Uterine Transplants

I just knew it was going to happen; I could feel it in the air: a live and healthy baby delivered from a transplanted uterus.

It was the womb’s turn. After all, people have been trying to transplant stuff since anatomy began. Unfortunately, before the concepts of physiology, infection and immune rejection were appreciated, they all failed. Miserably.

There were exceptions, of course, such as the successful kidney transplant between identical twins in 1954 -where their immune systems were obviously identical as well- but until the ability to avoid the toxicity of anti-rejection drugs was improved, organ exchanges were limited to the desperate or the foolhardy.

A few solitary successes occurred late in the 19th century with skin grafting, but until good immune suppressors like cyclosporin (1970) were developed, most organs –that is to say, most patients– didn’t survive for more than two or three weeks.

And then it took off. Kidney transplants are now routine; heart transplants -while more dramatic because of the need for a healthy organ from an individual who is unfortunately unable to use it any more- no longer garner headlines like Dr. Christian Barnard’s first success in 1967.

And the list of organs being transplanted is beginning to read like an anatomy textbook. Everything from pancreas to lung, combo packs like heart/lung, and even an entire face in 2013. If you can name it, somebody somewhere is trying to transplant it. So it was surprising that the poor uterus was left sitting in the shadows for so long.

In fairness, though, it had been attempted several times before in various medical centers, with little success –ie  ability to do what the uterus was designed to do: incubate and deliver a  live, healthy baby. Not until the 2013 transplant in Gothenburg Sweden, with Dr. Brannstrom’s surgical team was a live baby born from a uterus a year after it was installed. Everything seemed to work –the recipient began to menstruate regularly- so one year after the transplant, having cryopreserved an embryo beforehand, it was placed into the uterus and followed closely as it developed.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61728-1/abstract

The baby was born prematurely (at 31 weeks and 5 days, rather than at the average 40 weeks) because, although blood supply to the uterus was apparently normal, the patient developed pre-eclampsia (pregnancy-related high blood pressure) and there were some problems with the baby’s heart rate that apparently mandated delivery.

Were these complications the result of the transplanted organ (the donor was an unrelated 61 year old post-menopausal woman), the immosuppressants (she was on a triple therapy consisting of tacrolimus, azathioprine, and corticosteroids), or just bad luck? And would such a transplant be able to function normally –like a transplanted heart, say- and contract efficiently enough to enable labour and vaginal delivery? Or would a caesarian section be required in all cases? It’s probably too early to say.

So congratulations to the parents and the transplant team. Fortunately, the need for uterine transplantation is uncommon, and adoption, or even surrogacy remain as other less drastic options. But it seems to me there are issues that, despite the success, have yet to be adequately addressed.

Ethical issues, for one thing. Unlike, say heart or kidney transplants where death may ensue if transplantation is not available in a timely fashion, the uterus is not essential for the continuation of life. And the procedure entails sophisticated, difficult and risky surgery that is frought with possible life-theatening complications in and of itself –including, of course, rejection of the organ despite the immunosuppressants. The surgery, by the way, is far more arduous and byzantine than the routine hysterectomies that are over-performed around the globe –extra tissue has to be obtained along with additional dissection to be able to reconnect the arteries and veins efficiently. So both donor and recipient are at increased risks…

But what troubles me the most I suppose, are the possible long term effects of the immunosuppressants on the developing foetus growing inside the transplanted organ. Azathioprine, for example. It interferes with DNA synthesis, and inhibits the proliferation of quickly growing cells… That seems a lot like what needs to happen in a rapidly growing foetus, doesn’t it? Azathioprine is a pregnancy Category D substance: to be used in life-threatening emergencies only when no safer drug is available. And there is positive evidence of human foetal risk. Even tacrolimus doesn’t have a lot of available human studies in pregnancy.

No doubt safer and more predictable immunosuppressants will be found, but for now I remain concerned that we may be trading something away. Just because we can do something, doesn’t mean we should. Unlike other organ transplants where the risk is assumed by the recipient alone, uterine transplants for reproduction share the risks with a rapidly developing and vulnerable foetus which might not manifest any problems until years in the future.

I realize I may be dismissed as a male Cassandra, a person who cannot see dawn through the warp and weft of the cobwebs of his past, but sometimes we have to stand back for a moment. Sit down and think things through. Decide whether we’ve gained more than we’ve lost, and whether it will be too late to change our minds if and when some damage is revealed.

In this case, one would be well to think of Mabeth’s dilemma:

I have no spur to prick the sides of my intent, but only Vaulting ambition, which o’erleaps itself

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The Wandering Womb

The science that brought you heart transplants, kidney transplants, and even lung transplants, is at it again -with a vengeance. Well, maybe I shouldn’t word it that strongly -I’m sure the folks that thought this one up assumed they were doing some good. And maybe they are… I mean, Science is good, right?

