Advancing in the name of science and humanity

Around 25 per cent of IVF pregnancies result in multiple births, a rate 20 times higher than after natural conception – and this is the biggest risk for women undergoing IVF.

“Many patients perceive twins as a positive outcome,” says Stuart Lavery, a gynaecologist and director of IVF Hammersmith. But the risks are “very serious”, including premature birth, miscarriage and complications during labour.

Single embryo transfer, where just one embryo is transplanted back into the womb, is increasingly used to minimise this risk. Crucially, this does not necessarily reduce a couple’s overall chance of conceiving. The IVF pregnancy rate has remained constant even as the rate of multiples has dropped – from 27 per cent in 2008 to 20 per cent in 2011.

In 2011, 17 per cent of women chose single embryo transfer, even when several embryos were available. Improved embryo freezing and selection techniques can give couples the best chance of success with this option. “It’s not just about getting people pregnant; it’s about getting them pregnant safely”, says Neil McClure, professor of obstetrics and gynaecology at Queen’s University Belfast.

A cycle of IVF may produce several viable embryos and those that are not used can be frozen. Embryo freezing is a delicate process because water inside can turn into ice crystals, damaging the cells. Traditionally doctors have cooled the embryo over several hours to minimise damage, but in a new technique, called vitrification, the embryo is cooled so quickly that water does not form crystals and so could make subsequent cycles more successful.

“Vitrification is becoming the standard method,” says Dr Raj Mathur, a gynaecologist at Addenbrookes Hospital in Cambridge. “Around 85 to 90 per cent of embryos frozen in this process survive once they’ve thawed. In slow freezing, the survival rate is around 65 to 70 per cent. But comparisons are difficult because vitrification usually uses embryos at the blastocyst stage, around five days, while slow freezing uses embryos at two to three days, when the rate of loss is naturally higher.”

You could create eggs or sperm at any stage… women wouldn’t have to worry about reproductive ageing

Mitochondrial diseases happen when structures called mitochondria, which usually produce energy, are damaged by genetic mutations and this stops the cell from functioning properly. These can cause specific conditions, such as Leigh’s disease, as parts of the body affected are those that have the highest energy demands, for example the brain, muscle, liver, heart and kidney. In this procedure, an embryo with mutated mitochondria has its nucleus removed and transferred to a healthy donor embryo.

Treatment with mitochondrial replacement is currently prohibited in the UK because it involves transferring an embryo with altered DNA. The baby would have DNA from three sources – mother, father and egg donor. But a consultation on these ethical issues by the Human Fertilisation & Embryology Authority in 2012 found broad public support for the procedure.

Around 1 in 200 children are born with mitochondrial disease each year, for these families the procedure could be “life changing” says Mr Lavery. Not only this, says Dr Mathur, the impact on scientific knowledge “could be just amazing”.

A new piece of technology, which photographs embryos around every ten minutes, is helping doctors to select the best. This technique is just starting to be used clinically.

Lissa Goldenstein, president and chief executive of Auxogyn, developers of the Early Embryo Viability Assessment Test (Eeva), says “taking images of embryos is something that people have been doing for a long time”. But recent research has set parameters for what normal development looks like, for example rate of cell division. The Eeva system helps embryologists choose the most viable embryo using this data. 

Rob Smith, deputy laboratory manager at CRM London, a clinic trialing Eeva, says: “The pregnancy rate is tremendously high. We can pick with far greater accuracy which embryos need to be put back in.”

Conventionally, doctors look at an embryo once a day, getting only a brief snapshot of its development. This involves removing the embryo from its incubator, thus disturbing it. The EmbryoScope time-lapse system, developed by Unisense FertiliTech, has a built-in incubator which could help to counter this. Niels Ramsing, chief scientific officer of Unisense FertiliTech, says it “provides improved IVF treatment through highly stable incubation, which gives a basis for better selection”.

Comparative genomic hybridisation (CGH) is a novel way of screening embryos for chromosomal abnormalities, currently used in just a few clinics.

Abnormalities in chromosome number are a major cause or miscarriages and conditions, such as Down’s syndrome. CGH provides more detail than standard pre-implantation genetic screening. In CGH all 23 chromosome pairs are compared whereas standard screening can test up to 12 chromosome pairs.

Because this is new and has only been used in a small number of cases, it is not yet possible to say how successful it is. If doctors and patients are confident they’re putting the best embryos back into the womb, then single embryo transfer may be possible for all couples, which Mr Lavery describes as “the Holy Grail” of fertility treatment.

In future, people who can’t produce their own sperm or eggs could still have genetically related children. HFEA estimate that in five to ten years, eggs or sperm could be produced from stem cells and potentially used in treatment.

“This would be an amazing goal,” says Mr Lavery. “You could create eggs or sperm at any stage… women wouldn’t have to worry about reproductive ageing.”

But scientists are concerned that the very complex process needed to generate sperm and eggs could make chromosomal abnormalities and other severe genetic problems likely.

With these developments we are taking “incremental bites”, but we still have a way to go says Professor McClure. “We’re moving to a future where safety and better success rates go hand in hand,” adds Dr Mathur.