A 41-Year-Old Woman with Spontaneous Hemoperitoneum in Pregnancy at 28 Weeks

The patient was a 41-year-old woman (gravida 1, para 0) who had been diagnosed with diffuse adenomyosis on the posterior wall, which thickened to 5 cm in diameter, and her uterus was above the navel ( Figure 1 ). She desired to conceive, with an understanding of the risk of a pregnancy complicated by adenomyosis. Eventually, the patient conceived via artificial insemination. She was admitted at 12 weeks of gestation because of persistent severe lower abdominal pain. Her body temperature on admission was 37.4°C, white blood cell count (WBC) was 15 900/μL, and C-reactive protein (CRP) level was 8.99 mg/dL. There were no uterine contractions, and the cervical length was not shortened. Considering the possibility of intrauterine infection, antibiotics were administered; however, the levels of inflammatory markers (WBC and CRP) did not appear to improve ( Figure 2 ). Magnetic resonance imaging (MRI) at 13 weeks of gestation showed hemorrhagic changes in the posterior wall adenomyosis; however, there were no findings suggestive of an abscess ( Figure 3 ). Antibiotics were discontinued at 14 weeks of gestation because it was presumed that the lower abdominal pain and elevated inflammatory markers were caused by local inflammation of the adenomyosis rather than by an infection. Hydroxyprogesterone caproate was administered because of its anti-inflammatory properties. The abdominal pain and fever gradually resolved, and inflammatory markers gradually decreased. Ultrasonography showed that there was no remarkable change in the adenomyosis lesion in the second trimester. The estimated fetal weight corresponded to gestational age. At 28 weeks and 0 days of gestation, the patient suddenly had severe and persistent abdominal pain, which she had not previously experienced. Her blood pressure was 158/85 mm Hg, heart rate 61 beat per min, and oxygen saturation 99%. Immediate transabdominal ultrasonography revealed no findings suggestive of placental abruption or uterine rupture. A prolonged fetal heart rate deceleration was noted 17 min after the onset of abdominal pain. With the diagnosis of fetal distress, an emergency cesarean delivery was performed under general anesthesia. A 907-g female infant with an Apgar score of 2 at 1 min and 3 at 5 min and an umbilical artery blood pH of 7.15 was delivered and admitted to the Neonatal Intensive Care Unit. Blood pooled in the abdominal cavity, extending from the vesicouterine pouch to the upper abdomen ( Figure 4 ). Veins around endometrial lesions on the serosal surface of the uterine posterior wall were considered to be the cause of the intraperitoneal hemorrhage. Considering the possibility of bleeding from the tissue surrounding the uterus, no tissue samples were collected for histopathological analysis. Hemostasis was achieved through coagulation and compression. The total blood loss was 2020 g. After the cesarean delivery, the patient’s blood pressure was 140/86 mm Hg and heart rate was 55 beats per min. The hemoglobin level decreased to 7.7 g/dL, but no blood transfusion was required. Contrast-enhanced MRI performed on postoperative day 8 showed extensive hemorrhagic infarction in the posterior wall of the adenomyosis ( Figure 5 ). The postoperative course was uneventful, and the patient was discharged from the hospital 15 days after surgery. Her menstruation resumed 1 month after the delivery. She was treated with gonadotropin-releasing hormone antagonist, followed by the insertion of a levonorgestrel-releasing intrauterine system to prevent recurrence of severe dysmenorrhea and menorrhagia. The infant underwent ductus arteriosus closure at 33 days of age for patent ductus arteriosus. Additionally, the baby had a tracheostomy at 103 days of age for subglottic stenosis. The baby was discharged at 132 days of age.

Spontaneous hemoperitoneum in pregnancy (SHiP) is defined as nontraumatic, acute intra-abdominal bleeding during pregnancy or the postpartum period, and it is a potentially life-threatening pregnancy complication for mother and child [ 1 ]. The perinatal mortality rate of SHiP is as high as 26.9% [ 1 ], and the complication requires prompt diagnosis and treatment [ 2 ]. Endometriosis has been reported to be involved in the development of SHiP [ 2 , 3 ]. We report the case of a 41-year-old woman with adenomyosis who developed hemoperitoneum due to endometriosis at 28 weeks of pregnancy.

