Ruptured Ectopic Pregnancy Misdiagnosed with Ruptured Corpus Luteum: A Case Report and Literature Review.

A 22-year-old female experienced her last menstrual period 3 weeks before admission. She had severe lower abdominal pain several days before admission, and despite treatment with tranexamic acid, the vaginal bleeding persisted for 3 weeks. She also experienced dizziness and dyspnea on exertion. After visiting a local clinic, she was diagnosed with a luteal cyst rupture and given analgesics and transamine. However, due to persistent lower abdominal pain and vaginal bleeding, she sought a second opinion at our hospital. The patient had no significant medical history, was sexually active, and nulliparous. Her menstruation was regular with a 28-day cycle and 7-day duration. She had no drug or food allergies and had not traveled overseas in the past 3 months. Her father had a history of hypertension. The patient appeared ill-looking on examination, but her vital signs were relatively stable, with a blood pressure of 109 / 68 mmHg and a pulse rate of 100 bpm. She was able to walk into the clinic. Her height, weight, and body mass index were 167 cm, 56.1 kg, and 20.1 kg/m 2 , respectively. She had no fever. A pervaginal examination revealed minor vaginal staining and an abdominal examination showed tenderness in the lower abdomen with normoactive bowel sounds but no rebound pain. A urine pregnancy test was positive, and her blood β-hCG level was 5553 mIU/mL. Her hemoglobin (Hb) level was 6.3 g/dL. A pelvic ultrasound on admission revealed an anteverted uterus with a pelvic hematoma measuring 5.2 cm ×4.8 cm. She was diagnosed with a stable ruptured ectopic pregnancy with a pelvic hematoma. She received a blood transfusion with two units of packed red blood cells on admission days 1 and 2. By day 4, her Hb was 8.2 g/dL, and her hematocrit was 23.9%. After consulting with the patient and her family, she was given an intramuscular MTX injection (56 mg) under stable conditions. Her β-hCG levels decreased to 4428 mIU/mL by day 5 and 3879 mIU/mL by day 6. A follow-up transabdominal ultrasound showed an enlarged hematoma (10 cm ×9 cm). She was discharged on day 7 with stable vital signs and continued outpatient follow-up. Serial ultrasounds during follow-up showed the hematoma reduced in size to 9.4 cm after 18 days and 8.5 cm after 2 months [ Figure 1 ]. Her serial β-hCG levels were 3217, 1199, 838, and 723 mIU/mL on days 4, 11, 21, and 28 postdischarge, respectively. Due to a plateau in β-hCG levels on day 28, she received another MTX injection (50 mg). Subsequently, her β-hCG levels decreased to 189 and 33 mIU/mL after 7 and 14 days, respectively. Two months postdischarge, her β-hCG was 4.7 mIU/mL, and her Hb was 12.4 g/dL. Changes in β-hCG and Hb levels are illustrated in Figure 2 . Pelvic ultrasound of the pelvic hematoma. (a) Admission day 1 (5.2 cm, transvaginal, sagittal view), and (b) admission day 6 (10.4 cm, transabdominal, sagittal view). The hematoma became larger after admission. (c) 18 days after the 1 st day of admission (9.7 cm, transabdominal, sagittal view) and (d) at 2 months after the 1 st day of admission (8.5 cm, transabdominal, sagittal view). The hematoma became regressed compared to admission day Change in beta-human chorionic gonadotropin and hemoglobin during treatment. MTX: methotrexate

Ectopic pregnancy can be mistakenly reported as a ruptured corpus luteum due to similar symptoms such as abdominal pain and hemoperitoneum.[ 1 2 ] This misdiagnosis is particularly common in early pregnancy when ultrasound may not clearly show an intrauterine pregnancy.[ 3 ] Ovarian pregnancy, occurring on the corpus luteum, can also be misdiagnosed as a ruptured corpus luteum due to its presentation as a hemorrhagic ovary.[ 4 ] In rare cases, luteoma of pregnancy, a benign ovarian neoplasm, has been mistaken for ruptured ectopic pregnancy, leading to unnecessary surgery.[ 5 ] The difficulty in differentiation is compounded by positive pregnancy tests and ultrasound findings that may be inconclusive, especially in early pregnancy.[ 6 ] In some cases, laparoscopy or laparotomy is performed due to suspected ectopic pregnancy, only to reveal a ruptured corpus luteum.[ 1 ] Conversely, ectopic pregnancies, particularly cornual types, can be misdiagnosed as intrauterine pregnancies until rupture occurs.[ 6 ] These cases highlight the need for careful clinical assessment, skilled ultrasonography, and consideration of various differential diagnoses to avoid unnecessary surgeries and preserve fertility.[ 7 ] Awareness of these conditions is crucial for accurate diagnosis and appropriate management. We reported a case of a ruptured ectopic pregnancy previously misdiagnosed with ruptured corpus luteum with relatively stable vital signs and was successfully treated with methotrexate (MTX). She provided written consent and agreed to the publication of this case report.

