STUDY QUESTION To what extent is female preconception antibiotic use associated with fecundability? SUMMARY ANSWER Preconception antibiotic use overall was not appreciably associated with fecundability. WHAT IS KNOWN ALREADY Antibiotics are commonly used by women and are generally thought to be safe for use during pregnancy. However, little is known about possible effects of antibiotic use on fecundability, the per-cycle probability of conception. Previous research on this question has been limited to occupational rather than therapeutic exposure. STUDY DESIGN, SIZE, DURATION We analyzed data from an Internet-based preconception cohort study of 9524 female pregnancy planners aged 21–45 years residing in the USA and Canada who had been attempting to conceive for six or fewer cycles at study entry. Participants enrolled between June 2013 and September 2020 and completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever came first. The questions pertaining to antibiotic type and indication were added to the PRESTO questionnaires in March 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS We assessed antibiotic use in the previous 4 weeks at baseline and on each follow-up questionnaire. Participants provided the name of the specific antibiotic and the indication for use. Antibiotics were classified based on active ingredient (penicillins, macrolides, nitrofurantoin, nitroimidazole, cephalosporins, sulfonamides, quinolones, tetracyclines, lincosamides), and indications were classified by type of infection (respiratory, urinary tract, skin, vaginal, pelvic, and surgical). Participants reported pregnancy status on follow-up questionnaires. We used proportional probabilities regression to estimate fecundability ratios (FR), the per-cycle probability of conception comparing exposed with unexposed individuals, and 95% confidence intervals (CI), adjusting for sociodemographics, lifestyle factors, and reproductive history. MAIN RESULTS AND THE ROLE OF CHANCE Overall, women who used antibiotics in the past 4 weeks at baseline had similar fecundability to those who had not used antibiotics (FR: 0.98, 95% CI: 0.89–1.07). Sulfonamides and lincosamides were associated with slightly increased fecundability (FR: 1.39, 95% CI: 0.90–2.15, and FR: 1.58 95% CI: 0.96–2.60, respectively), while macrolides were associated with slightly reduced fecundability (FR: 0.70, 95% CI: 0.47–1.04). Analyses of the indication for antibiotic use suggest that there is likely some confounding by indication. LIMITATIONS, REASONS FOR CAUTION Findings were imprecise for some antibiotic classes and indications for use owing to small numbers of antibiotic users in these categories. There are likely heterogeneous effects of different combinations of indications and treatments, which may be obscured in the overall null results, but cannot be further elucidated in this analysis. WIDER IMPLICATIONS OF THE FINDINGS There is little evidence that use of most antibiotics is associated with reduced fecundability. Antibiotics and the infections they treat are likely associated with fecundability through differing mechanisms, resulting in their association with increased fecundability in some circumstances and decreased fecundability in others. STUDY FUNDING/COMPETING INTEREST(S) This study was supported through funds provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (R01-HD086742, R21-HD072326). L.A.W. has received in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, Fertility Friend, and Kindara for primary data collection in PRESTO. The other authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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女性怀孕计划者的抗生素和生育能力：一项前瞻性队列研究

研究问题 女性孕前使用抗生素在多大程度上与生育能力相关？总结 答案 总体而言，孕前抗生素的使用与生育能力没有明显关联。已知情况 女性通常使用抗生素，一般认为在怀孕期间使用是安全的。然而，关于抗生素使用对生育力的可能影响知之甚少，即每个周期的受孕概率。以前对这个问题的研究仅限于职业性暴露，而不是治疗性暴露。研究设 参与者在 2013 年 6 月至 2020 年 9 月之间注册，并完成了长达 12 个月或直到报告怀孕（以先到者为准）的基线和双月随访问卷。与抗生素类型和适应症有关的问题于 2016 年 3 月添加到 PRESTO 问卷中。参与者/材料、设置、方法 我们在基线和每个后续问卷中评估了过去 4 周内的抗生素使用情况。参与者提供了特定抗生素的名称和使用适应症。抗生素根据活性成分（青霉素、大环内酯类、呋喃妥因、硝基咪唑、头孢菌素、磺胺类、喹诺酮类、四环素类、林可酰胺类）分类，适应症按感染类型（呼吸道、泌尿道、皮肤、阴道、盆腔和外科）分类. 参与者在随访问卷中报告了怀孕状况。我们使用比例概率回归来估计受孕率 (FR)、与未暴露个体相比的每周期受孕概率和 95% 置信区间 (CI)，并根据社会人口学、生活方式因素和生育史进行调整。主要结果和机会的作用 总体而言，基线过去 4 周内使用抗生素的女性与未使用抗生素的女性具有相似的生育能力（FR：0.98，95% CI：0.89-1.07）。磺胺类和林可酰胺类与生殖能力略有增加相关（FR：1.39，95% CI：0.90-2.15，FR：1.58 95% CI：0.96-2.60），而大环内酯类与生殖能力略有降低相关（FR：0.70， 95% CI：0.47–1.04）。对抗生素使用适应症的分析表明，适应症可能存在一些混淆。限制、谨慎的原因 由于在这些类别中使用抗生素的人数很少，因此某些抗生素类别和使用适应症的结果并不准确。适应症和治疗的不同组合可能存在异质效应，这可能在整体无效结果中被掩盖，但无法在本分析中进一步阐明。研究结果的更广泛意义 几乎没有证据表明使用大多数抗生素会降低受孕能力。抗生素及其治疗的感染可能通过不同的机制与生殖能力相关，导致它们在某些情况下与生殖能力增加有关，而在其他情况下与生殖能力降低相关。研究资金/竞争利益 本研究由美国国立卫生研究院 Eunice Kennedy Shriver 国家儿童健康与人类发展研究所 (R01-HD086742, R21-HD072326) 提供资金支持。LAW 已收到来自 Swiss Precision Diagnostics、Sandstone Diagnostics、Fertility Friend 和 Kindara 的实物捐赠，用于 PRESTO 的主要数据收集。其他作者没有要披露的利益冲突。试用注册号 不适用。和 Kindara 用于 PRESTO 中的主要数据收集。其他作者没有要披露的利益冲突。试用注册号 不适用。和 Kindara 用于 PRESTO 中的主要数据收集。其他作者没有要披露的利益冲突。试用注册号 不适用。