Management and Therapy of Early Pregnancy Complications: First and Second Trimesters

8. Cervical Pregnancy

Togas Tulandi1, 2  Audrey Gilbert Luis Alonso Pacheco Andrea Tinelli5, 6, 7, 8   and Antonio Malvasi9, 10  

(1)

Reproductive Medicine, McGill University, Montréal, QC, Canada

(2)

Department of Obstetrics and Gynecology, McGill University Health Center, Montréal, QC, Canada

(3)

Department of Obstetrics and Gynecology, McGill University, Glen Site, 1001 boulevard Decarie Room D05-2570, Montréal, QC, H4A 3J1, Canada

(4)

Unidad Endoscopia, Centro Gutenberg, Malaga, Spain

(5)

Department of Obstetrics and Gynecology, Vito Fazzi Hospital, Lecce, Italy

(6)

Laboratory of Human Physiology, The International Translational Medicine and Biomodelling Research Group, Department of Informatics and Applied Mathematics, Moscow Institute of Physics and Technology (State University), Dolgoprudny, Moscow Region, Russia

(7)

Institute of Physics and Technology (State University), Moscow, Russia

(8)

Division of Experimental Endoscopic Surgery, Imaging, Technology and Minimally Invasive Therapy, Department of Obstetrics & Gynecology, Vito Fazzi Hospital, Lecce, Italy

(9)

Department of Obstetrics and Gynecology, Santa Maria Hospital, G.V.M. Care and Research, Bari, Italy

(10)

International Translational Medicine and Biomodelling Research Group, Department of Applied Mathematics, Moscow Institute of Physics and Technology (State University), Moscow Region, Russia

Togas Tulandi (Corresponding author)

Email: togas.tulandi@mcgill.ca

Audrey Gilbert

Email: audrey.gilbert@mail.mcgill.ca

Luis Alonso Pacheco

Email: luisalonso2@gmail.com

Andrea Tinelli

Email: andreatinelli@gmail.com

Antonio Malvasi

Email: antoniomalvasi@gmail.com

8.1 Introduction

Cervical ectopic pregnancy is defined as implantation of a fertilized ovum in the endocervical canal (Fig. 8.1). The estimated incidence is 1 in 1000–18,000 pregnancies [15]. It represents less than 1 % of all ectopic pregnancies and constitutes the least common site of ectopic pregnancy. The classical clinical presentation of cervical pregnancy is painless first-trimester vaginal bleeding followed by massive hemorrhage, which could lead to life-threatening situations (Fig. 8.2) [67]. In early reports, the mortality rate could be as high as 40–45 % [8] and the hysterectomy rate was up to 90 % of cases [9]. Today, hysterectomy might still be needed but death at least in developed countries is practically nil [10].

A339784_1_En_8_Fig1_HTML.gif

Fig. 8.1

Cervical ectopic pregnancy is defined as implantation of a fertilized ovum in the endocervical canal, located between external uterine orifice (EUO) and internal uterine orifice (IUO)

A339784_1_En_8_Fig2_HTML.gif

Fig. 8.2

The cervical pregnancy could lead to life-threatening situations for massive hemorrhage, usually without pain

8.2 Pathogenesis

There are two main theories to explain the occurrence of cervical pregnancy: accelerated transport of the blastocyst through the endometrium and delayed implantation and late fertilization of the ovum inside the cervical canal [11]. Risk factors for cervical pregnancy include current use of intrauterine device, history of uterine instrumentation such as curettage, previous cesarean deliveries, the presence of uterine myoma, and intrauterine adhesions [47]. In vitro fertilization treatment also plays a role in the increased incidence of cervical pregnancies [112]. Risk factors for cervical pregnancy are shown in Table 8.1[13]. The main risk factor is previous history of uterine curettage that can be found in up to 70 % of cases [214].

Table 8.1

Risk factors for cervical pregnancy

1. Previous history of uterine curettage

2. Preceding instrumentation of endocervical canal

3. Presence of intrauterine device

4. Uterine fibroids

5. Cesarean scar and uterine surgery

6. Assisted reproduction techniques

7. Intrauterine adhesions (Asherman)

8. Atrophic endometrium and chronic endometritis

9. Uterine and cervical anomalies

8.3 Clinical Manifestations

The main clinical symptom of cervical pregnancy is painless vaginal bleeding usually during the first trimester, although there are some reports of bleeding in the second trimester. It can be mild bleeding or spotting or can be a massive life-threatening bleeding. Another symptom is abdominal cramps. In a series of 89 patients reported by Ushakov et al., vaginal bleeding was associated with abdominal cramps in 26 % of cases [1].

