Prophylactic antibiotics for uterine evacuation procedures to manage miscarriage

Procedural management of early pregnancy loss (EPL) involves removing any residual pregnancy tissue from the uterus. Clinical evidence and guidance are clear that antibiotic treatment is needed for women experiencing EPL, with signs and symptoms of infection. However, it is less clear whether prophylactic antibiotics are routinely required during procedural management in those without features of infection.

To evaluate the effectiveness of routine antibiotic prophylaxis for women undergoing uterine evacuation procedures to manage early pregnancy loss.

We searched the Cochrane Fertility Regulation Review Group trials register, CENTRAL, MEDLINE, Embase, Global Health (Ovid), Scopus (conference abstracts only), and grey literature in October 2023. We checked references and contacted study authors and experts in the field to identify additional studies.

We included randomised controlled trials comparing prophylactic antibiotics with placebo or no treatment. Trials with a cluster-randomised design and trials published only in abstract form were also eligible for inclusion. We included all types of EPL managed with surgical uterine evacuation. There was no gestational age limit. We excluded women with signs and symptoms of infection.

Two review authors independently assessed trials for inclusion and risk of bias, extracted and checked data for accuracy, and assessed the certainty of evidence using the GRADE approach. We contacted the authors of the ongoing trial for additional information.

We included six RCTs with a total of 4371 participants undergoing uterine evacuation procedures to manage EPL. Prophylactic antibiotics may have little or no effect on uterine infection after uterine evacuation for EPL compared with placebo or no treatment, but this evidence was uncertain (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.47 to 1.28; I² = 50%; 6 studies, 4371 participants; low-certainty evidence).   Sensitivity analysis of three studies including 3737 participants (85% of total participants) showed that when only studies with low risk of bias were meta-analysed, the effect was larger and of high certainty, resulting in a 43% reduction in the risk of developing a uterine infection (RR 0.57, 95% CI 0.37 to 0.86; I² = 0%; 3 studies, 3737 participants; high-certainty evidence). Both the overall estimate and the sensitivity analysis limited to studies with low risk of bias were consistent with a reduction in uterine infection with prophylactic antibiotics. A single study reported on adverse effects. Prophylactic antibiotics likely result in little or no difference in the risk of vomiting (RR 1.20, 95% CI 0.61 to 2.38; 1 study, 3404 participants; moderate-certainty evidence), and likely result in little or no difference in the risk of having diarrhoea (RR 0.92, 95% CI 0.51 to 1.65; 1 study, 3404 participants; moderate-certainty evidence). Prophylactic antibiotics may increase the risk of allergy (RR 3.01, 95% CI 0.12 to 73.76; 1 study, 3404 participants; low-certainty evidence); the study reported no cases of anaphylaxis (very low-certainty evidence). Prophylactic antibiotics may reduce the need for antibiotic treatment to treat infection, but the evidence is very uncertain (RR 0.94, 95% CI 0.54 to 1.64; I² = 63%; 3 studies, 3574 participants; very low-certainty evidence). Meta-analysis of three studies also found that prophylactic antibiotics may reduce hospitalisation for treatment of infection, but the effect was very uncertain (RR 0.76, 95% CI 0.40 to 1.46; I² = 0%; 3 studies, 3859 participants; very low-certainty evidence).

When all studies were considered, the evidence suggested that routine antibiotic prophylaxis may reduce uterine infection amongst women undergoing uterine evacuation procedures to manage early pregnancy loss (EPL), but the evidence is of low certainty. It is important to note that the quality of the evidence included was seriously affected by poor follow-up and high non-compliance with antibiotic prophylaxis. A sensitivity analysis based on three trials assessed to have low risk of bias (85% of the total participants), demonstrated a larger effect size with high certainty, resulting in a 43% reduction in the risk of uterine infection rates with antibiotic prophylaxis. Prophylactic antibiotics may reduce hospitalisation for treatment of infection, and may reduce the need for a course of antibiotics to treat infection after uterine evacuation procedures to treat EPL, but this evidence is very uncertain. Data were limited and uncertain with regard to potential adverse effects, such as vomiting, diarrhoea, allergy, and anaphylaxis.