Construction of deep learning-based convolutional neural network model for automatic detection of fluid hysteroscopic endometrial micropolyps in infertile women with chronic endometritis.

OBJECTIVE(S): Chronic endometritis (CE) is a localized mucosal inflammatory disorder associated with female infertility of unknown etiology, endometriosis, tubal factors, repeated implantation failure, and recurrent pregnancy loss, along with atypical uterine bleeding and iron deficiency anemia. Diagnosis of CE has traditionally relied on endometrial biopsy and detection of CD138(+) endometrial stromal plasmacytes. To develop a less invasive diagnostic system for CE, we aimed to construct a deep learning-based convolutional neural network (CNN) model for the automatic detection of endometrial micropolyps (EMiP), a fluid hysteroscopy (F-HSC) finding recognized as tiny protrusive lesions that are closely related to this disease. STUDY DESIGN: This is an in silico study using archival images of F-HSC performed at an infertility center in a private clinic. A total of 244 infertile women undergoing F-HSC on the days 6-12 of the menstrual cycle between April 2019 and December 2021 with histopathologically-confirmed CE with the aid of immunohistochemistry for CD138 were utilized. RESULTS: The archival F-HSC images of 208 women (78 with EMiP and 130 without EMiP) who met the inclusion criteria were finally subjected to analysis. Following preprocessing of the images, half a set was input into a CNN architecture for training, whereas the remaining images were utilized as the test set to evaluate the performance of the model, which was compared with that of the experienced gynecologists. The sensitivity, specificity, accuracy, precision, and F1-score of the CNN model-aided diagnosis were 93.6 %, 92.3 %, 92.8 %, 88.0 %, and 0.907, respectively. The area under the receiver operating characteristic curves of the CNN model-aided diagnosis (0.930) was at a similar level (p > .05) to the value of conventional diagnosis by three experienced gynecologists (0.927, 0.948, and 0.906). CONCLUSION: These findings indicate that our deep learning-based CNN is capable of recognizing EMiP in F-HSC images and holds promise for further development of the computer-aided diagnostic system for CE.

Preconceptual administration of doxycycline in women with recurrent miscarriage and chronic endometritis: protocol for the Chronic Endometritis and Recurrent Miscarriage (CERM) trial, a multicentre, double-blind, placebo-controlled, adaptive randomised trial with an embedded translational substudy.

INTRODUCTION: Recurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The aetiology of CE remains uncertain. An association between CE and recurrent miscarriage has been shown. This study will aim to determine if preconceptual administration of doxycycline, in women with recurrent miscarriages, and CE, reduces first trimester miscarriages, increasing live births. METHODS AND ANALYSIS: Chronic Endometritis and Recurrent Miscarriage is a multicentre, double-blind adaptive trial with an embedded translational substudy. Women with a history of two or more consecutive first trimester losses with evidence of CE on endometrial biopsy (defined as ≥5 CD138 positive cells per 10 mm2) will be randomised to oral doxycycline or placebo for 14 days. A subset will be recruited to a mechanistic substudy in which microbial swabs and preintervention/postintervention endometrial samples will be collected. Up to 3062 women recruited from 29 National Health Service (NHS) hospital sites across the UK are expected to be screened with up to 1500 women randomised in a 1:1 ratio. Women with a negative endometrial biopsy (defined as <5 CD138 positive cells per 10 mm2) will also be followed up to test validity of the tool. The primary outcome is live births plus pregnancies ≥24 + 0 weeks gestation at the end of the trial, in the first or subsequent pregnancy. Secondary clinical outcomes will also be assessed. Exploratory outcomes will assess the effect of doxycycline treatment on the endometrial microbiota, the differentiation capacity of the endometrium and the senescent profile of the endometrium with CE. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the NHS Research Ethics Committee Northwest-Haydock (19/NW/0462). Written informed consent will be gained from all participants. The results will be published in an open-access peer-reviewed journal and reported in the National Institute for Health and Care Research journals library. TRIAL REGISTRATION NUMBER: ISRCTN23947730.

