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.

Precision Medicine for Chronic Endometritis: Computer-Aided Diagnosis Using Deep Learning Model.

Chronic endometritis (CE) is a localized mucosal infectious and inflammatory disorder marked by infiltration of CD138(+) endometrial stromal plasmacytes (ESPC). CE is drawing interest in the field of reproductive medicine because of its association with female infertility of unknown etiology, endometriosis, repeated implantation failure, recurrent pregnancy loss, and multiple maternal/newborn complications. The diagnosis of CE has long relied on somewhat painful endometrial biopsy and histopathologic examinations combined with immunohistochemistry for CD138 (IHC-CD138). With IHC-CD138 only, CE may be potentially over-diagnosed by misidentification of endometrial epithelial cells, which constitutively express CD138, as ESPCs. Fluid hysteroscopy is emerging as an alternative, less-invasive diagnostic tool that can visualize the whole uterine cavity in real-time and enables the detection of several unique mucosal findings associated with CE. The biases in the hysteroscopic diagnosis of CE; however, are the inter-observer and intra-observer disagreements on the interpretation of the endoscopic findings. Additionally, due to the variances in the study designs and adopted diagnostic criteria, there exists some dissociation in the histopathologic and hysteroscopic diagnosis of CE among researchers. To address these questions, novel dual immunohistochemistry for CD138 and another plasmacyte marker multiple myeloma oncogene 1 are currently being tested. Furthermore, computer-aided diagnosis using a deep learning model is being developed for more accurate detection of ESPCs. These approaches have the potential to contribute to the reduction in human errors and biases, the improvement of the diagnostic performance of CE, and the establishment of unified diagnostic criteria and standardized clinical guidelines for the disease.

Commonalities and Disparities between Endometriosis and Chronic Endometritis: Therapeutic Potential of Novel Antibiotic Treatment Strategy against Ectopic Endometrium.

Chronic endometritis (CE) is a local mucosal inflammatory disorder of the uterine lining, which is histopathologically recognized as the unusual infiltration of CD138(+) plasmacytes into the endometrial stromal compartment. Accumulating body of research documented that CE is associated with female infertility and several obstetric/neonatal complications. The major cause of CE is thought to be intrauterine infection represented by common bacteria (Escherichia coli, Enterococcus faecalis, Streptococcus, and Staphylococcus), Mycoplasma/Ureaplasma, and Mycobacterium. Additionally, local dysbiosis in the female reproductive tract may be involved in the onset and development of CE. Antibiotic treatments against these microorganisms are effective in the elimination of endometrial stromal plasmacytes in the affected patients. Meanwhile, endometriosis is a common female reproductive tract disease characterized by endometriotic tissues (ectopic endometrium) growing outside the uterus and potentially causes chronic pelvic symptoms (dysmenorrhea, dyspareunia, dyschezia, and dysuria), infertility, and ovarian cancers. Endometriosis involves endocrinological, genetic, and epigenetic factors in its etiology and pathogenesis. Recent studies focus on immunological, inflammatory, and infectious aspects of endometriosis and demonstrate several common characteristics between endometriosis and CE. This review aimed to better understand the immunological and microbial backgrounds underlying endometriosis and CE and look into the therapeutic potential of the novel antibiotic treatment strategy against endometriosis in light of endometrial infectious disease.

Challenges in Clinical Diagnosis and Management of Chronic Endometritis.

Chronic endometritis (CE) is a local mucosal infectious and inflammatory disorder characterized by unusual filtration of CD138(+) endometrial stromal plasmacytes. CE is attracting attention due to its potential association with infertility of unknown etiology, repeated implantation failure, recurrent pregnancy loss, and several maternal/neonatal complications. Due to the variance in study design among researchers, universal diagnostic criteria remain to be established for the clinical diagnosis and management of CE. This review article aims to summarize current knowledge and provide insights into unsolved questions on CE to establish clinical guidelines for the disease from the viewpoint of human reproduction.

Genital tract dysbiosis in infertile women with a history of repeated implantation failure and pilot study for reproductive outcomes following oral enteric coating lactoferrin supplementation.

