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Stopping the conveyor belt – cancer and fertility

by Guest Author on 20 Nov 2018

Our runner-up in this year’s Max Perutz Science Writing Award was Briet Bjarkadottir, an MRC PhD student at the University of Oxford. By understanding how chemotherapy drugs can cause infertility she’s hoping to find a less invasive way to protect fertility in girls and women with a cancer diagnosis.

Briet Bjarkadottir & Fiona Watt

Briet Bjarkadottir & Fiona Watt

Jane is experiencing the worst day of her life. Her six-year-old daughter, Lily, has just been diagnosed with cancer. The doctor is describing the treatment plan for the next few months: several rounds of chemotherapy to hopefully kill off the cancer cells. He even mentions the possibility of a bone marrow transfer. All of this is way too much to take in – how can a little girl, who was happily playing on holiday a few weeks ago, be so sick?

The doctor then says something which makes Jane’s head spin even more: the chemotherapy could make Lily infertile, and they need to decide whether to freeze one of her ovaries for the future.

A thousand different thoughts and questions race through Jane’s head. The doctor mentioning Lily’s future gives her mother hope that the treatment will work, but how can a child’s fertility be in danger when she hasn’t even gone through puberty? Is the danger to her future fertility great enough to warrant a potentially risky operation to remove one of her ovaries? What about Lily’s own choice? She’s much too young to grasp the idea of fertility; she won’t understand why she needs to have the surgery. And what if she decides not to have children later in life?

This is a situation that I think no person should have to struggle with when confronted with a cancer diagnosis.

Infertility is a possible side effect of chemotherapy for both children and adults. While chemotherapy drugs are intended to kill cancer cells, most do not target these cells specifically and can cause collateral damage. Other cells that grow fast (like cancer cells do) can also be destroyed by the drugs; this is why people sometimes lose their hair.

Our reproductive organs, ovaries or testicles, can also be damaged by chemotherapy. But how are the ovaries affected?

It helps to think of the female reproductive lifespan as a conveyor belt. A girl is born with a supply of immature eggs; these are all the eggs she will ever have. From birth, groups of immature eggs are constantly being added to the conveyor belt from the supply, and as the eggs move along they start to grow and mature.

The eggs are discarded at different points along the conveyor belt, and once a girl has gone through puberty a single mature egg will reach the end of the conveyor every month and be ovulated.

At any given moment, the conveyor belt contains eggs that are at different stages of growth, and immature eggs are only placed on the belt once space has formed at the end. The conveyor belt keeps running until the immature egg supply is exhausted and the woman goes through menopause.

Some chemotherapy drugs kill growing eggs, causing a new group of immature eggs to be taken from the supply and added to the conveyor. The supply itself is thought to be safe from the chemotherapy, as scientists think the eggs only become vulnerable once they start to grow. However, with each cycle of treatment, more and more eggs are removed from the supply and put on the conveyor until finally the egg supply is exhausted and the conveyor belt stops, causing infertility.

Freezing an ovary is the only way to protect the future fertility of someone as young as Lily. Other options exist for adult women, such as freezing mature eggs or embryos. However, all of these options are invasive and don’t offer a guarantee of having a child.

My PhD is focused on finding a less invasive way to protect fertility in girls and women. At the moment, I’m looking at how exactly chemotherapy drugs affect the egg supply to see if they are truly unaffected if they haven’t yet started to grow.

Next I will start testing compounds that have the potential to be able to prevent these immature eggs from growing, stopping the conveyor belt temporarily and protecting the eggs from damage by chemotherapy drugs. To do this I grow small pieces of ovarian tissue in the laboratory and study the effects chemotherapy drugs and compounds have on the eggs. This tissue comes from girls and women who have had their ovaries frozen before starting cancer treatment and have donated a small portion to medical research.

Once I find a compound that is able to stop the conveyor belt I hope it can be given to patients alongside chemotherapy treatment, and once the cancer treatment is finished, the conveyor belt would start up again and the patient would have normal fertility. In the future I hope that no one confronted with a cancer diagnosis has to go through the process Jane and her daughter Lily did, and can instead focus their energy on battling the disease.

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