Randomised Trial of Lipiodol Uterine Bathing Effect (LUBE) in Women with Endometriosis-Related Infertility

Abstract

BACKGROUND: We aimed to assess whether lipiodol alters endometrial gene expression through a uterine bathing effect that might enhance receptivity to embryo implantation. METHODS: An open-label randomised controlled trial design in a single-centre tertiary infertility service. Twelve women with endometriosis (n [Formula: see text] 11) or previous successful lipiodol procedure (n [Formula: see text] 1) were randomised to receive immediate or delayed lipiodol hysterosalpingography, followed by endometrial biopsy. Endometrial samples were assessed for gene expression, using Affymetrix microarrays and validation studies using reverse transcriptase quantitative polymerase chain reaction analysis. Subsequent endometrial gene expression responses to treatment and clinical fertility outcomes were assessed. RESULTS: Eleven of 12 women had successful endometrial sampling procedures. Nine women had successful pregnancies within the 9-month follow-up phase. Following lipiodol bathing we identified 20 down-regulated and 13 up-regulated genes with p [Formula: see text] 0.05 and with magnitude of change [Formula: see text]1.5-fold in at least three of the four women, with osteopontin being the only gene down-regulated in all four women. CONCLUSIONS: This study supports the concept of a uterine bathing effect of lipiodol altering endometrial biology and gene expression. Whether regulation of inflammation and immune response pathways by lipiodol might contribute to an increase in endometrial receptivity to embryo implantation merits further investigation.

Uterine bathing with sonography gel prior to IVF/ICSI-treatment in patients with endometriosis, a multicentre randomised controlled trial

“…Theoretically, local injury of the endometrium might also be applied by infusion of intrauterine fluids or gels. Since previous studies have suggested that uterine bathing with Lipiodol ® might have an effect on endometrial receptivity by immunomodulation ( Johnson et al , 2005 ; Johnson, 2014 ; Johnson et al , 2019 ), we aimed to investigate the effect of mechanical stress on the endometrium by uterine bathing with an pharmacologically neutral non-embryotoxic gel (ExEm-gel ® ). ExEm-gel ® is frequently used during fertility work-up and is registered and marketed in the Netherlands for GIS procedures ( Exalto et al , 2014 ).…”

“…This hypothesis is supported by data from a randomised controlled animal study ( Johnson et al , 2005 ) in which treatment with Lipiodol ® (vs. infusion with saline vs. sham treatment) altered the dendritic cell population of the endometrium in mice, suggesting a Lipiodol-induced favourable uterine immune response. Endometrial gene transcript regulation during Lipiodol ® uterine bathing has also demonstrated a downregulation of endometrial Osteopontin, a molecule that could be interfering with implantation receptivity in women with endometriosis ( Johnson et al, 2019 ). In order to investigate the effectiveness of pre-IVF uterine bathing with Lipiodol ® in women with endometriosis or RIF, the IVF-LUBE trial was performed ( Reilly et al , 2019 ).…”

Iodine and other factors associated with fertility outcome following oil-soluble contrast medium hysterosalpingography: a prospective cohort study

“…Nonetheless, several mechanisms have been proposed, including a mechanical flushing effect (7), an immune-biological peritoneal bathing effect (8), and an immune-biological uterine bathing effect (9). The other hypothesis is that iodine in OSCM could contribute to this fertility improvement (10).…”