Post-embryo transfer interventions for assisted reproduction technology cycles

Abstract

In women undergoing in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), embryos transferred into the uterine cavity can be expelled due to many factors including uterine peristalsis and contractions, low site of deposition and negative pressure generated when removing the transfer catheter. Techniques to reduce the risk of embryo loss following embryo transfer (ET) have been described but are not standard in all centres conducting ET. To evaluate the efficacy of interventions used to prevent post-transfer embryo expulsion in women undergoing IVF and ICSI. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials to June 2014 and PubMed, MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, World Health Organization ICTRP, and trial registers from inception to June 2014, with no language restrictions. Additionally, we handsearched reference lists of relevant articles, and ESHRE and ASRM conference abstracts. We included randomised controlled trials (RCTs) of interventions used to prevent post-transfer embryo expulsion in women undergoing IVF and ICSI. Two review authors independently screened titles and abstracts and reviewed the full-texts of all potentially eligible citations to determine whether they met our inclusion criteria. Disagreements were resolved by consensus. Two review authors independently extracted data and assessed the risk of bias of included trials using standardised, piloted data extraction forms. Data were extracted to allow intention-to-treat analyses. Disagreements were resolved by consensus. The overall quality of the evidence was rated using GRADE methods. We included four RCTs (n = 1392 women) which administered the following interventions: bed rest (two trials), fibrin sealant (one trial), and mechanical closure of the cervix (one trial). Our primary outcome, live birth rate, was not reported in any of the included trials; nor were the data available from the corresponding authors. For the ongoing pregnancy rate, two trials comparing more bed rest with less bed rest showed no evidence of a difference between groups (odds ratio (OR) 0.88; 95% confidence interval (CI) 0.60 to 1.31, 542 women, I(2) = 0%, low quality evidence). Secondary outcomes were sporadically reported with the exception of the clinical pregnancy rate, which was reported in all of the included trials. There was no evidence of a difference in clinical pregnancy rate between more bed rest and less bed rest (OR 0.88; 95% CI 0.60 to 1.31, 542 women, I(2) = 0%, low quality evidence) or between fibrin sealant and usual care (OR 0.98; 95% CI 0.54 to 1.78, 211 women, very low quality evidence). However, mechanical closure of the cervix was associated with a higher clinical pregnancy rate than usual care (OR 1.92; 95% CI 1.40 to 2.63, very low quality evidence). The quality of the evidence was rated as low or very low for all outcomes. The main limitations were failure to report live births, imprecision and risk of bias. Overall, the risk of bias of the included trials was high. The use of a proper method of randomisation and allocation concealment was fairly well reported, while only one trial clearly reported blinding. There was no evidence that any of the interventions had an effect on adverse event rates but data were too few to reach any conclusions. There is insufficient evidence to support any specific length of time for women to remain recumbent, if at all, following embryo transfer, nor is there sufficient evidence to recommend the use of fibrin sealants added to the embryo transfer fluid. There is very limited evidence to support the use of mechanical pressure to close the cervical canal following embryo transfer. Further well-designed and powered studies are required to determine the true effectiveness and safety of these interventions.