Chronic Endometritis and Its Impact on Female Fertility: A Comprehensive Review

By CARE Fertility & Women’s Health

May 2025

Disclaimer: Please note that this medical review is intended for informational purposes only and should not be considered as medical advice. It has been prepared with the assistance of artificial intelligence and has not undergone peer review by medical professionals. Consult with a qualified healthcare provider for personalized medical guidance and treatment. The information provided herein is not a substitute for professional medical advice.

1. Introduction to Chronic Endometritis and its Relevance in Fertility

1.1. Definition of Chronic Endometritis (CE)

Chronic endometritis (CE) is a persistent inflammatory condition of the endometrium, the lining of the uterus. It is primarily characterized by the infiltration of plasma cells within the endometrial stroma.¹ This inflammation is typically subtle and often results from microbial colonization not associated with pregnancy, lasting for 30 days or more.¹ Beyond plasma cell presence, other histological features include edema, an increased density of stromal cells, and a dissociated maturation pattern between the epithelial cells and stromal fibroblasts.² The chronic and often inconspicuous nature of this inflammation distinguishes CE from acute endometritis and contributes significantly to diagnostic challenges and an underestimation of its true prevalence in relevant patient populations.

1.2. Etiology and Pathophysiology

The etiology of CE primarily involves the ascension of microorganisms from the lower genital tract, such as the cervix and vagina, into the endometrial cavity.¹ While the precise cause is often elusive, identified pathogens are frequently part of a polymicrobial infection. Common bacteria implicated include Streptococcus species, Escherichia coli, Enterococcus faecalis, and Ureaplasma urealyticum.¹ Unlike acute endometritis, where sexually transmitted infections like Chlamydia trachomatis and Neisseria gonorrhoeae are primary causes, these are not the most common etiologies in CE.¹ Non-infectious factors have also been linked to CE, including the presence of intrauterine devices (IUDs), endometrial polyps, and submucosal leiomyomas.¹ Identified risk factors for developing CE include the use of IUDs, a history of multiple pregnancies (multiparity), previous abortions, and abnormal uterine bleeding.¹

The pathophysiology of CE begins with microbial presence in the endometrium, which triggers an immune response and sustained chronic inflammation. A hallmark of this response is the significant infiltration of endometrial stromal plasmacytes.¹ This involves the migration of B lymphocytes from circulation into the endometrial stroma, where they locally mature into plasma cells.³ These plasma cells then produce various immunoglobulins (IgM, IgA, IgG), which are thought to negatively affect the process of embryo implantation.³ The inflammatory milieu is further characterized by elevated levels of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). These cytokines may increase local estrogen synthesis within endometrial glandular cells, potentially contributing to hysteroscopic features like micropolyps.¹ This complex inflammatory cascade fundamentally alters the endometrial microenvironment, thereby impairing endometrial receptivity and the ability of an embryo to implant and develop successfully.³ Understanding these multifaceted causes and mechanisms is paramount for devising effective diagnostic strategies and targeted therapeutic interventions, especially given the polymicrobial nature and potential non-infectious contributors that can complicate straightforward antibiotic treatments.

1.3. Prevalence

The reported prevalence of CE varies considerably across different populations and studies. In the general female population, estimates range from approximately 10% to 11%.² However, the prevalence is significantly higher among women experiencing infertility, with figures ranging broadly from as low as 2.8% to as high as 56.8%.⁷ One study identified CE in 19.46% of infertile women compared to 7.7% in fertile controls.⁹ While another study focusing on candidates for in vitro fertilization (IVF) reported a prevalence of 21.1%.¹¹

Even more striking are the prevalence rates in specific subgroups of infertile women facing particular challenges:

• Recurrent Implantation Failure (RIF): In women who have experienced multiple failed embryo transfers despite good quality embryos, CE prevalence is reported to be between 14% and 67.5%.⁷

• Recurrent Pregnancy Loss (RPL): Among women who have suffered two or more miscarriages, CE prevalence ranges from 9.3% to 67.6%.⁷ A meta-analysis indicated a CE rate of 37.6% in RPL cases versus 16.4% in controls.⁹

This wide variability in reported prevalence is not merely a reflection of different patient cohorts but is fundamentally driven by the lack of standardized diagnostic criteria and methodologies used across studies.¹² Factors such as the specific diagnostic tests employed (e.g., hysteroscopy, histology with or without immunohistochemistry), the threshold for plasma cell counts, the timing of endometrial biopsy relative to the menstrual cycle, and the characteristics of the population under investigation all contribute to these discrepancies. This lack of diagnostic standardization directly impacts the perceived clinical significance of CE and hampers efforts to establish universal screening guidelines, creating a cycle of diagnostic uncertainty and variable clinical practice. Nevertheless, the consistently higher prevalence in infertile populations, particularly those with RIF and RPL, underscores CE's potential importance as a modifiable factor contributing to these challenging reproductive outcomes.

1.4. Clinical Presentation

A significant challenge in recognizing CE is its often asymptomatic nature, or its presentation with only non-specific and mild symptoms.² Many women with CE may not exhibit any overt signs, leading to the condition being overlooked unless specifically investigated in the context of infertility.

When symptoms do manifest, they can be vague and easily attributable to other gynecological conditions. These may include:

• Abnormal uterine bleeding (e.g., intermenstrual bleeding, menorrhagia)²

• Chronic pelvic pain or discomfort²

• Dyspareunia (painful intercourse)²

• Leukorrhea (abnormal or increased vaginal discharge)²

• Recurrent cystitis or vaginitis²

The predominantly asymptomatic or mildly symptomatic nature of CE, coupled with its significant association with challenging infertility scenarios like RIF and RPL, positions it as an insidious and often overlooked pathology. This suggests that CE might be a crucial, yet frequently missed, factor in the diagnostic workup of a substantial portion of infertile patients who have otherwise unexplained reproductive failures. The silent presentation means that without a high index of suspicion and specific diagnostic testing, CE may remain undiagnosed, potentially contributing to ongoing fertility struggles.

2. Diagnosis of Chronic Endometritis

The diagnostic process for CE involves several modalities, each with its own strengths and limitations. The lack of a single, universally accepted diagnostic pathway contributes to the variability in its reported prevalence and challenges in clinical management.

2.1. Hysteroscopy

Hysteroscopy allows for direct visualization of the endometrial cavity and can reveal signs suggestive of inflammation. Typical hysteroscopic findings associated with CE include¹:

• Focal or diffuse hyperemia: This appears as reddened areas on the endometrial surface.

• Stromal edema: This can cause the endometrium to appear unusually thick and pale, particularly when observed during the follicular phase of the menstrual cycle, a time when it is normally thinner.

• Micropolyps: These are small, typically 1–2 mm, protrusions from the endometrial surface, which are considered a hallmark feature by some.⁵

• "Strawberry aspect": This describes a pattern of diffuse hyperemia interspersed with small white spots, resembling the surface of a strawberry.¹

The diagnostic accuracy of hysteroscopy alone for CE is a subject of ongoing discussion. Some studies have reported high sensitivity (ranging from 86% to 100%) and high negative predictive value (NPV, from 92% to 100%), suggesting it can be a useful tool for ruling out CE if the visual appearance is normal.¹¹ For example, one study involving IVF candidates reported a sensitivity of 68.4%, specificity of 87.3%, NPV of 91.17%, positive predictive value (PPV) of 59.1%, and an overall accuracy of 83.3% for hysteroscopy in diagnosing CE confirmed by histology.¹¹ However, other research indicates more modest accuracy; one large study found an overall accuracy of only 67% and cautioned that hysteroscopy should not replace histologic examination, as it may tend to overdiagnose CE.¹⁷ Conversely, it has also been suggested that while hysteroscopy might overdiagnose, histopathological evaluation could underdiagnose the condition.¹⁶ Thus, while hysteroscopy provides valuable visual clues and allows for targeted biopsies, its subjective interpretation and variable accuracy mean it is generally considered more of a screening or guiding tool rather than a standalone definitive diagnostic method.