PURPOSE: We prospectively investigated if oral enteric coating lactoferrin supplementation improves the reproductive outcomes in infertile women with a history of repeated implantation failure (RIF) and non-Lactobacillus-dominant (Lactobacillus rate < 90%) microbiota (NLDM) in vaginal secretions (VS)/endometrial fluid (EF). METHODS: Paired VS/EF samples were obtained from RIF women and control infertile women (non-RIF group) for microbiome analysis. Chronic endometritis (CE) was diagnosed histopathologically and hysteroscopically. In a pilot study, oral enteric coating lactoferrin (700 mg/day, at least 28 consecutive days) was administered to eligible patients with NLDM in VS/EF. Their reproductive outcomes in the subsequent vitrified-warmed embryo transfer cycles were followed up. RESULTS: While CE was more prevalent (OR 2.41, 95% CI 1.02-5.63, p = 0.042) in the RIF group (29.1%, n = 117) than in the non-RIF group (14.5%, n = 55), The NLDM rate was similar between the two groups (44.4 vs 52.7%). Lactoferrin supplementation improved NLDM in 43.2% of RIF women (n = 37). Within the RIF group, the live birth rate in the subsequent cycles was higher (OR 10.67, 95% CI 1.03 - 110.0, p = 0.046) in women with improved microbiota (57.1%, n = 14) than in those with unimproved microbiota (11.1%, n = 9). CONCLUSION: Unlike CE, NLDM was not unique to RIF but was common in infertile women. Although the therapeutic effect of the oral lactoferrin supplementation on NLDM was limited in a pilot study, the reproductive outcomes were better in RIF women who overcame NLDM than in those who failed. Randomized controlled trials are required to confirm the results. TRIAL REGISTRATION NUMBER AND DATE FOR PROSPECTIVELY REGISTERED TRIALS: UMIN-CTR 000036990, June 7, 2019.

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.

Differential Vaginal Microbiota Profiling in Lactic-Acid-Producing Bacteria between Infertile Women with and without Chronic Endometritis.

PURPOSE: Chronic endometritis (CE) is an infectious and inflammatory disorder associated with infertility of unknown etiology, repeated implantation failure, and recurrent pregnancy loss. In the current clinical practice, intrauterine interventions such as endometrial biopsy/histopathologic examinations and/or hysteroscopy are required for the diagnosis of CE. In this study, we analyzed the microbiota in vaginal secretions (VS) as a potential prediction tool for CE in infertile women. METHODS: Using next-generation sequencing analysis, we compared the VS and endometrial fluid (EF) microbiota in infertile women with (n = 20) or without CE (n = 103). RESULTS: The detection rate of Streptococcus and Enterococcus as well as the bacterial abundance of Atopobium and Bifidobacterium in the VS microbiota was significantly lower in the CE group than in the non-CE group. Meanwhile, the detection rate and bacterial abundance of Lactobacillus in the EF and VS microbiota were at similar levels between the two groups. CONCLUSION: These findings suggest that VS microbiota in infertile women with CE is characterized by the reduction in Bifidobacterium and lactic-acid-producing bacteria other than Lactobacillus. Our results hold promise for the prediction of CE, not by somewhat interventional intrauterine procedures, but by less invasive VS sampling. TRIAL REGISTRATION NUMBER: UMIN000029449 (registration date 6 October 2017).

Chromosomal copy number analysis of products of conception by conventional karyotyping and next-generation sequencing.

PURPOSE: Chromosomal abnormalities are a major cause of spontaneous abortion, and conventional G-banded karyotyping (G-banding) is mainly utilized for chromosomal analysis. Recently, next-generation sequencing (NGS) has been introduced for chromosomal analysis. Here, we aimed to investigate the applicability and utility of NGS-based chromosomal analysis of products of conception (POC) on chorionic villus samples from spontaneous abortion. METHODS: The results of chromosomal analysis of 7 chorionic villus samples from spontaneous abortion were compared between conventional G-banding and NGS-based chromosomal copy number analysis. Age dependency and frequency of each chromosomal aneuploidy were evaluated for 279 cases analyzed by NGS. RESULTS: Excluding two cases (culture failure and maternal cell contamination), the results were consistent between G-banding and NGS. For cases analyzed by NGS, the rate of chromosomal abnormality increased in a maternal age-dependent manner. The frequency of each chromosomal aneuploidy detected by NGS was almost the same as that previously reported. Finally, NGS analysis was possible for difficult cases by G-banding analysis, such as culture failure, maternal cell contamination, long-term storage cases, and low cell number. CONCLUSIONS: Chromosome analysis using NGS not only obtains comparable results to conventional G-banding, but also can analyze POC more accurately and efficiently.