8.4 Diagnosis

In the past, diagnosis was usually made by the pathology of surgical specimens after hysterectomy (Fig. 8.3) [1519]. In 1911, Rubin established four diagnostic criteria for the diagnosis of cervical pregnancy; those criteria are still valid today (Table 8.2). In current clinical practice, ultrasound is the most important tool after history and physical examination (Fig. 8.4a, b). It allows early identification of cervical pregnancy even before it becomes symptomatic.

A339784_1_En_8_Fig3_HTML.jpg

Fig. 8.3

On the left a uterus (A) post hysterectomy for complicated cervical pregnancy, with a Kocher forceps inside the perforated cervix and ectopic pregnancy (below) (B); on the right, a uterus after cervical pregnancy rupture, with a destroyed anterior cervical wall

Table 8.2

Diagnostic criteria for cervical pregnancy

1. Cervical glands must be present opposite the placental attachment

2. The attachment of the placenta to the cervix must be intimate

3. The placenta must be below the peritoneal reflection of the anterior and posterior surfaces of the uterus

4. Fetal elements must not be present within the uterine cavity

A339784_1_En_8_Fig4_HTML.gif

Fig. 8.4

(a) Ultrasonographic sagittal section of a uterus with a cervical pregnancy at 6 weeks gestation; it shows fetal cardiac activity; (b) a diagram of transvaginal ultrasonographic scan of a cervical pregnancy in the anterior cervical wall

Paalman and Mc Elin described clinical criteria of cervical ectopic pregnancy [16]. They include painless vaginal bleeding after amenorrhea with closed or partially open external os and disproportionally enlarged cervix with products of conception entirely confined within the endocervix. Ultrasound criteria of cervical pregnancy include enlargement of the cervix, uterine enlargement, diffuse amorphous intrauterine echoes, and absence of intrauterine pregnancy (Fig. 8.5). Other ultrasound diagnostic criteria are location of the products of conception below the internal os and barrel-shaped and dilated cervical canal (Fig. 8.6). Jurkovic proposed two additional criteria to differentiate cervical pregnancy from spontaneous miscarriage. They are the “sliding sign” and the visualization of peritrophoblastic blood flow with the use of color Doppler (Fig. 8.7) [20]. The sac that slides with slight pressure of the ultrasound probe on the cervix suggests no intimate attachment between the cervix and the endocervical tissue; this is an abortion in progress. Table 8.3 demonstrates ultrasound criteria for the diagnosis of cervical pregnancy as published by Ushakov et al. Using those criteria, diagnosis of cervical ectopic pregnancy can be established in over 85 % of cases. 3D ultrasound can also be used to allow accurate view of the endometrial cavity and the cervix [21], and MRI can be considered in difficult cases. Jung reported a case series in which all patients with cervical pregnancy showed intracervical heterogeneous hemorrhagic mass with densely enhancing papillary solid components [22].

A339784_1_En_8_Fig5_HTML.jpg

Fig. 8.5

An ultrasonographic sagittal scan of a posterior cervical pregnancy under the internal uterine orifice, according to Paalman and Mc Elin criteria; schematic representation of a posterior cervical pregnancy

A339784_1_En_8_Fig6_HTML.jpg

Fig. 8.6

A ultrasonographic sagittal scan showing location of the products of conception below the internal orifice

A339784_1_En_8_Fig7_HTML.jpg

Fig. 8.7

The ultrasonographic image shows the peritrophoblastic blood flow with the use of color Doppler

Table 8.3

Ushakov’s sonographic criteria for cervical pregnancy

1. Gestational sac situated in the endocervical canal

2. Presence of some intact cervical tissue between the GS and the internal orifice

3. Trophoblast invasion of the endocervical tissue

4. Embryonal or fetal structures, in particular pulsating heart, in the ectopic GS

5.Empty uterine cavity

6. Endometrial decidualization

7. Sand-glass shaped uterus

8. Doppler detection of peritrophoblast arterial flow

8.5 Differential Diagnosis

The differential diagnosis includes spontaneous abortion in progress at the level of the endocervical canal (Fig. 8.8), cervico-isthmic intrauterine pregnancy (Fig. 8.9), and cesarean scar pregnancy (Fig. 8.10). In cesarean scar pregnancy, the gestational sac is surrounded by the myometrium and/or fibrous scar tissue and completely separated from the uterine cavity [23]. Sonographic criteria of cesarean scar pregnancy include an empty uterine cavity and endocervical canal, location of the gestational sac peripherally within the anterior portion of the lower uterine segment, deficient or absent myometrium between the gestational sac and the bladder, and complete encasement of the gestational sac by the myometrium and/or fibrous scar tissue [24]. It is important to note that the cesarean scar defect can be located at the cervico-isthmic junction. Gubbini et al. found that cesarean scar defect is present in the inferior third of the cervical canal in 21.9 % of patients [25]. The main point to differentiate between cervical and cervico-isthmic pregnancies is cervical dilatation and the location of the pregnancy in relation to the internal os. In cases of cervical pregnancy, the internal os is closed. It can be identified at the level of the insertion of the uterine arteries [26].

