Association of vaginal bacterial communities and reproductive outcomes with prophylactic antibiotic exposure in a subfertile population undergoing in vitro fertilization: a prospective exploratory study

Uterine Biology

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VOLUME 2, ISSUE 1, P71-79, FEBRUARY 01, 2021


Ashley M. Eskew, M.D., Molly J. Stout, M.D., Bronwyn S. Bedrick, M.D., Joan K. Riley, Ph.D., Brandi N. Herter, B.S., Haley Gula, M.S., Emily S. Jungheim, M.D., Kristine M. Wylie, Ph.D. 



To determine whether prophylactic azithromycin is associated with the vaginal bacterial microbiome and clinical outcomes in subfertile women undergoing in vitro fertilization (IVF).


Prospective exploratory cohort study.


Single academic fertility center.


Subfertile women aged 18–43 years undergoing their first IVF cycle and fresh embryo transfer.


Primary exposure to prophylactic azithromycin (1 g orally) once at baseline.

Main Outcome Measures

The primary outcome was the effect of azithromycin on the vaginal microbiome compared with a no-azithromycin group at 3 time points throughout the IVF cycle (baseline, retrieval, and embryo transfer). The secondary outcomes were associations of vaginal bacterial communities with clinical outcomes.


A planned a priori exploratory cohort of 27 subjects (12 in the azithromycin treatment group and 15 in the no-azithromycin group) contributed 79 vaginal swabs for the analysis as part of an ongoing randomized, controlled noninferiority trial. No specific taxa were associated with azithromycin or pregnancy at any time point. Azithromycin did not affect alpha diversity or community stability. Although there were trends of a lower bacterial load and higher percentage of Lactobacillus species in the azithromycin group at the time of transfer, these were not statistically significant. In women who did not become pregnant, the percentage of Lactobacillus species was lower (P = .048; Hodges-Lehmann estimate of difference, 0.41; 95% confidence interval, 0.08–0.65) and the change in community composition over time was higher. The percentage of Lactobacillus species at baseline was not predictive of the percentage of Lactobacillus species at the time of embryo transfer.


Prophylactic azithromycin at baseline is not associated with changes in vaginal bacterial communities. Bacterial community features at the time of embryo transfer are associated with pregnancy. Bacterial community structures at baseline are not predictive of those at the time of embryo transfer.

Clinical Trial Registration Number


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.