The ability to shift fertilization into a lab dish has revolutionized infertility treatment, and rewritten some of the basic tenets of reproduction. But does IVF make children more vulnerable to cancer and certain cognitive or other developmental issues? In the largest study to date looking at the connection between IVF procedures and neurological disorders, scientists found a significant risk of intellectual disabilities.
The researchers studied 2.5 million Swedish children, and compared those born via IVF with those who were conceived naturally. “For IVF there are known risks already, such as birth defects and cancer, and now mental retardation should perhaps be added,” says the study’s lead author Sven Sandin of King’s College in London.
Specific procedures, such as IVF that involved more manipulation of the sperm to promote fertilization, were more likely to be associated with higher rates of neurological issues than IVF without it. That suggests that male-based fertility issues may have a stronger correlation with later cognitive deficits. “That brings us to consider that there might be some genetics involved in severe male-factor [infertility], but it is extremely important for my patients with male-factor [infertility] not to freak out and think they are the significant risk. The total number of babies with problems with IVF, and even male factor, are small,” says Dr. Avner Hershlag, chief of the Center for Human Reproduction at North Shore University Hospital in Manhasset, N.Y., who was not involved with the study.
Fertility treatment may change the way certain genes function when they are passed from parent to child in a process known as ‘genomic imprinting’.
These faults in genes are linked to childhood cancers, Danish researchers have stated.
Researcher warn these changes could be triggered by aspects of fertility treatment such as exposure to hormones, semen preparation, freezing embryos, growth conditions of embryos or delayed insemination.
In vitro fertilisation (IVF) is among the most widely used fertility techniques, with hundreds of thousands of babies born around the world each year.
There is a greater risk of birth defects and developmental problems among multiple births, which are more common with IVF since doctors often transfer several embryos during a cycle, to improve a woman’s chances of becoming pregnant. “I call it the epidemic of multiple births that our field has created by transferring multiple embryos into the uterus. It has brought up a lot of medical and health issues for the babies as well as for the moms,” says Hershlag. To avoid the added risks associated with multiple births, many centers now only transfer one to three embryos at a time.
With the first babies born through IVF now reaching their mid-30s, more studies are examining what the lasting legacy of IVF might be. In October, research presented at the American Academy of Pediatrics National Conference and Exhibition in New Orleans found that among 4,795 babies born after IVF and 46,025 infants who were conceived naturally, 3,463 babies developed congenital birth defects. But that doesn’t necessarily mean that the IVF treatments are responsible. In a study from March, for example, researchers reported that neurological problems among IVF babies were more likely brought about by factors related to infertility and not the treatments themselves.
Linked To Cancer
Research, in the journal Fertility and Sterility, reviewed 25 studies from 12 developed countries, including the US, the UK, Denmark, France and Israel, from 1990 to 2010.
‘The results of the largest meta-analysis on this topic to date indicate an association between fertility treatment and cancer in offspring,’ wrote author Dr Marie Hargreave, of the Danish Cancer Society research centre, Copenhagen.
‘The etiology [origin] of childhood cancer is still largely unknown, but it has been hypothesized that fertility treatment may play a role.’
One theory is that anti-oestrogen drugs that stimulate ovulation are similar to diethylstilbestrol, a drug once given to pregnant women to stop complications, but later linked to childhood cancer.
The researchers stressed that the risk of cancer among children born after fertility treatment remains low.
They wrote: ‘Infertile couples may already have an increased number of epigenetic defects...which come to light through the treatment process.’
Children are 2.6 times more likely to become ill with acute lymphoblastic leukaemia (ALL), the most common type of childhood leukaemia, if their mothers had been treated with ovary-stimulating drugs.
They had a 2.3-fold increased risk of suffering the rarer form of the disease, acute myeloid leukaemia (AML).
Dr Jeremie Rudant, from the Centre for Research in Epidemiology and Population Health at the French research institute INSERM in Villejuif, Paris, said: 'It has always been hypothesised that assisted reproductive technologies may be involved in the onset of childhood cancer as they involve repeated treatment at the time of conception and or manipulation of the sperm and egg. And it is now established that a majority of acute leukaemia have a pre-natal (pre-birth) origin.
Most children in the studies were born after IVF but some couples used other techniques such as intra-cytoplasmic sperm injection or intrauterine insemination.
Dr Allan Pacey, the chairman of the British Fertility Society, said: ‘Although this paper reports an apparent increase in the incidence in childhood cancer, the association is small and it is still not possible to say whether it is a consequence of IVF or the underlying infertility of the parents.’
Cancer is the second biggest cause of death of children in developed countries. Around 1,600 children are diagnosed each year in Britain.
A spokesman for the Human Fertilisation and Embryology Authority said: ‘A recent UK study found there to be no increased risk of cancer to children as a result of assisted reproduction treatment.’
Geeta Nargund is medical director at Create Health Clinics, which promotes ‘mild IVF’, with fewer fertility jabs and lower dosages. She said: ‘This is an interesting study which raises concerns about potential long-term effects of fertility treatment on children.’