A study has shown that the chemotherapy drug etoposide can affect the development of fetal ovarian tissue in mice. The findings suggest that chemotherapy treatment given to pregnant women with cancer during their second trimester could reduce the future fertility of baby girls.
Researchers at the University of Edinburgh studied the effects of etoposide on lab-grown ovarian tissue from mouse fetuses, both before and after follicle formation. They showed that exposure of the tissue to medium to high doses of this drug before the follicles had formed could reduce follicle formation by up to 90 percent.
However, exposure to the same amounts or higher concentrations of etoposide after the formation of follicles in neonatal mouse ovaries had no effect, suggesting that the timing of the treatment could be a crucial factor in how it may affect future fertility.
Lead author, Professor Norah Spears, from the Centre for Integrative Physiology, said: 'If the results we have seen in these mouse studies are replicated in human tissue, it could mean that girls born to mums who are taking etoposide during pregnancy have a reduced fertility window.' Follicles are responsible for producing eggs, and a lower follicle count can result in women undergoing the menopause earlier than usual.
One in a thousand pregnant women is diagnosed with cancer. Etoposide is routinely used by the NHS to treat several types of cancer during the second and third trimester of pregnancy because of its low risk of causing birth defects and spontaneous abortion. However, the longer term effects for fetuses have not yet been fully explored.
Women acquire their reproductive capacity before birth, during the second and third trimester of their mothers' pregnancy. Specialised cells, called primordial germ cells, drive formation of all their eggs, which are then stored in the developing fetal ovaries from that point on. This study suggests that etoposide can harm these germs cells and the developing follicles.
Professor Adam Balen, chairman of the British Fertility Society and a representative of the Royal College of Obstetricians and Gynaecologists, said that 'while this is important information for pregnant women who may need chemotherapy, it is too early to say the degree to which this study carried out in mice might relate to humans'.
The researchers say that if the findings are verified in women, affected baby girls should be warned of their reduced fertility in later life and offered fertility options. However, these risks should be also weighed against the benefits of taking etoposide, Professor Balen added.
'We must also weigh any benefits of cancer treatment against these potential risks. These decisions should be made jointly between a woman and her specialist healthcare team,' he said.