SHiP is a relatively rare condition and is associated with serious adverse pregnancy outcomes [ 1 ]. The overall prevalence of SHiP in pregnancies complicated by endometriosis is estimated to be 0.4%, and endometriosis is considered a major risk factor for SHiP [ 3 – 6 ]. In addition, maternal age over 35 years has been reported as a risk factor for SHiP [ 2 ]. In the present case, a 41-year-old woman with adenomyosis developed SHiP due to peritoneal endometriosis at 28 weeks. The detailed mechanism by which endometriosis causes bleeding during pregnancy remains unknown; however, decidualization of ectopic endometrial stroma, vascular walls, and peritoneal endometriosis sites can be involved in the pathogenesis [ 7 ]. It has been hypothesized that endometrial stromal cells invade blood vessels, narrowing the vessel lumen, and increase back pressure [ 8 ] or that the shedding of the endometrium causes adjacent vessels to rupture [ 5 ]. The most common site of bleeding is the uterine wall, as was observed in our case, followed by the round ligament and adnexa [ 9 ]. Patients with a history of abdominopelvic surgery have been reported to be at a higher risk of SHiP, suggesting that intra-abdominal inflammation or adhesions may be involved [ 2 ]. In the present case, there were severe endometriotic adhesions in the pelvic cavity, which may have contributed to the development of SHiP. Acute abdominal pain, flank pain, and fetal heart rate deceleration may be present at the onset of SHiP and can lead to anemia and hypovolemic shock [ 3 ]. However, these symptoms can be seen in placental abruption or uterine rupture; therefore, it is difficult to suspect SHiP based on these symptoms alone [ 9 ]. It is common to diagnose SHiP based on intraoperative findings [ 1 , 9 ]. Ultrasonography has been reported to be useful in the diagnosis of SHiP [ 1 , 3 ]. However, if there is only a small amount of bloody ascites and the uterus is enlarged, the diagnosis of SHiP on ultrasonography can be difficult. In this present case, blood that pooled in the vesicouterine pouch could not be detected by transabdominal ultrasonography. Puncturing the pouch of Douglas to check non-coagulable blood can be useful for the diagnosis of SHiP [ 3 ]. Computed tomography or MRI should be considered for patients with stable hemodynamics, as it allows for prompt diagnosis of SHiP and identification of the bleeding site [ 6 ]. A limitation of our study is the lack of histopathological examination, because specimens were not sampled during surgery. Perinatal and maternal mortality rates for SHiP have been reported to be 26.9% and 1.7%, respectively [ 1 ]. In a review of 54 cases of SHiP associated with endometriosis, 6% of cases required emergency hysterectomy, with a mean estimated blood loss of approximately 1957 mL [ 7 ]. In the present case, the decision of cesarean delivery was decided 17 min after the onset of abdominal pain. Fetal cardiotocogram or blood test could not be performed because of the emergency situation. Timely management with surgical intervention is necessary, taking into consideration the hemodynamic status of the patient and the gestational age of the fetus [ 3 ]. Poor prognosis (fetal death, neonatal death, miscarriage, and umbilical artery blood ≤ pH 7.1) was more common in cases with less than 32 weeks of gestation, cases with a preoperative diagnosis of placental abruption, and out-of-hospital cases [ 9 ]. SHiP can occur at any time between 6 weeks of gestation and the postpartum period [ 3 , 10 ], but it is most common during the third trimester of pregnancy [ 10 ]. This can be due to decreased progesterone levels in the third trimester, which increase the expression of inflammatory cells that promote peritoneal hemorrhage [ 6 ]. If SHiP occurs in the second trimester, hemostasis alone and continued pregnancy can be options [ 11 ]. It has been noted that pregnancies achieved via assisted reproductive technology and complicated with endometriosis can have a higher incidence and severity of SHiP than spontaneous pregnancies complicated with endometriosis [ 4 , 12 ]. According to a recent study, 0.3% of 362 pregnant women with endometriosis who conceived through assisted reproductive technology developed SHiP. It is hypothesized that the high hormonal levels associated with assisted reproductive technology pregnancies exacerbate ectopic decidualization [ 2 ]. Pregnant women with endometriosis, particularly those with deep peritoneal endometriotic lesions, who conceived using assisted reproductive technology may require careful management for the development of SHiP [ 12 ]. However, little evidence exists on indications for surgery to prevent the onset of SHiP, and accumulating cases are required to identify the risk factors for SHiP. Uterine adenomyosis is a condition in which endometrial or endometrial-like cells invade the myometrium, causing uterine enlargement. The true prevalence of adenomyosis is unknown; however, the estimated prevalence has been reported to be 8.8% to 61.5% [ 13 ]. The frequency of pregnancies complicated by adenomyosis is increasing owing to the increase in patient age of marriage and childbearing [ 14 ]. However, there are few reports on the effect of adenomyosis on perinatal outcomes. Junctional zone thickening in adenomyosis is believed to cause placental hypoplasia, leading to late miscarriage, pre-term delivery, fetal growth restriction, and preeclampsia [ 15 ]. Furthermore, prostaglandins, which are increased in patients with adenomyosis, promote uterine contractions and cervical canal dilatation and are considered a cause of preterm delivery [ 16 ]. Women with adenomyosis should be informed of pregnancy risk before conception; in addition, their treatment should be carefully managed during pregnancy. Degeneration of adenomyosis is extremely rare. Symptoms of adenomyosis degeneration include fever, abdominal pain, and elevated levels of inflammatory markers [ 17 ]. As these symptoms can be observed in intrauterine infections, it is difficult to distinguish between the 2 conditions based on symptoms alone. MRI can show specific findings of adenomyosis degeneration, which can help differentiate it from an infection [ 18 ]. In our case, MRI at 13 weeks of gestation revealed a hemorrhagic focus inside the adenomyosis. Within the adenomyosis, there were findings suggestive of hemorrhagic degeneration; T1- and T2-weighted images showed hyperintensity and heterogeneous hyperintensity with a hypointense rim, respectively [ 18 ]. Progesterone leads to decidualization and subsequent atrophic changes in the endometrium. Owing to their anti-inflammatory properties, progesterone agents are considered effective against endometriosis- and adenomyosis-associated pain [ 19 ]. In the present case, hydroxyprogesterone caproate was administered to reduce focal inflammation in adenomyosis. It is unclear whether hydroxyprogesterone caproate has an anti-inflammatory effect on focal inflammation during pregnancy with adenomyosis; therefore, further research is required to determine this.

Pregnancies complicated by endometriosis or adenomyosis should be managed perinatally, considering the possibility of SHiP. If acute abdominal pain or fetal heart rate deceleration occurs during pregnancy, intraperitoneal bleeding should be investigated. If SHiP is suspected, open hemostasis or cesarean delivery should be considered.