Abstract
Objective
Pulmonary complications related to ovarian hyperstimulation syndrome (OHSS) can occur following assisted reproductive technologies (ART). However, bloody pleural effusions are exceedingly rare. We present a case of a patient who underwent ART treatment and developed OHSS, subsequently experiencing bilateral massive bloody pleural effusion.
Case Report
A 32-year-old woman with primary infertility underwent in vitro fertilization (IVF) treatment. After oocyte retrieval, she presented to the emergency department with a chief complaint of abdominal distention and chest pain. Ovarian hyperstimulation syndrome, complicated by bilateral massive bloody pleural effusion (exudative), was diagnosed. Her d-dimer was initially elevated, then decreased gradually, and her shortness of breath improved. The patient was discharged without any clinical sequelae.
Conclusion
OHSS can lead to life-threatening complications such as pleural effusion and, in rare cases, bloody pleural effusion. Following oocyte retrieval, an elevated d-dimer level has no specific diagnostic role and should only be used to rule out thromboembolic events.
Introduction
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication due to the administration of exogenous gonadotrophin. It can be a severe complication of assisted reproductive technologies (ART) and could be potentially lethal [ ]. OHSS is marked by increased capillary permeability that causes fluid shift from the intravascular space to the extravascular compartments [ ]. Symptoms range from mild abdominal pain, bloating, and nausea to severe disease characterized by hemoconcentration, anuria, anasarca, ascites, hydrothorax, hemodynamic instability, or acute respiratory distress syndrome (ARDS) [ , ].
The pulmonary complications of OHSS include dyspnea, pulmonary edema, ARDS, pulmonary thromboembolism, and pleural effusion, which may cause atelectasis with subsequent ventilation-perfusion mismatch and hypoxemia [ ]. Isolated pleural effusion is a relatively rare presentation of OHSS, with exudate being more common, and is predominantly observed on the right side [ ]. Hemorrhagic pleural effusions are remarkably uncommon. To the best of our knowledge, only three cases have been reported: isolated unilateral bloody pleural effusion, thoracic endometriosis unmasked by OHSS, and spontaneous bloody pleural effusion with a history of COVID-19 [ ]. For further discussion and a better understanding of the clinical course, we presented this case of bilateral bloody pleural effusion following oocyte retrieval.
Case presentation
A 32-year-old female with underlying arrhythmia disease had primary infertility for two years due to anovulation and uterine factors. Her menstrual cycle was irregular, with 35–37 days intervals. Her operation history was unremarkable, and she had a serum anti-Mullerian hormone (AMH) of 3.8 ng/ml. She has received oral ovulation induction drugs for several courses but remained unable to conceive. After shared-decision making, she decided to directly receive in vitro fertilization (IVF) instead of intrauterine insemination.
She received her first IVF treatment with gonadotropin-releasing hormone antagonist protocol. The antrum follicle count was 11 (right 6#, and left 5#). She underwent controlled ovarian stimulation (COH) since menstrual cycle day 3 on a dose of 225 IU r-FSH plus r-LH in a 2:1 ratio (follitropin alfa and lutropin alfa; Pergoveris®, Merck Serono S.p.A, Bari, Italy). Low-dose aspirin (100 mg/day) was added during the COH and stopped on the day of trigger. On the 12th day of ovarian stimulation (14th from the last menstrual period, trigger day), she had 15# right follicles and 10# left follicles over 10 mm. Four follicles were more than 18 mm. Estradiol (E2) was 10,000 pg/ml, and luteinizing hormone (LH) was 1.44 mIU/ml on the trigger day. Ovarian retrieval was performed 36 h after dual triggering [ ] with the administration of one dose of GnRH agonist with 2 mg leuprolide acetate (Lupro, 2 mg/0.4 ml, Nang Kuang, Taiwan, equivalent to 0.2 mg triptorelin) and half a dose (125 μg) of human chorionic gonadotropin (hCG) (Ovidrel®, 250 μg, Merk Serono, Modugno, Italy). A total of 16# mature oocytes were retrieved. She was prescribed seven daily oral doses of dopamine agonist and three daily subcutaneous doses of GnRH antagonists (to enhance luteolysis and suppress ovarian enlargement) for the prevention of ovarian hyperstimulation syndrome [ ], and the freezing-all policy was implemented due to a high risk of OHSS.
