Ibuprofen taken by women in their first three months of pregnancy might reduce a daughter’s number of eggs, potentially affecting the child’s future fertility, according to research carried out on human cells in the lab.

It is generally thought that women are born with a fixed number of eggs, although controversial recent research has challenged the idea that adult ovaries are unable to produce more.



Previous work in rodents has suggested that painkillers including ibuprofen might affect the ovaries and hence fertility, while recent research in men has linked prolonged high doses of ibuprofen to disruption of male sex hormones. Up to 30% of women are thought to take ibuprofen during pregnancy.



“We know that fertility rates have declined over recent years, and essentially we are looking for a potential reason why that might be the case,” said Rod Mitchell, co-author of the research from the University of Edinburgh. “Because it is a relatively recent decline, it is felt that environmental factors [including painkillers] in addition to societal factors might have a role to play.”

Writing in the journal Human Reproduction, Mitchell and colleagues from France and Denmark report how they examined the impact of ibuprofen on developing ovaries using ovarian tissue taken from 185 terminated human foetuses aged between seven and 12 weeks.



In the first step of the study, the team analysed blood taken from the umbilical cords of 13 of the foetuses whose mothers had taken ibuprofen in the hours before termination, to reveal that ibuprofen did indeed cross the placental barrier.



For each of the 185 foetuses, tissue was then cultured under multiple conditions, with one sample exposed to no ibuprofen and others bathed in various concentrations of the drug in a dish, reflecting concentrations that would circulate in humans.

After seven days, compared to samples not exposed to ibuprofen, those bathed in the painkiller at a concentration on a par with the cord blood levels had an average of 50% fewer ovarian cells, and between 50 and 75% fewer “germ cells” – cells that develop into eggs. This was down to an increase in cell death and fewer cells multiplying.

Further experiments showed that the damage began as early as two days after exposure to the ibuprofen for foetuses aged 8–12 weeks. After a five day recovery period for a subset of the samples, only a partial recovery from the effects of the ibuprofen was observed, but only germ cells appeared to bounce back.

But Mitchell cautions that the situation in the body might differ from that in a dish, that it is not clear what level of germ cell loss would be tolerated before fertility is affected, or whether the ovaries could more fully recover over a longer period.



“If we see effects on germ cells, which we do in the dish, that could indicate that there are potential for effects in ‘real life’ and potential for effects on fertility – but we haven’t shown or proved that by what we have done [in this study],” he said.



For pregnant women, he added “The advice doesn’t change,” noting that they should take painkillers only when necessary, and at the lowest dose for the shortest time possible. Currently pregnant women are advised to choose paracetamol over ibuprofen, and not to take ibuprofen after 30 weeks.

William Colledge, professor of reproductive physiology at the University of Cambridge, who was not involved in the research, said the study was interesting since it looked at a period in which women might not realise they were pregnant. But he had reservations.

“It is a big step to go from something that happens in the petri dish to saying, well, that definitely may happen in a pregnant woman – although it shows that we could be cautious,” he said, adding that the number of germ cells in the ovaries naturally declines from a peak of about three million mid-pregnancy. “At best [women] are only releasing one [egg] each month. So you can cope with the loss of quite a lot of these eggs,” he said.