Efficacy of atosiban for repeated embryo implantation failure: A systematic review and meta-analysis

Abstract

BackgroundRepeated embryo implantation failure (RIF) posed a significant challenge in assisted reproduction. Evidence of its therapeutic effectiveness including atosiban used around embryo transfer to improve pregnancy outcomes in RIF patients undergoing in vitro fertilization-embryo transfer (IVF-ET) remained inconsistent. This study aimed to explore the efficacy of atosiban on pregnancy outcomes of patients with RIF who received IVF-ET. MethodsThe research was designed using the PICOS format. A systematic search of four English databases, PubMed, EMBASE, Web of Science, Cochrane Library, and one Chinse database, China National Knowledge Infrastructure (CNKI) was conducted. The time range was from inception to December 10, 2022. Then trials comparing the efficacy of atosiban and control group on pregnancy outcomes in RIF patients who receive IVF-ET were included. Subgroup analysis and sensitivity analysis were performed to reduce the influence of heterogeneity between included studies. Risk ratio (RR) and 95% confidence interval (CI) were calculated. The main outcome measure was clinical pregnancy rate (CPR). For the analyses, StataMP 17.0 (Stata Corporation, USA) was used.ResultsTwo prospective randomized controlled trials (RCTs), one prospective cohort study and four retrospective cohort studies were included. Our results showed that atosiban was associated with higher clinical pregnancy rate (RR=1.54, 95% CI: 1.365–1.735, P < 0.001, I2 = 0.0%). The results of subgroup analysis based on study types (prospective randomized controlled clinical trial, retrospective cohort study and prospective cohort study) showed that in all types of studies, CPR of atosiban group was significantly higher than controlled group. The results of subgroup analysis based upon the diagnostic criteria of number of previous embryo transfer failures showed that the intervention of atosiban improved the CPR whether in participants with 2 previous ET failures or in participants with 3 previous ET failures. Nevertheless, the incidence of ectopic pregnancy, multiple pregnancy, and miscarriages were not significantly different between the case and control groups.ConclusionFor women who are undergoing IVF-ET and have experienced repeated embryo implantation failure, atosiban may be an important factor in enhancing pregnancy outcomes. To confirm this conclusion, more thorough, prospective randomized controlled studies of sizable sample sizes with well design are required.

Efficacy of atosiban for repeated implantation failure in frozen embryo transfer cycles

“…In 2011, chou et al reported that a lower dosage of atosiban improved pregnancy outcomes of patients with RIF, but the number of recruited patients was small 20 . Another study by Wang et al 33 discovered RIF patients presented with higher clinical pregnancy rates with the administration of atosiban in IVF-ET cycles, without significant changes in ectopic rate, multiple-gestation pregnancy rate, and miscarriage rate. Ng et al 34 found that 800 patients receiving IVF were selected from Guangzhou, Hong Kong, and Ho Chi Minh City and admitted in a multicenter, randomized, and double-blind trial.…”

Atosiban interacts with growth hormones as adjuvants in frozen-thawed embryo transfer cycles

“…In the present study, we used a total dose of 37.5mg atosiban in the study. According to the published data, there have been various types of doses and modes of administration (bolus versus infusion) of atosiban as an adjuvant in ART and they may contribute to the heterogeneity of the studies ( 6 ). Nevertheless, the reviews of previous data ( 6 , 18 ) also suggested that the association between atosiban and ET outcomes is not necessarily linked to the dose of atosiban administration and the effect of different doses/modes of atosiban administration remained less clear.…”

“…of atosiban as an adjuvant in ART and they may contribute to the heterogeneity of the studies (6). Nevertheless, the reviews of previous data (6,18) also suggested that the association between atosiban and ET outcomes is not necessarily linked to the dose of atosiban administration and the effect of different doses/modes of atosiban administration remained less clear.…”

“…Atosiban is one of the few adjuvants that showed a trend toward increased clinical pregnancy rate in embryo transfer (ET) ( 2 ) with a supposed mechanism in antagonizing the oxytocin receptors and reducing the uterine contractions that might dislodge the transferred embryos. It also provided an option of adjuvants in patients with repeated embryo implantation failure (RIF) ( 6 ). Because the majority of RIF patients have unclear etiologies, the list of adjuvants in RIF patients is rapidly growing and a combination of adjuvants targeting different mechanisms is possibly recommended for them ( 6 ).…”

“…It also provided an option of adjuvants in patients with repeated embryo implantation failure (RIF) ( 6 ). Because the majority of RIF patients have unclear etiologies, the list of adjuvants in RIF patients is rapidly growing and a combination of adjuvants targeting different mechanisms is possibly recommended for them ( 6 ). Growth hormone (GH) provides another hopeful option for RIF that may improve endometrial growth and receptivity ( 7 ).…”