Chronic endometritis incidence in infertile women with and without polycystic ovary syndrome: a propensity score matched study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is known to be associated with chronic low-grade inflammation and endometrial dysfunction. Chronic endometritis (CE) is a type of local inflammation that can contribute to endometrial dysfunction in infertile women. Some clinicians recommend screening for CE in women at high risk, such as those with endometrial polyps. However, it is still uncertain whether there is a relationship between PCOS and CE, as well as whether women with PCOS require enhanced screening for CE. This study was to assess the incidence of CE among infertile women with PCOS by hysteroscopy combined with histopathology CD138 immunohistochemical staining of endometrium. METHODS: A total of 205 patients in the PCOS group and 4021 patients in the non-PCOS group from July 2017 to August 2022 were included in this retrospective study. After nearest-neighbor 1:4 propensity score matching (PSM), 189 PCOS patients were matched with 697 non-PCOS patients. Basic information was recorded. The CE incidence was compared. The risk factors affecting CE incidence were also analyzed. RESULTS: No significantly higher CE incidence in infertile women with PCOS were found either in total analysis or after PSM (P = 0.969; P = 0.697; respectively). Similar results were discovered in the subgroup of Body Mass Index (BMI) (P = 0.301; P = 0.671; P = 0.427; respectively) as well as the four PCOS phenotypes (P = 0.157). Intriguingly, the incidence of CE increased as BMI increased in the PCOS group, even though no significant differences were found (P = 0.263). Multivariate logistic regression showed that age, infertility duration, infertility type, PCOS, and obesity were not the independent risk factors affecting CE incidence. CONCLUSION: The incidence of CE in PCOS patients did not significantly increase compared to non-PCOS patients. Similarly, no significant differences in the incidence of CE were observed among different PCOS phenotypes. The current evidence does not substantiate the need for widespread CE screening among PCOS women, potentially mitigating the undue financial and emotional strain associated with such screenings.

The association between endometrial polyps, chronic endometritis, and IVF outcomes.

OBJECTIVE: Endometrial polyps (EPs) are one of the most common pathologies detected during the examination of the uterine cavity of infertile women. We aimed to demonstrate the relationship between EPs, chronic endometritis (CE) and in vitro fertilization (IVF) outcomes. PATIENTS AND METHODS: This retrospective study was performed on 394 hysteroscopically examined infertility cases. We performed polyp resections (PR) and extensive biopsies of the endometrium to demonstrate the association with clinical pregnancy (CP) by IVF. We performed statistical analysis to compare these associations. RESULTS: The incidence of CE was twice as high in the presence of EPs as in the absence of EPs. The associations between EPs and PR were found to be significant for positive CP outcomes. A significant difference in IVF outcome was found between the group with EPs and the group without EPs. All these associations were statistically significant (p < 0.05). CONCLUSIONS: We found a frequent association between EPs and CE. The pregnancy rate obtained after IVF was negatively affected by the presence of EPs. Treatment of these pathologies improved IVF outcomes.

Hysteroscopic features suggestive of chronic endometritis: a systematic review.

The purpose of this systematic review is to identify common hysteroscopic findings suggestive of endometritis, chronic or subclinical, based on current scientific evidence. Data sources were MEDLINE, Embase, PubMed and other sources of grey literature. Four (4) authors independently selected studies addressing hysteroscopic detection of CE based on specific and clearly stated hysteroscopic criteria. The diagnosis was confirmed by histologic assessment, as stated in the materials and methods of these studies included. The initial search identified 599 studies, of which 21 met the inclusion criteria. Significant heterogeneity among published studies on Chronic endometritis (CE) remains the main limitation in performing a metanalysis and further analysis of diagnostic accuracy on the subject. Hysteroscopy is an important diagnostic tool in cases of chronic endometritis when accompanied by endometrial biopsies. Clinicians relate hyperaemia and endometrial oedema with chronic endometritis while more than half include micropolyposis as a pathognomonic feature of this subclinical condition. Micropolyps, stromal oedema, haemorrhagic spots, strawberry aspect, and hyperaemia are proposed as adequate indicators of hysteroscopic evidence of CE according to the literature. The impact of CE in long-term reproductive outcomes remain unclear, thus clinicians ought to communicate this to the patients and provide treatment where clinically appropriate. In addition, we present hysteroscopic images of histologically confirmed CE cases that could play the role of a hysteroscopic atlas.

