Intramural ectopic pregnancy: a case and review of the literature

Intramural ectopic pregnancy: a case and review of the literature

European Journal of Obstetrics & Gynecology and Reproductive Biology 168 (2013) 129–133 Contents lists available at SciVerse ScienceDirect European ...

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European Journal of Obstetrics & Gynecology and Reproductive Biology 168 (2013) 129–133

Contents lists available at SciVerse ScienceDirect

European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb

Review

Intramural ectopic pregnancy: a case and review of the literature Emma Kirk a,*, Katie McDonald b, Julia Rees b, Abha Govind a a b

Department of Obstetrics and Gynaecology, North Middlesex University Hospital NHS Trust, Sterling Way, London N18 1QX, United Kingdom Department of Pathology, North Middlesex University Hospital NHS Trust, Sterling Way, London N18 1QX, United Kingdom

A R T I C L E I N F O

A B S T R A C T

Article history: Received 29 June 2012 Received in revised form 11 November 2012 Accepted 13 December 2012

An intramural ectopic is a rare type of ectopic pregnancy in which the gestational sac is implanted within the myometrium, separate from the endometrial cavity and Fallopian tubes. There are only 53 cases in the published literature. We report a case of intramural ectopic pregnancy treated surgically and review the published data on this rare type of ectopic pregnancy, with respect to aetiology, diagnosis and management. ß 2013 Elsevier Ireland Ltd. All rights reserved.

Keywords: Intramural ectopic pregnancy Ectopic pregnancy Transvaginal ultrasound

Contents 1. 2. 3.

4.

Introduction . . . . . . . Case . . . . . . . . . . . . . Discussion . . . . . . . . Incidence . . . . 3.1. Aetiology . . . . 3.2. Diagnosis . . . . 3.3. Management . 3.4. Conclusion . . . . . . . . References . . . . . . . .

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1. Introduction Whilst the majority of ectopic pregnancies are implanted outside the uterus, with the most common site being the Fallopian tubes, there are some ectopic pregnancies that are implanted within the uterus but outside the endometrial cavity. Those implanted in the cervix, interstitial segment of the Fallopian tube and the uterine scar of a caesarean section are recognized forms of such ectopic pregnancies. In addition it is possible for a pregnancy to implant within the myometrium, separate to the endometrial cavity and Fallopian tubes. This is called an intramural ectopic pregnancy and is thought to be the rarest of all ectopic pregnancies. We present a case of an intramural ectopic pregnancy and perform a review of the recent literature on this form of ectopic pregnancy. Published studies in the English language between 2000 and 2012 on intramural ectopic pregnancy were identified by

* Corresponding author. Tel.: +44 0208 887 2000. E-mail address: [email protected] (E. Kirk). 0301-2115/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejogrb.2012.12.036

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Medline search using the Keywords: intramural ectopic pregnancy. We found 21 published cases of intramural ectopic pregnancies. 2. Case A 25-year-old woman was referred to the Early Pregnancy Assessment Unit (EPAU) in her fourth pregnancy. Her first pregnancy was, unusually, complicated by rhesus isoimmunization and she underwent a lower segment caesarean section at 34 weeks for rising Anti-D titres. She denied previous miscarriage or termination but booking bloods did show unusual antibodies suggesting isoimmunization in a previously undocumented pregnancy. The second pregnancy was a first trimester complete spontaneous miscarriage. Her third pregnancy was again complicated by rhesus isoimmunization. She required an intra-peritoneal transfusion at 17 weeks for fetal anaemia and unfortunately had an intra-uterine fetal death a few days later. She delivered the fetus vaginally but needed surgical removal of the placenta. In this fourth pregnancy she presented with lower abdominal pain at 5+6 weeks gestation by her last menstrual period. There was

130

E. Kirk et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 168 (2013) 129–133

Fig. 1. Transvaginal scan image showing the ectopic pregnancy and the right ovary.

