Antibiotics and Fecundability Among Female Pregnancy Planners

A Prospective Cohort Study

Holly Michelle Crowe; Amelia Kent Wesselink; Lauren Anne Wise; Tanran R. Wang; Charles Robert Horsburgh Jr.; Ellen Margrethe Mikkelsen; Elizabeth Elliott Hatch

Disclosures

Hum Reprod. 2021;36(10):2761-2768. 

In This Article

Results

The analytic cohort included 9524 women with 5382 pregnancies and 36 353 menstrual cycles. During follow-up, 71% conceived based on life-table methods, 14% did not become pregnant within 12 cycles, 3% stopped trying to conceive, 7% began fertility treatment, 2% were still actively participating, and 21% were lost to follow-up. Loss to follow-up did not materially differ by antibiotic status (18% of antibiotic users and 22% of non-users). Of the 9524 participants in this study, 776 (8%) reported using antibiotics at baseline, and 758 (8%) reported using antibiotics during follow-up. A total of 1432 participants (15%) reported antibiotic use at any point during their participation in the study (baseline or follow-up), and 14% of these participants (n = 196) reported antibiotic use at multiple time points.

Baseline characteristics of antibiotic users and non-users (at any point during PRESTO participation) are presented in Table I. Antibiotic users more often had lower household income and lower educational attainment than non-users and were more likely to live in the southern USA.They were also slightly more likely to have ever smoked (27% vs 23%). A greater proportion of antibiotic users reported irregular menstrual cycles (20% vs 17%), used hormonal methods as their last method of contraception (42% vs 37%), and have a history of spontaneous abortion (29% vs 25%), infertility (12% vs 8%), or STI (18% vs 14%).

Overall, antibiotic use was not associated with fecundability. As shown in Table II, when antibiotic use was analyzed as a time-varying exposure, women who used antibiotics in the past 4 weeks did not have appreciably lower fecundability than those who had not used antibiotics (FR: 0.98, 95% CI: 0.89–1.07). When we restricted to the first cycle after use, we similarly found no appreciable relation between antibiotic use and fecundability (FR: 1.07, 95% CI: 0.94–1.23).

Antibiotic Class

The most commonly reported antibiotic class was penicillins, which accounted for 49% of total reported antibiotics. Macrolides, tetracyclines, and nitrofurantoin were also commonly reported, with each comprising approximately 9% of the reported antibiotics. The remaining antibiotics reported included (in order of frequency): cephalosporins (7%), quinolones (5%), nitroimidazole (5%), sulfonamides (4%), and lincosamides (2%).

The associations between use of specific antibiotic classes and fecundability are presented in Table III. The use of sulfonamides and lincosamides was 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 macrolide use was associated with slightly reduced fecundability (FR: 0.70, 95% CI: 0.47–1.04). There was little association between the use of other classes of antibiotics and fecundability. Estimates for use of several antibiotic classes were imprecise, owing to small numbers of women reporting use of these antibiotics.

Antibiotic Indication

A total of 1284 indications for antibiotic use were reported, as some women reported more than one indication for antibiotic use and others did not provide an indication. The most common indications for antibiotic use overall were respiratory infections and urinary tract infections, which together accounted for approximately half of all antibiotic use. Respiratory infections comprised 30% (n = 384) of reported indications and urinary tract infections comprised 23% of reported indications (n = 289). Vaginal or pelvic infections were listed as an indication for 15% of antibiotic prescriptions (n = 187). The most common indications for recurrent antibiotic use were urinary tract infection treatment or prevention, skin conditions including recurrent cysts, recurrent sinus infections, recurrent yeast infections, and malaria prophylaxis. Respiratory, surgical, skin, pelvic, and vaginal indications were most often treated with penicillins, while pelvic infections were most often treated with tetracyclines.

Generally, the use of an antibiotic for a given indication was not associated with fecundability. There was no substantial association between the use of an antibiotic for a respiratory, urinary tract, skin, or surgical infection when compared to no antibiotic use (Table IV). The use of an antibiotic for a vaginal or pelvic infection was associated with slightly reduced fecundability whether compared with use of an antibiotic for respiratory infection (FR: 0.80, 95% CI: 0.53–1.20, and FR: 0.75, 95% CI: 0.43–1.29, respectively (data not shown)) or compared with no antibiotic use (FR: 0.89, 95% CI: 0.58–1.37, and FR: 0.71, 95% CI: 0.40–1.27, respectively (Table IV)).

Results of the stratified analyses showed little evidence of effect measure modification by the stratification variables. Little difference in the effect of antibiotic use overall on time to pregnancy was found when stratifying by pregnancy attempt time at study entry or BMI (data not shown). We observed slightly lower fecundability among antibiotic users in women <30 years of age (FR: 0.88, 95% CI: 0.76–1.02), current smokers (FR: 0.84, 95% CI: 0.55–1.29), and women with a history of reproductive health conditions (FR: 0.86, 95% CI: 0.75–1.00), but not in women ≥30 years of age (FR: 1.08, 95% CI: 0.95–1.23), those who do not currently smoke (FR: 0.99, 95% CI: 0.90–1.09), and women without a history of reproductive health conditions (FR: 1.07, 95% CI: 0.93–1.22).

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