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Nonsteroidal Anti-Inflammatory Drugs and Reversible Female Infertility

Is There a Link?

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Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to women of child-bearing age. Three case series highlight the possibility of a link between NSAIDs and reversible infertility. The pharmacological target of NSAIDs is cyclo-oxygenase (COX), which catalyses the first rate-limiting step in the production of prostaglandins. COX-2, one of two isoenzymes, is active in the ovaries during follicular development. Its inhibition is thought to cause luteinised unruptured follicle (LUF) syndrome, an anovulatory condition characterised by clinical signs of ovulation but in the absence of follicular rupture and ovum release. The evidence linking regular NSAID use to reversible LUF syndrome comes from animal studies and three clinical studies. COX-2—deficient mice have severely compromised ovulation in the presence of apparently normal follicular development. Experimental administration of prostaglandins induced ovulation in rabbits and this was blocked by the administration of indomethacin. The three clinical studies demonstrated the induction of delayed follicular rupture or LUF in previously ovulating women by the administration of NSAIDs. A link can therefore be identified between NSAID use and reversible female infertility and NSAID withdrawal should be considered prior to or concurrent with fertility investigations.

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Acknowledgements

Dr Stone is funded by Tommy’s Campaign. We gratefully acknowledge their continued support. We would also like to thank Professor Peter Braude for his critical review of the manuscript.

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Correspondence to Catherine Nelson-Piercy.

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Stone, S., Khamashta, M.A. & Nelson-Piercy, C. Nonsteroidal Anti-Inflammatory Drugs and Reversible Female Infertility. Drug-Safety 25, 545–551 (2002). https://doi.org/10.2165/00002018-200225080-00001

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