It seems particularly fitting to congratulate a Swedish colleague who announced the world’s first successful uterine transplant the same week that the Nobel Prize for Physiology and Medicine is announced from Stockholm. Not that the transplant will earn him the Prize one day, which is awarded for a scientific breakthrough rather than a technical tour de force. Surgeons have long known how to hook up blood vessels, but have balked at challenges about transplant safety, longevity, and ethics.
Mats Brannström has been working on the project for about fifteen years, or as long as I have known him. We used to chat at fertility preservation conferences when I was working on ovarian transplants. My goal was frozen-preservation of ovaries for young cancer patients who were likely to be sterilized by chemotherapy or radiation: when they were clear of disease we would transplant the thawed organs back to restore natural menstrual cycles and fertility. Around the globe, over thirty patients have conceived healthy children after an ovarian transplant. I also worked with the brilliant surgeon, Sherman Silber of St. Louis, who restored years of menstrual cyclicity and fertility to women who had an ovary donated by their genetically-identical twin sister. There is no greater satisfaction for a researcher than to witness their work leaping from the laboratory to the clinic.
But transplanting reproductive tissue can be troubling, if not actually controversial. For us, it was the question of whether an ovary that was removed for storage before the disease was cured might seed cancer cells in the patient as a transplant? For womb transplanters, the major question they face is, “Why do it, when it is so risky?”
Mats explained that the idea didn’t come out of the blue: one of his patients asked if it could be done. She was having a hysterectomy and desperately wanted the experience of gestating a baby. Her inquiring mind set him on a journey to help women like herself. For women who still have ovaries, they can have in vitro fertilization (IVF) before surgery to store embryos in the freezer until they are ready for transfer to the transplant. But, unlike our identical twins, they need constant treatment with drugs to suppress the immune system that naturally tries to reject the foreign organ.
Objectors point out the alternatives for women who lack a uterus. First, there is child adoption, although not such an easy option as in the past. Second, there is surrogacy in which a “tummy mummy” is commissioned to carry the baby. This can be arranged either by conception in her own body, using sperm from the patient’s husband or a donor, or by IVF in which embryos from the commissioning couple are transferred to the third party, so the child is genetically related to them. But surrogacy is outlawed in some countries, including Sweden, as it is in some U.S. states and for Muslims.
Medical practitioners are less paternalistic than they used to be. In the past, they were more comfortable proscribing (as well as prescribing) treatment if it made them uneasy or in their clinical wisdom it did not seem to be in the best interests of their patient. Nowadays, as we come to our doctors after consulting other specialists and surfing the Internet for the latest medical research, we are increasingly telling them what we think they should do! In the parlance of bioethics, the Autonomy/ Beneficence pendulum is swinging from right to left, from B to A, which can take a doctor on a hike into swampy ethical territory. I sympathize with them for wondering why a hazardous uterine transplant should be attempted if it is not life-saving but, on the other hand, I think we ‘fertiles’ can too easily underestimate the grief of childlessness and the lengths that people will go to achieve one of the greatest joys in life—parenthood.
Most women who seek a transplant have had a hysterectomy to treat cancer or another medical condition. Some were born without a uterus because of a genetic abnormality with a name that can throw a student at exam time—Mayer-Rokitansky-Küster-Hauser syndrome. This was the condition that Queen Amalia of Oldenburg (1818-1875) had, and her inability to give King Otto an heir caused their expulsion from Greece. Perhaps a transplant would have saved the monarchy.
I don’t know who should take credit for the original idea of uterine transplantation. I don’t think I deserve that honor (if it is such), but exactly thirty years ago I mentioned it at a conference in another Nordic state, Finland. My suggestion didn’t cause any rumbles, as I expected, perhaps because the audience was too polite to pronounce me ‘off the wall.’ When I returned home to the Edinburgh Medical School, I took the opportunity one day to ask senior colleagues in the common room what they thought of the idea. The gray silence that followed spoke more than anything they might have uttered.
I never thought any more about it until I moved to McGill University and collaborated with a skillful Chinese microsurgeon. We transplanted ovaries, fallopian tubes, and segments of uterus en bloc from donor rats to sterile recipients. Treated with immunosuppressive drugs, the transplants survived and gestated healthy pups. But those were rats. Nobody talked about transplanting a human womb.
The first clinical case was reported in 2000 from Saudi Arabia. It ended in disaster. A blood clotting problem necessitated emergency removal of the womb, amid international criticism. The bad news did not deter a Turkish surgeon, who had famously performed the first full face transplant in his country. In 2013, all was going well when the 22 year-old patient conceived after embryo transfer, but when her fetus was scanned at 8 weeks it was found to have no beating heart and, sadly, had to be terminated.
Meanwhile, Professor Brannström was cautiously honing techniques, testing them in monkeys, and assembling a multidisciplinary team. Patients were carefully selected for the best chance of success, and most had recruited a relative or friend as a donor. Mats deserves credit for not rushing to be first, which is a great accolade in medicine and science.
Seven of the first nine transplants survived. It did not matter that some donors were postmenopausal, because the uterus ages far more slowly than the ovaries. The successful patient did, however, develop pre-eclampsia which forced an early delivery by Caesarean section. But mother and baby boy are doing well and I salute them and my old chum.
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