Impact of Intraoperative Factors on the Development of Postpartum Septic Complications.

Background and Objectives: Triclosan-coated sutures (antibacterial sutures) can reduce the risk of postoperative surgical site infection. This study aimed to investigate the effect of intraoperative factors, including antibacterial sutures, on the risk of postpartum septic complications. Materials and Methods: The prospective study included patients who underwent caesarean section. The exclusion criterion was chorioamnionitis. The investigation group patient's (n = 67) uterus and fascial sheath of the abdominal wall were sutured with triclosan-coated polyglactin 910 sutures during surgery. The control group consisted of 98 patients using uncoated polyglactin 910 sutures only. The patients were contacted by phone after the 30th postoperative day. Results: No significant difference was found between the investigation group and the control group in the development of postpartum endometritis (11.7% in the investigation group vs. 8.4% in the control group, p = 0.401), wound infection (6.3% vs. 3.6%, p = 0.444) or patients experienced any septic complication (15.9% vs. 12%, p = 0.506). Postpartum endometritis was more common in patients who underwent instrumental uterine examination during the surgery (23.8% vs. 18%, p = 0.043). A moderately strong correlation was found for haemoglobin level on the third-fourth postoperative day with the development of postpartum septic complications, p < 0.001, Pearson coefficient -0.319. Post-caesarean delivery septic complications were not statistically more common in patients with blood loss greater than 1 L. The incidence of post-caesarean endometritis was 13.4%, and wound infection was 4.8% in this study's hospital, having five to six thousand deliveries per year. Conclusions: Using antibacterial sutures during caesarean section does not affect the incidence of postpartum septic complications. Instrumental uterine examination during caesarean section increases the risk of post-caesarean endometritis and is, therefore, not recommended. Haemoglobin level on the 3rd-4th postoperative day, rather than the estimated blood loss during surgery, affects the development of postpartum septic complications.

Maternal obesity and the risk of postpartum infections according to mode of delivery.

OBJECTIVE: The aim of the present study was to assess the impact of different maternal Body Mass Index (BMI) classes on the risk of postpartum endometritis, wound infection, and breast abscess after different modes of delivery. Secondly to estimate how the risk of postpartum infection varies with different maternal BMI groups after induction of labor and after obstetric anal sphincter injuries. METHODS: A population-based observational study including women who gave birth during eight years (N = 841,780). Data were collected from three Swedish Medical Health Registers, the Swedish Medical Birth Register, the Swedish National Patient Register, and the Swedish Prescribed Drug Register. Outcomes were defined by ICD-10 codes given within eight weeks postpartum. The reference population was uninfected women. Odds ratios were determined using Mantel-Haenszel technique. Year of delivery, maternal age, parity and smoking in early pregnancy were considered as confounders. RESULTS: There was a dose-dependent relationship between an increasing maternal BMI and a higher risk for postpartum infections. Women in obesity class II and III had an increased risk for endometritis after normal vaginal delivery aOR 1.45 (95% CI: 1.29-1.63) and for wound infections after cesarean section aOR 3.83 (95% CI: 3.39-4.32). There was no difference in how maternal BMI affected the association between cesarean section and wound infection, regardless of whether it was planned or emergent. Women in obesity class II and III had a lower risk of breast abscess compared with normal-weight women, aOR 0.47 (95% CI: 0.38-0.58). The risk of endometritis after labor induction decreased with increasing maternal BMI. The risk of wound infection among women with an obstetrical sphincter injury decreased with increasing BMI. CONCLUSION: This study provides new knowledge about the impact of maternal BMI on the risk of postpartum infections after different modes of delivery. There was no difference in how BMI affected the association between cesarean section and wound infections, regardless of whether it was a planned cesarean section or an emergency cesarean section.

Establishment and verification of hysteroscopic scoring system for chronic endometritis in infertile patients. / ä¸å­•æ‚£è€ æ ¢æ€§å­å®«å† è†œç‚Žå®«è ”é•œè¯„åˆ†ç³»ç»Ÿçš„æž„å»ºåŠéªŒè¯.

