Do antibiotics before or at the time of embryo transfer improve outcomes in assisted reproductive technology (ART)?
– The findings do not support the use of antibiotics at the time of embryo transfer for the purposes of improving in vitro fertilization (IVF) success rates in any of the predetermined outcomes.
– In the one study that adequately addressed genital tract colonization rate (a measure of the number of bacteria within the genital tract), the use of antibiotics had no effect on clinical pregnancy rate.
How could antibiotics before or at the time of embryo transfer improve outcomes in IVF?
IVF and intracytoplasmic sperm injection (ICSI) are types of ART used to help people with fertility problems have a baby. During IVF/ICSI, an egg is removed from the woman's ovaries and fertilized with sperm in a laboratory. The resulting embryo(s) is transferred into the uterus (womb) via a thin tube passed through the cervix (opening to the uterus). Many variables affect the chance of pregnancy after an embryo transfer, including embryo quality and the conditions within the uterus (environment). High levels of bacteria in the upper genital tract may reduce pregnancy rates. Administration of antibiotics before embryo transfer may reduce the growth of these bacteria and improve the outcome of ART. In addition, there may be some types of bacteria that may be more favourable to pregnancy than others. Antibiotics may change this environment and thereby affect outcomes.
What did we want to find out?
This review considered whether antibiotics given before or at the time of embryo transfer affect pregnancy rates or other important outcomes in ART.
What did we do?
We searched for studies that compared antibiotics against no antibiotics before or at the time of embryo transfer in ART. We compared and summarized their results, and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found two studies that involved 377 women undergoing IVF/ICSI. One study had 350 women and the other had 27 women. Each study was conducted in one clinic in two different countries. All women had a stimulated IVF/ICSI cycle (where the women took medications to stimulate her ovaries to grow and mature multiple eggs) and embryo transfer. The studies gave different regimens of antibiotic (different types, doses and timings) and, in one study, all women received one dose of intravenous (into a vein) antibiotic during embryo transfer.
What are the limitations of the evidence?
We are uncertain whether antibiotics administered before or at the time of embryo transfer makes a difference to ART success despite possible changes to the bacteria within the genital tract. We are uncertain if the amounts of bacteria in the upper genital tract are changed because only one study provided information that we could use. The second study was small and all women received intravenous antibiotics during the embryo transfer, which may have affected results.
How up to date is this evidence?
The evidence is up to date to November 2022.
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.
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.
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.
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.
We included two randomized controlled trials (RCT) that compared antibiotics administered by any route versus no antibiotics prior to ET.
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.
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.