{"paper_id":"5cdf0b2d-b902-4942-989a-7cb9e373da2a","body_text":"Manuscript accepted for publication\n1 \nProvisionally accepted for publication \nCASE REPORT \nSpontaneous hemoperitoneum in pregnancy due to rupture of uterine vessels in woman \nwith endometriosis: a case report\nA\nntonio Maiorana, Giulia Zaccaria, Giovanni Parisi, Antonella Mercurio, Francesco Forlani *\nD\nepartment of Obstetrics and Gynecology, Arnas Civico Hospital, Palermo, Italy.\nDo\ni: 10.36129/jog.2023.124 \n*C\norresponding author: Francesco Forlani, Department of Obstetrics and Gynecology, Arnas\nCivico Hospital, Palermo 90100, Italy. Email: forlani81@gmail.com.\nORCID: 0000-0002-0583-8633. \nABS\nTRACT \nBackground. Spontaneous rupture of uterine vessels is a rare and life-threating event than can \nrarely occur during spontaneous and low-risk pregnancies. The definitive association between\nadverse obstetrical events and pelvic endometriosis is still under evaluation. We report a severe\ncase of spontaneous hemoperitoneum in pregnancy (SHiP) due to a rupture of the uterine vessels\nrelated to decidualized endometriosis.\nCase presentation. A 38-year-old primigravida woman at 33 weeks of pregnancy with an \nuncomplicated pregnancy and a history of endometriosis was admitted to the emergency room of\nour Institution, due to a spontaneous rupture of the right uterine vessels. An alive and vital baby\nwas delivered by hysterotomy. In order to achieve hemostasis,a total hysterectomy with bilateral\nsalpingectomy was performed. \nConclusions. In case of spontaneous rupture of uterine vessels and resulting hemoperitoneum,\nprompt diagnosis and treatment are the crucial points in order to minimize maternal and \nfetal/neonatal complications. Further studies are necessary in order to identify endometriosis as a \npossible cause of spontaneous rupture of uterine vessels in pregnancy.\nKey words\nSpontaneous rupture of uterine vessels; endometriosis; hemoperitoneum; case report\nI\nntroduction \nSpontaneous hemoperitoneum in pregnancy (SHiP) is a rare and dramatic complication correlated \nwith a high rate of maternal and fetal/neonatal mortality. Approximately only 100 cases have been \n\nManuscript accepted for publication\n 2 \nreported in the literature, and since 1950 the maternal mortality rate has been 49.3% [1] [2]. \nHowever, nowadays, thanks to medical advances, the mortality rate dropped to 3.6% [3] [4]. \nAlthough the etiology of SHiP remains unclear, hemodynamics and hormonal factors have been \ninvolved in the pathogenesis [1]. Endometriosis represents a benign chronic disease characterized \nby the presence of functional endometrial tissue out-side of the uterus. In this sense, the \nendometriotic lesions undergoing the process of decidualization generate a subsequent \ninflammatory microenvironment. For all these reasons, endometriosis has been suggested to be \ninvolved in the mechanisms of spontaneous rupture of uterine vessels during pregnancy [5]. \nBecause of the increased number of patients with severe endometriosis with the desire for fertility, \nphysicians would need to consider endometriosis-related SHiP among possible causes of \nhypotension and acute abdomen during the third trimester of pregnancy. Here, we describe a case \nof spontaneous hemoperitoneum in a healthy woman at 33 weeks of her first spontaneous \npregnancy. \n \nCase presentation \nA 38-year-old primigravida woman was admitted to the emergency room of our Institution for \nabdominal pain at week 33 of pregnancy. There was no history of vaginal bleeding, rupture of \nmembranes, abdominal trauma, previous abdominal surgeries, or drug assumptions. The patient \nhad a medical history of deep infiltrating endometriosis treated with progestin-only drugs with good \nresponse.  The pregnancy was spontaneous, and the antenatal course was uneventful until the \nadmission. On admission, the patient was hypotensive with a blood pressure of 80/50 mmHg, heart \nrate was 120 beats per minute, respiratory rate was 14 breaths per minute, and body temperature \nof 36.3°C. The physical examination detected a gravid abdomen, tender at the superior quadrants. \nNo dysuria, vomiting, or diarrhea was reported. The ultrasound assessment confirmed the \npresence of a singleton cephalic fetus with a normal biophysical profile, a regular placenta, and \nnormal amniotic fluid volume. Moderate maternal abdominal free liquid was detected. Cervical \nlength was 25 mm, and tocography revealed no uterine contractions. Her laboratory tests resulted \nin a hemoglobin level of 9.0 g/dL and 18.20 x 103/uL leukocytes. Metabolic hepatic panel and \nurinalysis were negative. Intramuscular steroid therapy was submitted in order to induce fetal lung \nmaturation.   \nAfter 6 hours, the value of haemoglobin level dropped to 7.9 g/dL, and the free abdomen liquid \ndetected at the ultrasound assessment was significantly increased. Moreover, the patient \npresented an exacerbation of abdominal pain, despite analgesic infusion.  \nTen hours after the arrival at the emergency room, considering the worsening of clinical features \nand the suspicious diagnosis of hemoperitoneum, the patient underwent urgent laparotomy. About \n1.5 L of free blood was aspirated from the abdominal cavity. The surgical exploration revealed a \nhematoma in the posterior and right uterine walls and active bleeding from the right uterine \nvessels. Moreover, there were several endometriotic foci in the pelvic peritoneum and severe \npelvic adhesions. There was no sign of uterine anomalies, such as arteriovenous malformation and \nuterine rupture. The surgery proceeded with a low-segment caesarean section and extraction of a \nmale fetus, alive and vital, weighed 1.400 kg, and with Apgar scores of 8 and 9 at the first and fifth \nminute, respectively. After uterine closure, persistent bleeding appeared from decidualized \nendometrial lesions on the posterior surface of the uterus and the right parametrium. Because of \nthe difficulty in achieving safe hemostasis without possible damage to the parametrial structures, \nwe decided to proceed with a total hysterectomy. After intraoperative patient’s oral consensus, a \ntotal hysterectomy with bilateral salpingectomy and ovarian preservation was performed. \nSuccessful hemostasis was finally achieved, and the abdominal wall was closed. Estimated blood \nloss during the hysterectomy was 700 mL, and no intraoperative transfusions were performed. No \nintraoperative and postoperative blood transfusions were performed. No complications were \n\nManuscript accepted for publication\n 3 \nreported, and the patient was discharged after 6 days. The infant had an uneventful course and \nwas discharged after few weeks in good condition. On histopathology examination, uterine, tubal, \nand right parametrial specimens have reported elements suggestive of endometriotic foci, such as \nhaemorrhagic infarction, fibrosis and prominent deciduoid changes.  \n \nDiscussion \nThe current study represents a clear case of spontaneous hemoperitoneum in pregnancy (SHiP) \nas direct consequence of spontaneous rupture of uterine vessels due to endometriotic lesions in an \notherwise uncomplicated pregnancy. \nEndometriosis has increased in recent decades and is frequently associated with infertility, pelvic \npain, and dysmenorrhea. Endometriosis is a very complex condition that could impact sexuality, \nquality of life and psychology of affected woman. Although these aspects could not be correlated to \nthe severity of disease, they have an important role on psychological wellbeing and interpersonal \nrelationships [6] [7]. Endometriosis can be correlated with pregnancy complications, such as \nsevere preeclampsia, placental abruption, placental abnormalities, premature rupture of \nmembranes, preterm birth, and retained placenta [8] [9]. \nSHiP is a rare and potentially life-threatening condition that occurs in pregnant women out-of-labor \nin 61% of cases, of which 39% happened between 33-37 weeks of gestation [10] [11]. According to \nthe International Network of Obstetric Survey Systems (INOSS), SHiP is defined as a non-\ntraumatic intraperitoneal hemorrhage during pregnancy up to 42 days postpartum, excluding \nectopic pregnancy, uterine rupture and cesarean section-associated bleeding [12]. \nIn literature, trends regarding parity, age, and length of gestation in patients with SHiP have not \nbeen documented [1]. \nIn a review of 25 cases of SHiP, endometriosis has been recognized as the major risk factor and \nthe spontaneous rupture of uterine vessels or direct bleeding of endometriotic lesions were the \nmost common findings .  \nMoreover, in a recent systematic review by Lier et al., the authors reported that the SHiP was \nassociated with rupturing utero-ovarian vessels in 57% of cases, endometriotic implants in 23% of \ncases, hemorrhagic nodules in 2% of cases, and a combination of these events in 20% of cases \n[13]. \nFurthermore, in almost half of the patients reported in the literature, the diagnosis of endometriosis \nwas misunderstood until the laparotomic visualization of endometriotic lesions and the histological \nconfirmation [10]. Conversely, in our case, the diagnosis of endometriosis was already known at \nthe time of clinical presentation, and the histopathologic examination of the samples confirmed the \npresence of decidualized ectopic endometrial tissue.  \nIt is well known that the phenomenon of decidualization during the first trimester of pregnancy \nconsists of the loss of pigmentation and fibrosis of endometriotic implants [10]. Recently, it has \nbeen supposed that the SHiP is linked to an involution of the decidualization process due to the \ndecrease of progesterone levels and a supposed progesterone resistance. This mechanism \ncauses the production of chemokine, proinflammatory cytokine, metalloproteinases, apoptotic \nfactors, cell death, and bleeding [10].  \nThe incidence of SHiP may be influenced by the use of assisted reproductive techniques (ART), as \nwomen with endometriosis could overcome subfertility/infertility problems [14]. The use of ART is \nlinked to a high dosage of progesterone, which can facilitate the process of decidualization. In a \nrecent review of 362 pregnancies reported from 2010 to 2018, Benaglia et al. documented that the \n\nManuscript accepted for publication\n 4 \nfrequency of SHiP in women with endometriosis submitted In vitro fertilization is 0.3% [15]. \nHowever, in our case, the patient had a spontaneous pregnancy. Besides endometriosis and ART \nas risk factors, a recent prospective population-based study reported some additional factors \nassociated with SHiP, such as multiple pregnancies, ≥35 years of age in mothers, and previous \nabdominal surgery [11]. \nAlthough the recent evidence, the etiopathogenesis of this condition remains unclear. Increased \nvenous pressure in utero-ovarian circulation due to pregnancy status or muscular activity such as \ndefecation and coughing could be possibly implicated in the pathophysiology of SHiP [16].  \nIn the literature, three factors have been described as explanations for spontaneous rupture of \nuterine vessels: vessels leakage caused by endometriosis-linked chronic inflammation; adhesions \nbetween vessels with relative tensions; decidualization of endometrial foci [5] [17] [18]. Our patient \nhad either a diagnosis of deep infiltrating endometriosis or pelvic adhesions. Indeed, during the \nsurgery, adhesiolysis was performed. Moreover, in a few cases, the origin of the bleeding remains \nunknown, even during laparotomy. During the surgery of our patient, arteries and superficial veins \nof the posterior surface of the uterus and right parametria have been involved in the bleeding. The \nsurgical visualization of the endometriotic implants’ bleeding and the medical history of our patient \nsuggest that the phenomenon of decidualization of endometriotic foci lead to massive and sudden \nhemoperitoneum in our patient.    \nIn all cases of spontaneous hemoperitoneum in pregnancy, the onset symptoms were acute or \nsubacute abdominal pain, free abdominal fluid, hypovolemic shock, and decreasing values of \nhemoglobin [10]. A prompt differential diagnosis is a crucial requirement. Placental abruption, \nuterine rupture, placenta percreta, appendix, hepatic, and splenic ruptures are the most common \npreoperative misdiagnosis. Vascular sources of hemoperitoneum in pregnancy should be \nconsidered as a result of the rupture of a visceral abdominal artery aneurysm such as splenic \nartery [1].  \nOur patient’s symptoms were similar to clinical presentation described in the literature. Lier et al. \nreported the most common signs of presentation of SHiP: subacute abdominal pain (94.9%), a \ndecreased level of hemoglobin (62.7%), imaging showing free peritoneal fluid (62.7%) [13]. The \nsensibility of contrast enhanced computed tomography in the identification of bleeding is \ndocumented, but maternal and fetal potential risks from ionizing radiation have to be considered. \nUltrasonography could be helpful for the detection and monitoring of abdominal free fluid, but the \nreal diagnosis is often obtained only by laparotomic exploration. In a preterm pregnancy, the \ndecision making should be balanced between risks related to prematurity, delayed diagnosis, and \nmaternal complications. In our case, the worsening symptoms and the hemoglobin drop level \nguided our decision on laparotomy.  \nSeveral questions remain unknown about the management of endometriosis in pregnancy: \nwhether any medical or surgical treatment of endometriosis in the preconception period would add \nany benefit and prevent pregnancy complications such as SHiP; whether adopting any particular \nmanagement in pregnancies with a previous diagnosis of endometriosis (in terms of follow-up and \nmode of delivery); whether to choose any specific flowchart in case of a pregnant woman with \nacute abdomen and free blood abdominal liquid. Yet, endometriotic lesions should be considered a \npossible cause of hemoperitoneum during the third trimester of pregnancy [5]. Rapid diagnosis and \nprompt intervention are essential to correctly manage such complicated cases.   \n \nConclusions \nIn conclusion, our case represents a rare case of SHiP related to endometriosis confirmed by \nhistologic examination. Moreover, a prompt diagnosis of SHiP was crucial in managing this unique \n\nManuscript accepted for publication\n 5 \nclinical scenario without either maternal or fetal complications. Exploring the association between \nthe diffusion of endometriosis and the severity of SHiP could be a new challenge.   \nIn consideration of the risk of spontaneous rupture of uterine vessels and SHiP, physicians should \nbe aware that prompt diagnosis and interventions are crucial to minimize maternal and \nfetal/neonatal morbidity and mortality. More attention to SHiP, with a particular focus on \nendometriosis as a cause, would help prevent maternal and fetal adverse events. \n \nAbbreviations  \nSHiP: Spontaneous Hemoperitoneum in Pregnancy; ART: assisted reproductive techniques.  \n \nCOMPLIANCE WITH ETHICAL STANDARDS \nAuthors contribution \nA.M., F.F.: Conceptualization; G.Z: Writing – original draft; A.M, F.F.: Writing – review & editing. \nA.M., G.Z., G.P ., A.M. F.F.: Data curation, Validation.  \nFunding  \nNone.  \nStudy registration \nNot applicable.  \nDisclosure of Interests  \nThe authors declare that they have no conflict of interests. \nEthical Approval \nNot applicable.  \nInformed consent  \nWritten informed consent was obtained from the patient for publication of this case report and \naccompanying images.  \nData sharing \nThe data that support the findings of this study are available from the corresponding author upon \nreasonable request. \nREFERENCES \n1. Hardin N, Delozier A, Alireza Torabi A, Laks S. Spontaneous Rupture of the Uterine Artery \nin an Otherwise Normal Pregnancy. J Radiol Case Rep. 2017; 11(7):7–13. doi: \n10.3941/jrcr.v11i1.2946. \n2. Hodgkinson CP, Christensen RC. Hemorrhage from ruptured utero-ovarian veins during \npregnancy; report of 3 cases and review of the literature. Am J Obstet Gynecol. 1950; 59(5):112–7. \ndoi: 10.1016/s0002-9378(16)39178-5.  \n3. Jang JH, Kyeong KS, Lee S, Hong SH, Ji I, Jeong EH. 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Four Case Reports of Endometriosis-Related Hemoperitoneum in \nPregnancy. Chin Med J (Engl). 2018; 131(4):502-504. doi: 10.4103/0366-6999.225048.  \n15. Benaglia L, Reschini M, La Vecchia I, Candotti G, Somigliana E, Vercellini P. Endometriosis \nand spontaneous hemoperitoneum in pregnancy: evaluation of the magnitude of the risk in women \nbecoming pregnant via in vitro fertilization. Fertil Steril. 2021; 115(4):1023-1028. doi: \n10.1016/j.fertnstert.2020.10.030.  \n16. Katorza E, Soriano D, Stockheim D, Mashiach R, Zolti M, Seidman DS, Schiff E, \nGoldenberg M. Severe intraabdominal bleeding caused by endometriotic lesions during the third \ntrimester of pregnancy. Am J Obstet Gynecol. 2007; 197(5):501.e1-4. doi: \n10.1016/j.ajog.2007.04.030. \n\nManuscript accepted for publication\n 7 \n17. Inoue T, Moriwaki T, Niki I. Endometriosis and spontaneous rupture of utero-ovarian vessels \nduring pregnancy. Lancet. 1992; 340(8813):240-1. doi: 10.1016/0140-6736(92)90506-x. \n18. Passos F, Calhaz-Jorge C, Graça LM. Endometriosis is a possible risk factor for \nspontaneous hemoperitoneum in the third trimester of pregnancy. Fertil Steril. 2008; 89(1):251-2. \ndoi: 10.1016/j.fertnstert.2007.02.009. \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n\nManuscript accepted for publication\n 8 \nFig. 1: The right parametrium and the posterior surface of the uterus are covered by blood clots as \nsite of active bleeding.    \n \n \nManuscript accepted for publication","source_license":"CC0","license_restricted":false}