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There could be a link between frozen-thawed embryo IVF and cancer risk

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Children born using IVF after the embryo has been frozen and thawed could possibly have a higher risk of cancer, according to international research. The team analysed medical data from nearly 8 million Nordic children, about 170,000 of whom were born using assisted reproductive technology including about 22,000 where the embryo was frozen and thawed. Among the children from frozen-thawed embryos, 48 went on to develop cancer, which the researchers say is a higher rate than spontaneously conceived children and children born using IVF with a fresh embryo. However, they say while the study was large, the rate of cancer was too small to be conclusive, and more research is needed to confirm whether the cancer risk is higher after frozen-thawed embryo IVF.

Journal/conference: PLOS Medicine

Link to research (DOI): 10.1371/journal.pmed.1004078

Organisation/s: University of Gothenburg, Sweden

Funder: The CoNARTaS has been supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk [grant number 71450] (AP), the Central Norway Regional Health Authorities [grant number 46045000] (SO), the Norwegian Cancer Society [grant number 182356–2016] SO), the Nordic Federation of Obstetrics and Gynaecology [grant numbers NF13041, NF15058, NF16026 and NF17043] (UBW, AT), the InterregO¨ resund- Kattegat-Skagerrak European Regional Development Fund (ReproUnion project) (AP), and by the Research Council of Norway’s Centre of Excellence funding scheme [grant number 262700] (SO), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG- 70940) (CB), the Hjalmar Svensson Foundation (UBW), and The Swedish Childhood Cancer Foundation (BL).

Media release

From: PLOS

In Nordic study, children born after frozen-thawed embryo transfer had higher cancer risk

Follow-up research is needed to confirm potential link between cancer and freeze-thaw strategy

A new study of more than 8 million children in Nordic countries suggests the possibility that children born after use of a fertility procedure known as frozen-thawed embryo transfer may have a higher risk of cancer than children born through other means. Nona Sargisian of the University of Gothenburg, Sweden, and colleagues present these findings on September 1st in the open-access journal PLOS Medicine.

Assisted reproductive technology (ART) allows an embryo to be created from a human egg and sperm in a laboratory. A doctor may immediately transfer the embryo to the uterus, or, in a practice that is increasing worldwide, the embryo might be frozen and later thawed before implantation. Prior research suggests that children born after frozen-thawed transfer may have higher short-term risk of certain medical issues than children born after fresh embryo transfer. However, potential long-term medical risks have been less clear.

To boost understanding, Sargisian and colleagues analyzed medical data from 7,944,248 children in Denmark, Finland, Norway, and Sweden. 171,744 were born after the use of ART, and 7,772,474 were conceived spontaneously without the use of assisted reproductive technology. Among those born after the use of ART, 22,630 were born after frozen-thawed transfer.

Statistical analysis of the data from national health registries showed that children born after frozen-thawed embryo transfer were at higher risk of cancer than children born after fresh embryo transfer and those without ART. When analyzed as a single group (i.e., those born after frozen-thawed transfer and fresh embryo transfer), however, the use of any type of ART did not have an increased risk of cancer. The most common types of cancer seen in this study were leukemia and tumors of the central nervous system.

The researchers emphasize that their findings should be interpreted with caution, since although the study was large, the number of children born after frozen-thawed embryo transfer who later developed cancer was low (48 cases), which could limit the statistical strength of the analysis.

Nonetheless, the findings may raise concerns about frozen-thawed embryo transfer. Future research will be needed to confirm a possible link between the procedure and increased risk of cancer, as well as any biological mechanisms that may underlie such risk.

Coauthor Ulla-Britt Wennerholm adds, “A higher risk of cancer in children born after frozen-thawed embryo transfer in assisted reproduction, a large study from the Nordic countries found. The individual risk was low, while at a population level it may have an impact due to the huge increase in frozen cycles after assisted reproduction. No increase in cancer was found among  children born after  assisted reproduction techniques overall.”

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Expert Reaction

These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.

Associate Professor Alex Polyakov is a Clinical Associate Professor at the Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne and a Consultant Obstetrician, Gynaecologist and Fertility Specialist at the Royal Women's Hospital, Melbourne. He is a Medical Director of Genea Fertility Melbourne.

During the process of IVF embryos are created by combining eggs and sperm in a dish. There are two options as to when to transfer them - it can either be done at the end of the stimulated cycle, so called 'fresh transfer', or embryos can be frozen and stored, to be transferred later, in a subsequent cycle. There are legitimate reasons to freeze embryos and not to do a 'fresh' transfer. These include prevention of complications, embryo genetic testing, etc. There is a worldwide trend to only perform 'frozen' transfers, even though the evidence of this strategy to be superior to fresh transfers is largely lacking. The study assessed the risk of childhood cancer in naturally conceived children, those who were conceived from a 'fresh' and 'frozen' embryo transfer. It found that the rates of childhood cancer were similar in children who were spontaneously conceived, compared to those who were conceived following a fresh transfer. On the other hand, those children that were conceived following a 'frozen' transfer had a significantly increased risk of developing a childhood cancer. The results must be interpreted with caution since the overall number of children who developed cancer was very small. Even in the 'frozen' transfer group, the rate of cancer remained very low (48 cancers in more than 22,000 children). The findings of this study should prompt re-evaluation of the current strategy of preferring 'frozen' to ‘fresh' transfers without medical indication.

Last updated: 18 Aug 2023 12:32pm
Declared conflicts of interest:
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