A339784_1_En_8_Fig8_HTML.jpg

Fig. 8.8

The image shows a spontaneous abortion in progress at the level of the endocervical canal

A339784_1_En_8_Fig9_HTML.jpg

Fig. 8.9

The image shows a cervico-isthmic intrauterine pregnancy at 9 weeks

A339784_1_En_8_Fig10_HTML.jpg

Fig. 8.10

The image shows a cesarean scar pregnancy at 5 weeks, with a 3D reconstruction of embryo

8.6 Management

Management of cervical pregnancy can be divided into conservative (with preservation of the uterus) or radical treatment. The conservative management includes medical, surgical, or combined treatment. The treatment depends on factors such as clinical hemodynamic condition, gestational age, available resources, and operator’s experience. The two main objectives in the management of cervical pregnancy are to minimize the risk for massive bleeding and to avoid the need for hysterectomy. Nonsurgical treatments include systemic administration of methotrexate (MTX), intra-amniotic injections of MTX (Fig. 8.11) or potassium chloride (KCL), and uterine artery chemoembolization with MTX [27]. Surgical treatment includes curettage followed by Foley balloon tamponade (Fig. 8.12) or a gentle digital removal of products of conception followed by a gauze tamponadeinto the cervix (Fig. 8.13) and vaginal approach or hysteroscopic removal of the products of conception (Fig. 8.14). Table 8.4 shows different treatments of cervical ectopic pregnancy. Combined treatment has also been described with over 80 % success rate. Nonsurgical treatment should be considered as the first line of treatment (Fig. 8.15).

A339784_1_En_8_Fig11_HTML.gif

Fig. 8.11

Medical treatment of cervical pregnancy by methotrexate injection

A339784_1_En_8_Fig12_HTML.gif

Fig. 8.12

The figure shows a Foley balloon tamponade after curettage for cervical pregnancy

A339784_1_En_8_Fig13_HTML.jpg

Fig. 8.13

Cervical pregnancy gently removed by digital maneuver

A339784_1_En_8_Fig14_HTML.jpg

Fig. 8.14

After cervical pregnancy removal, clinicians can use a gauze tamponade intracervically for hemostasis

Table 8.4

Treatment of cervical pregnancy

Conservative

Medical

 Methotrexate

 KCL

 Mifepristone

 H2O2 intrauterine

Surgical

 Suction evacuation

 Curettage

 Hysteroscopy resection

 Cerclage

 Vaginal cervicotomy

 Embolization

 Tamponade

 Laparoscospic assited

Radical

 Partial trachelectomy

 Hysterectomy

A339784_1_En_8_Fig15_HTML.jpg

Fig. 8.15

The image shows hysteroscopic removal of cervical pregnancy

8.7 Medical Treatment

8.7.1 Methotrexate

Methotrexate treatment is the treatment of choice for most cervical pregnancies. It can be administered systemically or intra-amniotically. Systemic administration of MTX is effective in treating cervical ectopic pregnancies. Kung et al. estimated a 91 % probability to preserve the uterus with the use of systemic methotrexate in cervical pregnancies at a gestational age less than 12 weeks regardless of the presence of fetal heart activity [28]. Methotrexate can be used in a single-dose regimen (50 mg/m2 intramuscular) or in a multiple-dose regimen (1 mg/kg body weight every other day) with folic acid rescue. However, experience with the use of MTX for treatment of cervical pregnancy is limited to case reports and small series.

The criteria for selecting appropriate candidates for medical treatment of cervical pregnancy are also unclear [29]. Yet, Hung et al. reported success with systemic methotrexate with high HCG levels of 125,000–135,000 mU/mL [10]. Methotrexate treatment is less effective when the following conditions are present: gestational age is greater than 9 weeks, beta-HCG level is more than 10,000 mIU/mL, fetal cardiac activity is present, and when the crown rump length is more than 10 mm [30]. Intra-amniotic administration of MTX with or without KCL has been shown to be effective in treating cervical pregnancy [31]. This procedure is performed under transvaginal ultrasound guidance. It is particularly useful in cases of heterotopic pregnancy where preservation of the intrauterine pregnancy is desired [3032]. Krissi et al. evaluated chemoembolization on 25 women with non-tubal ectopic pregnancies including ten cervical pregnancies. They administered multidose systemic methotrexate. The first methotrexate dose was administered by intra-arterial injection during catheterization prior to Gelfoam occlusion of the uterine arteries (Fig. 8.16). There were no failures in the cervical ectopic group with this technique. Mild side effects included abdominal discomfort, groin/leg pain, and puncture site infections. There were no serious complications and subsequent pregnancies were achieved in five women with cervical pregnancy [33]. Whether chemoembolization leads to a better outcome than multidose methotrexate alone is unclear. The side effects of methotrexate include gastrointestinal upset, stomatitis, elevated liver enzymes, thrombocytopenia, leukopenia, conjunctivitis, and fever [29]. Evidence of liver toxicity warrants cessation of the therapy [3435]. Live births after treatment of cervical pregnancy with systemic MTX treatment have been reported [1636].