no history of vaginal bleeding. The serum bhCG level was 3900 IU/ L. A transvaginal ultrasound (TVS) examination was performed, but as no pregnancy was visualized, she was classified as having a ‘pregnancy of unknown location’ (PUL) with a high suspicion of ectopic pregnancy. No free fluid was visualized in the pelvis. She was admitted for observation in view of her pain. The serum bhCG level repeated 48 hours later had risen to 11,203 IU/L. A repeat TVS again showed an empty endometrial cavity. A mass measuring 22 mm  22 mm  25 mm was seen in the right adnexa very close to the cornua. It appeared to contain an 11 mm gestational sac (Fig. 1). There was a small amount of blood in the pouch of Douglas. A diagnosis of a right-sided tubal ectopic pregnancy was made and the patient taken to theatre. At laparoscopy a 2 cm  2 cm  2 cm ectopic pregnancy was found to have ruptured through the posterior wall of the uterus. The site of rupture was posterior, inferior and medial to the origin of the right Fallopian tube. Both Fallopian tubes appeared normal throughout their entire length. There was 200 ml of hemoperitoneum and active bleeding from the site of the ectopic pregnancy. A laparotomy was performed due to the unusual location of the pregnancy and the ectopic pregnancy resected. Histological examination confirmed chorionic villi surrounded by myometrium with no identifiable Fallopian tube, confirming a diagnosis of intramural ectopic pregnancy (Fig. 2). 3. Discussion 3.1. Incidence Intramural ectopic pregnancies are extremely rare and represent less than 1% of all ectopic pregnancies [1]. Theodore Doderlein first described the condition in 1913 in a woman with adenomyosis. According to Karakok in 2002 the world literature had only 33 cases of intramural pregnancy [2]. Our own review of the literature published on intramural pregnancies since the year 2000 revealed 22 cases including our case, an additional 19 cases since the review by Karakok. The details of these are summarized in Table 1 [1–19]. There are now 53 cases in the published literature, including a Chinese case report from 2004 [20]. 3.2. Aetiology The exact aetiology and pathogenesis of intramural pregnancies are unclear. Theories include implantation in a focus of adenomyosis, invasion of the myometrium through microscopic tracts due to uterine trauma from surgical instrumentation or following difficult in vitro fertilization (IVF) transfers and external migration and implantation on the serosal surface of the uterus. In the 22 reported cases since 2000, of which the past obstetric and medical history was known, nine (56%) had a previous uterine curettage, three (19%) were known to have adenomyosis, three (19%) were the result of IVF or IUI and four (25%) had either a previous myomectomy or caesarean section [1–19]. In our case, the patient

Fig. 2. Image of histology slide showing chorionic villi and myometrial muscle fibres.

had had a previous uterine curettage following a second trimester loss and also had a history of previous caesarean section. 3.3. Diagnosis Historically the diagnosis of intra-mural pregnancy was not made until surgery for uterine rupture. Due to their anatomical location they may present later than some of the other types of ectopic pregnancy, allowing early containment of the products of conception [1]. Certainly there are reports of the diagnosis not being made until the third trimester [16,20]. Fait et al. describe a case that did not present until 30 weeks gestation [21]. It resulted in a live birth after caesarean hysterectomy. More recently a case has been described of a woman presenting at 26 weeks gestation with an acute abdomen and hypovolaemic shock [16]. Ultrasound examinations had been performed at 7 weeks and 13 weeks gestation and reported a normal intra-uterine pregnancy. At presentation an ultrasound scan showed a singleton fetus without a heart beat in the abdominal cavity and haemoperitoneum. A laparotomy was performed and the pregnancy was found to have ruptured out of the posterior surface of the uterus and implanted on the serosa, as was seen in the case described in this report. Similarly the diagnosis was not made until the time of rupture, although the gestation was only 6 weeks according to her last menstrual period. It is possible to diagnose an intra-mural pregnancy with ultrasound. It should be completely surrounded by myometrium and separate from the endometrial cavity. It may be difficult, however, to distinguish it from a degenerating fibroid, a pregnancy in a congenitally abnormal uterus, or from an interstitial or cornual ectopic pregnancy. Three-dimensional ultrasound and magneticresonance imaging may be useful in making a diagnosis [10,12,16]. In the 22 cases we present here, the diagnosis was definitely suspected in only 15 and this was not necessarily on the first ultrasound examination performed. Lack of knowledge about the condition and its rarity are possible reasons why the diagnosis may not be made on ultrasound. Our case was initially classified as a PUL, despite a high initial hCG level of 3900 IU/L. The question is: are intramural pregnancies more difficult to visualize or are they just missed? One of the reasons they may be missed is due to the operator not being aware of the possible diagnosis. As with our case, the most common misdiagnosis is probably another type of ectopic pregnancy – tubal, interstitial or cornual.