OBJECTIVES: To establish and verify a hysteroscopic scoring system for the diagnosis of chronic endometritis (CE) in infertile patients. METHODS: A total of 238 infertile patients who underwent hysteroscopy and endometrial biopsy in the Reproductive Medicine Center, Shijiazhuang Obstetrics and Gynecology Hospital Affiliated to Hebei Medical University from October 1 to December 31, 2019 were enrolled in the study. According to the results of CD138 immunohistochemistry, the patients were divided into CE group (n=73) and non-CE group (n=165). Univariate and binary logistic regression analyses were used to screen the risk factors of CE and a nomogram was establish for hysteroscopic scoring. Receiver operating characteristic (ROC) curve, calibration curve and Bootstrap resampling method were used to evaluate and verify the system. RESULTS: Univariate and binary logistic regression analyses showed that hyperemia area (HA) degree ≥2, micropolyps, polypoid hyperplasia of endometrium and history of ectopic pregnancy were independent risk factors for CE (all P<0.05). A nomogram was generated to establish a hysteroscopy scoring system based on the above four factors. The area under ROC curve of the hysteroscopy scoring system for predicting CE was 0.801 (95%CI:0.742-0.861), the sensitivity was 74.0% and the specificity was 73.9%. The calibration curve showed that the predicting value of the scoring system was highly consistent with the actual value. In the internal verification, the C-index was 0.7811. The predicting value of the verification group in the calibration curve was basically consistent with the actual value, indicating that the scoring system had good stability. CONCLUSIONS: The hysteroscopic scoring system composed of HA, micropolyp, polypoid hyperplasia of endometrium and history of ectopic pregnancy can effectively and intuitively predict CE, which is conducive to improving the diagnosis of CE.

Clinical evidence of positive correlation between intrauterine adhesions and chronic endometritis: a retrospective study.

OBJECTIVE: This study aimed to analyze the potential correlation between chronic endometritis (CE) and intrauterine adhesions (IUA) with its associated risk factors. PATIENTS AND METHODS: We retrospectively analyzed data from 131 patients who underwent hysteroscopic transcervical resection of adhesions (TCRA) for intrauterine adhesions at our hospital between February 2020 and February 2021. General clinical data were collected and analyzed using univariate, multifactorial, and logistic regression analyses. Patients with mild, moderate, and severe IUA were divided into two groups based on whether they coincided with CE (CE group) or not (NCE group). Logistic regression analysis of the factors associated with IUA was performed, and the recurrence rates of IUA after TCRA in the CE and NCE groups were registered. RESULTS: The risk of severe IUA was higher in patients with a higher number of abortions, higher number of indolent abortions, and CD138 positivity. In addition, the incidence of IUA combined with chronic CE varied when comparing the different IUA stages: 10.70% (3/28) for patients with mild IUA, 25.00% (7/28) for patients with moderate IUA, and 64.30% (18/28) for patients with severe IUA. The recurrence rates of IUA after TCRA in the CE and NCE groups were 69.20% (9/26) and 30.08% (4/67), respectively, in patients with moderate to severe IUA, and the differences were statistically significant (χ2=12.782, p=0.001). CONCLUSIONS: A correlation was observed between CE and IUA. Patients presenting both conditions had more severe IUA stage and higher recurrence rates after TCRA.

Endometriosis and infertility: the hidden link between endometritis, hormonal imbalances and immune dysfunctions preventing implantation!

Endometriosis is a chronic inflammatory condition affecting up to 10% of women of reproductive age and this, depending on its severity, very often leads to infertility. New research has shed light on the role of underlying endometritis due to the presence of inflammatory, non-oestrogen metabolising microbiome at the mucosal interface and this in turn leads to the activation of aggressive, non-tolerant immune cells in the endometrium. These immune cells require the presence of tolerance-inducing commensals such as Lactobacilli so as to allow the implantation of the fertilised egg. New therapies should be holistic and address both the dysbiosis as well as immune abnormalities. Routine immune monitoring of the immune cells derived from the endometrium and/or microbial profiling should recommended to better predict assisted reproduction outcomes in these couples.

The prevalence of endometrial polyp in women with tubal factor infertility is higher than male factor infertility: Is PID one of the causes of endometrial polyp?

