Intrauterine application of Budesonide-hyaluronic acid gel in patients with recurrent implantation failure and total loss of junctional zone differentiation on magnetic resonance imaging

Recurrent implantation failure (RIF) and repeated pregnancy loss remain major challenges in assisted reproductive technology, often without identifiable causes despite high-quality embryo transfers. Emerging evidence suggests that abnormalities in the junctional zone (JZ) of the uterus may impair implantation. To evaluate the efficacy of hysteroscopic (HSC) sub-endometrial exploration combined with intrauterine application of budesonide-enriched crosslinked hyaluronic acid (HA) gel on pregnancy outcomes in women with RIF and complete JZ loss on magnetic resonance imaging (MRI). This single-centre observational pilot study included 20 women with RIF and MRI-confirmed loss of JZ differentiation. All patients had excellent cryopreserved blastocysts, either from an egg donation program or derived from their own autologous oocytes (<37 years). Under conscious sedation, patients underwent HSC sub-endometrial exploration with micro-incisions at the lateral walls and fundus, followed by intrauterine instillation of budesonide-enriched HyaRegen® gel. [BioRegen Biomedical (Changzhou) Co., Ltd.]. Clinical pregnancy rate, live birth rate, and maternal/neonatal outcomes. Eighteen of 20 women (90%) conceived. In the donor group, all 9 pregnancies led to live births. In the autologous group, 8 of 9 pregnancies were successful; one was medically terminated at 20 weeks due to foetal malformation. All 17 neonates were healthy at birth and six-month follow-up. Preliminary observations of this novel approach suggest that it may contribute to improving implantation and live birth rates in women with unexplained RIF and JZ abnormalities. This study introduces a targeted intrauterine intervention for RIF patients with loss of JZ differentiation, combining HSC exploration and budesonide-HA gel therapy.