E. Kirk et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 168 (2013) 129–133

131

Table 1 Summary of intramural pregnancy case reports 2000–2012. Case Year

Author

Maternal Location of age pregnancy

Ultrasound features

Past gynaecological/ obstetric history

Management

25

22 mm  22 mm  25 mm adnexal mass containing an 11 mm gestational sac Ill-defined gestational sac and a fetus heart beat within the fundal myometrium

Previous LSCS and uterine curettage

Laparoscopy then laparotomy with excision

Previous LSCS. Previous salpingectomy for ectopic pregnancy

Laparoscopic removal. Injection with vasopressin and physiological saline then excision with a harmonic scalpel Laparotomy and excision

1

2012 This report

2

2010 Nabeshima et al. [19] 38

Fundal

3

2010 Glass et al. [18]

29

Posterior fundal

4

2010 Ong et al. [1]

36

Posterior

5

2010 Bouzari et

28

Posterior fundal

6

2010 Bouzari et al. [17]

32

Posterior

7

2009 Choi et al. [16]

37

8

2008 Caliskan [15]

21



9

2007 Kumtepe et al. [14]

38



10

2006 Sherer et al. [13]

36

Posterior

11

2006 Ko et al. [12]

28

Posterior

12

2006 Park et al. [11]

35

Posterior

13

2005 Lee et al. [10]

25

Right lateral

14

2004 Bhatia and Bentick [8]

28

Fundal

15

2004 Tay et al. [9]

al. [17]

Posterior

TVS appeared to show an intrauterine gestational sac. Uterine curettage was performed but no products of conception obtained. A pelvic MRI then showed a complex heterogenous mass 7.1 cm  6.1  5.3 cm involving the myometrium extending from the fundus 14 mm gestational sac remote from the endometrium located within the posterior myometrium of the uterus equidistant from the two uterine cornua. 3 mm fetal pole with a heart beat Fluid and a singleton fetus without any heart beat, in the abdominal cavity

G1. Tuberus sclerosis

G1. Adenomyosis

2 uterine curettage procedures for termination of pregnancy. Previous myomectomy Two well-defined gestational Previous uterine curettage sacs within the posterior procedure for termination of myometrium. MRI confirmed pregnancy an intra-mural twin pregnancy

Intra-mural cyst not connected with the endometrium A 3.9 mm  3.2 mm gestational sac with a yolk sac and an embryonic pole distinct from the endometrial cavity surrounded by the myometrium 22 mm gestational sac within the myometrium, 12 mm away from the endometrial cavity Initial TVS showed possible interstitial pregnancy. Following negative laparoscopy repeat TVS showed a highly vascular 2 cm intramural lesion Echogenic mass in the posterior uterine body (with an increased hCG level – 4 weeks after a curettage procedure) Gestational sac within the subserosal area of the posterior uterine wall Gestational sac with a fetal pole and yolk sac that was separated from the endometrium Complex mass in the left fundal region

Intramural sac in right posterior myometrium near the fundus. Endometrial echo seen to be clearly separate from the sac

IVF pregnancy. 2 previous uterine curettage procedures. Adenomyosis –

Intra-fetal injection of potassium chloride followed by intra-amniotic methotrexate injection

Laparotomy. The uterus was ruptured requiring repair

Single dose intra-muscular methotrexate (50 mg/m2)

Systemic and sonographyguided local methotrexate injection Expectant management

IUI pregnancy with ovulation Multiple dose systemic induction methotrexate

Human immunodeficiency infection. Previous complete molar pregnancy treated by uterine curettage and methotrexate 2 years earlier

Vaginal hysterectomy. Histology confirmed an intramural choriocarcinoma

5 uterine curettage Multiple dose systemic procedures for termination of methotrexate pregnancy. A cornual pregnancy treated with methotrexate and curettage IVF pregnancy. Previous Laparotomy and excision myomectomy G1. Previous right Laparotomy and excision adnexectomy for torsion of a dermoid cyst 3 uterine curettage procedures

Suction evacuation under laparoscopic guidance and systemic methotrexate therapy –

E. Kirk et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 168 (2013) 129–133

132 Table 1 (Continued ) Case Year

Author al. [7]