AIMS: Previous studies have shown an association between chronic endometritis and endometrial polyps, and only one study in infertile women reported an association between tubal obstruction and polyps. This study aimed to compare the prevalence of endometrial polyps in two groups of women with tubal factor infertility and male factor infertility to assess if is there any association between tubal factor infertility and endometrial polyps. METHODS: This case-control study was performed on infertile women. The case group included women with tubal factor infertility and the control group included all women with male factor infertility. In all patients, vaginal ultrasound was performed between days 8 and 12 of the menstrual cycle to diagnose endometrial polyp, its size, and number. Demographic and obstetrics variables were recorded. Patients underwent hysteroscopy and polypectomy and the diagnosis of the polyp was confirmed by pathology report. RESULT: In the present study, 245 people participated in two groups. There was a statistically significant difference between the two groups in terms of demographic and obstetric characteristics like type of infertility, duration of infertility, and gravidity. The prevalence of polyps in the tubal factor group was higher than in the male factor group (63 [60%] vs. 12 [9.8%]), and this difference was statistically significant (p = 0.0001). In addition, the prevalence of chronic endometritis in the tubal factor group was higher than in the male factor group (19 [18.8%] vs. 4 [3.3%]), and this difference was statistically significant (p = 0.001). CONCLUSIONS: In the present study, a strong association was observed between endometrial polyps and tubal obstruction, and considering that the most common cause of tubal obstruction is pelvic and genital infections, after confirmation with more studies, it may be possible to consider antibiotic treatment in these patients, especially in patients with recurrent polyps.

Significance of multiple myeloma oncogene 1 immunohistochemistry in chronic endometritis detection in patients with recurrent pregnancy losses: an observational study.

The most reliable chronic endometritis diagnosis is based on immunohistochemistry plasma cell identification in endometrial samples. Our study aimed to compare multiple myeloma oncogene 1 (MUM1) and syndecan-1/CD138 immunohistochemistry staining for chronic endometritis diagnosis among patients with recurrent pregnancy loss. We evaluated the presence of endometrial stromal changes. Fifty-four patients with a history of at least two intrauterine pregnancy losses underwent diagnostic hysteroscopy in the follicular phase of the cycle with endometrial aspiration biopsy. In all 54 cases, three successive sections were cut from each paraffin-embedded tissue block for hematoxylin and eosin (H&E), CD138 and MUM1 staining. The goal was to evaluate the level of agreement between the MUM1 and CD138 results and plasma cell detection rate in assessing the endometrial stromal changes. The concordance analysis between CD138 and MUM1 immunohistochemistry staining showed consistent results in 43 of 54 (79.6%) cases. The level of agreement was moderate, based on a Kappa value of 0.60. MUM1 immunostaining was positive for CE in more cases than CD138 staining, and this difference was statistically significant, showing a higher sensitivity of MUM1 in plasma cell detection (p=0.01). Endometrial stromal changes were observed in the majority of cases - 49/54 (90%). Samples without stromal changes were consistently negative for plasma cells using both CD138 and MUM1 staining. We demonstrated that MUM1 staining, used in conjunction with assessing endometrial stromal changes, contributes to a more accurate and comprehensive diagnosis of chronic endometritis.

New biopsy after antibiotic treatment: effect on outcomes of assisted reproduction in patients with infertility and chronic endometritis.

RESEARCH QUESTION: What is the effect of chronic endometritis on patients with infertility, the necessity of endometrial re-examination and the effect of improving chronic endometritis after one cycle of antibiotic treatment on pregnancy outcomes? DESIGN: Infertile patients (n = 4003) who underwent IVF and intracytoplasmic sperm injection treatment were included. Pregnancy outcomes of groups positive for chronic endometritis were compared with groups that were negative (group 1). Patients that were positive were divided into the chronic endometritis new biopsy group (group 2) and chronic endometritis non-re-examination group (group 3). After doxycycline treatment and re-examination, the chronic endometritis new biopsy group was divided into improved chronic endometritis group (ICE) and not-improved chronic endometritis group (NICE), and their general indicators and reproductive outcomes were compared. RESULTS: No significant difference was observed in embryo implantation, early or late pregnancy loss, ectopic pregnancy, clinical pregnancy and live birth rates between groups 2 and 3. The clinical pregnancy and live birth rates in the NICE group were significantly lower than those in the ICE group (P = 0.008 and P = 0.001, respectively). After controlling for potential confounding factors, age, average number of high-quality embryos, endometrial thickness on the day of embryo transfer and number and type of embryo transfer were factors associated with live birth rates. CONCLUSIONS: Endometrial re-examination of women with chronic endometritis treated with doxycycline had no effect on pregnancy outcomes. The first cycle of doxycycline treatment could effectively improve reproductive outcomes of women with five or more CD138+ cells/high-power field.

