Endometriosis-associated Maternal Pregnancy Complications - Case Report and Literature Review

! Endometriosis is a chronic disease that affects 4 – 30 % of all women of child-bearing age. The preva- lence is even higher among women with infertili- ty (up to 50 %) [1]. Dysmenorrhea is the main clin- ical symptom of the disease, which is character- ised by the presence of endometrial cells outside of the uterus. Endometriosis commonly occurs superficially in the peritoneal membrane howev- er it can also infiltrate deeply into e.g. the bladder, rectum and other bowel segments. Serious ma- ternal pregnancy complications mostly occur in association with this deeply infiltrating form of the disease. After data adjustment for age and gestational age women with endometriosis have tubal pregnan- cies almost three times more often (odds ratio 2.7 [95 % confidence interval 1.09 –6.72]), and al- most twice as many miscarriages (1.76 [1.44 – 2.15]) compared to women without endometrio- sis [2]. The same study, with a study population of 5375 patients, found increased risk of placenta praevia (OR 2.24), antenatal haemorrhage of un- certain cause (OR 1.67) and postpartum haemor- rhage (OR 1.26) [2]. Endometriosis does not always regress during pregnancy. Endometrial decidualisation in partic- ular is responsible for many of the complications occurring during pregnancy. Increased progester- one production is causative [3]. The risk of endo- metriosis complications is particularly high in the second half of pregnancy and during labour. Risks described in the literature include sponta- neous intraabdominal haemorrhage, uterine rup- ture, bowel perforation, endometriosis cyst perfo- ration and ovarian torsion in the presence of ovar- ian endometrioma.

! The incidence of endometriosis is increasing. Par- ticularly during pregnancy and labour, clinicians should be alert to possible endometriosis-associ- ated complications or complications of previous endometriosis treatment, despite a low relative risk. In addition to an increased rate of early mis- carriage, complications such as spontaneous bow- el perforation, rupture of ovarian cysts, uterine rupture and intraabdominal bleeding from decid- ualised endometriosis lesions or previous surgery are described in the literature. Unfavourable neo- natal outcomes have also been discussed. We re- port on an irreducible ovarian torsion in the 16th week of pregnancy following extensive endome- triosis surgery, and an intraabdominal haemor- rhage due to endometriosis of the bowel in the 29th week of pregnancy. Zusammenfassung ! Durch die zunehmende Inzidenz der Endometri- ose muss, trotz des geringen relativen Risikos, ge- rade während Schwangerschaft und Entbindung bei diesen Patientinnen an eine Komplikation durch Endometriose oder vorherige Therapie ge- dacht werden. Neben einer erhöhten Abortrate in der Frühschwangerschaft werden in der Literatur Komplikationen wie spontane Darm- und Ovari- alzystenruptur, Uterusruptur sowie intraabdomi- nale Blutungen durch dezidualisierte Endome- trioseherde oder vorangegangene Operationen beschrieben. In der Literatur wird sogar ein un- günstigeres neonatales Outcome diskutiert. Wir berichten über eine nicht mehr detorquierbare Stieldrehung in der 16. SSW nach ausgedehnter Endometrioseoperation und eine intraabdomina- le Blutung bei Darmendometriose in der 29. SSW. Endometriosis-associated Maternal Pregnancy Complications – Case Report and Literature Review Maternale Endometriose-assoziierte Schwangerschaftskomplikationen – Fallbericht und Literaturübersicht Authors J. Petresin, J. Wolf, S. Emir, A. Müller, A. S. Boosz Affiliation Frauenklinik, Städtisches Klinikum, Karlsruhe Key words l" endometriosis l" pregnancy l" complication l" delivery l" decidualization l" intraabdominal bleeding Schlüsselwörter l" Endometriose l" Schwangerschaft l" Komplikation l" Hämoperitoneum received 21. 10. 2015 revised 12. 1. 2016 accepted 17. 1. 2016

