Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure

Kitaya, Kotaro; Matsubayashi, Hidehiko; Takaya, Y.; Nishiyama, R.; Yamaguchi, Kensei; Takeuchi, Takumi; Ishikawa, Tomomoto

doi:10.1111/aji.12719

Cited by 186 publications

(281 citation statements)

References 25 publications

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“…The efficacy of oral antibiotic treatment for fertility was also elucidated. Kitaya et al conducted a prospective study and found that the LBR in the first ET cycle and three cumulative ET cycles in RIF patients cured by antibiotic treatment (32.8%, 38/116 and 38.8%, 45/116, respectively) was significantly higher than in RIF patients without CE (22.1%, 50/226 and 27.9%, 63/226, respectively) . In this study, the authors set RIF patients without CE as the controls, because almost all CE patients were cured by the antibiotic treatment.…”

Section: Treatment For Ce and Its Effect On Reproductive Outcomesmentioning

confidence: 85%

“…30 Kitaya et al also reported that 92.3% (108/117) of CE patients with RIF were cured by the same doxycycline regimen. 35 Additional treatment using a combination of ofloxacin (400 mg/day for 14 days) and metronidazole (500 mg/day for 14 days) cured the remaining 8 of 9 patients. Overall, the cure rate was 99.1% (116/117).…”

Section: Treatment For Ce and Its Effect On Reproductive Outcomesmentioning

confidence: 99%

“…Johnston‐MacAnanny et al reported that 66.7% (6/9, 9/10 CE patients were enrolled and one patient was not treated) of CE cases confirmed by IHC for plasma cell detection were cured by the administration of doxycycline (200 mg/day for 14 days); a second‐line regimen comprising ciprofloxacin and metronidazole (500 mg of each per day for 14 days) cured the remaining three patients . Kitaya et al also reported that 92.3% (108/117) of CE patients with RIF were cured by the same doxycycline regimen . Additional treatment using a combination of ofloxacin (400 mg/day for 14 days) and metronidazole (500 mg/day for 14 days) cured the remaining 8 of 9 patients.…”

Section: Treatment For Ce and Its Effect On Reproductive Outcomesmentioning

confidence: 99%

“…24,33,34 Within the uterine cavity of CE, common bacteria are usually present, 24,33,34 such as Streptococcus spp., Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus spp., Corynebacterium and Mycoplasma/Ureaplasma spp., which are frequently detected in microbial cultures or polymerase chain reaction tests for Mycoplasma/Ureaplasma DNA (Tables 1-2). 24,35,36 Thus, these bacteria obtained as a result of these cultures or PCR are currently thought to be the causal organisms of CE.…”

Section: Concept Of Cementioning

confidence: 99%

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Review: Chronic endometritis and its effect on reproduction

Kimura

Takebayashi

Ishida

et al. 2019

J of Obstet and Gynaecol

209

144

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Aim Chronic endometritis (CE) is a disease of continuous and subtle inflammation characterized by the infiltration of plasma cells in the endometrial stromal area. Although the clinical significance of CE has been thought in clinical practice for a long time because it is either asymptomatic or presents with subtle symptoms, recent studies have shown the potential adverse effects of CE on fertility. In the present review, we focus on the concept, diagnosis, etiology, pathophysiology, diagnosis, impact on reproduction and treatment for it to understand CE. Methods The published articles were reviewed. Results The prevalence of CE has been found to be 2.8–56.8% in infertile women, 14–67.5% in women with recurrent implantation failure (RIF), and 9.3–67.6% in women with recurrent pregnancy loss. Microorganisms are thought to be a main cause of CE, since antibiotic treatment has been reported to be an effective therapy for CE. Common bacteria are frequently detected in the uterine cavity of CE patients by microbial culture. In CE endometrium, the prevalence of immune cells and decidualization has been reported to be modified, and these modifications are thought to adversely affect fertility. The gold standard for the diagnosis of CE is the histological detection of plasma cells in the stromal area of the endometrium in endometrial specimens, although universally accepted criteria for the diagnosis of CE have not been determined. The treatment currently thought to be most effective for the recovery of fertility in CE is administration of oral antibiotics. Patients whose CE has been cured have been reported to have a higher ongoing pregnancy rate, clinical pregnancy rate, and implantation rate compared with patients with persistent CE. Conclusion CE greatly affects implantation and impairs fertility. Antibiotic administration is an effective therapeutic option. Pregnancy rate in in vitro fertilization is improved when CE is cured by antibiotic.