Maternal Location of age pregnancy

Ultrasound features

29

Fundal

39



G3 P1 Ill-defined mass measuring 3.0 cm  3.5 cm  2.0 cm within the fundal myometrium G4 P1 Amorphous echoes in the uterine cavity on TVS. CT revealed a trophoblastic tumour with deep invasion of the myometrium –

16

2004 Jin et

17

2004 Jin et al. [7]

18

2003 Dousias et al. [6]

19

2003 Ashraf [5]

20 21

2002 Karako¨k et al. [2] 2001 Bernstein et al. [4]

35

22

2001 Lone et al. [3]

40

Medial to round ligament Gestational sac seen surrounded by myometrium – Left side below A gestational sac with a yolk cornu sac distinct from the endometrial cavity, surrounded by myometrium A 4.5 cm  4.5 cm hypoechoic area within the myometrium which was suggestive of a fibroid close to the left cornu

3.4. Management As with other types of ectopic pregnancy, treatment can be surgical, medical or expectant. The type of treatment will depend on when in its natural history the intramural ectopic pregnancy is diagnosed. Historically these pregnancies were not diagnosed until the time of surgery, so management was by surgical excision often resulting in hysterectomy. In the case we present, whilst a diagnosis of ectopic pregnancy had been made, the myometrial location of the pregnancy was not recognized until the time of laparoscopy. As the pregnancy had ruptured, surgical treatment was needed. As in many cases reported in the literature, a laparotomy was performed with excision of the intramural pregnancy and the diagnosis was confirmed histologically. There is only one case report of successful laparoscopic removal: it describes laparoscopic excision of an intramural ectopic pregnancy with a harmonic scalpel following injection with vasopressin [19]. Once the gestational sac had been excised the myometrium and serosa were repaired with polyglactin suture and fibrin glue was used to complete haemostasis. Some intramural pregnancies are amenable to medical management. Methotrexate is the most commonly used drug and may be given locally or systemically. Bouzari et al. describe successful treatment of a posterior wall intramural pregnancy using a single dose of intramuscular methotrexate (50 mg/m2) [17]. A multiple dose regimen using alternate day intramuscular methotrexate (50 mg/m2) and leukoviron (0.1 mg/kg) for 8 days has also been described [12]. Methotrexate may also be injected intra-amniotically under ultrasound guidance with or without intra-foetal potassium chloride [1,16]. Expectant management has also been described. In one case, a diagnosis of intramural pregnancy was made laparoscopically [4]. As with our case, at laparoscopy a mass was seen bulging below the level of the cornu, but as there was no evidence of rupture and the bhCG level was very low (9.5 mIU) a decision was made for expectant management. The serum bhCG levels declined to undetectable levels within 10 days and a follow-up ultrasound performed after 8 days showed an irregular gestational sac consistent with a failed pregnancy to the left of the endometrial

Past gynaecological/ obstetric history

Management Laparotomy and excision

Subradical hysterectomy

Underwent a ‘myomectomy’ but pathology examination revealed chorionic villi consistent with an ectopic pregnancy –

Adenomyosis Previous uterine curettage for Expectant management a missed miscarriage

Previous uterine curettage for Diagnosed histologically after first trimester termination of hysterectomy performed for pregnancy metrorrhagia and lower abdominal pain

