WILL IVF work for you? A new calculator could give you the most accurate prediction yet of your chances of success.

Fertility doctors tend to base a woman’s odds of IVF success on her age and ovarian reserve – the number of follicles available for fertilisation. With this information they can decide whether or not to recommend treatment – which can be expensive, as well as mentally and physically demanding.

But existing models for predicting the outcome of IVF are based on limited, outdated information, says at the University of Birmingham, UK. IVF techniques have changed considerably since these models were developed – embryos are grown outside the body for longer, for example. Meanwhile, a decade of research has highlighted many new factors that can affect the outcome, including a woman’s weight, any previous pregnancies or miscarriages she might have had, the cause of infertility and how long a woman had been trying for a baby. Ethnicity also seems to play a role, although no one is sure why that should be.

To create a model that encompassed all these factors, Dhillon and her colleagues combed through data from almost 10,000 women who had their first round of IVF between 2008 and 2012. The data was taken from a UK-wide chain of fertility clinics, in which a quarter of women had their treatment covered by the NHS, while three-quarters paid privately. IVF was considered a success if a baby was healthy one month after birth.

The team then tested their model’s ability to predict the IVF outcomes of women who had attended the fertility clinics between 2012 and 2013 and found that it was correct 65 per cent of the time (Human Reproduction, ).

It’s not clear how accurate current predictions are. For example, a 32-year-old may be told that women her age have a 33 per cent chance of IVF success on average, but should she have any additional problems, such as a history of miscarriage, it is up to the doctor to make a “best guess” at predicting how this will affect her chances.

Older models do need to be updated, says at Hull York Medical School in the UK. “IVF is no easy choice, so couples really should be given the best, most accurate information available,” he says.

The new model is only based on women who are about to start their first cycle of IVF using fresh embryos. Such women are given hormone treatments to stimulate the production of eggs, which are then removed and fertilised with sperm in a lab. A healthy-looking embryo can then be implanted.

, a consultant embryologist at Guy’s and St Thomas’ Private Healthcare in London, says that couples should have more realistic expectations about IVF success rates, but isn’t convinced couples with low chances will change their minds, even with an updated test. “If you’re the one person it does work for, the statistics don’t matter,” she says.

(Image: David Curtis/Millennium Images, UK)

This article appeared in print under the headline “Best way yet to predict IVF success”

The global warming “hiatus” is just an illusion caused by inaccurate analysis, according to updated ocean observations and new data on surface temperatures. Instead of pausing over the past 15 years, temperatures continued to rise at a similar rate to that seen in the second part of the 20th century (Science, ).

Antelope killer found

More than half the world’s saiga antelope – some 134,252 animals – were wiped out in Kazakhstan in just three weeks. Now the culprit has been identified as haemorrhagic septicaemia, caused by the bacterium Pasteurella multocida, according to the World Organisation for Animal Health, which says the outbreak is now over.

Flying saucer splash

On Monday, NASA launched a test flight of its Low-Density Supersonic Decelerator, a disc-shaped re-entry craft designed to slow the descent of spacecraft landing on Mars. But its 30-metre-wide parachute failed to inflate, causing it to splash into the Pacific Ocean.

G7’s climate pledge

Leaders of seven of the world’s richest countries have committed to phasing out fossil fuels by the end of the century. They have also agreed to work towards limiting global warming to less than 2 °C above pre-industrial temperatures.

Freeze thaw ovary

A woman who had an ovary removed as a child and re-implanted as an adult has given birth. At the age of 13, before she started menstruating, the woman had chemotherapy that would have damaged her ovaries. To preserve her fertility, one was removed and then frozen. Ten years later it was thawed and implanted, enabling her to become pregnant (Human Reproduction, ).

For the first time, a woman who had an ovary removed as a child and part of it re-implanted as an adult has given birth. Her right ovary was removed at the age of 13, before she had started menstruating, because she was about to receive immunosuppressive therapy that would damage her fertility. Ten years later, it was thawed and part of it implanted, enabling her to become pregnant naturally.

This is good news for the many other girls and women who have their ovaries stored in freezers, but how does the treatment work, and what are the risks?

Why would someone have their ovaries removed?
Some medical treatments can trigger ovarian failure – essentially bringing on the menopause. Cancer drugs are particularly damaging, as are drugs used to lower your immune defences before receiving organ or tissue donation. In this case, the woman was given immunosuppressive therapy alongside a bone marrow transplant to treat her sickle-cell disease.

Although women who are about to undergo a damaging treatment can have their eggs frozen, girls who haven’t yet started to menstruate don’t have this option. Instead, girls can have part or all of an ovary removed and frozen, until they are ready to start a family.

How effective are ovarian transplants?
We don’t know. Thousands of women are thought to have had their tissue stored, but we don’t know how many have had their tissue thawed and re-implanted. We do know that there have been at least 30 successful pregnancies worldwide, using transplants of ovarian tissue that had been taken from adult women.

It was unclear whether parts of an ovary taken from a child would work in the same way. This case shows that it can, and that the transplanted tissue has a promising lifespan.