2.2. Endometrial Biopsy and Histopathology

The histological identification of plasma cells within the endometrial stroma, obtained via an endometrial biopsy, is widely regarded as the gold standard for diagnosing CE.² Plasma cells are not typically present in normal, healthy endometrial tissue outside of specific physiological circumstances like post-menstruation.
However, identifying these plasma cells using conventional Hematoxylin and Eosin (H&E) staining can be challenging for pathologists.² Plasma cells can morphologically resemble other mononuclear inflammatory cells, endometrial stromal cells that have a plasmacytoid appearance, or normal decidual cells, particularly during the late secretory phase of the menstrual cycle.² Characteristic features of plasma cells that aid in their identification include an eccentric nucleus, clumped "clock-face" chromatin, and a pale perinuclear halo (Golgi zone).² Despite being the gold standard, the inherent difficulties in H&E identification can lead to inter-observer variability and potential underdiagnosis if not performed by experienced pathologists or if plasma cell infiltration is sparse.

2.3. Immunohistochemistry (IHC)

To overcome the limitations of H&E staining, immunohistochemistry (IHC) for the marker CD138 (also known as Syndecan-1) has become an invaluable tool in diagnosing CE.⁶ CD138 is a transmembrane heparan sulfate proteoglycan that is strongly expressed on the surface of mature plasma cells and epithelial cells, but typically not on other endometrial stromal cells, lymphocytes, or mononuclear cells.²
The use of CD138 IHC significantly enhances the detection of plasma cells compared to H&E staining alone, thereby increasing diagnostic sensitivity and reducing inter-observer variability.² Some have suggested that CD138 staining can be used to highlight areas of interest within the biopsy sample, which can then be more closely examined with H&E for definitive plasma cell morphology, acknowledging that CD138 itself is not entirely specific to plasma cells in all contexts.¹⁸

2.4. Diagnostic Criteria and Controversies

Despite the advancements with CD138 IHC, a major point of contention in the field is the precise number of CD138-positive plasma cells per high-power field (HPF) or per tissue section that is required to establish a diagnosis of CE. There is currently no universally accepted consensus on this threshold.¹

Proposed diagnostic thresholds vary widely in the literature:

• The presence of ≥1 plasma cell in 10 HPFs.¹⁹

• The presence of ≥2 plasma cells per 10 HPFs.¹⁸

• The presence of ≥3 positive lesions (interpreted as CD138⁺ cells or clusters) per HPF, particularly when biopsies are taken during the proliferative phase.⁸

• The presence of ≥5 CD138⁺ cells in at least one HPF.⁸

• The International Working Group for Standardization of Chronic Endometritis Diagnosis proposed criteria of 1 to 5 endometrial stromal plasmacytes (ESPCs) per HPF, or discrete clusters of fewer than 20 ESPCs by CD138 staining.¹

This debate over CD138⁺ plasma cell count thresholds is not merely an academic disagreement but has profound implications for clinical research and patient care. The chosen threshold directly determines which patients are labeled with CE and subsequently offered treatment. This, in turn, influences the reported efficacy of interventions in clinical trials and meta-analyses. A stricter criterion might lead to treating only more severe cases, potentially showing greater treatment benefit if the effect is dose-dependent. Conversely, a looser criterion might include milder cases where treatment effects are less pronounced or even absent, thus diluting overall findings and making cross-study comparisons exceptionally challenging. This variability significantly impacts the ability to answer the critical question of whether treating CE is beneficial for fertility.

Further complicating the diagnostic landscape is the influence of the menstrual cycle phase on plasma cell numbers and CD138 expression.² CD138 expression in the endometrial stroma has been reported to be downregulated after ovulation, remaining low throughout the luteal phase.⁸ Consequently, the timing of the endometrial biopsy is crucial. Many recommend performing biopsies during the proliferative or early secretory phase, or hysteroscopy during the follicular phase, to optimize detection.¹ Furthermore, during the secretory phase, plasma cells might be confined to the basal layer of the endometrium, which could be missed if the biopsy is too superficial.² These pre-analytical variables—biopsy timing and depth—are not consistently standardized across studies or clinical practices, potentially leading to false-negative diagnoses and further confounding diagnostic accuracy and research consistency.

The overall diagnostic process for CE is thus characterized by an inherent imperfection due to the limitations of individual tools and the significant lack of consensus on interpretative criteria. Hysteroscopy provides valuable initial clues but has modest standalone accuracy.¹¹ Histology with H&E staining is considered the gold standard but can easily miss inconspicuous plasma cells.³ While CD138 IHC significantly boosts detection capabilities, its quantitative interpretation remains highly controversial and subject to cycle-dependent variations.¹ This sequence of diagnostic steps, each with its own set of challenges and interpretative debates, culminates in a "diagnostic cascade of uncertainty," making it difficult to establish a uniform approach to CE diagnosis. The absence of universally accepted diagnostic criteria remains a recurring theme and a significant impediment to progress in both clinical practice and research related to CE.¹

The following table summarizes the key diagnostic modalities for chronic endometritis:

Table 1: Diagnostic Modalities and Criteria for Chronic Endometritis

3. Management and Treatment of Chronic Endometritis

The primary goal of treating chronic endometritis in the context of infertility is to eradicate the underlying inflammation and presumed microbial infection, thereby restoring a receptive endometrial environment conducive to embryo implantation and successful pregnancy.

3.1. Antibiotic Therapy

Antibiotics are the cornerstone of CE management, reflecting the predominantly infectious etiology of the condition.

Common Regimens and Duration:

• Doxycycline: The most frequently cited first-line treatment is doxycycline, typically administered at a dose of 100 mg orally twice daily for 14 days.¹

• Combination Therapy for Resistant Cases: For cases that do not respond to doxycycline or where specific pathogens are identified through culture, a combination regimen is often employed. This commonly involves metronidazole (e.g., 500 mg orally daily or twice daily) and a fluoroquinolone such as ciprofloxacin (e.g., 400–500 mg orally daily or twice daily), also for a duration of 14 days.¹

• Other Regimens: Based on culture results or specific microbial suspicions, other antibiotics may be used. For instance, amoxicillin/clavulanate has been used for Gram-positive bacteria, and a combination of josamycin and minocycline for Mycoplasma or Ureaplasma infections.⁴ Broader CDC-recommended regimens for endometritis in general may also be considered, although these are not specifically tailored for CE in the infertility setting.¹

Efficacy in Eradicating CE (Cure Rates):
Reported cure rates with first-line antibiotic therapy are generally high, often stated to be over 80–90% in many sources.⁵ One source mentions a cure rate exceeding 90%.⁷
However, more detailed studies provide a more nuanced picture. One study reported a 68.5% clearance of CE after a single course of antibiotics (predominantly doxycycline), with this rate increasing to 88.3% after two courses of treatment.¹³ Another investigation found a 75.9% cure rate after one cycle of antibiotic therapy that included doxycycline.²⁴ These figures imply that a clinically significant proportion of patients, roughly 10–30%, may exhibit persistent disease after an initial course of standard antibiotic therapy. This highlights the need for robust second-line strategies and raises questions about underlying factors such as antimicrobial resistance or an incomplete diagnosis of all causative microbial agents.