DOI http://dx.doi.org/ 10.1055/s-0042-101026 Geburtsh Frauenheilk 2016; 76: 902–905 © Georg Thieme Verlag KG Stuttgart · New York · ISSN 0016‑5751 Correspondence Dr. med. Alexander Stephan Boosz Städtisches Klinikum Frauenklinik Moltkestraße 90 76133 Karlsruhe alexander.boosz@ klinikum-karlsruhe.de 902 Petresin J et al. Endometriosis-associated Maternal Pregnancy … Geburtsh Frauenheilk 2016; 76: 902 –905 Deutsche Version unter: http://dx.doi.org/ 10.1055/s-0042-101026 GebFra Science Case 1 ! A 33-year-old patient (gravida III, para I) had previously had ex- tensive endometriosis surgery in 2009. Amongst other proce- dures she had had an extensive peritonectomy for peritoneal en- dometriosis. She subsequently underwent unsuccessful fertility treatment. She ultimately fell pregnant naturally in 2011 and the child was born in 2012 by caesarean section without compli- cation. Her subsequent pregnancy, the one in question, was also natural. The patient presented to us from an external hospital at 15 + 4 weeks gestation with severe left-sided lower abdominal pain that had been present for 3 days. Ultrasound showed an adnexal mass measuring approx. 60 × 40 mm. Symptoms improved with con- servative management, and an expectant approach with analge- sia was agreed on with the patient. After 2 days the patient ʼs symptoms had not yet resolved and she was transferred to our hospital. On ultrasound the adnexal mass was found to have grown to a diameter of approx. 80 mm, the structure appearing mostly haemorrhagic. Under suspicion of a progressively enlarg- ing, haemorrhagic ovarian cyst with persistent symptoms the de- cision was made to perform a laparoscopy. Intraoperatively the uterus was appropriately enlarged for the pregnancy and the right adnex was normal. The left adnex was obviously enlarged, with black discolouration, and was adherent to the pelvic wall and sigmoid colon. After adhesiolysis and mobi- lisation of the sigmoid a necrotic adnexal torsion was found (l " Fig. 1 a and b). Detorsion was unsuccessful. The left broad liga- ment had evidently been broken through, and the left adnex was twisted 3 times on its long axis both in the region of the ovarian suspensory ligament and the ovarian ligament ( l " Fig. 1 a). Be- cause of the adnexal enlargement it was not possible to perform detorsion through the defect in the broad ligament. A left adnex- ectomy was thus performed ( l " Fig. 2). The patient was dis- charged home on the 4th postoperative day after an uneventful postoperative course. Fetal ultrasound before discharge was nor- mal, the patient delivered via repeat caesarean section in the 39th week of gestation. Case 2 ! This 25-year-old patient was admitted at 27 + 1 weeks gestation with vaginal bleeding and preterm labour. On history she was noted to have had a laparoscopic endometriosis operation in 2011 and a previous appendicectomy. At laparoscopy in an exter- nal centre endometriosis was noted between the rectum and posterior uterine wall but left in situ since consent to treat it op- eratively was lacking. Initially placental abruption was suspected, however this was not confirmed and RDS prophylaxis with celestan as well as tocolysis with fenoterol bolus was carried out. Ultrasound, laboratory pa- rameters and repeated CTGs showed no abnormalities. The pa- tientʼs symptoms improved under tocolysis and on the third day of admission had completely resolved, including the bleeding. CTG and cervical findings were persistently normal and she was discharged. At 28 + 2 weeks gestation she presented again, this time as an emergency, again with unusually heavy vaginal bleeding. The cervical length was 27 mm without funneling. She was admitted and tocolysis commenced with a partusisten bolus. On ultra- sound there was again no evidence of placental abruption. The following day the patient was noted to have extremely severe ab- dominal pain that made micturition impossible. There was still no ultrasound evidence of placental abruption and both fetal heart rate and doppler indices were normal. Clinical signs were however suggestive of peritonitis, with extreme abdominal pain Fig. 1 a and ba Case 1 – left adnexal torsion: The mass is twisted three times on its long axis between the ovarian suspensory ligament and the ovarian ligament. Detorsion was impossible due to the size of the mass. The surgical instrument on the left is in the previously fenestrated broad liga- ment. b Case 1 – haemorrhagic left adnex: Haemorrhagic infarction sec- ondary to torsion. The surface is ruptured on attempted detorsion with blunt instruments. Fig. 2 Case 1 – postoperative status, left pelvic wall: The left adnex has been removed. Excision was performed at the ovarian suspensory ligament (at bottom left of picture) and the ovarian ligament (top right). 903 Petresin J et al. Endometriosis-associated Maternal Pregnancy … Geburtsh Frauenheilk 2016; 76: 902 –905 Case Report and muscular defence, circulatory instability and raised CRP. At this point vaginal bleeding had stopped. The patient ʼs condition was considered life-threatening and in the presence of recurrent vaginal bleeding of unknown cause the decision was made to perform a caesarean section despite the early gestation. Since the aetiology of the acute abdomen was unknown it was decided to operate under general anaesthesia. At surgery an extensive haemoperitoneum was found. After delivery of the child some dark blood clot was found in the uterus at the placental margins indicating a marginal sinus haemorrhage or early, partial placental abruption. The child was delivered without complica- tion and after closure of the uterus the abdomen was explored to identify the source of the bleeding. Numerous actively bleed- ing serosal defects were found on the posterior uterine wall and anterior surface of the rectum, and a torn adhesion was found be- tween bowel (sigmoid colon/rectum) and uterus. Attempted hae- mostasis using sutures was unsuccessful due to tissue vulnerabil- ity. The posterior uterine wall was thus covered with haemostatic fibrin glue and compression applied. A Robinson drain was also inserted. There were no postoperative complications, blood transfusion was not necessary and the patient was discharged on the 5th postoperative day.