I’ve always believed that the world is filled with answers just waiting for the right questions. If there’s a problem, grab an answer, then look around for the appropriate question; you might get lucky. That’s how it used to be done… Too random? Well then create a problem nobody’s thought of. Then solve it. I can think of several transplant problems one might want to create and then solve. It might make sense to attempt to transplant bowels, for example -you never know when a new set might come in handy. Or how about eyes? They’re useful… And then there is always somebody looking for a new pair of ovaries. For that matter, limbs would be big -entire limbs, not just their parts.  Tongues..? The list goes on. But a uterus? http://www.bbc.co.uk/news/health-25716446

I have to admit I am conflicted on this issue. On the one hand, it would seem natural for a woman without one to want one -a uterus does all sorts of important stuff: carrying babies springs immediately to mind. But hold on. A uterus placed in someone else’s body is in a foreign country. It is a stranger at a family party and after being roundly embarrassed and then exposed as someone they don’t know, it is immediately rejected and shown the door. Explanations just don’t work under those circumstances without drugging the entire family into submission. And don’t forget, the uterus doesn’t merely show up because it got the wrong address; it was likely recruited for a specific and important job. No one orders a new one just to re-create the painful periods of their youth, nor in order to keep a ready supply of fibroids on hand.

No. Odds on, it will be recruited as a biological isolette. An incubator. But fetuses are notoriously sensitive to chemicals as they are developing and so what keeps the incubator alive and well, had better have a similar effect on the incubee. And the only way to keep the body from destroying the transplanted uterus is with anti-rejection drugs -immune-suppressors- which are toxic. Swords of Damocles.

Obviously a similar situation obtains with a transplanted kidney going through pregnancy -it needs immune suppression, too. But although the demands on kidney function change with the constantly moving target of pregnancy requirements, one might argue that there are some fundamental differences that separate kidney function from uterine function in a pregnancy.

First, there is the obvious need for a fertilized egg to actually implant itself in the wall of the stranger -this is the bond that ultimately creates the placenta which in turn nourishes the developing fetus. I can’t imagine this is easy at the best of times. So, the uterine muscle must have a smoothly functioning mechanism to allow an attachment that is not impeded by any inflammatory response from the immune system, or inhibitory effect by the drugs. It has to be a strong and functional union because that union will have to allow for the growth and changing metabolic and nourishment needs dictated by it’s totally dependent passenger for the entire pregnancy: a Gordian knot…

That uterus will also have to grow as the baby grows inside it. Grow -not merely stretch. Too much stretching without concomitant growth might irritate the muscle fibers and cause them to do what muscles all over the world have been taught to do under the circumstances: contract. In obstetrical terms, this is sometimes known as labour… Admittedly, hormones from the placenta and who knows where else will normally have a role to play in keeping the uterus relaxed and quiet -coordinating things. But a transplanted uterus, already confused by its new digs and having to contend with a whole bagful of noxious chemicals may well react differently: like an already rebellious teenager in a new and (maybe) abusive foster-home… (Uhmm, okay that metaphor was probably a bit of a stretch as well…)

And if the pregnancy actually succeeded and made it to an acceptable state of viability for the baby, a Caesarian section would be necessary -I can’t see the uterus cooperating sufficiently to agree to any kind of productive and efficient labour. That’s fine, of course: under the circumstances a Caesarian delivery would likely be the safer option. Perhaps even a Caesarian hysterectomy, because I suspect the uterus would only be a single use entity after what it would have been through and so require removal anyway.

So, what am I saying? I suppose the first thing is that I congratulate the surgical teams for their success in many of the transplants so far and I wish them and the recipients the best of luck. It was inevitable that someone would try it some time, I guess. But remember, successful transplant does not necessarily imply successful function. I have to admit that it is a procedure I will watch with much interest, but from the corner of the room. If all goes well, it will surely be a boon for those women who have lost their uteri through surgery or disease, or even in the genetic lottery that occasionally intervenes so tragically in some lives. Until now, I suppose, adoption would have been the only option, but I understand the wish to gestate one’s own baby with one’s own eggs and in one’s own body.

Maybe, someday, uterine transplants will be viewed much like heart transplants… and yet they are not. Let us not forget that unlike hearts or kidneys, unlike lungs or livers that are transplanted only in extremis and when all other less drastic options have failed, with uterine transplants, survival of the recipient without the organ is not at stake; survival of the baby in utero is, however. And it’s not just survival, we’re aiming for either… It’s the healthy survival of an initially normal fetus that has developed and grown in an abnormal environment. Heaven only knows, enough can go wrong in a normal uterus -even with the best of care- let alone one stitched in place and clothed in chemical soup.

Perhaps I’m viewing this as an elder who has seen many promising ideas go badly wrong -think, for example of thalidomide and the developmental anomalies it produced in fetuses. Or DES for threatened miscarriages that resulted, among other things, in clear cell carcinoma of the vagina. So my advice is one of caution. Just because we can do it, doesn’t mandate that it must be done… Should be done. Ideas come and go -that’s what they’re for after all; it’s how we make progress. Improve things… But in this case, the results may influence -even malign- future generations; the results may be future generations. Let’s get it right -we’re not just dealing with kidneys here.