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

Abstract

Objective: To determine whether prophylactic azithromycin is associated with the vaginal bacterial microbiome and clinical outcomes in subfertile women undergoing in vitro fertilization (IVF). Design: Prospective exploratory cohort study. Setting: Single academic fertility center. Patients: Subfertile women aged 18-43 years undergoing their first IVF cycle and fresh embryo transfer. Intervention: 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. Results: 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 ¼ .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.

Vaginal dysbiosis – the association with reproductive outcomes in IVF patients: a systematic review and meta-analysis

“…A total of 75 citations were excluded based on title and abstract. Hence, a total of 16 citations [15,16 && , [19][20][21]29,[30][31][32][33][34][35][36][37][38][39] were assessed for eligibility by examination of the full text. Seven studies were removed due to study design [29,[33][34][35][36]38,39] and four were removed as it was not possible to extract pregnancy outcome data for the meta-analysis [30][31][32]37].…”

“…In the repeated literature search, two articles [17 ▪▪ ,22 ▪▪ ] met the eligibility criteria, as the authors of Van den Tweel et al provided data upon request [17 ▪▪ ]. Thus, a total of eight studies were included [15,16 ▪▪ ,17 ▪▪ ,19–21,22 ▪▪ ,23 ▪ ] and added to the 17 studies [4,25–27,44–56] previously included in a systematic review and meta-analysis published by our group [1]. Thus, the present meta-analysis included 25 studies [4,15,16 ▪▪ ,17 ▪▪ ,19–21,22 ▪▪ ,23 ▪ ,25–27,44–56], comprising 6835 IVF patients.…”

“…Thus, a total of eight studies were included [15,16 ▪▪ ,17 ▪▪ ,19–21,22 ▪▪ ,23 ▪ ] and added to the 17 studies [4,25–27,44–56] previously included in a systematic review and meta-analysis published by our group [1]. Thus, the present meta-analysis included 25 studies [4,15,16 ▪▪ ,17 ▪▪ ,19–21,22 ▪▪ ,23 ▪ ,25–27,44–56], comprising 6835 IVF patients. The full selection of the studies is shown in the flow diagram, Fig.…”

“…Seven studies used antibiotics during IVF treatment, possibly resulting in biased results [19,46,48,50,51,60]. In the study by Zeng et al Despite treatment, the results of the study suggest that BV might still adversely affect pregnancy.…”

“…To evaluate the quality of the individual studies, the Newcastle-Ottawa Scale (NOS) [ 18 ] was performed for each study included in our systematic review and meta-analysis [ 15 , 16 ▪▪ , 17 ▪▪ , 19 – 21 , 22 ▪▪ , 23 ▪ ], as presented in Supplementary Material 2. We did not use GRADE [ 24 ] for assessing the quality of evidence per outcome.…”