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Section: Treatment For Ce and Its Effect On Reproductive Outcomesmentioning

confidence: 85%

Section: Treatment For Ce and Its Effect On Reproductive Outcomesmentioning

confidence: 99%

Section: Treatment For Ce and Its Effect On Reproductive Outcomesmentioning

confidence: 99%

Section: Concept Of Cementioning

confidence: 99%

See 2 more Smart Citations

Review: Chronic endometritis and its effect on reproduction

Kimura

Takebayashi

Ishida

et al. 2019

J of Obstet and Gynaecol

209

144

View full text Add to dashboard Cite

show abstract

“…8,9 Chronic endometritis refers to inflammation of the endometrium and is often caused by gram-negative bacterial strains such as Escherichia coli and Gardnerella vaginalis or by Ureaplasma urealyticum and Mycoplasma species. 11,12 Interestingly, endometritis is also common in the dairy industry, and bovine uterine infections are estimated to cost the United States 650 million dollars annually. A recent study of infertile women with RIF identified chronic endometritis in almost 34% of their study population, although others have reported the prevalence as high as 57% in women with RIF.…”

mentioning

confidence: 99%

New models of lipopolysaccharide‐induced implantation loss reveal insights into the inflammatory response

Moustafa

Joseph

Taylor

et al. 2019

American J Rep Immunol

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Problem Chronic endometritis, inflammation of the uterizzvvne lining caused by common gram‐negative bacterial strains or mycoplasma, has been associated with unexplained implantation failure and infertility. However, limited models of bacteria‐induced implantation loss exist to study the molecular changes that occur in vivo. The goal of this study was to provide a new resource to study the process of bacteria‐induced inflammation and implantation loss utilizing common experimental models: C57Bl/6 mice and primary human endometrial stromal cells. Method of study Prior to implantation, mated C57Bl/6 females were administered vehicle (saline) or gram‐negative bacterial lipopolysaccharide (LPS) at a range of concentrations by intraperitoneal injection. Implantation sites were counted, and uteri were harvested to evaluate the molecular changes that accompany LPS‐mediated implantation loss. Primary human endometrial stromal cells were decidualized in vitro in the presence and absence of LPS. Total RNA and conditioned media were harvested to evaluate the expression of known decidualization‐associated genes and various cytokines and chemokines. Results Lipopolysaccharide treatment resulted in fewer implantation sites in mice, decreased expression of decidualization‐associated genes, and altered expression and release of cytokines and chemokines. Immunohistological analysis of the uterus from LPS‐exposed mice demonstrated increased apoptosis and decreased proliferation during decidualization. Conclusion Lipopolysaccharide exposure disrupted implantation and decidualization in mice and human endometrial stromal cells. This model could be used to study the pathophysiology of implantation failure in patients with chronic endometritis or to test potential therapeutic interventions.

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Impact of chronic endometritis on endometrial receptivity analysis results and pregnancy outcomes

Kuroda

Horikawa²,

Moriyama³

et al. 2020

Immunity Inflam & Disease

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Background The aim of this study is to evaluate the relationship between chronic endometritis (CE) and a personalized window of implantation (WOI), identified by results of endometrial receptivity analysis (ERA), and pregnancy outcomes following embryo transfer (ET) based on the ERA outcomes. Methods The single‐center, cross‐sectional study was designed. The study population consisted of 101 infertile women who underwent endometrial sampling between June 2018 and February 2020. We recruited 88 patients who underwent ERA testing and immunohistochemistry of the plasma cell marker CD138 to diagnose CE within 3 months of testing. Subjects were divided into three groups as follows: 33 without CE (non‐CE group); 19 with untreated CE at ERA testing (CE group); and 36 successfully treated for CE before ERA testing (cured‐CE group). CE diagnosis was defined as ≥5 CD138‐positive plasma cells per 10 random stromal areas at ×400 magnification. Results In non‐CE, CE, and cured‐CE groups, the numbers of CD138‐positive cells were 0.7 ± 1.0, 28.5 ± 30.4, and 1.3 ± 1.3, respectively (p < .001). The rates of “receptive” endometrium in non‐CE and cured‐CE groups were 57.6% (19 women) and 50.0% (18 women), respectively; however, in the CE group, this rate was significantly lower than the other two groups (p = .009) at only 15.8% (3 women). After CE were treated prior or posterior to the ERA test in cured‐CE or CE groups, the clinical pregnancy rates at the first ET in non‐CE, CE, and cured‐CE groups were 77.8% (21/27 cycles), 22.2% (4/18 cycles), and 51.7% (15/29 cycles), respectively (p < 0.001). Conclusion CE had detrimental effects on the individual WOI, leading to embryo–endometrial asynchrony; therefore, diagnosis and treatment of CE should be done before ERA testing.

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Live birth rate following oral antibiotic treatment for chronic endometritis in infertile women with repeated implantation failure

Abstract: Chronic endometritis was found in one-third of infertile women with RIF. The oral antibiotic treatment against CE might be a promising therapeutic option for infertile women with RIF.

Cited by 186 publications

References 25 publications

Review: Chronic endometritis and its effect on reproduction

Review: Chronic endometritis and its effect on reproduction

New models of lipopolysaccharide‐induced implantation loss reveal insights into the inflammatory response

Impact of chronic endometritis on endometrial receptivity analysis results and pregnancy outcomes

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