One day after egg retrieval, she presented with abdominal distension and pain at an outpatient clinic. Ultrasound confirmed multiple ovarian corpus luteums and little ascites. The patient was highly suspected of OHSS and advised on expectant management and detailed education. Post retrieval day 4, she presented to the emergency department (ED) with chest tightness, pain, dysphagia, decreased urine amount, and mild dyspnea. On physical examination, her heart rate was 84 beats/min, blood pressure was 108/72 mmHg, and O 2 saturation was 98 % breathing room air. There were reduced breath sounds and stony dullness at the bilateral lower chest. The abdomen had distension but no tenderness. The blood parameters indicated elevated d-dimer (3.94 mg/L) without hemoconcentration, and the rest of the biochemistry data were within the normal range. Chest X-ray ( Fig. 1 ) showed bilateral pleural effusion with right side dominance. Hence, a pigtail catheter was inserted at the right side under ultrasound guidance. More than 500 ml of hemorrhagic fluid was drained ( Fig. 2 ). Right-sided pleural fluid analysis showed an exudative effusion with a protein 3.3 g/dL, lactate dehydrogenase 137 U/L, glucose 94 mg/dL, pH 7.0, leukocyte count 1052/μL, and red blood cell count 14000/μL ( Table 1 ). The cytology of pleural fluid was negative for malignancy. The fluid gram stain, culture, TB-PCR, and acid-fast stain were negative. Chest computed tomography angiography (CTA) was negative for pulmonary embolism.
| Pleural fluid studies | Right pleural fluid | Left pleural fluid |
|---|---|---|
| Appearance | Cloudy | Cloudy |
| Color | Orange | Orange |
| SP. Gravity | 1.037 | 1.023 |
| Protein, g/dL | 3.3 | 3.2 |
| LDH, U/L | 137 | 92 |
| Glucose, mg/dL | 94 | 101 |
| pH | 7.0 | 7.9 |
| RBC, /uL | 14,000 | 17,000 |
| Neutrophil, % | 44 | 12 |
| Lymphocyte, % | 16 | 9 |
| Monocyte, % | 28 | 28 |
| Mesothelial cell, % | 12 | 51 |
| Pleural/Serum LDH ratio | 0.86 | 0.49 |
| Pleural/Serum protein ratio | 0.54 | 0.52 |
Post retrieval day 5, after admission, laboratory analysis reported leukocytosis (13100/uL) with segment predominant (78.5 %), elevated CRP (22.37 mg/L), hyponatremia (133 mEq/L), hypoalbuminemia (3.3 g/dL), and elevated d-dimer (4.84 mg/L). Hematocrit (37.7 %), hemoglobin (12.1 g/dL), platelet count, renal, hepatic, and coagulation profiles were within normal range. The urine pregnancy test was negative. Transabdominal ultrasonography revealed multicystic lesions over bilateral adnexa and enlarged ovaries up to 8 × 6 cm and 9.1 × 5.0 cm on the right and left, respectively (length × width), with fluid accumulation over Cul-de-sac and Morrison pouch. A diagnosis of severe ovarian hyperstimulation (abdominal distension, enlarged ovaries, ultrasound evidence of ascites, hyponatremia, and pleural effusion) [ ] was made.
The patient was closely monitored according to her symptoms, urinary output, body weight, abdominal circumference, and drainage from the pigtail (summarized in Fig. 4 ). Continuous intravenous fluid (0.9 % NaCl saline and human albumin solution) administration was implemented to correct her hyponatremia and hypoalbuminemia. We initially did not administer a prophylactic dose of low molecular weight heparin due to right bloody pleural effusion and normal hematocrit. Besides, owing to the complaint of persistent dysphagia, we arranged an esophagogastroduodenoscopy, which showed a hiatal hernia, multiple patched gastric ulcers, and drug-induced esophageal ulcer compatible with her history.
