Mikkelsen EM, Ulrichsen SP, Johannesen BR, Laursen ASD, Wise LA, Hatch EE, Rothman KJ, Wesselink AK, Crowe H, Sorensen HT. Preconception use of antibiotics and fecundability: a Danish prospective cohort study. Fertil Steril. 2023 Sep 1;120(3 Pt 2):650-9. doi: 10.1016/j.fertnstert.2023.04.030

OBJECTIVE: To assess the association between preconception antibiotic use and fecundability, the per menstrual cycle probability of conception.

DESIGN: SnartForaeldre.dk, a Danish prospective cohort study of women trying to conceive (2007-2020).

SUBJECTS: 9,462 female participants, median age 29 years at enrollment.

EXPOSURE: Antibiotic use was defined by filled prescriptions retrieved from The Danish National Prescription Registry, using Anatomical Therapeutic Chemical codes, and modeled as time-varying (menstrual cycle-varying) exposure.

MAIN OUTCOME MEASURES: Pregnancy status was reported on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Fecundability ratios (FR) and 95% confidence intervals (CI) were computed using proportional probabilities regression models, with adjustment for age, partner age, education, smoking, folic acid supplementation, BMI, parity, cycle regularity, timing of intercourse, and sexually transmitted infections.

RESULTS: During all cycles of observation, the percentage of participants filing at least one antibiotic prescription was 11.9%; 8.6% had a prescription for penicillins, 2.1% for sulphonamides, and 1.8% for macrolides. Based on life-table methods, 86.5% of participants conceived within 12 cycles of follow-up. Recent preconception antibiotic use was associated with reduced fecundability (≥1 prescription vs. none: adjusted FR= 0.86, 95% CI: 0.76-0.99). For participants using penicillins, sulphonamides, or macrolides, the adjusted FRs were 0.97 (95% CI: 0.83-1.12), 0.68 (95% CI: 0.47-0.98), and 0.59 (95% CI: 0.37-0.93), respectively.

CONCLUSION: Preconception use of antibiotics, specifically sulphonamides and macrolides, was associated with decreased fecundability compared with no use. The observed associations may plausibly be explained by confounding by indication, as we lacked data on indication for the prescribed antibiotics. Consequently, we cannot separate the effect of the medication from the effect of the underlying infection.

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