of operating without informed consent.  

The writings of Peter Kandela 

Peter Kandela was an Iraq-born doctor that lived in the United Kingdom. In one  of his Lancet articles (Lancet. 1998 Oct 1;352:S7-11) he described himself with these words: 

“Peter Kandela is a general practitioner and medical writer. In 1978, he  became a founder member of the British Medical Group of Amnesty  international and in 1989 he co-founded Physicians for Human Rights (UK). Since then. he has taken part in various fact-finding missions for both organisations, and is currently an adviser to a number of human rights  groups. For nearly two decades he has been contributing features on  medical and human rights issues to The Lancet and other medical  journals: and he is an editorial adviser for the Harvard journal Health and  Human Rights. In 1994, Dr Kandela was elected a member of the Royal  Institute of international Affairs and he is currently President of Physicians for Human Rights (UK). “

As part of his work in human rights, he participated in missions in Kashmir, Kuwait, Egypt, South Africa, and Rwanda, researching the living conditions in the prisons. He wrote about access to healthcare for undocumented immigrants, the role of medical journals in reporting human rights violations,  the perception of AIDS in Arab countries, and female genital mutilation. For the 175th anniversary of The Lancet, he wrote a series of 11 articles remembering great moments in which the journal had made a difference in society, published in the column Sketches from The Lancet. There, he recalled the beginning of the publication as a rudimentary form of piracy, where university lectures were reproduced for the students that couldn’t afford tuition, or its campaign against the amputation of the clitoris in England in the 1880s, a claimed remedy for  hysteria, convulsion or sterility. Dr. Kandela passed away in 2012.  

What follows is the original article written by him and deleted by The Lancet, with the hope that Saudi Arabia won’t delete it from here too:

Uterine transplantation failure causes Saudi Arabian government clampdown

A government directive has been sent to all hospitals in Saudi Arabia, stating that no new surgical procedures are to be done unless permission has been granted.  

Anyone doing a surgical procedure for which there is no precedent within the  country will be asked to explain themselves to a committee of specialists set  up for the purpose – unless there is clinical evidence from overseas supported  by published evidence. 

This directive was issued following widespread reporting of the case of a woman who received a womb transplant. The possibility of such a transplant attracted great public interest, but about a month after the failure of this  attempted surgery, the Ministry of Health acted to stop any further “experimental” operations. 

The attempted transplant was done by a Saudi medical team led by Wafa Faquih. But soon after the operation the new womb was rejected and had to be removed. Much of the controversy surrounding this case stems from the family of the donor who claim that she was “tricked” into providing the organ. They have now lodged an official complaint against Faquih and his medical team. It is alleged that Faquih was treating the donor for an ovarian cyst at the University Hospital Jeddah, but made arrangements for the cyst to be removed at the King Fahad Hospital in Jeddah which in fact has no department of  gynaecology. The relatives claim that the surgery took many hours, during which Faquih left the theatre and requested consent to remove the patient’s womb, following the discovery of a “tumour”. There was no mention of any transplantation at the time during the surgery. But a few days later a hospital employee told the patient’s family what had happened and local newspapers began to report the story.  

The donor is currently being treated at the King Abdul Aziz hospital in Jeddah where her family claim that she has severe problems following the surgery including the severance of the left ureter. Naturally they are asking whether the tumour really existed in which case the womb would not be suitable for transplant, or whether claims of a tumour were fabricated in which case there was no justification for removal of the womb. 

The investigation of this case will no doubt be significant in influencing  attitudes to the regulation of new surgical procedures in Saudi Arabia in the future. 

Peter Kandela

2 comments on “The first uterus transplant, or how Lancet apologised to Saudis

  1. Pingback: Come battezzare un parassita – ocasapiens

  2. Pingback: El primer trasplante de útero, o como The Lancet se disculpó con los saudíes – Martín Endara Coll

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