Abstract
Background
Hemorrhagic ascites is a rare clinical manifestation of endometriosis, often misdiagnosed due to its resemblance to malignancy. This study aims to highlight diagnostic and management challenges by presenting three cases.
Case presentation
Three nulliparous women presented with abdominal distension, pelvic pain, and large-volume bloody ascites. One had concurrent right-sided hemorrhagic pleural effusions. Imaging studies showed deep infiltrating endometriosis (DIE) without ovarian endometriomas in two patients. Laparoscopic surgery confirmed extensive endometriosis with 2–4 L of bloody ascitic fluid. Histopathological examination excluded malignancy and confirmed endometriosis. Postoperative medical therapy included hormonal suppression.
Conclusion
Bloody ascites is an uncommon but important presentation of severe endometriosis. These cases highlight the importance of considering endometriosis in the differential diagnosis of bloody ascites, particularly in reproductive-aged women. Surgical diagnosis and histopathologic confirmation are essential to rule out malignancy. A multidisciplinary approach and individualized fertility planning are crucial in managing these complex cases.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12905-025-03864-3.
Keywords: Endometriosis, Neoplasms, Ascitic fluid
Introduction
Endometriosis is a non-cancerous, estrogen-dependent condition marked by the presence of endometrial tissue located outside the uterine cavity. This tissue can be implanted within intrapelvic and extra pelvic including the ovaries, peritoneum, lungs, and even diaphragm [1]. Clinical manifestations differ based on the location of endometrial lesions implantation. Common symptoms encompass chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility [2]. Endometriosis is a prevalent condition that impacts approximately 10% of women in their reproductive years [3]. A rare form of endometriosis characterized by significant hemorrhagic ascites presents with signs and symptoms similar to those of ovarian cancer [4]. The initial description of endometriosis-associated ascites is ascribed to Breus in 1954 for the first time [5]. To date, the literature has recorded fewer than 100 instances of hemorrhagic ascites that are associated with endometriosis [6]. Considering the high stress of the patients and the confusion of the clinicians in the definitive diagnosis and the lack of a specific treatment approach in the case of bloody ascites, in this article we decided to describe three cases of patients referred to our endometriosis referral center, to clarify the patient demographics and symptoms of the disease, intending to improve gynecologists’ clinical recognition of hemorrhagic ascites related to endometriosis.
Case presentation 1
A 42-year-old virgin woman was referred to us following a diagnosis of endometriosis made during pathology examination.
The patient had been referred to a gynecology oncologist colleague with a complaint of abdominal distentionPelvic ultrasound revealed a right ovarian mass with solid components and a significant volume of ascites. The bloody nature of the fluid was confirmed through abdominal paracentesis and subsequent cytological analysis. An ultrasound revealed a right ovarian mass with solid components and significant amount of bloody ascites. Her tumor marker, CA125, was elevated at 127 U/ml. An MRI indicated severe ascites, adenomyosis, and a 45 × 27 mm cystic structure in the right ovary, raising the suspicion of a malignant process (Fig. 1).
Fig. 1.
Pelvic MRI: blue star: severe ascites fluid, blue arrow: cystic structure in right ovary
The patient underwent laparotomy by an oncology team, where surgical findings included, 4 L of bloody ascites across with severe adhesion of the cecum and appendix to the right adnexa and abdominal wall, complete obliteration of both the anterior and posterior cul-de-sac. Additionally, an omental mass and a cecal mass adhered to the abdominal wall were noted, while the left adnexa appeared normal. Surgery was performed with the collaboration of a colorectal surgeon, resulting in a right salpingo-oophorectomy, appendectomy, partial omentectomy, right hemicolectomy, and end-to-end ileocolic anastomosis. The frozen section analysis confirmed endometriosis without malignancy, and the permanent pathology also revealed endometriosis.
Following surgery, the patient was referred for follow-up and management of her endometriosis. She reported menarche at age 13 and had experienced severe dysmenorrhea (VAS: 10/10) since then. Despite using contraceptive pills, her dysmenorrhea persisted. Her past medical history was unremarkable, and a physical examination yielded normal results.
Six months post-operation, follow-up sonography revealed a left endometrioma measuring 27 × 19 mm and an 18 × 12 mm rectal nodule consistent with deep infiltrating endometriosis (DIE). CA125 and AMH levels were noted at 24 U/ml and 0.4 ng/ml, respectively. The patient opted against fertility preservation and began a medical treatment regimen consisting of letrozole (2.5 mg daily) and dienogest (2 mg daily). Follow-ups were scheduled every six months.
After 1.5 years of treatment, the patient reported no ascites. However, after two years, her FSH level had risen to 53.3 mIU/ml. Consequently, she was scheduled for surgery, which included a left salpingo-oophorectomy, segmental resection of rectal endometriosis, and a total laparoscopic hysterectomy due to abnormal uterine bleeding and adenomyosis. An omental flap was placed at the vaginal cuff. Final Histopathological analysis once again confirmed endometriosis.