Treatment for Resistant Cases:
As noted, a combination of ciprofloxacin and metronidazole is a common second-line approach for doxycycline-resistant CE.¹ Data from ¹³ indicated that this combination was frequently used as a second-line therapy following doxycycline failure. It is important to acknowledge that a subset of CE cases, estimated between 1% and 25%, may remain uncured even after two or more cycles of broad-spectrum antibiotics.²⁴ The growing concern over antimicrobial resistance (AMR) suggests that the current reliance on empiric broad-spectrum antibiotics for CE may become less effective over time.⁴ This evolving challenge could necessitate a shift towards more routine endometrial cultures with antibiotic sensitivity testing to guide therapeutic choices, or a greater exploration and validation of non-antibiotic adjunctive therapies.

The following table summarizes common antibiotic regimens for chronic endometritis and their reported cure rates:

Table 2: Common Antibiotic Regimens for Chronic Endometritis and Reported Cure Rates

Note: Cure rates can vary based on diagnostic criteria for CE, patient population, and specific study methodologies. BID = twice a day; PO = orally.

3.2. Alternative and Adjunctive Therapies

While antibiotics are the primary treatment for CE, there is interest in alternative and adjunctive therapies, particularly for resistant cases or when microbiome disruption is a concern. However, robust evidence for many of these in the specific context of CE-related infertility is limited in the available literature.

• Hysteroscopy and Endometrial Biopsy: Some evidence suggests that the diagnostic procedures themselves—hysteroscopy and endometrial biopsy—may exert a therapeutic effect. It has been postulated that hysteroscopy could physically remove bacterial biofilms, while endometrial biopsy (similar to endometrial scratching) might stimulate local immune responses or the secretion of cytokines and growth factors beneficial for implantation.² Hysteroscopic removal of biofilms or associated micropolyps is also mentioned as a potential intervention.²⁰

• Intrauterine Antibiotic Infusion: This approach has been mentioned as a promising option for resistant CE cases, delivering antibiotics directly to the site of inflammation.²⁰

• Other Therapies: Platelet-rich plasma (PRP) has been proposed as a potential therapy.²⁰ Therapies such as herbal products, acupuncture, and microwave physiotherapy are mentioned in the context of endometriosis or general pelvic pain but lack specific evidence for CE in infertility within the provided materials.²⁵ Dietary and lifestyle changes, including the use of probiotics and prebiotics to modulate the microbiome, are emerging areas of interest, though direct evidence for CE treatment is still developing.⁴

3.3. Role of Test-of-Cure

Following antibiotic treatment, confirming the eradication of CE is considered important by many clinicians and researchers. A follow-up endometrial biopsy, often with CD138 IHC, is commonly used as a "test-of-cure" (TOC) to ensure the resolution of inflammation.¹² One study detailed TOC rates, showing that 87.7% of treated patients underwent at least one TOC.¹³

However, there is not universal consensus on the necessity of a routine TOC. One source notes that "no consensus on whether a second biopsy is needed to confirm if the treatment has worked," suggesting variability in clinical practice.⁷ This lack of universal agreement on the necessity and methodology of a TOC creates a critical gap in both clinical management and research. If cure is not consistently verified, it becomes impossible to definitively attribute subsequent fertility outcomes to the successful eradication of CE. This ambiguity significantly complicates the evaluation of whether treating CE is truly "worth it" for improving fertility, as studies may inadvertently group patients who are truly cured with those who have persistent, albeit perhaps subclinical, inflammation. Such inconsistencies impact the interpretation of treatment efficacy studies and the ability to provide clear patient guidance.

4. Impact of Chronic Endometritis on Fertility

Chronic endometritis is increasingly recognized as a significant factor contributing to female infertility and adverse reproductive outcomes. Its impact is mediated through a complex interplay of inflammatory, immunological, hormonal, and potentially mechanical alterations within the endometrial environment.

4.1. Mechanisms of Infertility

CE appears to exert its detrimental effect on fertility not through a single pathway, but by orchestrating a multi-pronged disruption of the endometrial milieu. This multifaceted pathology helps explain its broad impact on implantation, pregnancy development, and maintenance. Key mechanisms include:

• Altered Endometrial Receptivity: This is a central consequence of CE. The chronic inflammation disrupts the finely tuned endometrial environment required for successful embryo implantation and development.² The endometrium may become hostile to the embryo due to the presence of inflammatory cells, abnormal secretions, and altered cellular signaling.

• Immune Dysregulation:

  • CE is characterized by an abnormal infiltration of lymphocytes, particularly B lymphocytes, which differentiate locally into plasma cells.³

  • These plasma cells produce excessive local antibodies (IgM, IgA, IgG), which are hypothesized to interfere with the implantation process.³

  • There are also alterations in the populations and activity of other crucial immune cells, such as Natural Killer (NK) cells and macrophages, which play vital roles in implantation and early pregnancy tolerance.²

• Cytokine and Chemokine Imbalance: The inflammatory state in CE leads to an abnormal production and balance of various cytokines and chemokines. For example, levels of pro-inflammatory cytokines like IL-1β and TNF-α are often increased, while levels of factors crucial for implantation, such as IL-11 and the chemokine CCL4 (involved in NK cell recruitment), may be decreased.¹ This dysregulation disrupts the critical signaling pathways necessary for embryo-endometrial dialogue, trophoblast invasion, and placentation.

• Hormonal Alterations: CE may lead to increased local estrogen synthesis within the endometrial glands.¹ There is also evidence suggesting potential progesterone resistance at the endometrial level.¹⁵ Studies have described an "out-of-phase" endometrial morphology in some women with CE, where the endometrium exhibits high expression of estrogen and progesterone receptors and markers of cell proliferation (like Ki-67) even during the secretory phase, when it should be differentiating under progesterone influence.²

• Altered Gene Expression: The chronic inflammation in CE can lead to dysregulation of gene expression critical for endometrial function. This includes genes involved in apoptosis (programmed cell death), such as BCL2, BAX, and CASP8, potentially leading to endometrial cell resistance to apoptosis and disturbed implantation processes.² An imbalance in factors like Insulin-like Growth Factor Binding Protein 1 (IGFBP1) and Insulin-like Growth Factor 1 (IGF1) can also create conditions unfavorable for embryonic development.³

• Altered Uterine Contractility: CE has been associated with abnormal uterine peristalsis. Specifically, there can be a reduction in the normal retrograde (cervix-to-fundus) contractions that occur around the time of ovulation and implantation, which are important for sperm migration and embryo transport towards the implantation site.² Altered contractility could also contribute to symptoms like pelvic pain.

4.2. Association with Recurrent Implantation Failure (RIF)

RIF, defined as the failure to achieve a clinical pregnancy after multiple transfers of good-quality embryos, is a deeply frustrating scenario in assisted reproductive technology (ART). CE is frequently identified in women with RIF, with reported prevalence rates varying widely, typically between 14% and 67.5%.² One study specifically linked CE in RIF patients to lower implantation rates, around 11.5%.²⁸ This high prevalence has led many to consider CE a potentially treatable cause of RIF.

