Meta-analysis of intrauterine hCG perfusion efficacy in recurrent implantation failure as defined by ESHRE guidelines

Abstract

Purpose This study evaluates the efficacy of intrauterine hCG perfusion for RIF, as defined by ESHRE 2023 guidelines, highlighting hCG as a cost-effective alternative to other immunotherapies, especially suitable for less developed regions. It aims to clarify treatment guidance amidst previous inconsistencies. Methods This meta-analysis, registered with PROSPERO (CRD42024443241) and adhering to PRISMA guidelines, assessed the efficacy and safety of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in RIF. Comprehensive literature searches were conducted through December 2023 in major databases including PubMed, Web of Science, Embase, the Cochrane Library, and key Chinese databases, without language restrictions. Inclusion and exclusion criteria were strictly aligned with the 2023 ESHRE recommendations, with exclusions for studies lacking robust control, clear outcomes, or adequate data integrity. The risk of bias was evaluated using the Newcastle-Ottawa Scale, ROBINS-I, and RoB2 tools. Data analysis was performed in R using the ‘meta’ package, employing both fixed and random effect models to account for study variability. Subgroup analyses by dosage, volume, hCG concentration, timing of administration, and type of embryo transfer were conducted to deepen insights, enhancing the reliability and depth of the meta-analysis in elucidating the role of hCG perfusion in RIF treatments. Results Data from 13 studies, comprising six retrospective and six prospective studies from single centers, along with one multi-center RCT, totaling 2,157 participants, were synthesized to evaluate the effectiveness of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in patients with RIF. Significant improvements were observed in clinical pregnancy and embryo implantation rates across various dosages, timing of administration, and embryo developmental stages, without impacting miscarriage rates. Notably, the most significant efficacy within subgroups occurred with a 500 IU dosage and perfusion parameters of ≤ 500µL volume and ≥ 2 IU/µL concentration. Additionally, a limited number of studies showed no significant increases in ectopic pregnancy or multiple pregnancy rates, and a modest improvement in live birth rates, although the small number of these studies precludes definitive conclusions. Conclusions The analysis suggests that intrauterine hCG perfusion probably enhances embryo implantation, clinical pregnancy, and live birth rates slightly in RIF patients. Benefits are indicated with a dosage of 500 IU and a maximum volume of 500µL at concentrations of at least 2 IU/µL. However, substantial heterogeneity from varying study types and the limited number of studies necessitate cautious interpretation. These findings underscore the need for more rigorously designed RCTs to definitively assess the efficacy and safety.