Characterization of Microbiota in Endometrial Fluid and Vaginal Secretions in Infertile Women with Repeated Implantation Failure.

Studies suggest that persisting intrauterine bacterial infectious conditions such as chronic endometritis potentially impair the embryo implantation process. The microbial environment in the female reproductive tract, however, remains largely undetermined in infertile patients with a history of repeated implantation failure (RIF). Using next-generation sequencing, we aimed to characterize the microbiota in the endometrial fluid (EF) and vaginal secretions (VS) in women with RIF. Twenty-eight infertile women with a history of RIF and eighteen infertile women undergoing the first in vitro fertilization-embryo transfer attempt (the control group) were enrolled in the study. On days 6-8 in the luteal phase of the natural, oocyte-pickup, or hormone replacement cycle, the paired EF and VS samples were obtained separately. Extracted genomic DNA was pyrosequenced for the V4 region of 16S ribosomal RNA using a next-generation sequencer. The EF microbiota had higher α-diversity and broader bacterial species than the VS microbiota both in the RIF and control groups. The analysis of the UniFrac distance matrices between EF and VS also revealed significantly different clustering. Additionally, the EF microbiota, but not the VS microbiota, showed significant variation in community composition between the RIF group and the control group. Burkholderia species were not detected in the EF microbiota of any samples in the control group but were detectable in a quarter of the RIF group. To our best knowledge, this is the first study investigating the microbiota in the paired EF and VS samples in infertile women with RIF.

Endometritis: new time, new concepts.

Endometritis is subdivided into two categories. Acute endometritis is symptomatic and characterized by microabscess formation and neutrophil invasion in the endometrial superficial epithelium, gland lumina, and uterine cavity. Chronic endometritis is rather silent and recognized as unusual plasmacyte infiltration in the endometrial stromal areas. Over the last decade, studies have disclosed the potential association between poor reproductive outcomes and endometritis, particularly chronic endometritis. The aim of this review is to address the current literature surrounding chronic endometritis and highlight recent advances in the research of this long-neglected gynecologic disease.

Minimum values for midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin.

OBJECTIVE: The aim of the study was to assess the lower limits of midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin stimulation. RESULTS: We included 297 pregnant cycles of 297 women and assessed midluteal plasma progesterone and estradiol concentrations and pregnancy outcomes, retrospectively. These cycles were compared with the non-pregnant cycles (406 cycles) of the same women who became pregnant. Mean midluteal plasma P4 and E2 concentrations were significantly (P < 0.01) higher in pregnant cycles (14.5 and 188.5 pg/mL) than in non-pregnant cycles (10.7 and 162.6 pg/mL). The 5 percentiles of progesterone and estradiol in pregnant cycles were 5.6 and 70.2 pg/mL, respectively. The lowest progesterone and estradiol levels in pregnant cycles were 2.3 and 23.4 pg/mL, respectively. In non-pregnant cycles, many women had low P4 levels that were less than 5.6 ng/mL. Subgroup analyses showed slight differences among the four groups, which may have been due to the ovarian function of each group. Miscarriage was not related to progesterone and estradiol concentrations. These values may be useful for the evaluation of necessary values for pregnancy with timed intercourse or intrauterine insemination.

Is a high serum copper concentration a risk factor for implantation failure?