cavity. In another case, an initial ultrasound examination revealed a 3.9 mm  3.2 mm gestational sac with a yolk sac and an embryonic pole separate from the endometrial cavity surrounded by myometrium [15]. Serum bhCG levels were taken two days apart and decreased from 16.3 mIU/L to 1.53 mIU/L. Repeat ultrasound examinations showed smaller and irregular gestational sacs. Finally, as with some other forms of non-tubal ectopic pregnancy, surgical management theoretically increases the risk of uterine rupture in the event of a future pregnancy. Our patient was keen to try for another pregnancy but was advised to defer this for 12–24 months. 4. Conclusion This case and review of the literature highlight the difficulty in the diagnosis of intramural ectopic pregnancy. A possible diagnosis of non-tubal ectopic pregnancy should be suspected in women classified as a PUL with high initial serum hCG levels. Although rare, the incidence could be on the increase as more cases are recognized. It is possible to diagnose them pre-operatively on ultrasound but even the most experienced sonographers may only see a handful during their lifetime. Clinicians should be aware of the risk factors for such pregnancies and the different management options. References [1] Ong C, Lin-Lin S, Chia D, Choolani M, Biswas AB. Sonographic diagnosis and successful management of an intra-mural ectopic pregnancy. Journal of Clinical Ultrasound 2010;38:320–4. [2] Karako¨k M, Balat O, Sari I, Kocer NE, Erdogan R. Early diagnosed intramural ectopic pregnancy associated with adenomyosis: report of an unusual case. Clinical and Experimental Obstetrics and Gynecology 2002;29:217–8. [3] Lone FW, Aziz AB, Khan MN, Pervez S. A case of intramural pregnancy: the importance of differentiation from fibroid uterus. Australian and New Zealand Journal of Obstetrics and Gynaecology 2001;41:337–8. [4] Bernstein HB, Thrall MM, Clark WB. Expectant management of intramural ectopic pregnancy. Obstetrics and Gynecology 2001;97:826–7. [5] Ashraf M. Intramural pregnancy. Journal of the American Association of Gynecologic Laparoscopists 2003;10:7–8. [6] Dousias V, Stefos T, Chouliara S, Stefanou D, Kamina S, Lolis D. Intramural pregnancy with negative maternal serum b-HCG. European Journal of Obstetrics Gynecology and Reproductive Biology 2003;111:94–5.

E. Kirk et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 168 (2013) 129–133 [7] Jin H, Zhou J, Yu Y, Dong M. Intramural pregnancy: a report of 2 cases. Journal of Reproductive Medicine 2004;49:569–72. [8] Bhatia K, Bentick B. Intramural molar pregnancy: a case report. Journal of Reproductive Medicine 2004;49:689–92. [9] Tay KW, Cheung W, Mok KM. Intramural pregnancy. Journal of the American Association of Gynecologic Laparoscopists 2004;11:447. [10] Lee GSR, Hur SY, Kown I, Shin JC, Kim SP, Kim SJ. Diagnosis of early intramural ectopic pregnancy. Journal of Clinical Ultrasound 2005;33:190–2. [11] Park WI, Jeon YM, Lee JY, Shin SY. Subserosal pregnancy in a previous myomectomy site: a variant of intramural pregnancy. Journal of Minimally Invasive Gynecology 2006;13:242–4. [12] Ko HS, Lee Y, Lee HJ, et al. Sonographic and MR findings in 2 cases of intramural pregnancy treated conservatively. Journal of Clinical Ultrasound 2006;34:356–60. [13] Sherer DM, Stimphil R, Hellman M, et al. Transvaginal sonographic findings of isolated intramural uterine choriocarcinoma mimicking an interstitial pregnancy. Journal of Ultrasound in Medicine 2006;25:791–4. [14] Kumtepe Y, Borekci B, Polat P, Cetinkaya K, Kadanali S. The rarest form of ectopic pregnancy: intramural ectopic pregnancy and medical treatment. Journal of the Turkish German Gynecological Association 2007;8:416–9.

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[15] Caliskan E, Cakiroglu Y, Corakci A. Expectant management of an intramural ectopic pregnancy in a primagravid woman. Journal of the Turkish German Gynecological Association 2008;9:234–6. [16] Choi DH, Kwon H, Kim YS, Kim JH. Intramural pregnancy associated with adenomyosis after in vitro fertilization and embryo transfer: a case report. Journal of Reproductive Medicine 2009;54:255–8. [17] Bouzari Z, Keshani M, Yazdani S, Barat S, Zinalzadeh M. Intramural pregnancy. Journal of Obstetrics and Gynaecology 2010;30:195–6. [18] Glass T, Smith P, Hodges R, Holmes HJ. Intramural pregnancy presenting in a patient with tuberous sclerosis. Journal of Clinical Ultrasound 2010;38:393–6. [19] Nabeshima H, Nishimoto M, Utsunomiya H, et al. Total laparoscopic conservative surgery for an intramural ectopic pregnancy. Diagnostic and Therapeutic Endoscopy 2010;504062. [20] Meng SM, Meng SQ. Rupture of uterus in intra-mural pregnancy – a case report. Zhonghua Fu Chan Ke Za Zhi 2004;39:429. [21] Fait G, Goyert G, Sundareson A, Pickens A. Intramural pregnancy with fetal survival: case history and discussion of etiologic factors. Obstetrics and Gynecology 1987;70:472–4.