September 1, 2022

expert reaction to study looking at children born after frozen-thawed embryo transfer and cancer risk

A study published in PLOS Medicine looks at cancer risk in children born after frozen-thawed embryo transfer.

Prof Daniel Brison, Scientific Director of the Department of Reproductive Medicine, University of Manchester, said:

“This study showing an increased risk of cancer in children born from frozen embryo transfer has been carried out by a well known research group using a well established cohort of children born in the Scandinavian countries, and should be taken seriously.

“However, as the authors note, the result should be interpreted very cautiously and should certainly not be a cause for alarm among children born after frozen embryo transfer, their parents, couples considering Assisted Reproduction Treatment (ART), nor professionals considering offering frozen embryo transfer.  The use of frozen embryo transfer brings substantial benefits as part of ART treatment, as the authors of this study correctly note.

“The main reason for caution regarding the results is that the number of cases of cancer identified in this study in children born after frozen transfer was very low, increasing the risk that the finding is due to chance.  In addition, the majority of other large population studies carried out in the US, previously in the same cohort in Scandinavia, and here in the UK using the Human Fertilisation and Embryology Authority register of ART births, have not shown an increase in cancer after frozen embryo transfer.  Thus there is a possibility that factors other than frozen embryo transfer were associated with this new finding.  In particular, the authors do not seem to have been able to carry out a sibling comparison, looking at cancer rates in children born to the same parents, one from fresh and one from frozen embryo transfer.  This is important to rule out parental factors which might be associated with the cancers and to pinpoint whether or not the technique of frozen embryo transfer is responsible.  In fact a very recent large UK population study has shown that when such sibling comparisons are made, increases in adverse health outcomes which appear to have been associated with ART are much less strong when comparing siblings, suggesting that parental factors play an important role.

“This study should however be taken seriously by the research community, ART regulators and those who hold national registries of ART treatment, and funding bodies.  This should act as a call for much needed further research into long term health outcomes in ART children.  If indeed frozen embryo transfer is associated with an increase in childhood cancer then it will be important to establish causality, to identify which part of the procedure might be responsible, and to use that information to make the procedure even safer.”

Rachel Cutting, Director of Compliance and Information, Human Fertilisation & Embryology Authority (HFEA), and former embryologist, said:

“Our latest data shows there were 25,000 frozen embryo transfers in a year in the UK.

“These findings should be interpreted with caution, as the number of children born after frozen-thawed embryo transfer in this study, who later developed cancer, was very low; 30.1 in 100,000 births.

“Health outcomes in children conceived using Assisted Reproductive Technology is a high priority for the HFEA and we provide high-quality information for patients and professionals using the new and emerging research we monitor.  Anyone considering fertility treatment can access this, and other impartial information on fertility treatments and UK licenced clinics at www.hfea.gov.uk.”

Prof Alastair Sutcliffe, Professor of General Paediatrics, UCL, said:

“As the use of Assisted Reproductive Technology (ART) grows the number of ART conceived individuals born grows likewise so studies of downstream effects are important too.

“Here the (accurate) press release suggests that there is a possible small increase in cancer risk after embryo freeze thawing.  Correctly this suggestion needs to be treated with caution as the findings could be explained by a random high.  There is a strong move in ART towards freeze thawing embryos that are excess after an initial ART cycle after the couple want a further child or more importantly after the first attempt at IVF fails.  This is efficient and also safe as this avoids the replacement of more than one embryo at once thus the risk of higher order births (twins, three four or more).

“So in this context any putative risks need to be offset against the utility of freezing.

“Should practice change as a consequence of this study?  Definitely not.

“Should parents be concerned?  Ditto.

“Are larger studies needed?  Yes.”

Dr Alison Campbell, Chief Scientific Officer, CARE Fertility Group, said:

“The large investigation of almost 8 million Nordic children by Sarisian and colleagues is highly impressive.  Studies like this are very challenging to undertake and such follow up data are not readily accessible in many countries.

“The study includes analysis of health data accumulated over almost four decades.  Over this time, fertility laboratory practices, and in particular methodologies for freezing and thawing of embryos has changed.  As has public health and lifestyle.  As the authors note, these factors, and many others, have not been included in the analyses but may impact the outcomes.

“Embryo cryopreservation and frozen embryo transfer is an integral and established part of fertility treatment, and an absolute necessity for some fertility treatment and patients.  It is used to maximise efficiency of each ovarian stimulation; to safely conserve embryos, and the risks and benefits are considered for each patient.

“People who have children born following frozen embryo transfer should not be unduly concerned by the findings because the actual number of children affected by cancer, following frozen embryo transfer, is too small to draw firm conclusions.”

‘Cancer in children born after frozen-thawed embryo transfer: A cohort study’ by Nona Sargisian et al. was published in PLOS Medicine at 19:00 UK time on Thursday 1 September 2022.

DOI: 10.1371/journal.pmed.1004078

Declared interests

Prof Daniel Brison: “I have no conflicts to declare, other than holding external grant funding to do research into the health outcomes of ART children.”

Rachel Cutting: “No conflicts.”

Prof Alastair Sutcliffe: “I am studying this same topic in the UK.”

For all other experts, no reply to our request for DOIs was received.