Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis.
Vitagliano Amerigo,Saccardi Carlo,Noventa Marco,Di Spiezio Sardo Attilio,Saccone Gabriele,Cicinelli Ettore,Pizzi Sara,Andrisani Alessandra,Litta Pietro Salvatore
Fertility and sterility
OBJECTIVE:To evaluate the impact of antibiotic therapy for chronic endometritis (CE) on IVF outcome. DESIGN:Systematic review and meta-analysis. SETTING:Not applicable. PATIENT(S):Infertile women with history of recurrent implantation failure, defined as two or more failed ETs, undergoing one or more IVF cycle(s). INTERVENTION(S):The review was registered in PROSPERO (CRD42017062494) before the start of the literature search. Observational studies were identified by searching electronic databases. The following comparators were included: women with CE receiving antibiotics vs. untreated controls; women with cured CE vs. women with persistent CE; and women with cured CE vs. women with normal endometrial histology (negative for CE). The summary measures were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN OUTCOME MEASURE(S):Clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR/LBR), implantation rate (IR), miscarriage rate. RESULT(S):A total of 796 patients (from five studies) were included. Women receiving antibiotic therapy (without the histologic confirmation of CE cure) did not show any advantage in comparison with untreated controls (OPR/LBR, CPR, and IR). Patients with cured CE showed higher OPR/LBR (OR 6.81), CPR (OR 4.02), and IR (OR 3.24) in comparison with patients with persistent CE. In vitro fertilization outcome was comparable between women with cured CE and those without CE (OPR/LBR, CPR, and IR). Miscarriage rate was not significantly different between groups. CONCLUSION(S):Chronic endometritis therapy may improve IVF outcome in patients suffering from recurrent implantation failure. A control biopsy should always confirm CE resolution before proceeding with IVF.
10.1016/j.fertnstert.2018.03.017
Review: Chronic endometritis and its effect on reproduction.
Kimura Fuminori,Takebayashi Akie,Ishida Mitsuaki,Nakamura Akiko,Kitazawa Jun,Morimune Aina,Hirata Kimiko,Takahashi Akimasa,Tsuji Shoko,Takashima Akiko,Amano Tsukuru,Tsuji Shunichiro,Ono Tetsuo,Kaku Shoji,Kasahara Kyoko,Moritani Suzuko,Kushima Ryoji,Murakami Takashi
The journal of obstetrics and gynaecology research
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.
10.1111/jog.13937
Correlation between hysteroscopy findings and chronic endometritis.
Song Dongmei,Li Tin-Chiu,Zhang Yun,Feng Xiangdong,Xia Enlan,Huang Xiaowu,Xiao Yu
Fertility and sterility
OBJECTIVE:To evaluate the role of hysteroscopy in the diagnosis of chronic endometritis (CE). DESIGN:Retrospective cohort study. SETTING:University teaching hospital. PATIENT(S):A consecutive series of 1,189 cases of diagnostic hysteroscopy. INTERVENTION(S):Endometrial biopsy specimens were obtained after hysteroscopy for routine histology and immunohistochemistry for plasma cells using a CD138 epitope. MAIN OUTCOME MEASURE(S):Observer variability, sensitivity, specificity, and accuracy of the hysteroscopic features in the diagnosis of CE. RESULT(S):Immunohistochemistry of biopsy specimens showed presence of CD138 cells in 322 of 1,189 cases (27.1%). Among cases that tested positive for CD138 cells, the prevalence of hysteroscopic features was as follows: endometrial hyperemia, 169 of 322 (52.5%); endometrial interstitial edema, 27 of 322 (8.4%); and micro-polyps, 11 of 322 (3.4%). The κ value of intraobserver and interobserver agreement on the presence or absence of the hysteroscopic feature of CE was 0.86 and 0.73, respectively. The sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of the presence of one or more hysteroscopy features were 59.3%, 69.7%, 42.1%, 82.8%, and 66.9%, respectively. CONCLUSION(S):The finding of endometrial hyperemia, micro-polyps or endometrial interstitial edema during hysteroscopy should alert to the diagnosis of CE, but the overall accuracy of hysteroscopic examination with regard to the diagnosis of CE is only 67%, so it should not be used to replace histologic examination as the diagnostic tool of choice. In women in whom a diagnosis of CE is considered likely, endometrial biopsy should be obtained to examine plasma cells by immunohistochemistry, which should remain the preferred method for diagnosis.
10.1016/j.fertnstert.2018.12.007
Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women.