BACKGROUND: Copper-containing contraceptive devices may deposit copper ions in the endometrium, resulting in implantation failure. The deposition of copper ions in many organs has been reported in patients with untreated Wilson's disease. Since these patients sometimes exhibit subfertility and/or early pregnancy loss, copper ions were also considered to accumulate in the uterine endometrium. Wilson's disease patients treated with zinc successfully delivered babies because zinc interfered with the absorption of copper from the gastrointestinal tract. These findings led to the hypothesis that infertile patients with high serum copper concentrations may have implantation failure due to the excess accumulation of copper ions. The relationship between implantation (pregnancy) rates and serum copper concentrations has not yet been examined. The Japanese government recently stated that actual copper intake was higher among Japanese than needed. Therefore, the aim of the present study was to investigate whether serum copper concentrations are related to the implantation (pregnancy) rates of human embryos in vivo. METHODS: We included 269 patients (age <40 years old) who underwent vitrifying and warming single embryo transfer with a hormone replacement cycle using good blastocysts (3BB or more with Gardner's classification). Serum hCG, copper, and zinc concentrations were measured 16 days after the first date of progesterone replacement. We compared 96 women who were pregnant without miscarriage at 10 weeks of gestation (group P) and 173 women who were not pregnant (group NP). RESULTS: No significant differences were observed in age or BMI between the groups. Copper concentrations were significantly higher in group NP (average 193.2 µg/dL) than in group P (average 178.1 µg/dL). According to the area under the curve (AUC) on the receiver operating characteristic curve for the prediction of clinical pregnancy rates, the Cu/Zn ratio (AUC 0.64, 95% CI 0.54-0.71) was a better predictor than copper or zinc. When we set the cut-off as 1.59/1.60 for the Cu/Zn ratio, sensitivity, specificity, the positive predictive value, and negative predictive value were 0.98, 0.29, 0.71, and 0.88, respectively. CONCLUSIONS: Our single-center retrospective study suggests that high serum copper concentrations (high Cu/Zn ratio) are a risk factor for implantation failure.

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

PROBLEM: The aim of this prospective study was to investigate the prevalence of chronic endometritis (CE) in infertile women with a history of repeated implantation failure (RIF) and to determine whether oral antibiotic treatment improves their live birth rate in the following embryo transfer (ET) cycles. METHOD OF STUDY: Endometrial biopsy samples obtained from infertile women with RIF were subjected to immunohistochemistrical/histopathologic diagnosis of CE. Following antibiotic administration to the RIF/CE group, their histopathologic cure rate, microbial detection rate, and reproductive outcome in the subsequent ET cycles were prospectively studied. RESULTS: 33.7% of infertile women with RIF were diagnosed with CE. Following the first-line doxycycline treatment, the histopathologic cure rate in the subsequent endometrial biopsy was 92.3%. Following the second-line metronidazole/ciprofloxacin treatment, the overall cure rate was 99.1%. The live birth rate in the first ET cycle (P=.031, RR 1.48, 95% CI 1.03-2.12) and cumulative three ET cycles (P=.037, RR 1.39, 95% CI 1.02-1.90) following antibiotic treatment in the cured RIF/CE group (32.8% and 38.8%, respectively) was significantly higher than in the RIF/non-CE group (22.1% and 27.9%, respectively). CONCLUSION: 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.

Clinical background affecting pregnancy outcome following local endometrial injury in infertile patients with repeated implantation failure.

Local endometrial injury (LEI) has been performed as a promising medical intervention to improve the pregnancy outcome in infertile women suffering from repeated implantation failure (RIF) in in vitro fertilization-embryo transfer cycles. The effect of LEI, however, remains controversial. The aim of this retrospective study was to identify the subgroups of patients with RIF who benefit from LEI. We compared the clinical parameters between the patients who had had a clinical pregnancy in the subsequent embryo transfer cycle following the LEI cycle (LEI-CP group, n = 94) and those who had resulted in negative pregnancy test (LEI-NP group, n = 114). The female age, basal follicle stimulating hormone concentration, number of past oocyte pickup cycles, and embryos/blastocysts transferred in the past three RIF cycles were significantly (p < 0.047) lower in the LEI-CP group than the LEI-NP group. The prevalence of polycystic ovarian syndrome was significantly (p = 0.0059) higher in the LEI-CP group than in the LEI-NP group. These findings suggest that LEI is most effective to improve the pregnancy outcome in patients undergoing RIF with uncompromised ovarian reserve, particularly in those with polycystic ovarian syndrome.

Chronic Endometritis: Potential Cause of Infertility and Obstetric and Neonatal Complications.

Chronic endometritis (CE) is a local inflammatory disease characterized by unusual plasmacyte infiltration in the endometrial stromal areas. CE has been neglected in gynecologic practice, as it is a less symptomatic benign disease that requires demanding and time-consuming histopathologic examinations for the definite diagnosis. Recent studies, however, suggest the association of CE with infertility and obstetric and neonatal complications. In this review article, we aimed to update the knowledge on epidemiology, etiology, and pathogenesis of CE as well as discuss its clinical management from diagnosis to treatment.

Effect of early endometriosis on ovarian reserve and reproductive outcome.