However, the relationship between CE and RIF is not without controversy. A notable meta-analysis by Vitagliano et al.⁹ found no significant association between CE and RIF in their pooled data (Odds Ratio: 1.10, 95% Confidence Interval [CI] 0.26–4.61, p = 0.90). In their analysis, CE rates were comparable in women with RIF (6.35%) and control groups (5.8%). This striking contradiction in meta-analytic findings represents a critical research problem. The discrepancy likely stems from significant heterogeneity in how RIF is defined across primary studies (e.g., number of failed transfers, number and quality of embryos transferred), the varying diagnostic thresholds used for CE, and differences in the selection of control groups. Until these methodological inconsistencies are addressed and resolved through more standardized research, the true nature and strength of the relationship between CE and RIF will remain contentious, thereby impacting clinical guidance for the diagnostic workup of RIF patients.

4.3. Association with Recurrent Pregnancy Loss (RPL)

In contrast to RIF, the association between CE and RPL (typically defined as two or more miscarriages) appears to be stronger and more consistently reported in the literature. Prevalence rates of CE in RPL patients range from 9.3% to as high as 67.6%.² The meta-analysis by Vitagliano et al.⁹, which found no link with RIF, did find a strong and statistically significant association between CE and RPL. They reported a CE rate of 37.6% in RPL cases compared to 16.4% in controls (OR: 3.59, 95% CI 2.46–5.24, p < 0.00001). Another source cited similar figures, with a 37.6% CE rate in RPL patients versus 16.4% in controls.²⁶ This consistent link suggests that the inflammatory endometrial environment in CE plays a significant role not only in preventing initial implantation but also in compromising the maintenance of an early pregnancy. This makes the diagnosis and treatment of CE particularly relevant in the evaluation and management of women experiencing RPL.

4.4. Effects on Fertility Outcomes (Untreated CE)

Untreated CE has a demonstrably negative impact on a range of fertility outcomes, both in natural conception attempts and in ART cycles. The stark figures reported in various studies underscore the clinical significance of this condition.

• Implantation Rates (IR): Women with RIF who are diagnosed with CE have been shown to have significantly lower implantation rates. One study reported an IR of only 15% in CE patients with RIF, compared to 46% in RIF patients without CE.²⁹ Another noted an IR of 11.5% in CE patients with RIF.²⁸

• Clinical Pregnancy Rates (CPR): CPRs are generally reduced in women with untreated CE.¹⁴ For instance, one study reported a CPR of 33% in women who had persistent CE even after an initial attempt at treatment, implying a poor prognosis if the condition is not resolved.²⁸

• Live Birth Rates (LBR): This is perhaps the most critical outcome, and LBRs are markedly lower in the presence of untreated CE.

  • In women with RPL and untreated CE, the LBR can be exceptionally low, around 7%.²⁹

  • One review citing a study indicated LBRs of approximately 6–15% in untreated CE patients compared to 60–65% in treated patients undergoing fresh day 3 embryo transfers.¹

  • Another study reported an LBR of only 5.6% for patients with untreated CE.¹³

  • Following IVF, one study cited by Pereira et al.¹⁴ (Cicinelli et al.) found an LBR of 13% in an untreated CE group. Similarly, women with persistent CE after an initial treatment attempt had an LBR of 13.3%.²⁸

• Miscarriage Rates (MR): Untreated CE is associated with a significantly higher risk of miscarriage.

  • One study cited by MiscarriageMD.com reported a miscarriage rate of 56% in untreated women with CE, compared to 15% in those who received treatment.³¹

  • A meta-analysis by Pereira et al. found that women with CE had a statistically significant higher rate of miscarriage (p = 0.0002) compared to controls.¹⁴

The consistently reported, dramatically poor reproductive outcomes in women with untreated CE, particularly the very low LBRs and high MRs, especially in populations like those with RPL, strongly argue for considering CE as a significant and potentially reversible cause of reproductive failure. This positions CE screening and subsequent treatment, if diagnosed, as a potentially high-yield intervention in select infertile populations who are struggling to achieve a successful pregnancy.

5. Efficacy of Treatment in Improving Fertility Outcomes: Is It Worth Treating?

The question of whether treating chronic endometritis translates into improved fertility outcomes is central to its clinical management and is a subject of considerable research and debate. While many studies suggest benefits, particularly when CE is successfully eradicated, conflicting evidence and methodological limitations in the existing literature create a complex picture.

5.1. Evidence Supporting Improved Fertility Outcomes Post-Treatment

A substantial body of evidence, including several systematic reviews and meta-analyses, indicates that successful antibiotic treatment of CE can lead to significant improvements in various fertility parameters.

• Live Birth Rates (LBR):

  • A meta-analysis by Pereira et al. (2023) found that women without CE (either never had it or were treated and cured) had significantly higher LBRs (p=0.004) compared to women with active CE. They cited a study by Cicinelli et al. (2015) where LBR was 60.8% in cured CE patients versus 13.3% in those with persistent CE after IVF.¹⁴ Another Cicinelli et al. study (2014) reported an LBR of 60% in treated CE patients versus 13% in an untreated group.¹⁴

  • A meta-analysis by Vitagliano et al. (2018), focusing on RIF patients, demonstrated that cured CE was associated with a markedly higher ongoing pregnancy rate/live birth rate (OPR/LBR) with an OR of 6.81 compared to persistent CE. Furthermore, IVF outcomes were comparable between women with cured CE and those who had no CE.³²

  • A study by Liu et al. (2023) found LBRs to be significantly higher for patients with cleared CE (34.1%) compared to those with untreated CE (5.6%, p=.014). The LBRs for the cleared CE group were similar to those for patients who never had CE (29.3%).¹³

  • In RPL patients, McQueen et al. (2014) reported an increase in LBR from 7% before antibiotic treatment to 56% after treatment.³³

  • Zhang et al. (2023), studying women with unexplained infertility, found a "baby-carrying home rate" of 60% in the treated CE group versus 36.2% in an unexamined control group (p=0.006).³⁴

  • An abstract of a systematic review and meta-analysis by Takebayashi et al. (2022) reported a pooled risk ratio (RR) for live birth of 2.98 for successful CE treatment compared to persistent CE.²⁰

• Clinical Pregnancy Rates (CPR):

  • The meta-analysis by Pereira et al. (2023) also showed that the group without CE had a higher CPR (p≤0.00001).¹⁴
    Vitagliano et al. (2018, RIF patients) found that cured CE was associated with a higher CPR (OR 4.02) compared to persistent CE.³²

  • Cicinelli et al. (2015, RIF patients) reported a CPR of 65.2% in cured CE patients versus 33.0% in those with persistent CE.²⁸

  • Takebayashi et al. (2022, abstract) reported an RR of 2.25 for CPR with successful CE treatment versus persistent CE.²⁰

• Implantation Rates (IR):

  • The meta-analysis by Vitagliano et al. (2018, RIF patients) showed that cured CE was associated with a higher IR (OR 3.24) compared to persistent CE.³²

• Miscarriage Rates (MR):

  • Pereira et al. (2023, meta-analysis) found that women with CE had a higher MR (p=0.0002), and the group without CE (treated/cured or no CE) had fewer miscarriages.¹⁴

  • A meta-analysis by Vitagliano et al. (2022) indicated that women with CE who received antibiotics had a lower MR (OR 0.25, p=0.03) compared to untreated controls.¹²

  • One study cited in ³¹ reported a dramatic reduction in MR from 56% in untreated women to 15% in treated women.
    Zhang et al. (2023, unexplained infertility) observed a spontaneous abortion rate of 2.2% in the treated CE group compared to 16.0% in the unexamined group (p=0.049).³⁴

This substantial body of evidence strongly suggests that effective treatment leading to the resolution of CE can normalize or significantly enhance reproductive potential, making a compelling case for intervention.