Ectopic pregnancy and ruptured corpus luteum can present similar clinical and imaging features, leading to potential misdiagnosis. Ruptured corpus luteum cysts are a common cause of acute pelvic pain in women of reproductive age.[ 8 ] Symptoms include abdominal pain, rebound tenderness, and potential hemodynamic compromise.[ 9 ] While most cases resolve spontaneously with conservative management, surgical intervention may be necessary for larger cysts, significant free fluid, or hemodynamic instability.[ 10 ] Computed tomography can help differentiate between ruptured ovarian corpus luteal cyst and ruptured ectopic pregnancy based on cystic shadow size and pelvic effusion depth.[ 11 ] Ultrasound classification of ovarian pregnancy into ruptured and unruptured types can aid in the diagnosis, with unruptured cases showing characteristic solid hyperechoic rings or masses.[ 12 ] However, ruptured ovarian pregnancies often lack specific ultrasound features and may be mistaken for ruptured ectopic pregnancy or corpus luteum.[ 12 ] In early pregnancy, differentiating between ruptured ectopic pregnancy and ovarian hemorrhage can be challenging, as demonstrated in a case of ruptured corpus luteum initially considered possible ectopic pregnancy.[ 13 ] Furthermore, rare conditions such as tubal choriocarcinoma can mimic ectopic pregnancy, emphasizing the importance of follow-up and histopathological examination for accurate diagnosis.[ 14 ] Recent research has explored management strategies for pregnancies of unknown location (PUL) and ectopic pregnancies. A randomized clinical trial found that active management of persistent PUL resulted in higher resolution rates and fewer unscheduled interventions compared to expectant management, though patients preferred the latter.[ 15 ] Another study highlighted the importance of accurate nonviability diagnosis, as current hCG rise thresholds may be misinterpreted.[ 16 ] To avoid potential harm to normal early pregnancies, a “wait-and-see” approach with serial hCG testing and repeated ultrasounds is recommended in unclear cases, rather than immediate surgical intervention.[ 16 ] For postmolar pregnancy surveillance, a cost-effectiveness analysis suggested that prolonged hCG monitoring after normalization is not cost-effective, particularly for partial moles.[ 17 ] However, a case report demonstrated successful expectant management of tubal ectopic pregnancy with close monitoring of hCG levels and ultrasound findings.[ 18 ] To avoid potential harm to normal early pregnancies, a “wait-and-see” approach with serial hCG testing and repeated ultrasounds is recommended in unclear cases, rather than immediate surgical intervention.[ 3 ] These studies emphasize the need for careful consideration of management strategies in early pregnancy complications, balancing clinical outcomes, patient preferences, and cost-effectiveness. Ectopic pregnancy is a life-threatening condition that can be treated medically with MTX in hemodynamically stable patients.[ 19 ] The success of MTX treatment is influenced by initial β-hCG levels, with higher success rates observed when β-hCG is below 4000 IU/L.[ 20 ] However, MTX can still be effective for higher β-hCG levels, including cases exceeding 10,000 IU/L.[ 20 ] The change in β-hCG levels between initial treatment and day 4 or 7 is a crucial predictor of treatment success, with a <5% change associated with higher rupture risk. Combining MTX with mifepristone has shown promise in treating interstitial pregnancies, even with high β-hCG levels. These findings suggest that MTX therapy can be a safe and effective option for treating various types of ectopic pregnancy, including those with relatively high β-hCG levels. In conclusion, we described a case with ruptured ectopic pregnancy misdiagnosis with a ruptured corpus luteum cyst and successfully treated by MTX. Ectopic pregnancy and ruptured corpus luteum may present similar clinical and imaging features, leading to potential misdiagnosis. To avoid potential harm to normal early pregnancies, a “wait-and-see” approach with serial hCG testing and repeated ultrasounds is recommended in unclear cases, rather than immediate surgical intervention. This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and its amendments. The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Conceptualization, D-C.D.; methodology, D-C.D.; formal analysis, WYS.S.; data curation, WYS.S. and M-K. H. Writing —original draft preparation: WYS.S. D-C.D.: Writing —review and editing: D–C.D. All the authors have read and agreed to the published version of the manuscript. All data generated or analyzed during this study are included in this published article. Prof. Dah-Ching Ding, an editorial board member at Gynecology and Minimally Invasive Therapy , had no role in the peer review process of or decision to publish this article. All authors declared no conflicts of interest in writing this paper.