A339784_1_En_8_Fig16_HTML.jpg

Fig. 8.16

An intrauterine arterial catheterization, with injection of Gelfoam for the occlusion of the uterine arteries

8.7.2 Potassium Chloride (KCl)

Direct injection of KCL (3–5 mL of 2 meq/mL) into the fetal heart under transvaginal ultrasound guidance is often used to induce fetal demise and was first described for this purpose in 1988 [37]. Direct intracardiac injection produces asystole in the fetus. It can be a valid option when the gestational age is more than 9 weeks and in cases of heterotopic pregnancy. The combination of KCl with methotrexate reduces the failure rate of medical treatment in cases with positive heartbeat [6].

8.7.3 Mifepristone

Mifepristone is a selective progesterone receptor modulator that has been used as an abortifacient. It induces decidual necrosis and leads to detachment of the products of conception. A combination of mifepristone with methotrexate improves the success rate of conservative treatment of ectopic pregnancies, reduces the dose of methotrexate, and decreases blood loss during curettage [38].

8.7.4 Intrauterine Irrigation with H2O2

Kim et al. reported a case series of ten patients with cervical pregnancy treated by hysteroscopy. They irrigated the uterine cavity with 3.5 % H2O2 to reduce bleeding during the procedure [39]. H2O2 produces cell death due to release of free oxygen and causes vasoconstriction resulting in atrophy of the embryonic gestational sac and trophoblastic cells.

8.8 Surgical Treatment

8.8.1 Suction

Fylstra reported successful treatment of 13 cases of early cervical ectopic pregnancies [40]. He suggested that first-trimester cervical pregnancies, even in cases of heterotopic pregnancies, could be easily treated with suction curettage. The cervical stroma was first infiltrated with vasopressin and cerclage suture was placed high on the cervix. The efficacy and safety of this technique remain to be seen.

8.8.2 Curettage Followed by Foley Balloon Tamponade

The possibility of cervical bleeding can be minimized by ligation of the cervical branch of the uterine arteries, cervical cerclage, or uterine artery embolization. Before each surgical maneuver, the surgeon should well expose the cervix by a valve (Fig. 8.17) and then proceed by curettage (Fig. 8.18). It is advisable to administer vasopressin intracervical before conducting the curettage (Fig. 8.19): 20–30 mL of vasopressin (0.5 U/mL) is injected with a 21 gauge needle circumferentially into the cervical stroma [20]. Bleeding could be controlled by inserting a Foley catheter with a 30 mL balloon into the dilated cervix for 24 h. In order to secure the catheter in place, a purse string suture is placed around the external cervical os.

A339784_1_En_8_Fig17_HTML.jpg

Fig. 8.17

Exposure of the cervix with vaginal retractors, as the first step of any surgical treatment

A339784_1_En_8_Fig18_HTML.jpg

Fig. 8.18

Intracervical vasopressin injection before conducting the curettage of cervical pregnancy

A339784_1_En_8_Fig19_HTML.jpg

Fig. 8.19

Cervical gentle curettage of pregnancy

8.8.3 Hysteroscopic Removal

Ash and Farrel first reported hysteroscopic management of cervical pregnancy [41]. The hysteroscopic approach allows a complete resection of the gestation under direct vision. This method can also be used for treatment of heterotopic pregnancy [42].

8.8.4 Cervical Cerclage

Scott first described this technique in 1978 [43]. Mashiach published a case series in which he performed a cerclage to treat the cervical ectopic pregnancy [44]. The cerclage technique selected was Shirodkar over McDonald due to its placement in a higher localization on the cervix (Fig. 8.20a, b). They argued some advantages of this method as better control of the massive bleeding, avoidance of systemic side effects of methotrexate, and possibility of use in cases of heterotopic pregnancy.