5.2. Studies Showing Limited or No Benefit of CE Treatment

Despite the positive findings, several studies and reviews have cast doubt on the universal efficacy of CE treatment or have reported no significant improvement in key fertility outcomes.

• A meta-analysis by Kato et al. (2022) concluded that oral antibiotic treatment for CE did not significantly increase the implantation rate (OR 1.02), intrauterine pregnancy rate (OR 1.08), or live birth rate (OR 1.13).³⁵ This finding is in direct contrast to other meta-analyses and represents a significant point of contention.

• The meta-analysis by Vitagliano et al. (2022), while demonstrating benefits for cured CE versus persistent CE, found that when comparing women with CE who merely received antibiotics (cure not necessarily confirmed or uniformly defined across all pooled studies for this specific comparison) against untreated controls, there was no statistically significant difference in OPR/LBR (p=0.09) or CPR (p=0.36), although miscarriage rates were lower.¹²

• A study by Zhang Q et al. (2023) presented a nuanced finding: patients with antibiotic-cured CE (defined in their study as <5 CD138+ cells/HPF) still experienced a higher rate of subsequent pregnancy loss compared to patients who had no history of CE (21.2% vs 14.2%). Importantly, this study found no significant differences in biochemical pregnancy rates, clinical pregnancy rates, or live birth rates between these two groups (cured CE vs. no CE).²¹ This suggests that even if plasma cell counts are reduced below a certain threshold, underlying endometrial dysfunction might persist.

• Referencing earlier work, ²⁸ mentions that Kasius and coworkers had reported minimal clinical implication of CE, diagnosing it in only about 2% of asymptomatic infertile patients and finding that IVF/ICSI outcomes were not negatively affected by its presence.

• An editorial by Urman & Yakin (2024) states that "clinical improvement in fertility remains controversial" and that "clinical evidence is still weak about a causative link between CE and reproductive failure".³⁶

These contrasting findings highlight that the benefits of CE treatment may not be universal or as substantial as some reports suggest. It also raises questions about whether current treatment paradigms fully address the underlying pathology or if the definition of "cure" based solely on plasma cell counts is adequate.

5.3. Quality of Evidence and Limitations of Existing Studies

The conflicting conclusions in the literature can be largely attributed to significant limitations and inconsistencies in the available evidence base.

• Heterogeneity: There is substantial heterogeneity across studies regarding:

  • Diagnostic criteria for CE: Variations in plasma cell thresholds, diagnostic methods (H&E, CD138 IHC, hysteroscopy), and biopsy timing are rampant.¹²

  • Patient populations: Studies include diverse groups such as RIF, RPL, general infertility, and unexplained infertility, each with different baseline prognoses.¹²

  • Definitions of RIF/RPL: These definitions themselves can vary between studies.

  • Antibiotic regimens: Type, dose, and duration of antibiotic treatment are inconsistent.¹²

  • Confirmation of cure: The practice and methodology of a test-of-cure vary significantly, with some studies confirming histological resolution and others not.¹²

  • Study design: Most available data comes from observational studies (retrospective or prospective cohorts).¹²

• Lack of High-Quality Randomized Controlled Trials (RCTs):
  There is a widely acknowledged and critical shortage of large, well-designed RCTs. RCTs are essential for establishing definitive causality and treatment efficacy by minimizing bias. The repeated calls for such trials across multiple sources underscore that the current reliance on observational studies and meta-analyses of heterogeneous data is insufficient to definitively guide clinical practice.¹²

• Confounding Factors:
  The endometrial biopsy procedure itself, used for diagnosis and test-of-cure, might have an independent therapeutic effect (often referred to as endometrial injury or "scratching"), which could confound the assessment of benefits attributable solely to antibiotic treatment.²

These limitations make it exceedingly difficult to draw firm, universally applicable conclusions and largely explain the divergent results observed in systematic reviews and meta-analyses. The pivotal question "Is treating CE worthwhile for fertility?" is thus mired in controversy. This discrepancy likely arises from critical methodological differences in how "treatment" is defined (e.g., simply administering antibiotics versus confirming histological cure) and the stringency of diagnostic criteria for CE used in the primary studies included in these meta-analyses. This makes it challenging for clinicians to make fully evidence-based decisions.

5.4. Patient Populations That May Benefit Most

Despite the overall controversies, there is a recurring suggestion in the literature that certain patient populations are more likely to benefit from CE screening and treatment. These are typically groups where other causes of infertility have been excluded or are less amenable to treatment, making CE a tangible therapeutic target.

• Recurrent Implantation Failure (RIF) and Recurrent Pregnancy Loss (RPL):
  These two groups are consistently highlighted. Given the high prevalence of CE in these challenging populations and the potential for CE to be a correctable factor contributing to their reproductive failures, screening and treatment are often considered.⁷ One source specifically suggests that patients with RPL and RIF are likely the primary beneficiaries of screening and treatment.³⁷ The meta-analysis by Vitagliano et al. (2022) focused its analysis on women with RIF and RPL.¹²

• Unexplained Infertility:
  Patients with unexplained infertility may also benefit, as CE can be an occult underlying cause of their inability to conceive.¹¹ One study demonstrated improved outcomes in unexplained infertility patients who were treated for CE.³⁴

• Failed Euploid Embryo Transfers:
  It has been suggested that considering CD138 testing for CE may be appropriate for patients who have experienced a minimum of two failed transfers of genetically normal (euploid) embryos.²²

Targeting these specific high-risk or refractory populations for CE screening and treatment may represent a more evidence-informed approach until broader consensus and higher-quality evidence emerge.

The following table summarizes key meta-analyses on chronic endometritis treatment and fertility outcomes, illustrating the ongoing debate:

Table 3: Summary of Meta-Analyses on Chronic Endometritis Treatment and Fertility Outcomes

IR=Implantation Rate; IUPR=Intrauterine Pregnancy Rate; OPR=Ongoing Pregnancy Rate; OR=Odds Ratio; RR=Risk Ratio. Note: Details for CI and p-values are provided where available in the snippets.

The study by Zhang Q et al.²¹ introduces a further layer of complexity, suggesting that current definitions of "cure" based on plasma cell counts below a certain threshold may be insufficient. If antibiotic-cured CE still carries a higher risk of pregnancy loss, and even sub-threshold inflammation (e.g., 1–4 CD138⁺ cells/HPF) is detrimental compared to an endometrium with zero plasma cells, it implies that: (a) current antibiotic therapies may not fully resolve all aspects of endometrial dysfunction caused by CE, even if plasma cell numbers are reduced, or (b) our diagnostic criteria for both active CE and what constitutes a "cure" are not sensitive enough to identify ongoing subtle pathology. This points towards a need to look beyond mere plasma cell counts for a comprehensive assessment of endometrial health and treatment success.

6. The Role of the Endometrial Microbiome

The understanding of the uterine environment has evolved significantly, moving away from the traditional view of a sterile cavity to the recognition of a complex endometrial microbiome. This paradigm shift has profound implications for understanding the pathogenesis of conditions like chronic endometritis and for developing novel diagnostic and therapeutic strategies.

