Randomized Controlled Trial of Berberine in Combination With Doxycycline in the Treatment of Chronic Endometritis

Summary

Study Subjects: Eligible patients were initially diagnosed with chronic endometritis (CE) by CD138 testing through outpatient hysteroscopy. Positive CD138 expression is defined as at least one or more positive-staining plasma cells per 10 high-power fields identified as positive, and less than one positive-stained plasma cell identified as negative \[8\]. All patients signed an informed consent form prior to participating in the study, and the study followed the principles of the Declaration of Helsinki. Inclusion Criteria: Diagnosis of chronic endometritis by CD138 immunohistochemistry; Age≥ 20 years old, females of childbearing age; Agree to undergo hysteroscopy and hysteroscopic endometrial biopsy; No serious systemic disease; There are no contraindications to oral administration of doxycycline hydrochloride and berberine hydrochloride. Exclusion criteria: patients with pregnancy status, uterine malignant disease, hormone therapy within 3 months, glucose-6 phosphate dehydrogenase deficiency, hemolytic anemia, hypersensitivity to berberine hydrochloride or doxycycline. In addition, berberine hydrochloride has fewer oral adverse reactions, occasional nausea and vomiting, rash and drug fever, which disappear after stopping the drug. If the patient takes the wrong or missed medication, it is excluded. Withdrawal criteria: If the patient has corresponding adverse reaction symptoms, those with mild symptoms can be temporarily observed, and if the symptoms are severe, they can be transferred to the Department of Gastroenterology for diagnosis and treatment, and those who need to stop the drug will be withdrawn from this study.

Timeline

Start

2025-03-15

Primary completion

2026-11-30

Completion

2026-12-31

Publications

• Results McQueen DB, Bernardi LA, Stephenson MD. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise. Fertil Steril. 2014 Apr;101(4):1026-30. doi: 10.1016/j.fertnstert.2013.12.031. Epub 2014 Jan 23.
• Results Cicinelli E, Matteo M, Tinelli R, Lepera A, Alfonso R, Indraccolo U, Marrocchella S, Greco P, Resta L. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015 Feb;30(2):323-30. doi: 10.1093/humrep/deu292. Epub 2014 Nov 10.
• Results Hirata K, Kimura F, Nakamura A, Kitazawa J, Morimune A, Hanada T, Takebayashi A, Takashima A, Amano T, Tsuji S, Kaku S, Kushima R, Murakami T. Histological diagnostic criterion for chronic endometritis based on the clinical outcome. BMC Womens Health. 2021 Mar 4;21(1):94. doi: 10.1186/s12905-021-01239-y.
• Results Chen YX, Gao QY, Zou TH, Wang BM, Liu SD, Sheng JQ, Ren JL, Zou XP, Liu ZJ, Song YY, Xiao B, Sun XM, Dou XT, Cao HL, Yang XN, Li N, Kang Q, Zhu W, Xu HZ, Chen HM, Cao XC, Fang JY. Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. Lancet Gastroenterol Hepatol. 2020 Mar;5(3):267-275. doi: 10.1016/S2468-1253(19)30409-1. Epub 2020 Jan 8.
• Results Shakeri F, Kiani S, Rahimi G, Boskabady MH. Anti-inflammatory, antioxidant, and immunomodulatory effects of Berberis vulgaris and its constituent berberine, experimental and clinical, a review. Phytother Res. 2024 Apr;38(4):1882-1902. doi: 10.1002/ptr.8077. Epub 2024 Feb 15.
• Results Kuroda K, Takamizawa S, Motoyama H, Tsutsumi R, Sugiyama R, Nakagawa K, Sugiyama R, Kuribayashi Y. Analysis of the therapeutic effects of hysteroscopic polypectomy with and without doxycycline treatment on chronic endometritis with endometrial polyps. Am J Reprod Immunol. 2021 Jun;85(6):e13392. doi: 10.1111/aji.13392. Epub 2021 Jan 27.
• Results Singh N, Sethi A. Endometritis - Diagnosis,Treatment and its impact on fertility - A Scoping Review. JBRA Assist Reprod. 2022 Aug 4;26(3):538-546. doi: 10.5935/1518-0557.20220015.

Drugs

Indications