A339784_1_En_8_Fig20_HTML.jpg

Fig. 8.20

(ab) The cervical ectopic pregnancy treatment can be performed by a cerclage, the technique selected was Shirodkar (a), with a Hegar dilator put inside the cervix during surgery, and a cervicotomy (b) of the localized pregnancy into the cervix, prior to reconstitute the cervical integrity with cerclage

8.8.5 Vaginal Approach

The vaginal approach was first described by Matracaru [45]. With this technique, the bladder is first dissected off the cervix, and blood vessels at each side are clamped. A longitudinal incision is made along the anterior cervical wall from external to internal os and the products of conception are removed, and then the surgery is completed by suturing the cervix and removing the clamps (Figs. 8.218.228.238.248.258.268.278.288.29, and 8.30). This technique was later modified later by Akutagawa [46] who ligated the descending branches of the uterine arteries with absorbable suture (Figs. 8.318.328.338.348.358.36, and 8.37).

A339784_1_En_8_Fig21_HTML.jpg

Fig. 8.21

Matracaru operation; first step is the exposure of the cervix with vaginal retractors

A339784_1_En_8_Fig22_HTML.jpg

Fig. 8.22

Incision of the anterior cervical wall

A339784_1_En_8_Fig23_HTML.jpg

Fig. 8.23

Bipolar coagulation of the highly vascularized anterior cervical wall

A339784_1_En_8_Fig24_HTML.jpg

Fig. 8.24

The surgeon dissects by scissors, the anterior cervical wall to expose the cervical pregnancy

A339784_1_En_8_Fig25_HTML.jpg

Fig. 8.25

Once the plane of dissection is reached, the surgeon performs the dissection of the pregnancy from the cervix by scissors

A339784_1_En_8_Fig26_HTML.jpg

Fig. 8.26

The surgeon cuts the cervix over pregnancy, to better expose the ectopic gestational sac

A339784_1_En_8_Fig27_HTML.jpg

Fig. 8.27

The surgeon removes, the cervical pregnancy from the uterine cervix digitally

A339784_1_En_8_Fig28_HTML.jpg

Fig. 8.28

Once pregnancy is removed, the cervix is exposed and ready to be reconstructed by suturing; the surgeon inserts a dilator into the cervix, as a guide to suture preserving cervical patency

A339784_1_En_8_Fig29_HTML.jpg

Fig. 8.29

Suturing of the cervix to reconstruct its anatomy

A339784_1_En_8_Fig30_HTML.jpg

Fig. 8.30

Suturing with a dilator inside the cervical canal

A339784_1_En_8_Fig31_HTML.jpg

Fig. 8.31

Akutagawa operation: incision of the anterior cervix to create a cervical flap

A339784_1_En_8_Fig32_HTML.jpg

Fig. 8.32

Circular incision of the uterine cervix and exposure of the anterior cervical wall

A339784_1_En_8_Fig33_HTML.jpg

Fig. 8.33

The surgeon starts to dissect, digitally, the connective tissue over the descending branches of the uterine arteries

A339784_1_En_8_Fig34_HTML.jpg

Fig. 8.34

The surgeon dissects with a scalpel the connective tissue of the anterior cervical wall, to expose the vascularized area over ectopic pregnancy

A339784_1_En_8_Fig35_HTML.jpg

Fig. 8.35

The surgeon dissects using a gauze the connective tissue and exposes the descending branch of the uterine arteries

A339784_1_En_8_Fig36_HTML.jpg

Fig. 8.36

The surgeon ligates the descending branches of the uterine arteries with absorbable suture

A339784_1_En_8_Fig37_HTML.jpg

Fig. 8.37

At the end of the operation, before suturing the dissected tissue, a gauze is inserted into the dissected space anterior to the cervix to facilitate hemostasis (gauze to be removed before suturing)

8.8.6 Uterine Artery Embolization

Lobel et al. first used uterine artery embolization to decrease the cervical blood supply [47]. This procedure is usually used in combination with curettage.

8.8.7 Tamponade

Cervical tamponade after removal of a cervical pregnancy has been a standard method to minimize massive vaginal bleeding. It can be achieved with insertion of Foley catheter balloon or a sterile gauze intracervically [48]. It is usually left intracervically for at least 24 h.

8.8.8 Laparoscopic-Assisted Treatment

A more invasive technique to reduce bleeding from a cervical pregnancy is laparoscopic occlusion of the uterine arteries [4950].

8.9 Radical Treatment

8.9.1 Trachelectomy

Kamoi et al. described surgical treatment of cervical pregnancy with “partial trachelectomy” [51]. The procedure is performed by ligating the descending branches of the uterine arteries, circumcision of the vaginal fornix and a partial resection of the cervical wall with the products of conception, and reconstruction of the cervix and vagina. Another option is abdominal trachelectomy [52].