6.1. Current Understanding

It is now well-accepted that the endometrium, like other mucosal surfaces, harbors its own unique microbial community, albeit typically with a low biomass compared to sites like the vagina or gut.²

• Healthy Endometrial Microbiome: In healthy reproductive-age women, a Lactobacillus-dominant microbiome is generally considered beneficial and is associated with successful reproductive outcomes, including higher rates of embryo implantation and live birth.⁴¹ Lactobacilli contribute to maintaining a healthy endometrial environment, partly through the production of lactic acid, which helps maintain a low pH and inhibit the growth of pathogenic organisms.

• Endometrial Dysbiosis: An imbalance in this microbial community, often characterized by a reduction in Lactobacillus species and an overgrowth of other bacteria (non-Lactobacillus-dominated microbiota), is termed endometrial dysbiosis. This state has been increasingly linked to various reproductive pathologies, including CE, general infertility, RIF, and endometriosis.² Specific bacteria such as Gardnerella, Streptococcus, Atopobium, Prevotella, Pseudomonas, and Acinetobacter have been identified in dysbiotic endometrial environments or in association with CE.³

• Dynamic Nature: The composition of the endometrial microbiota is not static; it can fluctuate in response to hormonal changes throughout the menstrual cycle, as well as other factors like age and immune responses.⁴¹

• Immune Interaction: There is a constant and intricate interaction between the microorganisms residing in the endometrium and the local maternal immune system. A balanced microbiome is thought to contribute to immune tolerance necessary for embryo implantation and pregnancy maintenance, while dysbiosis can trigger pro-inflammatory responses that impair endometrial receptivity.⁴⁰

This recognition of an endometrial microbiome fundamentally reframes chronic endometritis. It shifts the perspective from a simple infectious disease model, where the presence of a specific pathogen directly causes disease, to a more complex dysbiosis model. In this model, CE may arise not just from the detrimental effects of invading pathogens but also from the loss of protective functions normally provided by a healthy, Lactobacillus-dominant microbiome.

6.2. Implications for CE Pathogenesis, Diagnosis, and Treatment

The microbiome perspective has significant implications for how CE is understood, diagnosed, and managed:

• Pathogenesis: CE may be more accurately viewed as a manifestation of endometrial dysbiosis rather than solely an infection by one or more specific pathogenic bacteria.⁴ The altered microbial landscape can lead to chronic inflammation and immune dysregulation characteristic of CE.

• Diagnosis: Current diagnostic methods for CE primarily focus on identifying plasma cells (a marker of inflammation) or, less commonly, specific pathogens through culture. The microbiome perspective suggests that future diagnostic approaches may need to incorporate comprehensive assessments of the entire endometrial microbial community, for example, using techniques like 16S rRNA gene sequencing.² This could provide a more complete picture of endometrial health than plasma cell counts alone.

• Treatment: The mainstay treatment for CE currently relies on broad-spectrum antibiotics. While these aim to eradicate presumed pathogens, they carry an inherent risk of further disrupting the endometrial microbiome by indiscriminately eliminating beneficial commensal bacteria alongside harmful ones.¹² This could paradoxically contribute to treatment failure, recurrence of CE, or persistent subfertility even if histological markers like plasma cells are reduced. This highlights a critical limitation of the current therapeutic approach. Future treatment strategies might therefore evolve to include microbiome-modulating interventions, such as:

  • Probiotics: Administration of beneficial bacteria, particularly Lactobacillus species, to help restore a healthy endometrial environment.

  • Prebiotics: Substances that promote the growth of beneficial bacteria.

  • Dietary Interventions: As the gut microbiome can influence the reproductive tract microbiome, dietary changes may play a role.⁴

  • More Targeted Antimicrobials: If specific dysbiotic patterns are identified, more targeted antimicrobial therapy might be possible, minimizing damage to the commensal flora.

The exploration of the endometrial microbiome opens new avenues for understanding the complex etiology of CE and for developing more personalized and potentially less disruptive therapeutic strategies that aim not just to eliminate inflammation but to restore a healthy and receptive endometrial ecosystem.

7. Controversies, Unresolved Questions, and Future Directions

Despite growing recognition of chronic endometritis as a potential factor in female infertility, the field is fraught with controversies, unresolved questions, and a clear need for further research to establish definitive guidelines for diagnosis and management.

7.1. Standardization of Diagnostic Criteria

This remains arguably the most significant unresolved issue in the study of CE. The lack of universal consensus on diagnostic criteria severely hampers progress in both clinical practice and research.¹ Key areas of debate include:

• Plasma Cell Thresholds: There is no agreement on the minimum number of CD138-positive plasma cells per high-power field or tissue section required to confirm a diagnosis of CE. Proposed cut-offs vary widely, from ≥1 to ≥5 or more, or specific cluster definitions.¹ This variability means a patient diagnosed with CE in one center might not meet the criteria in another.

• Optimal Biopsy Timing and Technique: The influence of the menstrual cycle phase on plasma cell detection and the necessary depth of biopsy to capture basal inflammation are not consistently standardized.²

• Role and Interpretation of Hysteroscopic Findings: While hysteroscopy offers direct visualization, the diagnostic accuracy of its findings (micropolyps, hyperemia, edema) is debated, and interpretation can be subjective.¹¹ The absence of a universally accepted "gold standard" for diagnosing CE has limited efforts to accurately determine its prevalence, understand its natural history, and rigorously study treatment efficacy.⁴³ Without standardization, comparing results across studies is extremely challenging, and developing evidence-based clinical guidelines remains difficult.

7.2. Optimal Treatment Strategies and Management of Resistant CE

While antibiotics are the primary treatment, several questions persist regarding optimal therapeutic approaches:

• Ideal Antibiotic Regimen: The most effective antibiotic(s), optimal dosage, and duration of treatment for CE are not definitively established. Current practice often relies on empiric broad-spectrum antibiotics, primarily doxycycline.¹

• Management of Resistant CE: A notable percentage of patients (10–30%) fail to respond to initial antibiotic courses.¹³ Clear guidelines for managing these resistant or persistent cases, including the best second-line antibiotic choices or the role of alternative therapies, are lacking.

• Antimicrobial Resistance (AMR): The global rise in AMR is a significant concern that could further compromise the efficacy of current antibiotic regimens for CE.⁴ This underscores the potential need for more routine microbial culture and sensitivity testing to guide antibiotic selection, rather than relying solely on empiric therapy.

• Role of Non-Antibiotic Therapies: The efficacy and appropriate application of non-antibiotic or adjunctive therapies (e.g., intrauterine antibiotic infusions, hysteroscopic interventions, microbiome modulation) require more rigorous investigation.⁴

7.3. Long-Term Fertility Outcomes Post-Treatment

Most studies on CE treatment focus on reproductive outcomes in the immediate subsequent ART cycle or pregnancy attempt. There is a paucity of robust data on:

• Long-term fertility: The sustained impact of CE treatment on fertility over several years.

• Recurrence rates of CE: How often CE recurs after successful treatment and what factors predict recurrence.

• Subsequent pregnancy outcomes: Outcomes of pregnancies conceived long after CE treatment. The findings by Zhang Q et al.²¹, suggesting that even histologically "cured" CE may be associated with a persistent increased risk of pregnancy loss, raise critical questions about the true long-term resolution of endometrial dysfunction and the adequacy of current "cure" definitions. This highlights the need for studies with longer follow-up periods to understand the complete picture.

