Effects of Fibroid Size and Hyaluronan-Enriched Transfer Medium on Clinical Pregnancy and Live Birth: A Retrospective Study

Objective: Non-cavity-distorting intramural fibroids have been linked to poorer reproductive outcomes in assisted reproduction, yet strategies to counteract this effect remain underexplored. This study examined whether a hyaluronan-enriched transfer medium (EmbryoGlue®) is associated with clinical pregnancy and live birth in women with such fibroids undergoing frozen-thawed single blastocyst transfer, and whether any such association depends on fibroid size. Methods: We conducted a single-center retrospective cohort analysis of 515 women, aged 20–37 years, carrying the International Federation of Gynecology and Obstetrics (FIGO) type 3–5 non-cavity-distorting intramural fibroids, who underwent frozen-thawed single blastocyst transfer between January 2021 and December 2025. Of these, 232 received a hyaluronan-enriched transfer medium and 283 received a standard medium. Clinical pregnancy served as the primary endpoint; positive pregnancy test, live birth, and early pregnancy loss were secondary endpoints. Multivariable logistic regression was used to identify independent predictors of clinical pregnancy and live birth and to test for an interaction between EmbryoGlue use and fibroid size. Results: Women who received EmbryoGlue had higher rates of positive pregnancy test (50.0% vs. 32.9%; p < 0.001), clinical pregnancy (40.5% vs. 26.9%; p = 0.001), and live birth (30.2% vs. 19.1%; p = 0.003) than those in the control group. After adjustment, and taking a fibroid size of 3 cm as the reference point, EmbryoGlue use remained associated with greater odds of clinical pregnancy (adjusted odds ratio [aOR] 2.05, 95% CI 1.20–3.50; p = 0.008). A significant interaction between EmbryoGlue use and fibroid size emerged for both clinical pregnancy (aOR 1.74, 95% CI 1.13–2.68; p = 0.011) and live birth (aOR 1.68, 95% CI 1.06–2.67; p = 0.028): the association between EmbryoGlue and reproductive outcomes was not uniform but depended on fibroid size, with the widest gap between groups seen among women with fibroids exceeding 4 cm. Conclusions: Among women with non-cavity-distorting intramural fibroids undergoing frozen-thawed single blastocyst transfer, EmbryoGlue use was linked to more favorable reproductive outcomes overall, an association that varied by fibroid size and was most pronounced above 4 cm. These findings warrant confirmation through prospective randomized trials before influencing clinical practice.