Overexpression of hypoxia-inducible factor 1α and excessive vascularization in the peri-implantation endometrium of infertile women with chronic endometritis.

Objective: Chronic endometritis (CE) contributes to impaired endometrial receptivity and is closely associated with poor in vitro fertilization (IVF) outcomes. However, the mechanisms underlying CE are unclear. Here, we investigated the role of the hypoxic microenvironment and endometrial vascularization in the peri-implantation endometrium of infertile women with CE. Methods: This retrospective study involved 15 fertile women and 77 infertile patients diagnosed with CE based on CD138+ ≥1/10 high-power fields (HPFs). The CE patients were divided into Group 1 (CD138+ 1-4/10 HPFs, 53 cases) and Group 2 (CD138+ ≥5/10 HPFs, 24 cases). The expression levels of hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor A (VEGFA), and vascular endothelial growth factor receptor 2 (VEGFR2) in peri-implantation endometrium were assessed by qRT-PCR and western blot analyses. Spatial levels of HIF1α, VEGFA, and VEGFR2 in various endometrial compartments was determined using immunohistochemistry and H-score analysis. Microvascular density (MVD) was determined using CD34 staining and scored using Image J. Finally, we used qRT-PCR to assess changes in the expression of HIF1α, VEGFA, and VEGFR2 in CE patients after treatment with first-line antibiotics. Results: Relative to Group 1 and control group, during the implantation window, protein and mRNA levels of HIF1α, VEGFA, and VEGFR2 were markedly high in Group 2 (P<0.05). H-score analysis showed that HIF1α, VEGFA, and VEGFR2 in the luminal, glandular epithelium, and stromal compartments were markedly elevated in Group 2, comparing to control group and Group 1 (P<0.05). Moreover, markedly elevated MVD levels were observed in Group 2. Notably, the above indexes did not differ significantly in the control group versus Group 1. Treatment with antibiotics significantly suppressed the endometrial HIF1α and VEGFA levels in CE-cured patients. Conclusions: Here, we for the first time report the upregulation of HIF1α, VEGFA, and VEGFR2, as well as excessive endometrial vascularization in the peri-implantation endometrium of CE patients. Our findings offer new insights into reduced endometrial receptivity in CE-associated infertility.

A case of discrepancy between three ERA tests in a woman with repeated implantation failure complicated by chronic endometritis.

BACKGROUND: Endometrial receptivity array (ERA) is used to determine the timing of embryo transfer (ET) synchronized with the window of implantation (WOI). The effectiveness and evaluation of ERAs in women with recurrent implantation failure remain controversial. We report the case of a patient with recurrent implantation failure that raises the issue of reproducibility of ERA tests. CASE REPORT: A 36-year-old Japanese woman with secondary infertility who had previously given birth failed to conceive after three frozen-thawed embryo transfer (FET) cycles. An ERA test was conducted to confirm the WOI. The first ERA test was performed 125 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (post-receptive) phase, and recommended retesting 101 h after progesterone exposure. A simultaneous chronic endometritis (CE) test showed a score of 3. After the antibiotics administration to treat CE, the second ERA test was performed after 101 h of progesterone exposure. The laboratory reported that the endometrium had not reached the WOI and estimated the WOI to be 113 ± 3 h after progesterone exposure. The third ERA test was performed 113 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (pre-receptive) phase and estimated the WOI to be 137 ± 3 h after progesterone exposure. A CE test performed at the same time as the second and third ERA tests showed a score of 1 for the collected endometrium. According to the third ERA test results, the vitrified-warmed blastocyst was transferred at 137 h of progesterone exposure. Pregnancy was achieved and the patient had an uncomplicated vaginal delivery at 39 weeks. One year later, another pregnancy was achieved after FET at 137 h of progesterone exposure, and the patient delivered at 33 weeks due to an unexpected membrane rupture. CONCLUSION: Because the results of the ERA test may vary in the presence of CE, CE should be diagnosed simultaneously with or before conducting ERA tests. If CE is diagnosed, ERA testing should be performed after treatment with antimicrobials or other drugs.

