Intravesical application of birth tissue has been reported to inhibit inflammation, alleviate collagen fiber accumulation, and enhance bladder tissue generation. We have previously reported that intra-detrusor micronized amnion monolayer (AM) injections provide short-term clinical improvement in refractory IC/BPS patients. Herein, we evaluate the therapeutic responses and adverse events of micronized amnion/chorion bilayer (AC) in patients with refractory IC/BPS with 6months follow-up. Fifteen patients affected by IC/BPS who failed conventional therapy received 100mg of reconstituted micronized AC was injected intra-detrusor via cystoscopy under general anesthesia, using a 23-gauge needle. Twenty 0.5-mL injections were administered into the lateral and posterior bladder walls, avoiding the dome and trigone. Changes in interstitial cystitis symptom index (ICSI), Interstitial cystitis problem index (ICPI), Bladder pain/ interstitial cystitis symptom score (BPIC-SS) and Overactive Bladder Assessment Tool (OAB), from baseline to 6months post-injection were evaluated retrospectively.The safety of injections was analyzed. Fifteen total refractory IC/BPS patients with an average age of 41.1 ± 14.5years were included in the study, receiving intra-detrusor injections of 100mg of micronized AC. One month after injections, significant improvement in IC/BPS symptom scores was noted in all patients. All patients maintained a sustained clinical response at 6months post-injection. No product-related adverse events were observed. Our findings indicate that the AC formulation significantly reduces time to symptom relief in patients with refractory interstitial cystitis/bladder pain syndrome (IC/BPS) and maintains a sustained response up to 6months post-injection. These results suggest a promising clinical benefit of using an amnion/chorion bilayer product for treating IC/BPS. Further research is needed to confirm these findings and assess the long-term durability of this treatment approach. This study represents the first evidence supporting the clinical advantages of an amnion/chorion bilayer product in managing IC/BPS.