Endometrial cavity fluid: Clinical significance, pathophysiology and implications for fertility and assisted reproductive technology: A narrative review

Endometrial cavity fluid (ECF) is a frequently encountered ultrasonogra phic finding in gynecological and fertility practice. While small, transient amounts of fluid may be physiological, persistent or excessive accumulation is often associated with underlying pathology and adverse reproductive outcomes. The presence of ECF has generated particular interest in infertility a nd assisted reproductive technology (ART), where its impact on implantation and pregnancy ou tcomes remains controversial. This narrative review explores the etiology, pathophysiology, diagnostic assessment, and clinical implications of endometrial cavity fluid, with emphasis on its assoc iation with endometriosis, tubal disease, uterine infection, and IVF/ICSI outcomes. Emerging evidence on endometrial fluid as a potential non-invasive biomarker source is also discussed.

Endometrial cavity fluid, infertility, endometriosis, hysteroscopy, in vitro fertilization

The endometrium is the specialized mucosal lining of the uterus, a hollow muscular organ that supports embryo implantation and fetal development [1] . Cyclical changes in endometrial structure and secretory activity are essential for reproductive success. The presence of fluid within the endometrial cavity, however, may disrupt this finely regulated environment. Endometrial cavity fluid is increasingly detected with the widespread use o f high-resolution transvaginal ultrasonography [11] . Although minimal fluid can be a normal physiological finding, particularly around ovulation, persistent or excessive ECF has been associated with infertility, pelvic pathology, and poor outcomes following assisted repro duction. Understanding the clinical relevance of ECF is therefore essential for gynecologist s and fertility specialists. Definition and Ultrasonographic Assessment of Endometrial Cavity Fluid Endometrial cavity fluid is defined sonographically as an echoluscent or hypoechoic area distending the uterine cavity, typically visualized in the sagittal plane. It is often described as a central fluid collection separating the anterior and posterior endometrial linings. The degree of fluid accumulation is commonly quantified using the a nteroposterior diameter (APD), measured as the maximal distance between the opposing endometrial surfaces. In the presence of fluid, true endometrial thickness is calculated by subtracting the maximal fluid diameter from the total endometrial measurement between the myometrial-end ometrial interfaces. These parameters allow standardized assessment and comparison across studies. Etiology of Endometrial Cavity Fluid The etiology of ECF remains multifactorial and, in some cases, controversial. Recognized associations include: Tubal Pathology Hydrosalpinx is one of the most established causes of ECF [1, 2] . Retrograde flow of inflammatory tubal fluid into the uterine cavity can lead to persistent fluid accumulation, which is toxic to embryos and adversely affects implantation. International Journal of Gynaecology Sciences 2026; 8(1): 01-03 ~ 2 ~ International Journal of Gynaecology Sciences https://www.gynaecologyjournal.net Uterine and Endometrial Factors Subclinical endometritis, uterine adhesions, retained products, and intrauterine foreign bodies may contribute to fluid accumulation through chronic inflammation and altered endometrial permeability. Endometriosis Endometriosis is an estrogen-dependent chronic gynecological disease characterized by the presence of endometrial-like tissue outside the uterine cavity [3, 4] . Affecting approximately 10-32% of women of reproductive age, it is strongly associated with infertility and pelvic pain. Although laparoscopy remains the gold standard for diagnosis, there is increasing interest in non-invasive diagnostic approaches. Chronic inflammation, altered cytokine profiles, and abnormal endometrial secretory function in women with endometriosis may contribute to abnormal fluid dynamics within the uterine cavity. Endometrial cavity fluid has therefore been investigated as a potential biological medium for biomarker discovery in this population. Ovulatory and Hormonal Factors Polycystic ovarian syndrome (PCOS), anovulation, and estrogen-progesterone imbalance may also predispose to ECF through altered endometrial maturation and glandular secretion. Physiological Versus Pathological Fluid Small volumes of endometrial fluid may be observed during the periovulatory period or immediately following menstruation and are generally considered physiological. In contrast, persistent fluid, fluid associated with pain, bleeding, or infection, or fluid detected during embryo transfer cycles is more likely to be pathological and clinically significant. Fluid containing blood may suggest cyst rupture, endometrial trauma, or ectopic pathology, while purulent fluid raises suspicion of infection requiring antibiotic therapy. Endometrial Cavity Fluid and Endometriosis: Diagnostic Implications Endometriosis remains a diagnostic challenge due to its heterogeneous presentation and reliance on surgical confirmation. Non-invasive tests, including serum biomarkers such as CA-125 and imaging modalities, lack sufficient sensitivity and specificity, particularly in early disease. Proteomic and molecular studies have demonstrated that endometrial fluid contains cytokines, growth factors, and proteins reflective of the intrauterine environment.^8-10 Endometrial fluid aspirate can be obtained using an embryo transfer catheter during routine gynecological examination without anesthesia. This minimally invasive approach has shown promise as a source of biomarkers for endometriosis, although further validation is required before clinical application. Impact of Endometrial Cavity Fluid on IVF and ICSI Outcomes The effect of ECF on ART outcomes remains controversial. Several studies have reported reduced implantation and pregnancy rates in the presence of persistent ECF, particularly when fluid is present at the time of embryo transfer [1, 2] . Proposed mechanisms include mechanical flushing of embryos, embryotoxic effects of inflammatory mediators, and impaired endometrial receptivity. Conversely, some studies suggest that transient fluid that resolves before embryo transfer may not adversely affect outcomes. As a result, management strategies vary widely among fertility centers. Management Strategies Common approaches to ECF in ART include postponement of embryo transfer with a freeze-all strategy, treatment of underlying infection, surgical management of hydrosalpinx, and hysteroscopic evaluation of the uterine cavity. Aspiration of endometrial fluid immediately prior to embryo transfer using an embryo transfer catheter has been described as a simple and potentially effective intervention [11] . However, this approach may be associated with psychological distress due to cycle cancellation or repeated procedures, underscoring the need for individualized patient counseling. IVF Protocol Considerations Various ovarian stimulation protocols, including long GnRH agonist, GnRH antagonist, and microdose flare-up protocols, are used in patients with ECF based on individual characteristics. Monitoring with serial transvaginal ultrasound is essential. Triggering is typically achieved with GnRH agonist or human chorionic gonadotropin, followed by oocyte retrieval 36 hours later. Many centers adopt a freeze- all approach in the presence of significant ECF. Future Directions Further research is needed to clarify the threshold at which ECF becomes clinically significant, to standardize diagnostic criteria, and to validate endometrial fluid biomarkers for non- invasive diagnosis of endometriosis and other uterine pathologies.

Endometrial cavity fluid represents a complex clinical finding with implications for fertility, gynecological health, and assisted reproduction. While small, transient fluid collections may be physiological, persistent or pathological ECF warrants thorough evaluation. Advances in imaging, hysteroscopy, and molecular analysis of endometrial fluid hold promise for improved diagnosis and management of infertility-related conditions.

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