8.9.2 Hysterectomy

After the laparoscopic removal of cervical pregnancy [53] (Fig. 8.38a, b), hysterectomy is the final measure to treat patients with cervical pregnancy. Before the 1980s, the hysterectomy rate for cervical pregnancy was around 70 %. Today, only cases undetected until the second trimester might require a hysterectomy; yet the total rate of hysterectomy is only around 5 % [54].

A339784_1_En_8_Fig38_HTML.jpg

Fig. 8.38

(ab) During the laparoscopic approach after dissection of the bladder flap, the surgeon incises the anterior cervical wall (a), to remove gestational tissue (b) and sutures the cervical edges to reconstruct the cervix

8.9.3 Monitoring Results

Conservative treatment of cervical pregnancy should be followed by close follow-up with serial measurements of B-HCG levels and sonographic evaluation if needed. It is important to note that there is no direct correlation between the decrease of the HCG levels and the regression of the mass. If serum HCG levels decrease between 9 and 17 days, regression of the mass takes around 40 days [35].

8.9.4 Obstetric Outcomes After Cervical Pregnancy

Subsequent pregnancies after successful medical or surgical treatment of cervical ectopic pregnancy have been described [55]. The best interval of pregnancy after methotrexate treatment is still unclear [56]. Some studies reported that methotrexate can still be found in the cells for 8 months after being administered systemically [56]. In general, most clinicians advise the patient not to conceive only 3 months after methotrexate treatment.

8.10 Conclusion

Cervical ectopic pregnancy is a rare event that can result in loss of fertility. However, today most cervical pregnancies can be diagnosed early allowing fertility-sparing treatments. Systemic methotrexate has resulted in high rates of successful treatment with no documented long-term effects on future fertility. Intra-amniotic injections, uterine artery embolization, curettage with Foley balloon tamponade, and hysteroscopic removal can be reserved for cases that have failed methotrexate or that have contraindications to its use.

References

1.

Ushakov FB, Elchalal U, Aceman PJ, Schenker JG (1997) Cervical pregnancy: past and future. Obstet Gynecol Surv 52(1):45–59PubMed

2.

Parente JT, Ou CS, Levy J, Legatt E (1983) Cervical pregnancy analysis: a review and report of five cases. Obstet Gynecol 62(1):79–82PubMed

3.

Vela G, Tulandi T (2007) Cervical pregnancy: the importance of early diagnosis and treatment. J Minim Invasive Gynecol 14(4):481–484PubMed

4.

Shavell VI, Abdallah ME, Zakaria MA, Berman JM, Diamond MP, Puscheck EE (2012) Misdiagnosis of cervical ectopic pregnancy. Arch Gynecol Obstet 285(2):423–426PubMed

5.

Yankowitz J, Leake J, Huggins G, Gazaway P, Gates E (1990) Cervical ectopic pregnancy: review of the literature and report of a case treated by single-dose methotrexate therapy. Obstet Gynecol Surv 45(7):405–414PubMed

6.

Cipullo L, Cassese S, Fasolino L, Fasolino MC, Fasolino A (2008) Cervical pregnancy: a case series and a review of current clinical practice. Eur J Contracept Reprod Health Care 13(3):313–319PubMed

7.

Martinelli P, Maruotti GM, Oppedisano R, Agangi A, Mazzarelli LL, Votino C et al (2007) Is uterine artery embolization for cervical ectopic pregnancy always safe? J Minim Invasive Gynecol 14(6):758–763PubMed

8.

Marcovici I, Rosenzweig BA, Brill AI, Khan M, Scommegna A (1994) Cervical pregnancy: case reports and a current literature review. Obstet Gynecol Surv 49(1):49–55PubMed

9.

Vilos G, Abu-Rafea B, Kozak R (2005) Safe resectoscopic evacuation of a 10-week viable cervical pregnancy after transfemoral bilateral uterine artery embolization. Fertil Steril 84(2):509PubMed

10.

Hung TH, Jeng CJ, Yang YC, Wang KG, Lan CC (1996) Treatment of cervical pregnancy with methotrexate. Int J Gynaecol Obstet 53(3):243–247PubMed

11.

Kouliev T, Cervenka K (2010) Emergency ultrasound in cervical ectopic pregnancy. J Emerg Med 38(1):55–56PubMed

12.

Ginsburg ES, Frates MC, Rein MS, Fox JH, Hornstein MD, Friedman AJ (1994) Early diagnosis and treatment of cervical pregnancy in an in vitro fertilization program. Fertil Steril 61(5):966–969PubMed

13.

Boyko TR, O’brien JF (2001) Cervical pregnancy: a case report. Ann Emerg Med 38(2):177–180PubMed

14.