Association between hysteroscopic features of chronic endometritis and pregnancy outcomes of patients after in vitro fertilization: a retrospective cohort study.

This retrospective cohort study explored the morphological features of chronic endometritis (CE) and pregnancy outcomes during in vitro fertilization (IVF) in women with CE (429) at Yantai Yuhuangding Hospital between January 2017 and September 2018. The primary outcome was the clinical pregnancy rate (CPR). The women displayed haemorrhagic spots (175), hyperaemia (122), micropolyps (75), hyperaemia combined with micropolyps (49) and others (8). The CPR and live birth rate (LBR) were different among the hysteroscopic features of CE in fresh embryo transfer cycles (p = .002, p = .011). The miscarriage and premature birth rates were not significantly different among groups (p > .05). Hyperaemia (0.47 [95% CI, 0.29; 0.77]), micropolyps (0.40 [95% CI, 0.23; 0.72]), hyperaemia combined with micropolyps (0.35 [95% CI, 0.18; 0.69]) and others (0.36 [95% CI, 0.19; 0.69]) were associated with the CPR. In conclusion, the hysteroscopic features of CE are associated with IVF pregnancy outcomes, and there were differences in pregnancy outcomes with different CE hysteroscopic features.IMPACT STATEMENTWhat is already known on this subject? Chronic endometritis (CE) is associated with adverse pregnancy outcomes such as infertility, premature delivery and miscarriage. CE can reduce the success rate of pregnancy and even lead to obstetric and neonatal complications, and is an adverse factor for the success of in vitro fertilization (IVF). There are different types of CE, but their impact on IVF outcomes is unknown.What the results of this study add? The CPR and LBR were different among the hysteroscopic features of CE in fresh embryo transfer cycles (p = .002, p = .011). The miscarriage and premature birth rates were not significantly different among groups (p > .05). After adjustment, the multivariable analysis showed that hyperaemia (OR = 0.47, p = .002), micropolyps (OR = 0.40, p = .002), hyperaemia combined with micropolyps (OR = 0.35, p = .002) and others (OR = 0.36, p = .002) were associated with the CPR among patients with CE.What the implications are of these findings for clinical practice and/or further research? The hysteroscopic features of CE are associated with IVF pregnancy outcomes, and there were differences in pregnancy outcomes with different CE hysteroscopic features. Hence, women with repeated IVF failure should undergo hysteroscopy to examine for the presence of CE and its nature.

Decreased Fertility in Women with Cesarean Scar Syndrome Is Associated with Chronic Inflammation in the Uterine Cavity.

Chronic inflammation in cesarean scar defect contributes to secondary infertility in women with cesarean scar syndrom; however, it remains unclear about the situation of inflammation in uterine cavity in women with cesarean scar syndrome. This ambidirectional cohort study aimed to explore the effect of inflammation in the uterine cavities of women with cesarean scar syndrome on infertility at a single university hospital. The frequency of chronic endometritis in infertile patients was retrospectively compared between the cesarean scar syndrome group and non-cesarean scar syndrome group. The frequency of endometriosis was also investigated in patients with cesarean scar syndrome who underwent laparoscopy. The level of tumor necrosis factor-α and interleukin-1ß in the uterine cavity was prospectively evaluated in the cesarean scar syndrome group and in women with a history of cesarean section (control group) using an enzyme-linked immunosorbent assay. There was a significant difference in the incidence of chronic endometritis between the cesarean scar syndrome and non-cesarean scar syndrome groups (65.8% and 46.0%, respectively, p = 0.0315). Endometriosis was detected in 51 (70%) patients with laparoscopy. Tumor necrosis factor-α and interleukin-1ß levels in the cesarean scar syndrome group were significantly higher than those in the control group (p = 0.0002 and p = 0.0217, respectively). Our findings suggest that one cause of secondary infertility in women with cesarean scar syndrome is embryo implantation failure-associated chronic endometritis, endometriosis, and chronic inflammation in the uterine cavity.

