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

Abstract

Background: 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.

Objectives: 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).

Methods: 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.].

Main outcome measures: Clinical pregnancy rate, live birth rate, and maternal/neonatal outcomes.

Results: 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.

Conclusions: 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.

What is new?: This study introduces a targeted intrauterine intervention for RIF patients with loss of JZ differentiation, combining HSC exploration and budesonide-HA gel therapy.