Accumulating evidence suggests that advanced (moderate/severe) endometriosis negatively affects female fecundity, whereas the influence of early (minimal/mild) endometriosis on human reproduction remains unclear. Recent studies showed that the presence of the early pelvic endometriosis lesions deteriorates the ovarian reserve, luteal function, and fertilization rate in infertile women undergoing in vitro fertilization-embryo transfer treatment, but not their final reproductive outcome. Meanwhile, laparoscopic resection of early endometriosis lesions may be a promising therapeutic option to improve the fecundity of the affected subfertile women. Insufficient evidence on the relationship between early endometriosis, ovarian reserve, and reproductive outcome warrants further investigations.

Comprehensive endometrial immunoglobulin subclass analysis in infertile women suffering from repeated implantation failure with or without chronic endometritis.

PROBLEM: Chronic endometritis (CE) is a local inflammatory condition with unusual plasmacyte infiltration in the endometrial stromal area. CE is frequently found in infertile women with repeated implantation failure (RIF). In this study, we comprehensively investigated the endometrial immunoglobulin (Ig) subclass expression in infertile women suffering from RIF with versus without CE. METHOD OF STUDY: Endometrial biopsy specimens obtained from 28 infertile women with RIF and CE (the RIF-CE group), 23 infertile women with RIF but without CE (the RIF-non-CE group), and 22 proven fertile women undergoing hysterectomy for benign endometrial pathology (the control group) were immunostained for Ig subclass expression. RESULTS: The density of IgM+, IgA1+, IgA2+, IgG1+, and IgG2+ stromal cells were significantly higher in the RIF-CE group than that in the RIF-non-CE and control group. The density of IgG2+ stromal cells was significantly higher than that of any other Ig subclass-positive cells (P<0.045) in the RIF-CE group. In serial section staining, the immunoreactivity for CD138 and Ig subclasses in the endometrial stroma was detectable in adjacent cells of some specimens in the RIF-CE group. CONCLUSIONS: The endometrium of infertile women with RIF-CE was characterized by increase in IgM, IgA, and IgG expression and predominance of IgG2 over other Ig subclasses.

Low follicular fluid tyrosine concentration in infertile women with ovarian hyperstimulation syndrome.

The aim of this study was to compare the branched-chain amino acid (BCAA) and tyrosine concentration in the follicular fluid of infertile women with and without ovarian hyperstimulation syndrome (OHSS) in an in vitro fertilization program combined with controlled ovarian stimulation. Follicular fluid was aspirated during oocyte retrieval from 20 infertile patients who developed moderate-to-severe OHSS and 20 age- and body mass index-matched normoresponders. BCAA and tyrosine concentration were measured using enzymatic methods. The follicular fluid BCAA concentration was similar between the two groups (P=0.55), whereas tyrosine concentration was significantly lower in the OHSS compared to that in the normoresponder group (P=0.027) and the BCAA/tyrosine ratio was significantly higher in the OHSS compared to that in the normoresponder group (P=0.034). These results suggest an association between low follicular fluid tyrosine concentration and OHSS. Dopamine receptor agonists may be used as potential anti-OHSS medicines and tyrosine, as a dopamine precursor, may play a role against the development of OHSS.

Unusual inflammation in gynecologic pathology associated with defective endometrial receptivity.

Human cycling endometrium displays a series of periodic transitions unique to this mucosal tissue, which includes rapid proliferation, secretory transformation, physiological angiogenesis, interstitial edema, and menstrual shedding. Among these properties of the endometrium are the inflammatory changes that occur dynamically across the menstrual cycle. Immunocompetent cell composition and inflammatory gene expression pattern in the human endometrium drastically fluctuate from the proliferative phase to the secretory phase, particularly at the time of ovulation. These local immune responses are fine-tuned by the direct or indirect action of two representative ovarian steroids, estradiol and progesterone, and are essential for successful blastocyst implantation. Meanwhile, studies have been accumulating the evidence that such physiological endometrial inflammatory status is altered in the presence of certain gynecologic pathologies. Given that blastocysts are semi-allografts for maternal tissue, even subtle alterations in endometrial immunity potentially have a negative impact on implantation process. In this article, we aimed to review and discuss the physiological and pathological mucosal inflammatory conditions that can affect endometrial receptivity.