A STUDY OF REPRODUCTIVE IMMUNITY IN THE PRESENCE OF UTERINE LEIOMYOMA

Abstract

OBJECTIVE: The objectives of this study were to characterise alterations in the serum immune environment in the presence of non-cavity distorting fibroids, during different phases of the menstrual cycle. MATERIALS AND METHODS: This prospective study examined the presence of 65 serum immunological analytes in 15 patients with non-cavity distorting fibroids, compared to 36 controls, according to menstrual cycle phase. Patients were recruited from St Marys Hospital, Manchester University NHS Foundation Trust, in the United Kingdom. Patients underwent an ultrasound scan to classify the type of fibroid and an outpatient hysteroscopy to exclude cavity distorting fibroids. The control group were patients with proven fertility attending the colposcopy clinic at St Marys Hospital. Serum samples were obtained and stored at -80c. A Luminex multiplex assay was performed (Biotechne R&D Systems). Data was analysed on Graphpad Prism, with appropriate statistical tests. Potential protein-protein interactions and functional associations between the identified analytes were explored using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins). RESULTS: In the presence of non-cavity distorting fibroids, there appears to be an alteration in several serum immunological analytes. There appears to be a reduction in CXCL1, CCL20 and VCAM 1 in the proliferative phase, and CD26L/L-Selectin, Proteinase 3, TNFSF13B, CCL11, IL17 and LIGHT in the early secretory phase. There appears to be an increase in CXCL2 and CXCL5 in both the early and mid-secretory phase. In the mid-secretory phase there seems to be increased levels of CCL5, CCL4, LIGHT, IL1 alpha, CXCL16, S100A9, S100A12, D-dimer, and EGF, alongside a decrease in IL18. After correction for multiple hypothesis testing, CXCL16 was found to be significantly higher in the mid-secretory phase in the fibroid group. STRING analysis demonstrated numerous functional interactions between the proteins. Notably, the interactions between CCL11, CXCL2, CXCL1 and CXCL5, which are produced by macrophages, neutrophils and fibroblasts, demonstrated high confidence. Functional enrichment analysis suggests the presence of a potentially pro-inflammatory systemic immune landscape in the presence of non-cavity distorting fibroids. CONCLUSIONS: There is evidence of systemic immune dysregulation in the presence of non-cavity distorting fibroids, with a notable increase in CXCL16 during the mid-secretory phase. This finding may have broader implications for immune changes during the window of implantation. Several leukocytes merit further exploration. Currently, non-cavity distorting fibroids are not thought to impact reproductive outcome. Further studies are warranted to see if these fibroids require treatment in patients undergoing fertility treatment.

Date of Award	1 Aug 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Elizabeth Mann (Supervisor) & Lamiya Mohiyiddeen (Supervisor)