Pisarska MD, Carson SA (1999) Incidence and risk factors for ectopic pregnancy. Clin Obstet Gynecol 42:2–8PubMed

15.

Chetty M, Elson J (2009) Treating non-tubal ectopic pregnancy. Best Pract Res Clin Obstet Gynaecol 23(4):529–538PubMed

16.

Paalman RJ, Mc Elin TW (1959) Cervical pregnancy. Review of the literature and presentation of cases. Am J Obstet Gynecol 77:1261–1270PubMed

17.

Kobayashi M, Hellman LM, Fillisti LP (1969) Ultrasound: and aid in the diagnosis of ectopic pregnancy. Am J Obstet Gynecol 103(8):1131–1140PubMed

18.

Raskin MM (1978) Diagnosis of cervical pregnancy by ultrasound: a case report. Am J Obstet Gynecol 130:234–235PubMed

19.

Timor-Tritsch IE, Monteagudo A, Mandeville EO, Peisner DB, Anaya GP, Pirrone EC (1994) Successful management of a viable cervical pregnancy by local injection of methotrexate guided by transvaginal ultrasonography. Am J Obstet Gynecol 170(3):737–739PubMed

20.

Jurkovic D, Hacket E, Campbell S (1996) Diagnosis and treatment of early cervical pregnancy: a review and a report of two cases treated conservatively. Ultrasound Obstet Gynecol 8(6):373–380PubMed

21.

Sherer DM, Gorelick C, Dalloul M, Sokolovski M, Kheyman M, Kakamanu S et al (2008) Three-dimensional sonographic findings of a cervical pregnancy. J Ultrasound Med 27(1):155–158PubMed

22.

Jung SE, Byun JY, Lee JM, Choi BG, Hahn ST (2001) Characteristic MR findings of cervical pregnancy. J Magn Reson Imaging 13(6):918–922PubMed

23.

Little EA, Moussavian B, Horrow MM (2010) Cesarean delivery scar ectopic pregnancy. Ultrasound Q 26(2):107–109PubMed

24.

Tan G, Chong YS, Biswas A (2005) Caesarean scar pregnancy: a diagnosis to consider carefully in patients with risk factors. Ann Acad Med Singapore 34(2):216–219PubMed

25.

Gubbini G, Centini G, Nascetti D, Marra E, Moncini I, Bruni L et al (2011) Surgical hysteroscopic treatment of cesarean-induced isthmocele in restoring fertility: prospective study. J Minim Invasive Gynecol 18(2):234–237PubMed

26.

Gun M, Mavrogiorgis M (2002) Cervical ectopic pregnancy: a case report and literature review. Ultrasound Obstet Gynecol 19(3):297–301PubMed

27.

Farabow WS, Fulton JW, Fletcher V Jr, Velat CA, White JT (1983) Cervical pregnancy treated with methotrexate. N C Med J 44(3):91PubMed

28.

Kung FT, Chang SY (1999) Efficacy of methotrexate treatment in viable and nonviable cervical pregnancies. Am J Obstet Gynecol 181(6):1438–1444PubMed

29.

Kim TJ, Seong SJ, Lee KJ, Lee JH, Shin JS, Lim KT et al (2004) Clinical outcomes of patients treated for cervical pregnancy with or without methotrexate. J Korean Med Sci 19(6):848–852PubMedPubMedCentral

30.

Verma U, Maggiorotto F (2007) Conservative management of second-trimester cervical ectopic pregnancy with placenta percreta. Fertil Steril 87(3):697.e13–6

31.

Jeng CJ, Ko ML, Shen J (2007) Transvaginal ultrasound-guided treatment of cervical pregnancy. Obstet Gynecol 109(5):1076–1082PubMed

32.

Kumar S, Vimala N, Dadhwal V, Mittal S (2004) Heterotopic cervical and intrauterine pregnancy in a spontaneous cycle. Eur J Obstet Gynecol Reprod Biol 112(2):217–220PubMed

33.

Krissi H, Hiersch L, Stolovitch N, Nitke S, Wiznitzer A, Peled Y (2014) Outcome, complications and future fertility in women treated with uterine artery embolization and methotrexate for non-tubal ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol 182:172–176PubMed

34.

Zakaria MA et al (2011) Conservative management of cervical ectopic pregnancy: utility of uterine artery embolization. Fertil Steril 95(3):872–876PubMed

35.

Song MJ et al (2009) Serial transvaginal sonographic findings of cervical ectopic pregnancy treated with high-dose methotrexate. J Ultrasound Med 28(1):55–61PubMed

36.

Piccioni MG et al (2015) Cervical ectopic pregnancy treated with systemic methotrexate and following successful term pregnancy: case report. J Obst Gynaecol 24:1–2

37.

