Multi-drug-resistant chronic endometritis in infertile women with repeated implantation failure: trend over the decade and pilot study for third-line oral antibiotic treatment

• Published in: Journal of assisted reproduction and genetics Vol. 39; no. 8; pp. 1839 - 1848
• Main Authors: Kitaya, Kotaro, Tanaka, Suguru E., Sakuraba, Yoshiyuki, Ishikawa, Tomomoto
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-08-2022; Springer Nature B.V
• Subjects: Anti-Bacterial Agents - therapeutic use; Antibiotics; Azithromycin; Azithromycin - therapeutic use; Chronic Disease; Drug resistance; Embryo Implantation; Embryo transfer; Endometritis; Endometritis - complications; Endometritis - drug therapy; Endometritis - epidemiology; Endometrium; Endometrium - pathology; Female; Gynecology; Human Genetics; Humans; Infertility, Female - therapy; Medicine; Medicine & Public Health; Microbiota; Moxifloxacin; Moxifloxacin - therapeutic use; Patients; Pharmaceutical Preparations; Pilot Projects; Prospective Studies; Reproductive Medicine; Reproductive Physiology and Disease; Retrospective Studies; Secretions; Chronic endometritis; Live birth rate; Microbiota; Oral antibiotic treatment; Repeated implantation failure; Multidrug resistance
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-022-02528-7

Purpose
To evaluate the yearly prevalence and annual transition of multi-drug-resistant-chronic endometritis (MDR-CE) in infertile women with a history of repeated implantation failure (RIF) and to establish the third-line antibiotic treatment regimen against MDR-CE.
Methods
This retrospective/prospective cohort and pilot study included 3473 RIF women between April 2010 and September 2021. The endometrial stromal plasmacyte density index (ESPDI) was calculated in 3449 CD138-immunostained endometrial sections to evaluate CE. The microbiota in the vaginal secretions and endometrial fluid was compared between 17 patients with MDR-CE and 16 patients with antibiotics-sensitive CE. In a pilot study, oral moxifloxacin (400 mg/day, 10 days,
n
 = 24) or azithromycin (500 mg/day, 3 days,
n
 = 24) was administered to eligible patients with MDR-CE.
Results
From April 2010 to March 2020, CE was detected in 31.4% of RIF women and MDR was detected in 7.8% of CE. While the prevalence of CE was stable for a decade, MDR in CE increased steadily (OR 8.27, 95% CI 2.58–26.43,
p
trend < 0.001). The bacterial species/communities unique to MDR-CE were not found. The histopathologic cure rate of MDR-CE was similar between the moxifloxacin and azithromycin groups (79.2% vs 75.0%, OR 1.27, 95% CI 0.32–4.89,
p
value 0.73), as well as reproductive outcomes in subsequent embryo transfer cycles.
Conclusion
In RIF women, MDR in CE increased over the decade. As a third-line treatment for MDR-CE, azithromycin may have a clinical advantage due to its shorter time administration periods.
Clinical trial number
ClinicalTrials.gov Identifier: UMIN-CTR 000029449/000031909.