Chemotherapy works against cancer by poisoning the cells. As such, few chemotherapy agents are safely prescribed to expectant women. Now, the list of available drugs shrink even further, as scientists find etoposides may affect not only the mother, but also damage the germ cells of the unborn daughter. This could mean girls born to mothers who were treated with etoposides during pregnancy could have reduced fertility outcome and even earlier menopause.
Etoposides are often used to treat leukemia, lymphoma, ovarian cancer, and testicular cancer. It works as a topoisomerase inhibitor, blocking the cancer cells’ ability to divide. This drug is considered to be safe for pregnant women in their second and third trimester of pregnancy (from 4 to 9 months).
But whether etoposides cause long-term health effects to the fetus has yet to be explored fully. “Studies looking at the effects of taking chemotherapy drugs during pregnancy have focused on the immediate effects, such as increased miscarriage rates or severe fetal abnormalities," said Norah Spears, scientist at the University of Edinburgh and senior author of the study.
To investigate chemotherapy in pregnancy, Spears and her team exposed fetal and neonatal mouse ovaries to etoposides. In particular, they timed the exposure to when the fetal ovarian follicles had yet to fully enclose an immature oocyte, an egg cell.
They found that this led to significant follicle deaths that correspond to the intensity of the etoposide doses. That is, at medium doses, follicle death rate was 72 percent, whereas at high doses, follicle death rate was 90 percent.
"In a study involving mouse tissue, we have shown that etoposide can damage the development of the ovaries while a fetus is in the womb. The drug affects the germ cells in the ovaries, which are the cells that give rise to eggs. This is important because it could mean that the fertility of the offspring could be affected in later life," explained Spears.
Unlike men, a woman’s biological reproductive potential (in terms of eggs), is set even before she is born. As such, the finding that a female fetus’ germ cells die in response to her mother’s chemotherapy treatment is highly worrisome.
"This study suggests that chemotherapy treatment may have important longer term effects on the babies of women who undergo chemotherapy while pregnant which would only become apparent in adulthood,” said Spears. “If the results we have seen in these mouse studies are found to be replicated in humans, some of that germ cell supply would be lost, which could later result in early menopause, thus reducing the woman's fertility window.” Spears cautions that the further research is needed to understand how etoposides may affect human fetuses.