7.4. Need for High-Quality Research

There is a consistent and urgent call from researchers across numerous studies for higher quality research to address the existing uncertainties. Specifically, there is a critical need for:

• Large-scale, multicenter, well-designed Randomized Controlled Trials (RCTs): RCTs are essential to definitively establish the efficacy of CE treatment for improving fertility outcomes, particularly live birth rates. These trials must employ standardized diagnostic criteria for CE, clearly defined treatment protocols (including management of resistant cases), consistent methods for confirming cure, and appropriate control groups.²

• Standardized Outcome Reporting: Consistent reporting of key fertility outcomes (implantation rates, clinical pregnancy rates, live birth rates, miscarriage rates) is necessary for meaningful comparison and meta-analysis.

Without such high-quality evidence, the debate surrounding the clinical significance and optimal management of CE in infertile women is likely to persist.

7.5. Emerging Research Areas and Future Directions

Despite the challenges, research into CE and its impact on fertility is a dynamic field with several promising future directions:

• Endometrial Microbiome Research: Deeper investigation into the composition and function of the endometrial microbiome in health and disease states like CE is crucial. This includes:

  • Identifying specific microbial signatures associated with CE and poor reproductive outcomes.

  • Understanding the mechanisms by which dysbiosis contributes to endometrial inflammation and receptivity defects.

  • Developing and testing microbiome-targeted therapies (e.g., probiotics, prebiotics, fecal microbiota transplantation, phage therapy) as alternatives or adjuncts to antibiotics.²

• Non-invasive Diagnostic Tools: Research into less invasive or non-invasive methods for diagnosing CE is warranted. This could involve identifying biomarkers in endometrial fluid, cervical secretions, or even blood that correlate with endometrial inflammation. Deep learning models analyzing hysteroscopic images are also being explored.⁴

• Improved Definition of "Cure": Future research needs to explore more comprehensive markers of endometrial health beyond just plasma cell counts to define true resolution of CE and restoration of optimal receptivity. This might include assessment of local immune cell profiles, cytokine patterns, or functional markers of receptivity.

• Personalized Medicine Approaches: Given the heterogeneity in CE presentation, etiology, and response to treatment, a shift towards more personalized management strategies may be beneficial. This could involve tailoring diagnostic workups and treatment plans based on individual patient characteristics, specific microbial profiles, and biomarkers of inflammation.

• Understanding Long-Term Impacts: Longitudinal studies are needed to better understand the long-term implications of CE and its treatment on reproductive health, including risks of recurrence and outcomes in subsequent pregnancies.

• Focus on Specific Patient Populations: Continued research focusing on high-risk populations like those with RIF and RPL will help refine indications for CE screening and treatment.³⁷

The field of chronic endometritis is rapidly evolving, with a growing number of publications in recent years indicating increasing research interest.⁴⁴ Addressing the current controversies and unresolved questions through rigorous, standardized research will be key to improving the care and reproductive outcomes for women affected by this subtle yet impactful condition.

8. Conclusion

Chronic endometritis is a persistent inflammatory condition of the endometrium, characterized primarily by the presence of plasma cells in the stroma. While often asymptomatic or presenting with only mild, non-specific symptoms, CE has been strongly associated with various forms of female infertility, including recurrent implantation failure and recurrent pregnancy loss. Its prevalence is notably higher in infertile populations compared to the general population, underscoring its potential clinical significance.

The diagnosis of CE remains a challenge due to the lack of universally standardized criteria. Hysteroscopy can provide visual clues, but histological examination of an endometrial biopsy, ideally enhanced by CD138 immunohistochemistry for plasma cell identification, is considered the cornerstone of diagnosis. However, significant controversy persists regarding the exact number of plasma cells required for a definitive diagnosis, the optimal timing of biopsy, and the interpretation of findings, all of which contribute to variability in reported prevalence and study outcomes.

Antibiotic therapy, most commonly with doxycycline, is the mainstay of treatment and generally yields high initial cure rates. However, a subset of patients experience persistent or resistant CE, necessitating second-line treatments and raising concerns about antimicrobial resistance. The role and efficacy of alternative or adjunctive therapies are still under investigation. Furthermore, consensus is lacking on the routine use of a "test-of-cure" to confirm CE eradication.

The impact of untreated CE on fertility is considerable, with evidence linking it to altered endometrial receptivity through immune dysregulation, cytokine imbalances, hormonal alterations, and changes in uterine contractility. This often translates to lower implantation rates, clinical pregnancy rates, and live birth rates, alongside higher miscarriage rates.

The critical question of whether treating CE improves fertility outcomes is complex. Numerous studies and several meta-analyses suggest that successful eradication of CE can significantly improve live birth rates and clinical pregnancy rates, particularly in women with RIF and RPL. However, other high-level evidence, including meta-analyses, has found no significant benefit of antibiotic treatment on these key outcomes, or has highlighted that even "cured" CE may be associated with ongoing reproductive challenges. These discrepancies are largely attributable to the profound heterogeneity in diagnostic criteria, patient populations, treatment protocols, and study methodologies across the existing literature, as well as a paucity of large-scale, high-quality randomized controlled trials.

The emerging understanding of the endometrial microbiome offers a new perspective, suggesting that CE may represent a state of dysbiosis rather than a simple infection. This has implications for future diagnostic and therapeutic strategies, which may need to focus on restoring a healthy microbial balance in addition to, or instead of, solely relying on broad-spectrum antibiotics.

In conclusion, chronic endometritis is a clinically relevant condition in the context of female infertility, particularly for women with RIF and RPL. While evidence suggests that treatment can improve reproductive outcomes in many cases, significant controversies and unresolved questions remain regarding its diagnosis, optimal management, and the true extent of its impact. Future progress hinges on the standardization of diagnostic criteria and the execution of robust, large-scale RCTs to provide definitive answers and guide evidence-based clinical practice. A deeper understanding of the endometrial microbiome and its role in CE pathogenesis will likely pave the way for more targeted and effective interventions. Until then, a nuanced, individualized approach to screening and treatment, particularly in high-risk infertile populations, is warranted.

Works cited

1. Endometritis - StatPearls - NCBI Bookshelf, accessed May 20, 2025, https://www.ncbi.nlm.nih.gov/books/NBK553124/

2. Chronic Endometritis: Old Problem, Novel Insights and Future ..., accessed May 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC6875860/

3. Chronic Endometritis: Old Problem, Novel Insights and Future ..., accessed May 20, 2025, https://www.ijfs.ir/article_45556.html

4. Chronic Endometritis and Antimicrobial Resistance: Towards a ..., accessed May 20, 2025, https://www.mdpi.com/2076-2607/13/1/197

5. Chronic endometritis: symptoms and treatment - URE, accessed May 20, 2025, https://fertilityclinicspain.com/chronic-endometritis-symptoms-and-treatment/

6. Chronic endometritis in in vitro fertilization failure patients, accessed May 20, 2025, https://www.obstetricgynecoljournal.com/articles/cjog-aid1073.php

7. What is chronic endometritis? What is its effect in fertility?, accessed May 20, 2025, https://www.institutobernabeu.com/en/blog/what-is-chronic-endometritis-what-is-its-effect-in-fertility/

8. The effect of the number of endometrial CD138+ cells on the pregnancy outcomes of infertile patients in the proliferative phase - Frontiers, accessed May 20, 2025, https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1437781/full

9. Chronic endometritis and recurrent reproductive failure: a systematic review and meta-analysis - Frontiers, accessed May 20, 2025, https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1427454/full

10. Chronic endometritis and recurrent reproductive failure: a systematic review and meta-analysis - PMC - PubMed Central, accessed May 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11403846/