The woman was 24 when she received the transplant, but shortly afterwards stopped trying to conceive while she was experiencing relationship problems. It was only later, at the age of 27, that she decided to try again. The doctors who treated the woman are confident that she should be able to have more children in future, should she want to.

What does it mean for other women?
The result is relevant for other women who had their ovaries frozen as children. Surgeons began to remove and store ovarian tissue in this way in the mid-1990s, and many of the children who had their tissue frozen then are now reaching child-bearing age, so we are likely to see many more cases like this soon.

But we still can’t be sure that very young children can expect as good results. By the time the woman in this case had her ovary removed, she had already started puberty. We have yet to learn whether tissue collected from 2-year-olds, for example, will help women conceive further along the line.

Are there any risks?
Yes. There is a chance that tissue taken from people before cancer treatment will be contaminated with their cancer cells. Implanting the cells could trigger a return of cancers like leukaemia in these people. This wasn’t a problem in this particular case, because the woman didn’t have cancer.

And there is a chance that harvesting and freezing ovarian cells could be harming them in ways that we don’t yet understand, says , a paediatric surgeon at Necker Hospital for Sick Children in Paris, France.

She says there is growing evidence that some IVF procedures may increase the risk of some disorders in children. We won’t know if similar risks apply to children born from thawed ovarian tissue until more people have tried the procedure.

What about boys and men?
Medical treatments can also damage the testes, leaving men infertile. Before starting such a treatment, men can choose to freeze and store ejaculated sperm. A few clinics have started offering young boys the option to remove and freeze parts of the testicle, but none have yet been implanted back.

That doesn’t mean we shouldn’t store the tissue anyway, though. Until 2004, when the first woman became pregnant after having her frozen ovary transplanted, doctors didn’t know if they’d be able to do anything useful with the pieces of ovary they had been freezing.

Journal reference: Human Reproduction, DOI: 10.1093/humrep/dev128

He has been called the world’s first stem cell baby. Zain Rajani was born three weeks ago in Canada after his parents opted for a . The procedure is supposed to enhance the quality of a woman’s eggs by injecting them with mitochondria taken from her ovarian stem cells.

Some media reports say this is the , but experts Â鶹´«Ă˝ spoke to were sceptical. Let’s weigh up the evidence.

So women have stem cells in their ovaries? Does this mean they can make new eggs? I thought women were born with all the eggs they were ever going to have.
That was the dogma until a few years ago, when a group at Massachusetts General Hospital in Boston discovered stem cells tucked away in the protective lining of the ovary that mature into fresh eggs. The finding suggested that new eggs are produced throughout life and was hailed as revealing that there are limitless eggs for IVF treatments. It was suggested at the time that this could also allow older eggs to be rejuvenated.

The team that made the discovery, led by Jonathan Tilly, then partnered with OvaScience. It was this company that .

How did the stem cells help Zain’s mother conceive?
The idea is that the mitochondria – cellular energy generators – in young, primitive cells function much better than those in the mature eggs collected for IVF. Collecting these mitochondria and injecting them into the prospective mother’s mature eggs is supposed to improve their quality. In its press release, OvaScience says: “This treatment is designed to improve egg health by increasing the eggs’ energy levels for embryo development.”

It seems to have worked, at least in the Rajani case?
It’s hard to draw any conclusions from the information released so far. The OvaScience press release says that “initial positive experiences of pregnancies with the treatment have been reported”.

Time magazine reports that . It also says that there have been no formal clinical trials of the procedure but that OvaScience are planning to carry out 1000 rounds of IVF around the world this year using Augment, partly to convince the US Food and Drug Administration to approve the treatment in the US.

Although the procedure appears to have worked for the Rajanis where traditional IVF failed, we don’t know for certain that Zain owes his existence to Augment. “The fact a baby has been born is one case, but you can’t prove that the technology they used is the one reason for this success,” says , a professor of reproductive medicine at Leeds Teaching Hospitals NHS Trust in the UK and chairman of the British Fertility Society.

When Â鶹´«Ă˝ contacted OvaScience for a response, they said: “The evidence is based on the mother’s medical history, including a prior IVF cycle failure which showed very poor embryo quality, as well as her diagnoses.

“There are other pregnancies in poor prognostic patients across all the clinics offering the treatment.”

What else do independent fertility researchers think?
Balen and others we contacted cited a lack of evidence that adding fresh mitochondria would help make old eggs youthful again. “The reason old eggs are less fertile is because they don’t have the integrity to go through cell division in an ordered way, which is why you get chromosome imbalances,” says Balen. “There’s no peer-reviewed evidence that mitochondria from immature eggs would correct this.”

“There’s a lack of evidence of efficacy, efficiency and safety,” says Alison Murdoch of Newcastle University, UK. “The problem in older women is the quality of the nuclear genome in their eggs, and adding more mitochondria will not help that problem,” she says. “Also, manipulation of the embryo at that very sensitive time could cause more problems for the nuclear genome, which is why safety data is critical.”