Six months following the operation, the patient expressed satisfaction with her quality of life, and no complications, such as fistula formation, were observed.
Case presentation 2
A 27-year-old nulligravida woman was referred to our clinic due to abdominal distension and bloody ascites. She experienced menarche at age 13 and had been suffering from severe dysmenorrhea (VAS: 10/10) since then, for which she used NSAIDs with little relief. After marriage, she developed dyspareunia, rated at 10/10 in severity, and chose not to take any medication. Her past medical history was unremarkable.
Six months prior to her referral, the patient noticed significant abdominal enlargement. Physical examination revealed generalized abdominal distension without tenderness. Imaging studies, including ultrasound and MRI, indicated massive ascites but did not reveal any other abnormalities. An abdominal paracentesis was performed, yielding exudative fluid with a cytology report that ruled out malignancy. The ascitic fluid analysis revealed RBCs at 50,000 and WBCs at 100. Tumor marker levels for CA125, HE4, and AMH were 18.5 U/ml, 35.5 pmol/L, and 3.4 ng/ml, respectively. Liver and renal function tests were within normal ranges., and an interferon-gamma release assay (IGRA) for tuberculosis was negative.
Given the reassuring AMH level, the patient’s anxiety regarding a potential malignancy, and her preference for surgical management without fertility preservation at that time, she was scheduled for diagnostic laparoscopy.
Due to the absence of a definitive diagnosis, the patient was scheduled for diagnostic laparoscopy. During the procedure, 3 L of bloody ascites were observed, along with adhesions between the rectosigmoid and the uterus, inflamed and thick peritoneum, and the ovaries adhered to the ovarian fossa without evidence of endometrioma. A partial omentectomy was performed, and the specimen was sent for frozen section analysis, which ruled out malignancy. Surgical intervention included the release of adhesions, resection of a thickened left uterosacral ligament, rectal shaving, and left salpingectomy. Pathological examination confirmed the presence of endometriosis. (Video clip 1)
The patient was subsequently treated with a medical regimen consisting of two doses of GnRH agonist (Zoladex, 10.8 mg) and daily administration of letrozole (2.5 mg, Letrax Aburaihan Pharmaceutical Company, Iran) and dienogest (2 mg, Verogest, Atipharmed, Iran).
Six months post-surgery, a follow-up sonography revealed just 150 cc of clear fluid in the anterior cul-de-sac and some adhesions in the posterior cul-de-sac. The patient continues her medication and reports satisfaction with her quality of life. She expresses a desire to conceive within the next few years.
Case presentation 3
A 31-year-old nulligravida woman was referred to our clinic with the concern of bloody ascites. Seven months prior, she underwent two thoracocentesis procedures for dyspnea caused by hemothorax. Due to unresponsiveness to catheterization and a significant hemothorax, she underwent exploratory right thoracoscopy (VAST), which involved the evacuation of 2 L of frank blood, thoracoscopic pneumolysis, lateral right thoracotomy, complete parietal pleurectomy and decortication, closure of a major bronchial fistula, and chemical pleurodesis with talc. Pathological examination at that time did not reveal any signs of endometriosis.
The patient reported experiencing severe dysmenorrhea (VAS: 10/10) and dyspareunia (VAS: 7/10). Recent sonography demonstrated a substantial amount of ascites. Cytology of the ascitic fluid was bloody but negative for malignancy, revealing a RBC count of 350,000 and WBC count of 500. Physical examination showed generalized abdominal distension without tenderness, and palpation during the vaginal examination revealed nodules.
With a BMI of 18 kg/m² and an unremarkable past medical history, transvaginal sonography identified four rectal endometriosis nodules, involvement of the uterosacral ligaments, retro-cervical tissue, and vaginal nodules, but both ovaries were unaffected (Fig. 2). Laboratory results indicated CA125 at 45.9 U/ml, HE4 at 35 pmol/L, and AMH at 1.7 ng/ml, with normal liver and renal function tests and IGRA test for tuberculosis was negative.
Fig. 2.
Trans -vaginal sonography: red arrow: Rectal nodule, blue star: severe ascites, green star: ovaries
The patient declined options for fertility preservation.
A laparoscopy was performed, revealing 3.5 L of bloody ascites and a frozen pelvis. Surgical intervention included total resection of deep infiltrating endometriosis (DIE) from the round ligament, uterosacral ligaments, retrocervical space, left paraureter, left ovarian fossa, and vagina, as well as segmental resection of rectosigmoid endometriosis (Video clip 2). The patient opted against a two-stage surgical approach, leading to the resection of vaginal nodules; however, the placement of an omental flap was not possible due to the omentum’s reduced size.
