Are Children Conceived from Frozen Embryos At Increased Risk for Cancer?

Building your family when you are infertile is an extraordinary leap of faith. You are placing your hopes and dreams for becoming a parent into the hands of doctors, lab technicians, and often anonymous donors who contribute egg or sperm to the process. Every step of the way you are hoping, wishing, praying that nothing goes wrong and that your child will come to you. And when he does?

You want to believe that the constant worry and myopic focus on the health of your body and of that growing embryo will go away.  Then you read an article in the news that flashes the headline, Children conceived from frozen embryos at increased risk for certain cancers, and you feel that worry blossom.

Are Your Frozen-Embryo-Conceived Babies At Risk for Cancer?

Recently a study was released that got the attention of the world of assisted reproductive technology, and it caused a lot of questions and concerns for a lot of people. Here’s an excerpt of the article that summarized the study:

Analyzing health records of more than a million Danish children, researchers found that babies conceived through assisted reproduction involving frozen embryo transfer were more than twice as likely to develop childhood cancer, particularly leukemia and neuroblastoma, a type of brain cancer, according to the report in JAMA.

“We did not find increased risks with other types of fertility treatments,” said study leader Marie Hargreave of The Danish Cancer Society Research Center, in Copenhagen.

Hargreave called for more research to validate her group’s findings. Moreover, “it is important to stress the fact that the increased risk is very small for the individual as childhood cancer is very rare,” she said in an email.

It’s a Question Worth Asking

The article goes on to say that the question of cancer risk is worth researching and considering. However, the experts agree that this particular study is not likely to fully answer all the questions:

The new study has looked at an important question, said Dr. Alan B. Copperman, director of the division of reproductive endocrinology and infertility at the Mount Sinai Health System in New York City.

But because the study looks only at an association, “it is not clear whether the finding is related to the procedure itself or the patients who needed the procedure,” Copperman said in an email. Beyond that, “any time a rare event is studied in a large retrospective study, the statistical precision to make accurate conclusions is limited.”

With that said, “prospective parents can be reassured that in 12.2 million ‘person-years’ of follow-up, that childhood cancer was diagnosed in less than 0.01% of children, regardless of whether or not IVF was used for conception,” Copperman noted.

Perspectives from Our Professionals

It’s tempting to spiral right into worry and fear over the long-term health of your child when you read a study like this one. These findings seem staggering to contemplate, and any parent of a child conceived by frozen embryos would have tons of questions. We sure did.

We turned to several of our Creating a Family board members for their thoughts. These board members are well-respected reproductive endocrinologists and researchers themselves, and they offered their wisdom and experience to consider when digesting the details of this study.

Julie Lamb, MD, FACOG, is a board-certified reproductive endocrinologist and infertility specialist at Pacific NW Fertility in Seattle and serves as clinical faculty at the University of Washington.  She shared with us what she has been telling her own patients since the study was released:

We are always paying close attention to new research, and we certainly don’t want to do anything that harms patients or children from IVF. This is a large study published in a prestigious journal, so it is getting a lot of coverage in the press. It is important to note that a lot has changed since the study period in terms of culture technique and freezing processes.  Any increase in cancer risk can be very scary, but the absolute risk is still very low (44 per 100,000 with frozen embryo transfer vs. 17-18 per 100,000 without frozen embryo transfer).

That idea of very low “absolute risk” was a common theme from all three board members.

Dr. Jason Franasiak is a board-certified Ob/Gyn, board-certified Technical Supervisor in Embryology and Andrology, and lead physician of RMA’s South Jersey – Marlton Office. As Dr. Copperman had noted in the article, Dr. Franasiak was also careful to point out that association studies have challenges that must be considered:

This Danish study found an association with frozen embryo transfer and childhood cancer. No doubt, this is an important question. One of the challenges with association studies is it is difficult to determine if the findings are due to the intervention – i.e. frozen embryo transfer – or if they are due to the intrinsic characteristics of the couples who needed to have these procedures in order to have a child. We can be reassured by the finding that, regardless of whether fertility care was needed for conception or not, the risk of childhood cancer is very rare.

Finally, we checked in with board member Dr. Alexander Quaas, M.D., Ph.D. , a board-certified Reproductive Endocrinology and Infertility Specialist at Reproductive Partners Fertility Center – San Diego, and Assistant Professor at the University of San Diego, California. He broke his response out into several parts, sharing similar cautions that “associations do not imply causality,” and that the “absolute risk” for these types of childhood cancers is quite low. He ended his thoughts for us with an important distinction about the association that was discovered:

The findings from the Danish study that frozen embryo transfers (FETs) were associated with a slightly higher risk for certain types of cancer, are intriguing, and add to the existing body of literature on the topic.

While these findings are important and may ultimately add to the way we counsel patients about certain aspects of IVF treatment, it is important to remember that the study was a retrospective epidemiologic study with all the associated flaws of that type of study.

The study looked at associations of the exposure of assisted reproduction with a multitude of outcomes. Associations do not imply causality, and when many outcomes are assessed, it is more likely that significance is achieved for one outcome by chance alone.

Additionally, while there was an increased relative risk, the absolute risk for the types of cancers studied was still low.

And finally (and perhaps most importantly), when an association is studied in this fashion, it is unclear, and likely doubtful, that the association found is due to the intervention, and not to difference between the population exposed to the intervention and the whole population, in other words the difference between a population of patients with infertility, and the general population.

As the authors state, more research is necessary to validate and further investigate the findings.

So What’s A Parent to Do?

Being a well-informed parent is a double-edged sword. Staying abreast of research that helps you build and nurture your family can give you tools to be a great parent. But what you read can sometimes scare the living daylights out of you. We understand that.

We offer these practical suggestions to help you manage what you’ve learned about the study:

• Remember that the risk for childhood cancer is very low – “less than 0.01% of children, regardless of whether or not IVF was used for conception.”
• Talk with your reproductive specialist about your concerns. She knows your child’s conception history and is a resource for your questions.
• Balance the findings from this study (and others like it) by understanding the risks and flaws inherent to the study.
• The field of embryo freezing has changed a lot since this study was initiated, and reproductive science continues to advance at a rapid pace.
• Remember also that the field of cancer research is also advancing all the time. The connections between the two areas will benefit from continued studies like this one.

Every professional quoted in the original article and here for our post agrees on two things. First, more research is needed before we assume that children conceived by frozen embryo transplants are at grave risk. Second, assisted reproduction technology and research are evolving and growing. It’s a fascinating time to be part of reproductive sciences and we will certainly stay on top of studies like these.

Image Credit: Asian Development Bank