Has anything like this been done before?
Sort of. In 2001, Jacques Cohen at the Institute for Reproductive Medicine and Science at Saint Barnabas, in New Jersey, injected mitochondria from a donor egg into 30 eggs of infertile prospective mothers, a procedure known as ooplasmic transfer. The fact that this resulted in a handful of pregnancies is seen as supporting evidence for the Augment technique. “There are published clinical reports from multiple IVF clinics throughout the world which showed that using mitochondria from a younger woman’s donor egg significantly improved IVF success,” OvaScience told Â鶹´«Ă˝. “More than 50 babies were born from this technique, and those children are now in their late teens and early 20s”.

In Cohen’s case, the research was halted because the babies carried extra mitochondria from the donor, leading to an outcry over them having three parents.

Three-parent babies? That sounds familiar.
Yes. Both ooplasmic transfer and Augment have some parallels with mitochondrial replacement therapy, the controversial new type of IVF recently approved by the UK government. Like ooplasmic transfer, this results in children carrying DNA from three people. It was approved because it prevents parents from passing on untreatable mitochondrial diseases to the child. Because the Augment technique uses mitochondria from the mother’s ovarian stem cells rather than a donor, there is no three-parent ethical quagmire to wade through.

Rather than designing drugs to target hard-to-treat cancers, what if such cancers could be made susceptible to existing treatments? That is the intriguing possibility raised by the discovery of a genetic switch that may be able to turn the most troublesome breast cancer into one of the easiest to tackle. The finding could also apply to stubborn ovarian cancers.

. About 85 per cent of breast cancer tumours rely on the . That makes them relatively easy to treat: block those chemicals and the cancer will usually stop growing.

But the other 15 per cent of tumours are what is called , meaning that they don’t need either of the two hormones or HER2 to grow.

Generally, people with triple negative cancer tend to do worse than people with other types of the disease, with up to half of them dying within five years of diagnosis. But a sizeable portion of triple negative patients survive for significantly longer.

Different origins

A team led by from the Garvan Institute of Medical Research in Sydney, Australia, may have figured out why and hit on a way of making badly behaving cancer toe the line.

The team analysed the DNA of 80 women with triple negative cancer, looking for differences in their genes. They found that the tumours of women with the aggressive form produced a lot of a protein called ID4.

Subsequent mouse experiments revealed ID4 seems to be produced by healthy breast stem cells. The finding suggests that the aggressive form of triple negative breast cancer is a result of a cancerous mutation in a breast stem cell rather than a mutation in a breast tissue cell. What’s more, whole genome analyses of the two types of tumour – those that produce a lot of ID4 and those that don’t – revealed they are very different.

“We asked, at a whole genome level, what’s different? And in fact, they are very different,” says Swarbrick. “They seem to have a completely different history of development. We think they come from a different place.”

Adaptable roots

It makes sense that more aggressive cancers might have developed from stem cells, says Swarbrick, because stem cells share some of the characteristics of treatment-resistant cancers: they can move around, they are adaptable, and they are less sensitive to genetic damage from things like radiation.

When the team blocked the ID4 gene, which produces the ID4 protein, in mouse and test-tube models of the disease, the tumours stopped growing and a lot of other cancer-related genes in the tumour got shuffled around. Some switched on and some switched off. “Suddenly ID4 is acting as a switch, controlling whether a cell is allowed to activate these cancer-related genes,” says Swarbrick.

Fortuitously, the genes associated with cancers that respond to oestrogen treatment were some of the ones that got switched on – making the most aggressive, difficult-to-treat form of breast cancer look like one of the easiest to treat.

Cancer caricature?

More work is needed to see if that is actually the case, because other genes also play a role in whether a tumour is susceptible to hormone therapy. “We don’t know yet whether we are seeing a real oestrogen-dependent cancer after ID4 is blocked – or just a caricature of one,” says Swarbrick. The next step should help clarify things. Swarbrick says his team is already looking to see if the switched tumours respond to the oestrogen-blocking drug, tamoxifen.

“Maybe we can shift the tumour in the direction of the therapy rather than developing the therapy in the direction of the tumour,” says from the Peter MacCallum Cancer Centre in Melbourne, Australia.

Changing a triple negative breast cancer into one that is amenable to therapies we know work would be quite spectacular, says Ramsay.

Swarbrick says the worst ovarian cancers should be able to switch too, because they have a lot of similarities with triple negative breast cancer and ID4 has already been linked with them.

If the results are confirmed, the implications are manifold. In the short term, it will be a way of giving patients better information about their chances of survival.

In the medium term, because the two classes of triple negative cancer are so fundamentally different, there might be a way of better targeting current chemotherapies.

The long-term goal is to develop a drug that blocks ID4 in people, to specifically attack the most aggressive, hard-to-treat form of breast and, possibly ovarian, cancer.

“It may offer new treatment opportunities to thousands of women diagnosed with triple negative breast cancer,” says Swarbrick.

Journal reference: