Ibuprofen may harm fertility of female child

Pregnant women who take the pain killer ibuprofen in the first trimester of their pregnancy may be reducing the store of eggs in the ovaries of their daughters. Researchers have found the first evidence in human ovarian tissue that exposure to ibuprofen during the crucial first three months of fetal development results in a loss of the germ cells that go into making the follicles from which female eggs develop. The germ cells either died or failed to grow and multiply at the usual rate.

Female children are born with a finite number of follicles in their ovaries and this defines their future reproductive capacity as adults," explained Dr Séverine Mazaud-Guittot, a researcher at INSERM in Rennes, France, who led the study. "A poorly stocked initial reserve will result in a shortened reproductive life span, early menopause or infertility-events that occur later in life.

The development of the follicles in the fetus has not been completed by the end of the first trimester, so if the ibuprofen treatment is short then the ovarian reserve may recover to some extent. However,  two to seven days of exposure to ibuprofen dramatically reduced the germ cell stockpile in human fetal ovaries during the first trimester of pregnancy and the ovaries did not recover fully from this damage.

This suggests that prolonged exposure to ibuprofen during fetal life may lead to long-term effects on women's fertility and raises concern about ibuprofen consumption by women during the first trimester of pregnancy. Researcher obtained human fetuses between 7-12 weeks of development from legally induced terminations of pregnancy and with the mothers' consent.

Then they cultured the ovarian tissue in the laboratory; part of the tissue from each fetus was exposed to ibuprofen and a second part (the control) was not. Samples from 185 fetuses were analysed. They measured the quantity of ibuprofen in the blood in the umbilical cord in order to analyse how much the fetus would have been exposed to.

They found that ibuprofen crosses the placental barrier. The concentration in the umbilical cords of fetuses from mothers who ingested 800 mg (four pills of 200 mg) two to four hours before surgery is similar to the concentration that can be found in adult's blood for the same treatment. This shows that the fetus is exposed to the same concentration as the mother. In contrast to the fetal tissue that was not exposed to ibuprofen, the tissue that was exposed to concentrations of 10 μM (micromolar) of ibuprofen for a week had approximately half the number of ovarian germ cells 2.

There were fewer cells growing and dividing, more cells dying and a dramatic loss of germ cell numbers, regardless of the gestational age of the fetus. There were significant effects after seven days of exposure to 10 μM of ibuprofen, cell death occurred after two days of treatment. Five days after withdrawing ibuprofen, these harmful effects of ibuprofen were not fully reversed. Ibuprofen use should be restricted to the shortest duration and at the lowest dose necessary to achieve pain or fever relief, especially during pregnancy.
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