! Case 1 To our knowledge this is the first case report of an endometriosis complication in pregnancy occurring 5 years after previous sur- gery. It is conceivable that deperitonealisation ventral and dorsal of the left ovary had been performed. During surgery the ovary may have been fixed temporarily to the abdominal wall to assist the complicated operation. It is impossible to exactly estimate when the torsion occurred. The possibly long-standing torsion may only have become symptomatic when the cyst increased in volume in addition to uterine enlargement. Since ovary and Fallopian tube had completely twisted around the axis between the uterine suspensory ligament and the ovar- ian ligament adnexectomy was the only option. In view of the ex- treme pain the patient was experiencing we thought laparoscopy was indicated despite the minimally increased risk of intrauter- ine fetal death [4]. Case 2 This case illustrates a rare but typical endometriosis-associated pregnancy complication. Hospital admission and RDS prophy- laxis were undertaken in view of vaginal bleeding of uncertain cause. Within a few hours the pain had become extreme and there were clinical signs of an acute abdomen, together clearly in- dicating the need for further investigation. Laparoscopy may also have identified the problem, though the size of the uterus may have been limiting [5]. In the context of recent onset vaginal bleeding in association with acute, severe pain we felt immediate delivery of the baby was indicated since the patient ʼs condition was potentially life-threatening and the causative pathology still unknown. Intraabdominal bleeding Spontaneous peritoneal bleeding occurs in the second half of pregnancy, during labour and occasionally postpartum. The most important symptoms are acute or subacute abdominal pain fol- lowed by hypovolaemic shock and fetal distress [6]. The largest study on the incidence of haemoperitoneum in pregnancy is a retrospective analysis of 800 women from a period of 5 years. The study describes three women (0.38 %) with significant intra- abdominal bleeding during the third trimester due to endome- triosis [7]. There are also a few reports of stillbirths [8] and early neonatal deaths [9] due to fulminant haemoperitoneum causing hypovolaemic shock. In pregnant women with the triad of a history of previous endo- metriosis, severe abdominal pain and a fall in haemoglobin, in- traabdominal haemorrhage must be considered [10]. Endome- triosis can also rarely result in haemoperitoneum in non-gravid patients [11]. Endometrioma The incidence of adnexal tumours in pregnancy is approximately 4 % [12], the figure varying between studies. 11.5 % of these tu- mours are endometriomas [13]. It is not possible to estimate the incidence of endometrioma-associated complications as there are too few cases reported. To date there have been four case re- ports of perforated endometrioma during pregnancy [14]. Symp- toms are those of intraabdominal bleeding. Bowel perforation The incidence of this complication also remains unknown. A re- view article on the topic found 12 cases reports of bowel perfora- tion during pregnancy that were caused by endometriosis [15]. All cases presented with an acute abdomen. All patients had emergency operations, either a Hartmann ʼs procedure or a seg- mental resection. Sites of perforation were as follows: 2 × small bowel, 1 × coecum, 3 × appendix and 6 × rectum and sigmoid co- lon [15]. Bowel perforation is thought to be the result of in- creased traction on adherent endometriosis lesions by the grow- ing uterus in combination with intraintestinal pressure from fae- ces [16]. Uterine rupture Spontaneous uterine rupture during pregnancy is very rare in the context of adenomyosis without previous uterine surgery; two case reports exist [17, 18]. Recent publications describe intrapar- tum uterine rupture following previous surgery for cystic adeno- myosis [19, 20]. There is no clinical evidence supporting the re- section of adenomyosis to improve fertility. The danger of uterine rupture must be considered in future patient care, especially when surgery has resulted in larger myometrial defects [21]. An optimal myometrial thickness of 9 –15 mm following resection is described [22]. Surgery during pregnancy Symptomatic ovarian cysts are operated most commonly at the end of the first and beginning of the second trimesters [4]. In a retrospective analysis one third of cysts became evident because of ovarian torsion [4]. Laparoscopic access and operative manage- ment is possible up until the 26th to 28th week of gestation, de- pendant on the surgeon ʼs experience [23]. No general recommendation can be made to treat endometriosis operatively during or before pregnancy in order to avoid this complication, since there is no evidence that this improves preg- nancy or pregnancy outcome [24]. 904 Petresin J et al. Endometriosis-associated Maternal Pregnancy … Geburtsh Frauenheilk 2016; 76: 902 –905 GebFra Science

! The complications described here are rare (approx. 0.4 %). A com- prehensive history including symptoms of endometriosis and previous operations is decisive in the differential diagnosis. The risk of these endometriosis-associated complications is deter- mined by endometriosis severity (superficial or deep infiltrating) as well as the extent of previous surgery. When the clinical pre- sentation is unclear further investigation must be undertaken dependant on gestation and including diagnostic/operative lapa- roscopy when indicated. Alternatively there should be a low threshold for caesarean section, particularly at advanced gesta- tions. Elective caesarean section may be indicated for both com- pletely operated endometriosis and incompletely operated, deep infiltrating endometriosis. However, a general recommendation can not be made. Conflict of Interest ! None.

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