Postoperatively, the patient was treated with a medical regimen including letrozole (2.5 mg daily, Letrax Aburaihan Pharmaceutical Company, Iran), dienogest (2 mg daily, Verogest, Atipharmed, Iran), and one dose of GnRH agonist (Zoladex, 10.8 mg).
Two weeks after surgery, the patient reported fecal discharge from the vagina. A CT scan confirmed the presence of a rectovaginal fistula, necessitating an ileostomy. After two months, defecography indicated no fistula, leading to successful ileostomy repair. The patient is currently continuing her medication regimen and reports satisfaction with her quality of life.
Discussion
Hemorrhagic ascites is characterized by the presence of red blood cells (RBC) at a threshold of 10,000 per mm³ or greater. In cases where the ascitic fluid appears dark in color, RBC concentrations can reach approximately 50,000 per mm³ [7]. This condition can arise from various causes, including benign or malignant tumors, hemorrhagic pancreatitis, perforated gastrointestinal ulcers, and cirrhosis. Notably, there have been few case reports of hemorrhagic ascites occurring in patients with heart failure [8, 9].
In gynecology, ascites are commonly observed in women diagnosed with ovarian malignancies. However, various benign gynecological disorders can also lead to ascites, including:
Ovarian hyperstimulation syndrome.
Meigs syndrome.
Tuberculosis.
Benign ovarian tumors.
Fibroids.
Endometriosis.
This diversity complicates the process of reaching a definitive diagnosis [10–12]. In fact, fewer than 100 reports of hemorrhagic ascites associated with endometriosis exist in the literature [6].
Clinical presentation and diagnosis
The clinical presentation of hemorrhagic ascites linked to endometriosis can often be mistaken for that of ovarian cancer due to similarities in symptoms. Patients may experience abdominal enlargement, pain, decreased appetite, and weight loss, which can mimic atypical manifestations of cancer.
A meticulous assessment of the patient’s medical history and symptoms associated with endometriosis—such as dysmenorrhea, dyspareunia, and cyclical pain—is crucial for accurate diagnosis. To exclude tuberculosis, IGRA testing was performed in Cases 2 and 3, both yielding negative results. It was not performed in Case 1 due to a prior confirmed diagnosis. Additionally, clinicians must maintain a high degree of suspicion for potential malignancies that may arise from endometriosis, with a reported prevalence of malignancy in these patients ranging from 0.7–1.6% [13, 14]. In rare cases, endometriosis can undergo malignant transformation, leading to cancers such as endometrioid or clear cell carcinoma. These malignancies may present with ascites, which can be hemorrhagic [15].
Diagnostic imaging and challenges
MRI and ultrasound findings can aid in suspecting malignancy [16]. In our study, we documented three cases of hemorrhagic ascites associated with endometriosis. However, in two instances, MRI did not assist in the accurate diagnosis of endometriosis. In the first case, the initial diagnosis was completely incorrect, underscoring the necessity of consulting a qualified expert in endometriosis imaging.
The application of transvaginal ultrasound (TVS) serves as an effective and precise method for the non-invasive diagnosis of endometriosis. Despite its limitations, such as dependence on the operator’s skill, this imaging modality is cost-effective and allows clinicians to diagnose instances of ovarian and deep-seated disease. Many physicians continue to depend on surgical and histopathological confirmation as the standard of reference. This method is increasingly questionable and may not reflect current best practices [17].
TVS should only be performed by appropriately trained physicians, as the accuracy of this technique relies on the operator s knowledge and skill [18].
Misdiagnosis can lead to significant surgical interventions, such as hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy, and may compromise the chance of future fertility while leaving remnants of endometriosis in the pelvis. In Case 1, for example, the initial surgery failed to remove all DIE lesions. In Cases 2 and 3, the absence of ovarian cysts made malignancy less likely, and ultrasound findings of DIE and adhesions raised suspicion for endometriosis.
Given these complexities, the imperative to exclude malignancy is paramount. Therefore, it is advisable to confirm the diagnosis of endometriosis only after conducting surgical evaluation and histological examination of the excised specimens.
Pathophysiology of hemorrhagic ascites in endometriosis
The precise pathophysiological mechanisms underlying the development of endometriosis-related ascites remain poorly understood. Bernstein et al. were pioneers in investigating the pathogenesis of ascites associated with endometriosis. They proposed that endometrial cells present in the peritoneal cavity could stimulate peritoneal cells to produce ascitic fluid, although the specific mechanisms behind this stimulation are still unidentified.
An alternative hypothesis suggests that irritation of the peritoneum caused by the spontaneous rupture of endometriotic cysts may lead to the production of reactive peritoneal fluid [19]. However, in two cases from our report, the patients did not have endometriomas, indicating that this hypothesis may not apply universally and that additional mechanisms should be explored.
