Women who take ibuprofen in the first 24 weeks of pregnancy could reduce the fertility of their unborn daughters, according to a French study published today.
Researchers at INSERM, Rennes, say they have found the first evidence in human ovarian tissue that exposure to ibuprofen during the first three months of foetal development results in a “dramatic loss” of the germ cells that make the follicles from which female eggs develop.
Writing in Human Reproduction, they say that their findings raise concerns about the long-term effects of ibuprofen on the future fertility of women who were exposed to the pain killer in their mothers’ wombs.
“The development of the follicles in the foetus has not been completed by the end of the first trimester, so if the ibuprofen treatment is short then we can expect the ovarian reserve to recover to some extent,” said Dr Séverine Mazaud-Guittot.
“However, we found that two to seven days of exposure to ibuprofen dramatically reduced the germ cell stockpile in human foetal 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 foetal life may lead to long-term effects on women’s fertility and raises concern about ibuprofen consumption by women during the first 24 weeks of pregnancy. These findings deserve to be considered in light of the present recommendations about ibuprofen consumption during pregnancy.”
Dr Mazaud-Guittot and her colleagues obtained human foetuses between seven and 12 weeks of development from legally induced terminations and with the mothers’ consent.
They cultured the ovarian tissue in the laboratory and part of the tissue from each foetus was exposed to ibuprofen and a control part was not exposed.
The team analysed samples from 185 foetuses and the researchers found that ibuprofen crosses the placental barrier.
“The concentration that we found in the umbilical cords of foetuses from mothers who ingested 800 mg two to four hours before surgery is similar to the concentration that can be found in adult’s blood for the same treatment,” said Dr Mazaud-Guittot.
The foetal tissue that was exposed to concentrations of 10 µM of ibuprofen for a week had approximately half the number of ovarian germ cells.
“We found 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 foetus,” she said.
“There were significant effects after seven days of exposure to 10 µM of ibuprofen, and we saw cell death as early as after two days of treatment. Five days after withdrawing ibuprofen, these harmful effects of ibuprofen were not fully reversed.
“The wisest advice would be to follow currently accepted recommendations: paracetamol should be preferred to any anti-inflammatory drug up to 24 gestational weeks, and the latter should not be used thereafter. However, practitioners, midwifes and obstetricians are best placed to give expert advice: every mother and every pregnancy is unique.”
Leverrier-Penna S, Mitchell RT, Becker E et al. Ibuprofen is deleterious for the development of first trimester human fetal ovary ex vivo. Human Reproduction journal 2 February 2018. doi:10.1093/humrep/dex383 [abstract]
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