Zheng Xiaojing,O'Connell Catherine M,Zhong Wujuan,Poston Taylor B,Wiesenfeld Harold C,Hillier Sharon L,Trent Maria,Gaydos Charlotte,Tseng George,Taylor Brandie D,Darville Toni
Frontiers in cellular and infection microbiology
Sexually transmitted infection (STI) of the upper reproductive tract can result in inflammation and infertility. A biomarker of STI-induced upper tract inflammation would be significant as many women are asymptomatic and delayed treatment increases risk of sequelae. Blood mRNA from 111 women from three cohorts was profiled using microarray. Unsupervised analysis revealed a transcriptional profile that distinguished 9 cases of STI-induced endometritis from 18 with cervical STI or uninfected controls. Using a hybrid feature selection algorithm we identified 21 genes that yielded maximal classification accuracy within our training dataset. Predictive accuracy was evaluated using an independent testing dataset of 5 cases and 10 controls. Sensitivity was evaluated in a separate test set of 12 women with asymptomatic STI-induced endometritis in whom cervical burden was determined by PCR; and specificity in an additional test set of 15 uninfected women with pelvic pain due to unknown cause. Disease module preservation was assessed in 42 women with a clinical diagnosis of pelvic inflammatory disease (PID). We also tested the ability of the biomarker to discriminate STI-induced endometritis from other diseases. The biomarker was 86.7% (13/15) accurate in correctly distinguishing cases from controls in the testing dataset. Sensitivity was 83.3% (5/6) in women with high cervical burden and asymptomatic endometritis, but 0% (0/6) in women with low burden. Specificity in patients with non-STI-induced pelvic pain was 86.7% (13/15). Disease modules were preserved in all 8 biomarker predicted cases. The 21-gene biomarker was highly discriminatory for systemic infections, lupus, and appendicitis, but wrongly predicted tuberculosis as STI-induced endometritis in 52.4%. A 21-gene biomarker can identify asymptomatic women with STI-induced endometritis that places them at risk for chronic disease development and discriminate STI-induced endometritis from non-STI pelvic pain and other diseases.
10.3389/fcimb.2018.00307
The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology.
Moreno Inmaculada,Cicinelli Ettore,Garcia-Grau Iolanda,Gonzalez-Monfort Marta,Bau Davide,Vilella Felipe,De Ziegler Dominique,Resta Leonardo,Valbuena Diana,Simon Carlos
American journal of obstetrics and gynecology
BACKGROUND:Chronic endometritis is a persistent inflammation of the endometrial mucosa caused by bacterial pathogens such as Enterobacteriaceae, Enterococcus, Streptococcus, Staphylococcus, Mycoplasma, and Ureaplasma. Although chronic endometritis can be asymptomatic, it is found in up to 40% of infertile patients and is responsible for repeated implantation failure and recurrent miscarriage. Diagnosis of chronic endometritis is based on hysteroscopy of the uterine cavity, endometrial biopsy with plasma cells being identified histologically, while specific treatment is determined based on microbial culture. However, not all microorganisms implicated are easily or readily culturable needing a turnaround time of up to 1 week. OBJECTIVE:We sought to develop a molecular diagnostic tool for chronic endometritis based on real-time polymerase chain reaction equivalent to using the 3 classic methods together, overcoming the bias of using any of them alone. STUDY DESIGN:Endometrial samples from patients assessed for chronic endometritis (n = 113) using at least 1 or several conventional diagnostic methods namely histology, hysteroscopy, and/or microbial culture, were blindly evaluated by real-time polymerase chain reaction for the presence of 9 chronic endometritis pathogens: Chlamydia trachomatis, Enterococcus, Escherichia coli, Gardnerella vaginalis, Klebsiella pneumoniae, Mycoplasma hominis, Neisseria gonorrhoeae, Staphylococcus, and Streptococcus. The sensitivity and specificity of the molecular analysis vs the classic diagnostic techniques were compared in the 65 patients assessed by all 3 recognized classic methods. RESULTS:The molecular method showed concordant results with histological diagnosis in 30 samples (14 double positive and 16 double negative) with a matching accuracy of 46.15%. Concordance of molecular and hysteroscopic diagnosis was observed in 38 samples (37 double positive and 1 double negative), with an accuracy of 58.46%. When the molecular method was compared to microbial culture, concordance was present in 37 samples (22 double positive and 15 double negative), a matching rate of 56.92%. When cases of potential contamination and/or noncultivable bacteria were considered, the accuracy increased to 66.15%. Of these 65 patients, only 27 patients had consistent histological + hysteroscopic diagnosis, revealing 58.64% of nonconcordant results. Only 13 of 65 patients (20%) had consistent histology + hysteroscopy + microbial culture results. In these cases, the molecular microbiology matched in 10 cases showing a diagnostic accuracy of 76.92%. Interestingly, the molecular microbiology confirmed over half of the isolated pathogens and provided additional detection of nonculturable microorganisms. These results were confirmed by the microbiome assessed by next-generation sequencing. In the endometrial samples with concordant histology + hysteroscopy + microbial culture results, the molecular microbiology diagnosis demonstrates 75% sensitivity, 100% specificity, 100% positive and 25% negative predictive values, and 0% false-positive and 25% false-negative rates. CONCLUSION:The molecular microbiology method describe herein is a fast and inexpensive diagnostic tool that allows for the identification of culturable and nonculturable endometrial pathogens associated with chronic endometritis. The results obtained were similar to all 3 classic diagnostic methods together with a degree of concordance of 76.92% providing an opportunity to improve the clinical management of infertile patients with a risk of experiencing this ghost endometrial pathology.