Westendorp AK, Miny P, Holzgreve W, De Wilde R, Aydinli K (1988) Selective fetocide by direct intracardiac injection of isotonic potassium chloride. Arch Gynecol Obstet 244(1):59–62PubMed

38.

Shrestha E, Yang Y, Li X, Zhang Y (2011) Successful conservative management with methotrexate and mifepristone of cervical pregnancy. J Biomed Res 25(1):71–73PubMedPubMedCentral

39.

Kim JS, Nam KH, Kim TH, Lee HH, Lee KH (2008) Hysteroscopic management of cervical pregnancy with intrauterine irrigation with H2O2. J Minim Invasive Gynecol 15(5):627–630PubMed

40.

Fylstra DL (2014) Cervical pregnancy: 13 cases treated with suction curettage and balloon tamponade. Am J Obstet Gynecol 210(6):581.e1-5PubMed

41.

Ash S, Farrell SA (1996) Hysteroscopic resection of a cervical ectopic pregnancy. Fertil Steril 66(5):842–844PubMed

42.

Jozwiak EA, Ulug U, Akman MA, Bahceci M (2003) Successful resection of a heterotopic cervical pregnancy resulting from intracytoplasmic sperm injection. Fertil Steril 79(2):428–430PubMed

43.

Woodforde SJ, Diggory PLC, Edelman PJ (1978) Management of cervical pregnancy with circumsuture and intracervical obturator. Br Med J 1(6116):825

44.

Mashiach S, Admon D, Oelsner G, Paz B, Achiron R, Zalel Y (2002) Cervical Shirodkar cerclage may be the treatment modality of choice for cervical pregnancy. Hum Reprod 17(2):493–496PubMed

45.

Matracaru G (1968) A new method for the surgical treatment of the cervix pregnancy. Zentralbl Gynakol 90(37):1264–1268PubMed

46.

Akutagawa N, Nishikawa A, Saito T, Sagae S, Kudo R (2001) Conservative vaginal surgery for cervical pregnancy. BJOG 108:888–889PubMed

47.

Lobel SM, Meyerovitz MF, Benson CC, Goff B, Bengtson JM (1990) Preoperative angiographic uterine artery embolization in the management of cervical pregnancy. Obstet Gynecol 76(5 Pt 2):938–941PubMed

48.

Tinelli A, Malvasi A, Vergara D, Casciaro S (2007) Emergency surgical procedure for failed methotrexate treatment of cervical pregnancy: a case report. Eur J Contracept Reprod Health Care 12(4):391–395PubMed

49.

Choi HS, Kim NY, Ji YI (2015) Laparoscopic uterine artery occlusion before cervical curettage in cervical ectopic pregnancy: safe and effective for preventing massive bleeding. Obstet Gynecol Sci 58(5):431–434PubMedPubMedCentral

50.

Kung FT, Lin H, Hsu TY, Chang CY, Huang HW, Huang LY et al (2004) Differential diagnosis of suspected cervical pregnancy and conservative treatment with the combination of laparoscopy-assisted uterine artery ligation and hysteroscopic endocervical resection. Fertil Steril 81(6):1642–1649PubMed

51.

Kamoi S, Iwasaki N, Igarashi K, Asakura T, Watanabe M, Ohaki Y et al (2009) Partial trachelectomy: a new and final option for fertility-preserving management of cervical ectopic pregnancy. J Gynecol Surg 25(4):139–146

52.

Treviño-Salinas E, Ayuzo-del Valle C, Guzmán-López A, Dávila-Escamilla I, García-Lezama R, Pérez-Morones D et al (2015) Abdominal trachelectomy for cervical pregnancy: surgical conservative management. J Gynecol Surg 31(1):37–39

53.

Tinelli A, Tinelli R, Malvasi A (2009) Laparoscopic management of cervical-isthmic pregnancy: a proposal method. Fertil Steril 92(2):829.e3–6

54.

Hosni MM, Herath RP, Mumtaz R (2014) Diagnostic and therapeutic dilemmas of cervical ectopic pregnancy. Obstet Gynecol Surv 69(5):261–276PubMed

55.

Acosta DA (1997) Cervical pregnancy—a forgotten entity in family practice. J Am Board Fam Pract 10(4):290–295PubMed

56.

Frates MC, Benson CB, Doubilet PM, Di Salvo DN, Brown DL, Laing FC et al (1994) Cervical ectopic pregnancy: results of conservative treatment. Radiology 191(3):773–775PubMed

57.

Malvasi A, Tinelli A, Hudelist G, Tinelli R (2008) Exocervical pregnancy in a patient with intrauterine device: a case report. J Minim Invasive Gynecol 15(6):758–760PubMed