Antibiotics prior to or at the time of embryo transfer in ART.

BACKGROUND: After an assisted reproductive technology (ART) cycle, embryo transfer (ET) involves the placement of one or more embryos into the uterine cavity, usually by passing a catheter through the cervical os. Despite the transfer of high-quality embryos, many ETs do not result in a pregnancy. There are many factors that may affect the success of ET. There is some evidence to suggest that increased endocervical microbial colonization at the time of ET results in lower pregnancy rates. The association between the cervico-vaginal microbiome and reduced pregnancy rates after ET may indicate either pre-existing dysbiosis in this patient population, or that the passage of the ET catheter itself may be introducing microbes that alter the microbiome of the endometrial cavity or lead to infection. Such an upper genital tract infection, contamination or alteration may have a negative impact on implantation and in vitro fertilization (IVF) success rates by both endometrial and embryonic mechanisms. The administration of antibiotics at the time of ET has been suggested as an intervention to reduce levels of microbial colonization and hence improve pregnancy rates.

OBJECTIVES: To evaluate the benefits and harms of antibiotic administration prior to or at the time of embryo transfer (ET) during assisted reproductive technology (ART) cycles.

SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL (now containing output from two trial registers and CINAHL), MEDLINE, Embase and PsycINFO, together with reference checking and contact with study authors and experts in the field to identify additional studies. The search date was November 2022.

SELECTION CRITERIA: We included two randomized controlled trials (RCT) that compared antibiotics administered by any route versus no antibiotics prior to ET.

DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane, including assessing risk of bias of the included studies using the RoB 2 tool. The primary review outcome was live birth rate (LBR) or ongoing pregnancy, and secondary outcomes were clinical pregnancy rate (CPR), genital tract colonization rate, miscarriage rate, ectopic pregnancy rate, multiple pregnancy rate, fetal abnormalities, adverse events and pelvic infection.

MAIN RESULTS: We included two RCTs with 377 women in the review. Using the GRADE method, we assessed the certainty of the evidence as very low to low across measured outcomes. We are uncertain whether antibiotics given prior to or at the time of ET improved LBR (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.10 to 2.23; 1 study, 27 women; low-certainty evidence). The evidence suggests that if LBR without antibiotics was 60%, the rate with antibiotics would be between 13% and 77%. We are uncertain whether antibiotics given prior to or at the time of ET improve CPR (OR 1.01, 95% CI 0.67 to 1.55; I² = 0%; 2 studies, 377 women; low-certainty evidence). If the CPR without antibiotics was 37%, the rate with antibiotics would be between 29% and 48%. The administration of antibiotics prior to or at the time of ET may reduce genital tract colonization slightly (OR 0.59, 95% CI 0.37 to 0.95; 1 study, 130 women; very low-certainty evidence). If the genital tract colonization rate without antibiotics was 29%, the rate with antibiotics would be between 13% and 28%. However, this did not correspond to an effect on the pregnancy outcome. Only one study with low numbers of women reported on miscarriage rate, with one miscarriage reported in the group not receiving antibiotics (OR 4.04, 0.15 to 108.57; 1 study, 27 women; low-certainty evidence). There was insufficient evidence to reach a conclusion regarding adverse effects and other outcomes as no studies reported data suitable for analysis.

AUTHORS' CONCLUSIONS: We are uncertain if administration of antibiotics prior to or at the time of ET improves LBR in women undergoing ART based on a single study of 27 women with low-certainty evidence. We are uncertain whether there was a difference in CPR. There was evidence for a reduction in genital tract colonization rates, but the evidence was very low certainty. Data were lacking on other secondary outcomes. The pooled results should be interpreted with caution, due to the small number of women included in the analysis.