10.1016/j.ajog.2018.02.012
The impact of chronic endometritis on reproductive outcome.
Kasius Jenneke C,Fatemi Human M,Bourgain Claire,Sie-Go Daisy M D S,Eijkemans René J C,Fauser Bart C,Devroey Paul,Broekmans Frank J M
Fertility and sterility
OBJECTIVE:To assess the prevalence of chronic endometritis and the impact on the fertility of asymptomatic patients indicated for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. DESIGN:In the context of a randomized controlled trial, a hysteroscopy-guided endometrial biopsy was obtained and histologically examined. The live birth rate (including spontaneous pregnancies) after initiation of IVF/ICSI treatment of patients diagnosed with chronic endometritis was compared with the live birth rate of a randomly selected matched control group of patients without endometritis. SETTING:Two tertiary infertility care units. PATIENT(S):A total of 678 asymptomatic infertile women with a normal transvaginal ultrasound (TVS) who underwent diagnostic hysteroscopy before a first IVF/ICSI treatment cycle. INTERVENTION(S):Hysteroscopy guided endometrial biopsy. MAIN OUTCOME MEASURE(S):The prevalence of chronic endometritis and the live birth rate (including spontaneous pregnancies) within 3 years after initiation of the randomized controlled trial. RESULT(S):The prevalence of chronic endometritis in the 606 patients with an adequate biopsy was 2.8%. The cumulative live birth rate (including spontaneous pregnancies) did not significantly differ between patients with or without endometritis: 76% versus 54%. Also, the clinical pregnancy rate per embryo transfer was not significantly different (hazard ratio 1.456, 95% confidence interval 0.770-2.750). CONCLUSION(S):Chronic endometritis can be rarely diagnosed in a population of asymptomatic infertile patients with a normal TVS before a first IVF/ICSI treatment. Moreover, the reproductive outcome after initiation of IVF/ICSI was not found to be negatively affected by chronic endometritis. In conclusion, the clinical implication of chronic endometritis seems minimal.
10.1016/j.fertnstert.2011.09.039
Efficient treatment of chronic endometritis through a novel approach of intrauterine antibiotic infusion: a case series.
BMC women's health
BACKGROUND:Early diagnosis and efficient management of Chronic Endometritis (CE) in patients seeking fertility treatment are two components every practitioner wishes to address. With respect to endometrial restoration, antibiotic treatment appears to perform well. However, regarding the improvement of In Vitro Fertilization (IVF) success rates, literature evidence is inconclusive, and consensus on optimal treatment has yet to be reached. This manuscript uniquely brings to literature the first report on effective employment of intrauterine antibiotic infusion to treat CE and contribute to addressing the infertility related to it. CASE PRESENTATION:In this case series, we present 3 patients reporting numerous previous failed IVF attempts accompanied with diagnosed CE which failed to be properly treated in the past. Following initial assessment in our clinic and verification of CE findings, an oral antibiotic regime was administered based on the infectious agent detected. Re-evaluation concluded slightly improved microbiological environment in the endometrium but persisting inflammation. Antibiotic intrauterine infusion was proposed to the patients as an alternative practice. All our patients achieved a pregnancy shortly following intrauterine treatment with one patient reporting a live birth of twin babies and two patients currently reporting an ongoing pregnancy. CONCLUSIONS:The implications of this case series contribute to medical knowledge and extend to both effective treatment of CE and subsequent management of related infertility. The current line of treatment of CE through oral antibiotic regimes highlights the need for exploring new options and calls for larger studies on the clinical implication of their use. This novel approach enabled natural conception for patients presenting with established Recurrent Implantation Failure (RIF) having undergone numerous futile IVF attempts. The clinical impact from the practitioner's perspective is considerable allowing for an alternative line of treatment that merits further investigation.
10.1186/s12905-018-0688-8