Thursday October 22 2009
There is a big difference between rabbits and humans
Widespread coverage has been given to reports that the first human womb transplant could take place within two years.
Most newspapers said that research presented at an American fertility conference gives hope to thousands of women who are unable to give birth because they have a damaged uterus, had it removed through disease or because they were born without one.
The reported two-year estimate for the first human womb transplant is overly optimistic. There are several major hurdles to overcome before this could be considered ready for trials in humans. It would also involve a series of operations, carrying all of the usual risks, plus ones that are as yet unknown, for a non life-threatening condition.
Ethical considerations balancing risk against benefit, for both mother and child, also need to be taken into account.
Where did the news come from?
The research was carried out by a team led by Richard Smith, a consultant gynaecologist at Hammersmith hospital. It was presented at the American Society for Reproductive Medicine. The operations in rabbits were performed at the Royal Veterinary College, London, with full approval from the ethics committee.
This research has not been published in full, so this article is based on the conference abstract and newspaper reports.
What did the research involve?
This animal study aimed to transplant a uterus from a donor rabbit to a recipient rabbit using a “vascular patch technique”. This technique involved transplanting not just the uterus, but also major blood vessels, including the aorta.
The researchers carried out five transplants in rabbits, using five donors and five recipients. Two of the five recipient rabbits survived for nine and 10 months at which point post-mortem studies were carried out. Following transplant, these two were placed on immunosuppressant drugs, so that they did not reject the donor organs, and mated. Neither became pregnant.
The post-mortem studies showed that the transplants had been successful and the blood supply to the uterus was maintained, but that the fallopian tube (which carries the fertilised egg to the womb) was blocked, explaining the failure to conceive.
What did the researchers conclude?
The researchers concluded that they successfully transplanted uteruses in rabbits. They say this gives hope of fertility to women who are physically incapable of having babies due to an abnormal, damaged or absent uterus.
They state that they do not intend to cut and later join the fallopian tubes in humans as they did in these rabbits, probably due to differences in anatomy. As such, a human uterus might be transplanted with the tubes intact, making implantation possible. The BBC reports that they now intend to repeat the research in larger animals.
Has a womb transplant been carried out before?
There have been previous unsuccessful attempts to transplant wombs in larger animals and one reported attempt in a human.
A human womb transplant was first attempted in a woman from Saudi Arabia in 2000. This transplant was unsuccessful and it had to be removed after three months when a blood clot developed in one of the vessels to the organ.
The BBC reports the researchers as saying that this first transplant may have failed because surgeons had not worked out how to connect the blood vessels properly.
The lead researcher is reported as saying, "I think there are certain technical issues to be ironed out but I think the crux of how to carry out a successful graft that's properly vascularised [given a sufficient blood supply]...I think we have cracked that one."
Could this technique be used in humans?
- There are inherent differences between rabbits and humans. For example, female rabbits have a uterus that comes in two parts. They can also have litters of up to 13 kits (baby rabbits) at a time, with several different fathers. A rabbit gestation period is 30–32 days, compared to nine months in humans. The blood vessels are smaller and therefore harder to stitch together in rabbits. All these differences mean that it may be either easier or harder to transplant in humans, and it will only be possible to know for sure by attempting it.
- None of the rabbits became pregnant. The researchers have stated that, in future experiments, rabbits will be impregnated with embryos that have already been fertilised in the laboratory. This is an important step as it will need to be demonstrated that the transplanted organ can grow with pregnancy. This could be more problematic than usual when multiple delicate blood vessels have been joined together.
- The Times reports that if the technique was successfully applied to humans, women would need to undergo IVF to avoid complications such as an ectopic pregnancy (pregnancy outside the womb). Any offspring would also have to be born by caesarean section as a transplanted womb would be unlikely to withstand a normal birth.
- Womb transplants would only be temporary because the recipient would need to take immunosuppressant drugs to stop her body from rejecting it. The Times reports that recipients might be given two to three years to have a baby before the womb was removed. This would avoid the need for long-term immunosuppressant therapy. However, it is unclear whether it would be safer to continue taking the drugs while pregnant or to stop them and risk rejection.
If possible, when could it be used in humans?
- The researchers are reported as saying the first human womb transplant could be carried out within “two years”. However, at this stage it has only been shown that rabbits implanted with a donor uterus and its major vessels survived for up to 10 months. The rabbits did not become pregnant or give birth. There are several stages that still need to be achieved before it could be attempted in humans.
- Should the technique reach the stage where it can be performed in humans, medical ethics committees would need to weigh up the benefits against the risk of physical harm to the mother, rejection of the uterus during pregnancy and loss of the child, and the psychological effect of this loss.
Transplant recipients are prepared to put up with major risks in the early development of these techniques if their lives depend on it. For a non-life threatening condition, the procedure will need to be less risky, and the risks will need to be better defined. Perfecting the technique and proving its safety and suitability for use in humans will take substantial time, and probably much more than two years.
As Tony Rutherford, chairman of the British Fertility Society, said, "There is a big difference between demonstrating effectiveness in a rabbit and being able to do this in a larger animal or a human."