Another potential contributing factor involves the inflammatory response triggered by the influence of uterine hormones on ectopic endometriotic lesions [20]. Estrogen and progesterone can modulate inflammatory pathways, which may facilitate the development of ascites by promoting increased vascular permeability and fluid accumulation in the peritoneal cavity.
Recent research has provided valuable insights into the biochemical changes associated with endometriosis. For instance, a study by Polak et al. demonstrated that women with endometriosis exhibited significantly elevated levels of hemoglobin in their peritoneal fluid compared to both healthy controls and women with ovarian cysts. This finding suggests that hemorrhagic ascites may arise from increased vascular fragility or bleeding from ectopic endometrial tissue. Furthermore, antioxidant parameters showed significant diminishment in the peritoneal fluid of these patients, creating an oxidative environment that may exacerbate inflammation and contribute to ascitic fluid formation [21–23].
Interestingly, the most significant prevalence of hemorrhagic ascites associated with endometriosis has been documented in nulliparous women of African heritage [24]. All three patients in our study were nulliparous, further supporting this observation. Notably, two of these patients had rectal nodules and were classified as stage IV endometriosis according to the American Society for Reproductive Medicine (ASRM) classification. This suggests that bloody ascites are often observed in advanced cases of endometriosis, possibly due to extensive peritoneal involvement and increased vascularity.
Hemorrhagic pleural effusions are another phenomenon often observed in conjunction with hemorrhagic ascites in patients with endometriosis, primarily due to anatomical abnormalities in the diaphragm leading to the communication between the thoracic and abdominal cavities [6]. A systematic review indicated that the most frequent symptoms associated with these effusions included dyspnea (67%), predominantly unilateral (89%), often right sided (88.5%), and massive (56%). In our study, one patient presented with a severe right-sided bloody pleural effusion. This finding underscores the importance of considering endometriosis as a potential etiology in young women who present with right-sided hemorrhagic pleural effusions [25].
Fertility preservation
There are various methods available for fertility preservation in women suffering from endometriosis. These methods mainly consist of oocyte, embryo, and tissue cryopreservation. Alongside offering fertility preservation, it is essential for reproductive surgeons to employ fertility-conserving surgical techniques to reduce the likelihood of damaging ovarian reserve and enhance fertility results. It is crucial to recognize that not every woman with endometriosis will require fertility preservation methods, as each patient’s circumstances vary; therefore, care should be personalized. Fertility preservation techniques can be an important alternative for women with endometriosis who wish to maintain the possibility of future fertility. Gynecologists and reproductive surgeons should be well-informed about these options and engage in discussions with their patients affected by endometriosis who are contemplating future fertility [26]. It should be noted that patients with bloody ascites may develop ascites during ovulation induction. Thus, ovarian cryopreservation may present another choice [19].
In our study, none of the patients accepted fertility preservation. Due to the small number of endometriosis patients with bloody ascites, the data about fertility preservation is not available, and it is a challenging option in these patients.
Management of hemorrhagic ascites in endometriosis
The management of ascites associated with endometriosis primarily depends on the severity of the underlying condition. Treatment options typically include a combination of surgical intervention and medical therapy. In our study, we initially performed surgery to rule out malignancy and establish a definitive diagnosis. This approach is crucial, as misdiagnosis could lead to inappropriate and potentially harmful treatments, including invasive surgeries that jeopardize fertility.
After definitive diagnosis, medical therapy was pursued. All three patients experienced improvements in their quality of life and are currently under ongoing follow-up care. Regular monitoring is essential to assess the response to treatment and to manage any potential recurrence of symptoms or development of new complications.
In conclusion, while the pathophysiology of hemorrhagic ascites in endometriosis is complex and multifaceted, understanding these mechanisms can guide clinicians in making accurate diagnoses and tailoring effective treatment strategies. The holistic approach combining surgery and medical management appears beneficial in improving patient outcomes and quality of life in individuals affected by this challenging condition.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgements
The authors would like to thank the two patients for permission to share her medical history for educational purposes and publication.
Abbreviations
- DIE
Deep infiltrating endometriosis
- IGRA
Interferon gamma release assay
- IGRA
Interferon gamma release assay
- TVS
Transvaginal ultrasound
- ASRM
Merican society for reproductive medicine
Author contributions
E A, N Az, ZP, S A, T P: Design of study & final approach, E A, N Az, Z P: Patient recruitment & manuscript preparation; E A, N Az, ZP, S A, T P Patient recruitment, Patient recruitment;. All authors read and approved the final manuscript.
Funding
No financial support/funding was received for this study.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Consent for publication
Written informed consent was obtained from the all patients for publication of clinical details and images. A copy of the written consent is available for review by the editor of the journal.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Supplementary Materials
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.