COMMENTARY

How Pain Relievers May Affect Time to Pregnancy

Peter Kovacs, MD, PhD

Disclosures

February 27, 2017

Preconception Use of Pain-Relievers and Time-to-Pregnancy: A Prospective Cohort Study

McInerney KA, Hatch EE, Wesselink AK, Rothman KJ, Mikkelsen EM, Wise LA
Hum Reprod. 2017;32:103-111

Background

Painkillers are among the most commonly used medications. One study reported that in 2010, almost 20% of the adult population in the United States took aspirin at least three times a week and 12% regularly took a nonsteroidal anti-inflammatory drug (NSAID).[1]

NSAIDs work by inhibiting the cyclooxygenase (COX)-1 and COX-2 enzymes that are involved in prostanoid synthesis.[2] The effect of the different products may vary, however.[3] Because prostaglandins play an important role in ovulation and implantation, interfering with their synthesis could have a negative effect on reproduction.

This cohort study evaluated the impact of NSAID use on time to pregnancy.

Summary

This was a Web-based prospective cohort study. Researchers invited reproductive-aged women not using contraception who were in a heterosexual relationship to participate. Online questionnaires were used to collect demographic and reproductive data, as well as information on painkiller use and pregnancy status. Follow-up questionnaires were completed every 2 months for up to 12 months.

Pain medications were categorized as acetaminophen, ibuprofen, naproxen, aspirin, or opioid. The primary outcome was fecundability ratio, a measure of per-cycle probability of pregnancy comparing exposed vs nonexposed women. Demographic and reproductive confounders were adjusted during the analysis, and the results were stratified by age.

In total, 1763 women were included and 73% reported pain medication use in the month before completing the baseline survey. Ibuprofen was the most commonly used pain reliever. Here’s what the researchers found:

  • Fecundability ratio was not influenced by use of aspirin, acetaminophen, or ibuprofen.

  • Use of naproxen was associated with a reduced fecundability ratio (0.78; 95% confidence interval [CI], 0.64-0.97). Higher doses were associated with a greater reduction.

  • Naproxen combined with other pain relievers was also associated with reduced fecundability.

  • There was trend for a lower fecundability ratio with opioids, but because of small numbers, it did not reach statistical significance.

Viewpoint

Headache and musculoskeletal pain are the most common indications for pain relievers, but many women use pain medications to treat dysmenorrhea. Endometriosis, the most likely cause of dysmenorrhea, is also associated with a lower chance of conceiving. If its effect is augmented by NSAIDs, the fecundability ratio would even be lower.

In this study, when the analysis was restricted to women with painful menstruation, naproxen and opioid use was associated with a stronger negative impact on the fecundability ratio (0.7 [95% CI, 0.51-0.95] for naproxen; 0.7 [CI, 0.46-1.07] for opioid) compared with the entire study population.

The literature is divided on the impact of NSAIDs on reproduction. Matyas and colleagues[4] found that follicular-phase NSAID use was associated with less frequent anovulation and higher luteal-phase progesterone levels, suggesting improved ovulation. Jesam and colleagues,[5] however, reported a dose-dependent reduction in ovulation rates with meloxicam in healthy, sterilized women after drug exposure between days 5 and 22 of the menstrual cycle.

Current evidence suggests that some NSAIDs interfere with ovulation or implantation and, therefore, could lower a woman's chance of conceiving. Future prospective studies need to further evaluate these associations, the impact of the various available medications, and the impact of their dose.

Reproductive-aged women planning to become pregnant should be advised that some over-the counter or prescription pain medications (naproxen, opioids), when used regularly, may lower their chance of successfully conceiving. If necessary, products with no proven negative effect, such as aspirin and acetaminophen, should be used for the shortest possible duration.

Abstract

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