Retained pregnancy tissue after miscarriage is associated with high rate of chronic endometritis.

The objective of this study was to evaluate prevalence of chronic endometritis in a cohort of patients with retained pregnancy tissue (RPT) following miscarriage, with and without a history of recurrent pregnancy loss (RPL). In a cohort of our single academic fertility centre, we evaluated women with unexplained RPL (two or more losses) without evidence of RPT and women undergoing hysteroscopic resection of RPT following miscarriage. Endometrial samples underwent staining with H and E and CD138. A pathologist blinded to patient history recorded the number of plasma cells per 10 high power fields (HPF) and the presence or absence of endometrial stromal changes. Our main outcome measure was to measure the prevalence of chronic endometritis. Endometrial samples from 50 women with RPT following miscarriage and 50 women with unexplained RPL without evidence of RPT were reviewed. The prevalence of chronic endometritis was significantly higher in the RPT cohort (62% versus 30%). A multivariable regression demonstrated significantly higher odds of chronic endometritis in the RPT cohort, aOR 7.3 (95% CI 2.1, 25.5). We conclude that women with RPT following pregnancy loss have a high rate of chronic endometritis, suggesting that RPT is a risk factor for this disorder. Impact StatementWhat is already known on this subject? Known risk factors for chronic endometritis include a history of pelvic inflammatory disease, intrauterine polyps and fibroids. The aetiology for increased chronic endometritis among women with RPL is unknown.What do the results of this study add? The prevalence of chronic endometritis is significantly higher among women with retained pregnancy tissue (RPT) following miscarriage compared to women with RPL. These data presented suggest that RPT is associated with chronic endometritis among women with a history of miscarriage.What are the implications of these findings for clinical practice and/or further research? We suggest a pathologic evaluation for chronic endometritis be performed on all patients who undergo hysteroscopic resection of RPT following miscarriage. Our findings also suggest that a uterine cavity evaluation with hysteroscopy to evaluate for RPT may be reasonable in women with a history of miscarriage who are found to have chronic endometritis on endometrial biopsy. Further research is needed to determine if resection of retained tissue is sufficient to treat RPOC associated chronic endometritis, or if additional antibiotic treatment is necessary.

Association between interleukin-19 gene polymorphisms and maternal puerperal infection.

Any bacterial infection of the genital tract after childbirth is called maternal puerperal infection. This infection accounts for 13% of pregnancy-related deaths and is the fifth leading cause of maternal mortality. Endometritis (postpartum uterine infection) has been associated with preeclampsia and maternal lethal bleeding in recent decades. In some studies, the presence of meconium in the amniotic fluid has been implicated in the development of endometritis. The study aimed to evaluate the association between interleukin-19 gene polymorphisms and maternal puerperal infection. In this study, 300 pregnant women with a gestational age of at least 37 weeks were studied. Patients were divided into two groups of 150 controls and cases. In the case group, amniotic fluid was impregnated with meconium, and in the control group, it was clear fluid. Both groups underwent cesarean section, and all received prophylactic antibiotics before surgery. Patients were evaluated for purpura infection in the first 40 days after delivery. Five ml of venous blood was taken from each patient and transferred to a tube containing EDTA anticoagulant. Genomic DNA was isolated using a particular kit. Then, the polymerase chain reaction was performed by the ARMS method. Data were analyzed using the chi-square test and SPSS software version 19 in case and control groups. This study's results indicate no significant difference in the frequency of AG, GG, and AA genotypes at position rs2243191 and rs1028181 IL-19 gene polymorphism between patients with puerperal infection and the control group (P>0.05). Also, no significant difference was observed in the frequency of both G and A alleles in the mentioned situations between patients and the control group (P>0.05). Based on the results of this study, no significant relationship was observed between IL-19 gene polymorphism at rs2243191 and rs1028181 locus and puerperal infection.

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.

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.