11. (PDF) Prevalence of Chronic Endometritis in Infertile Women ..., accessed May 20, 2025, https://www.researchgate.net/publication/387423354_Prevalence_of_Chronic_Endometritis_in_Infertile_Women_Candidates_for_In-vitro_Fertilization_and_Diagnostic_Value_of_Hysteroscopy_in_its_Diagnosis

12. Impact of antibiotic treatment for chronic endometritis on ... - Frontiers, accessed May 20, 2025, https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.980511/full

13. Chronic endometritis: screening, treatment, and pregnancy ..., accessed May 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10504221/

14. Chronic endometritis and assisted reproduction: a systematic review and meta-analysis, accessed May 20, 2025, https://www.scielo.br/j/ramb/a/b6XJWbYpg8wmdMw5fQGL3mD/?lang=en

15. Chronic endometritis. Could it be the reason why you are not getting pregnant?, accessed May 20, 2025, https://clinicafertia.com/en/could-it-be-the-reason-why-you-are-not-getting-pregnant/

16. Hysteroscopic findings in chronic endometritis - PubMed, accessed May 20, 2025, https://pubmed.ncbi.nlm.nih.gov/34905882/

17. Correlation between hysteroscopy findings and chronic endometritis - PubMed, accessed May 20, 2025, https://pubmed.ncbi.nlm.nih.gov/30683588/

18. Journal Club Global: Clinical Evaluation and Management of Chronic Endometritis and Its Impact on Fertility | American Society for Reproductive Medicine, accessed May 20, 2025, https://www.asrm.org/journals/fertility-and-sterility/journal-club-global/jcg-clinical-eval-manage-endometritis/

19. Histological diagnostic criterion for chronic endometritis based on the clinical outcome, accessed May 20, 2025, https://www.researchgate.net/publication/349805058_Histological_diagnostic_criterion_for_chronic_endometritis_based_on_the_clinical_outcome

20. P-428 Fertility outcomes following treatment of chronic endometritis: a systematic review and meta-analysis | Request PDF - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/publication/361697942_P-428_Fertility_outcomes_following_treatment_of_chronic_endometritis_a_systematic_review_and_meta-analysis

21. Patients with antibiotic-cured endometritis still show increased pregnancy loss | Remembryo, accessed May 20, 2025, https://www.remembryo.com/patients-with-antibiotic-cured-endometritis-still-show-increased-pregnancy-loss/

22. Endometrial Biopsy Testing Options - Spring Fertility, accessed May 20, 2025, https://springfertility.com/press-releases/endometrial-biopsy-testing-options/

23. Chronic Endometritis: a Hidden Cause of Infertility - West Coast Fertility, accessed May 20, 2025, https://www.westcoastfertility.com/fertility-blog/chronic-endometritis-a-hidden-cause-of-infertility

24. Therapeutic efficacy of gentle endometrial curettage on antibiotic‐resistant chronic endometritis in infertile women - PMC, accessed May 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10318421/

25. The Complementary and Alternative Medicine for Endometriosis: A Review of Utilization and Mechanism - PMC - PubMed Central, accessed May 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC3950373/

26. Navigating Fertility Treatment with Endometritis: Key Insights for Patients, accessed May 20, 2025, https://www.inovifertility.com/blog/navigating-fertility-treatment-with-endometritis/

27. Chronic Endometritis Guide - Fertility Centers of New England, accessed May 20, 2025, https://www.fertilitycenter.com/fertility_cares_blog/chronic-endometriosis/

28. Prevalence of chronic endometritis in repeated unexplained ..., accessed May 20, 2025, https://academic.oup.com/humrep/article/30/2/323/726170

29. Unraveling Chronic Endometritis: A Review, accessed May 20, 2025, https://www.ijifm.com/abstractArticleContentBrowse/IJIFM/28449/JPJ/fullText

30. Effect of Chronic Endometritis Treatment on Pregnancy Rate in Unexplained Infertility: A Review Article, accessed May 20, 2025, https://www.ajol.info/index.php/ejhm/article/view/294147/276827

31. Why test for Chronic Endometritis in women with Recurrent Pregnancy Loss - MiscarriageMD, accessed May 20, 2025, https://www.miscarriagemd.com/news/why-test-for-chronic-endometritis-in-recurrent-pregnancy-loss1222021

32. Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: a systematic review and meta-analysis - PubMed, accessed May 20, 2025, https://pubmed.ncbi.nlm.nih.gov/29908776/

33. Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise, accessed May 20, 2025, https://www.researchgate.net/publication/259916826_Chronic_endometritis_in_women_with_recurrent_early_pregnancy_loss_andor_fetal_demise

34. The effect of chronic endometritis and treatment on patients with unexplained infertility, accessed May 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10311816/

35. Systematic review and meta-analysis for impacts of oral antibiotic ..., accessed May 20, 2025, https://pubmed.ncbi.nlm.nih.gov/35058127/

36. (PDF) Chronic endometritis and fertility: still a debatable issue, accessed May 20, 2025, https://www.researchgate.net/publication/386365923_Chronic_endometritis_and_fertility_still_a_debatable_issue

37. Should we stop screening for chronic endometritis? - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/publication/362050538_Should_we_stop_screening_for_chronic_endometritis

38. Chronic endometritis and assisted reproduction: a systematic review and meta-analysis - SciELO, accessed May 20, 2025, https://www.scielo.br/j/ramb/a/b6XJWbYpg8wmdMw5fQGL3mD/?format=pdf&lang=en

39. Chronic endometritis and assisted reproduction: a systematic review and meta-analysis, accessed May 20, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10578315/

40. The Role of Chronic Endometritis in Infertility and Recurrent Miscarriage: A Comprehensive Review, accessed May 20, 2025, https://saremjrm.com/article-1-320-en.pdf

41. The Role of Endometrial Microbiota in Fertility and Reproductive Health: A Narrative Review, accessed May 20, 2025, https://pubmed.ncbi.nlm.nih.gov/40099081/

42. The role of microbiome in female fertility and reproductive health - Contemporary OB/GYN, accessed May 20, 2025, https://www.contemporaryobgyn.net/view/the-role-of-microbiome-in-female-fertility-and-reproductive-health

43. Chapter 4 - Clinical Management of Chronic Endometritis in Recurrent Pregnancy Loss, accessed May 20, 2025, https://www.cambridge.org/core/product/294488E06EF7E506FC78ADF04BF4C633/core-reader

44. A bibliometric analysis of the frontiers and hotspots in chronic endometritis, accessed May 20, 2025, https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1559543/full

45. A bibliometric analysis of the frontiers and hotspots in chronic endometritis, accessed May 20, 2025, https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1559543/pdf

46. Chronic endometritis and recurrent reproductive failure: a systematic review and meta-analysis - ResearchGate, accessed May 20, 2025, https://www.researchgate.net/publication/383531084_Chronic_endometritis_and_recurrent_reproductive_failure_a_systematic_review_and_meta-analysis

. . .

CARE Fertility and Women’s Health is a leading fertility clinic, offering personalized care and advanced reproductive technology to help individuals and couples achieve their dream of parenthood. With state-of-the-art genetic testing, individualized treatment plans, and holistic support, we specialize in complex fertility cases and boast some of the highest success rates in Canada. 

Stay Informed! 

Follow us on social media for fertility tips, patient stories, and the latest advancements in fertility care. Facebook | Instagram | LinkedIn | X | TikTok | YouTube