Approximately 30% of pregnant women take the painkiller ibuprofen in the first 3 months of pregnancy. Ibuprofen works by inhibiting prostaglandin synthesis. It has long been known that this can affect pregnancy and/or embryo-fetal development. Data from epidemiological studies show an increased risk of miscarriages and malformations after the use of prostaglandin synthesis inhibitors in early pregnancy. The general recommendation is that ibuprofen should only be given during the first and second trimesters of pregnancy if absolutely medically necessary. At the same time, the dosage of ibuprofen should be kept as low as possible and the duration of treatment as short as possible. This applies to women trying to conceive as well as pregnant women during the first or second trimester of pregnancy. Ibuprofen is contraindicated during the third trimester of pregnancy as there is an increased risk of damage to the heart, lungs and kidneys of the unborn child. The mother may also experience an increase in bleeding time and inhibition of uterine contractions at the end of her pregnancy.

A current study looks at the possible long-term effects of giving ibuprofen on the pregnant women's future daughters. In this laboratory study, ibuprofen led to a pronounced loss of female germ cells. Ibuprofen works by inhibiting the enzyme cyclooxygenase (COX). Cyclooxygenase is required for the formation of prostaglandins, which are also required for the development of eggs in the fetal ovary. The research team led by Séverine Mazaud-Guittot, University of Rennes, Inserm, EHESP, Institut de Recherche en Santé, Environment et Travail, France, examined the effect of ibuprofen on the development of human eggs in a very strictly controlled design. The human ovaries came from 185 fetuses from legal abortions between 7 and 12 weeks of gestation. The ovarian tissue was cultured in the laboratory and ibuprofen was added to the nutrient solution at different concentrations over different times. The concentration of ibuprofen in the umbilical cord blood was also recorded in women who had taken ibuprofen 2-4 hours before the abortion.

For the first time, the research team was able to confirm that ibuprofen can cross the placental barrier directly. The ibuprofen concentration in the umbilical cord blood showed the same values ​​as in people who used a corresponding dose of ibuprofen for therapeutic purposes. The ovarian tissue of fetuses that had not previously had contact with ibuprofen through their mother was then exposed to various doses of ibuprofen. There was a greatly reduced cell growth and a dramatic decline in the number of eggs. This decline was not reversible after cessation of ibuprofen exposure. The germ cells from which the female eggs develop either died or stopped reproducing in their usual way.

Ovarian tissue after exposure to ibuprofen for seven days. The large brown cells are dying germ cells, and the small brown cells also die. Source: Severine Mazaud-GuiJot, INSERM

The authors raise concerns from the data that taking ibuprofen during early pregnancy could have negative long-term effects on girls' later fertility. Newborn girls are born with a finite number of follicles in their ovaries. These determine their later fertility in adulthood. A reduced endowment can lead to a shortened reproductive period, an earlier menopause or even infertility. All of this can arise decades later in life.

If taken for a short time, it is possible that the effect of ibuprofen on follicle formation may recover. However, the study showed that contact with ibuprofen over a period of 2-7 days can lead to a dramatic reduction in germ cells in the first trimester of pregnancy and that no complete recovery of the damage can be observed. This could mean that prolonged exposure to ibuprofen during the fetal period may lead to lasting negative effects on fertility.

This study was the first to examine the effect of ibuprofen on the ovarian tissue of female fetuses. For the first time, research confirmed that ibuprofen can cross the placenta during the first trimester of pregnancy. The research group carefully monitored the effects of ibuprofen on the cultured ovarian tissue in the laboratory. A portion of the tissue of each fetus was exposed to ibuprofen and another portion served as a control without ibuprofen exposure. The study has limitations, the effect was examined in the laboratory. Long-term effects were also not analyzed.

Like the findings on the negative long-term effects of paracetamol on unborn life, this study also shows that everyday painkillers such as paracetamol and ibuprofen can have lasting negative effects if taken during pregnancy. These effects could have implications for subsequent fertility decades after birth and well into the age of menopause and menopause. The findings once again make it clear that, given the high number of pregnant women taking painkillers, there is an urgent need for information about the treatment of pain during pregnancy. Painkillers during pregnancy should only be taken if they are absolutely necessary and then only in the lowest possible dose for the shortest possible time. It should be taken into account that painkillers such as ibuprofen or paracetamol only have a weak pain-relieving effect. They are unsuitable for severe pain. Especially during pregnancy, painkillers should not be taken without medical advice in order to weigh up the possible risks with regard to the expected effect. In particular, it should be taken into account that there are numerous non-drug treatment options for the prevention and acute treatment of pain.

 

Source:

Leverrier-Penna, S; Mitchell, Rod; Becker, Esther BE; Lecante, L; Ben Maamar, Millissia; Homer, N; Lavoué, Vincent; Kristensen, David M.; Dejucq-Rainsford, Nathalie; Jegou, B; Mazaud-guittot, Séverine / Ibuprofen is deleterious for the development of first trimester human fetal ovary ex vivo. In: Human Reproduction, February 2, 2018.

EurekAlert system: European Society of Human Reproduction and Embryology
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