April 1, 2019

expert reaction to study looking at association between IVF and risk of childhood cancers

Research published in JAMA Pediatrics found a small association of IVF with overall cancers of early childhood.

Prof Alastair Sutcliffe, Professor of General Paediatrics, University College London (UCL), said:

“The boon of fertility by IVF is a great thing for some couples and use year on year is rising (1.7% of births in the USA, 2.2% in the UK, 5% in France). There are an estimated 6 million births worldwide. The press release accurately calls for ongoing studies. Fortunately, cancer is a rare outcome in childhood and therefore the authors are right in calling for further studies as cases accumulate in the at risk population.

“Consistent with work performed in the UK involving 700,000 person years, this excellent American study which is nearly double the size likewise suggested that certain tumours were of higher risk after IVF conception, namely the exceptionally rare hepatoblastoma.

“This study did not adjust for birthweight and gestational age as they may be causally related to this type of cancer. This may well be true but it is not clear if the paper detected hepatoblastoma in normal birthweight children. Premature babies are sometimes fed with TPN (total parenteral nutrition) which is hepatotoxic.

“It is also recognized that at least in animal studies and limited human studies imprinting of genes is affected by culture media in the in vitro environment. So it is indeed plausible that this slight increase in hepatoblastoma is an effect of IVF process rather than the genetic nature of sub fertility.

Dr Anindita Roy, Associate Professor of Paediatric Haematology, MRC Weatherall Institute of Molecular Medicine, Department of Paediatrics at the University of Oxford, said:

“This study by Spector et al is one of the largest population based studies investigating the link between in vitro fertilization (IVF) and increased risk of childhood cancers. The study is robust in numbers of cases and controls studied; and the results point towards a small association of IVF with childhood cancers overall, but this did not depend on the mode of IVF or indication for IVF. This result is consistent with similar prospective studies carried out in the UK and in Nordic countries. It is interesting that this association is mainly driven by an increased risk of embryonal cancers, especially liver cancers.

“However, it is important to note that the increased risk of cancers might be due to other confounding factors that differ between IVF and non-IVF children, such as congenital anomalies, certain syndromes, and maternal causes for infertility that can also lead to inherited causes of cancer predisposition such as TP53 gene mutation. The fact that these factors were not evaluated in the study and a relatively short follow up of the children, could have potentially confounded the results. Therefore the causal significance of the association between IVF and childhood cancer cannot be definitively determined by this study, and further follow up studies may be necessary. A better understanding of the molecular mechanisms that drive an increased risk of embryonal cancers is also required. Nonetheless, the results of a large study of this nature is of benefit to fertility specialists, geneticists and paediatric haemato-oncologists when advising couples undergoing IVF treatment or counselling parents of a child born after IVF who develops cancer.”

Prof Chris Bunce, Professor of Translational Cancer Biology, University of Birmingham, said:

“In this study the authors describe their observation of a small, and marginally statistically significant, association between IVF and overall cancer in childhood. This was largely driven by an apparent increase in liver cancers in IVF babies and children. However, the numbers of liver cancers were small. The study included approximately 2.6 million babies and children with varying lengths of follow up post birth. However only 83 developed liver cancers. Although the scientific rigour of the study is sound, there remains a small possibility that the apparent differences in liver cancer incidences are not real. Furthermore, the authors commendably point out that differences other than natural or IVF conception could be the drivers for any differences in cancer rates. For example the mothers were on average 5-7 years older in IVF cases. Thus the take home message based on this study is that the risks of increased early cancers for IVF born babies and children is low.”

Prof Shirley Hodgson, Professor of Cancer Genetics, St George’s, University of London (SGUL), said:

“This is a reasonably large retrospective study in the US of children born after IVF treatment compared with those conceived naturally, which showed a slight increase in risk of hepatic tumours, nervous system tumours and other embryonal cancers in the IVF group. The follow up was short, to 5 years, and notably the average age of mothers in the IVF group was higher, so it was not possible to ascertain whether the important aetiological factors that could be implicated were infertility, age of the mother, or IVF, but is an important indicator of a small increased risk in the IVF group that deserves more study.”

Dr Jane Stewart, Chair, British Fertility Society said:

“This study suggests that following up on the health of IVF babies over time is a useful exercise. It does not, however, suggest that IVF causes these cancers.

“The research involved a large cohort, which improves reliability, but the researchers were not able to consider other factors that might lead to childhood cancers in this group.

“As with other similar studies, an association between IVF and cancer is found but it is impossible to say what the cause is. We still need to know whether it is the treatment itself or the underlying infertility that accounts for this difference. There are also lifestyle and other factors that could contribute to cancers in this group, which are not explored in the paper.”

‘Association of In Vitro Fertilization With Childhood Cancer in the United States’ by Logan Spector et al. was published in JAMA Pediatrics at 16:00 UK time on Monday 1st April.

Declared interests

Prof Alastair Sutcliffe: No declarations of interest

Prof Chris Bunce: No declarations of interest

Prof Shirley Hodgson: No declarations of interest

Dr Jane Stewart: No declarations of interest

None others received.