Journal of Obstetrics and Gynaecology, 2014; Early Online: 1–2 © 2014 Informa UK, Ltd. ISSN 0144-3615 print/ISSN 1364-6893 online

CASE REPORT

Cervical ectopic pregnancy treated with systemic methotrexate and following successful term pregnancy: case report. M. G. Piccioni, M. Framarino-dei-Malatesta, N. F. Polidori & E. Marcoccia DOI: 10.3109/01443615.2014.991288

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Department of Obstetrical, Gynecological and Urological Sciences, Policlinico Umberto I Roma, Sapienza University of Rome, Italy Correspondence: Dr. Eleonora Marcoccia, Department of Obstetrical, Gynecological and Urological Sciences, Policlinico Umberto I, Viale del Policlinico 155 00186 Roma, Italy. E-mail: [email protected]

Introduction Implantation of the zygote outside the uterine cavity occurs in 2% of all pregnancies. Cervical ectopic pregnancy characterised by implantation of fertilised ovum in the cervical mucosa represents less than 1% of all ectopic pregnancies, with an estimated incidence of one in 2500 to one in 12,000 pregnancies (Cepni et al. 2004). The most common predisposing factors are the previous dilatation and curettage, previous caesarean delivery, assisted reproduction technologies (ART), Asherman’s syndrome, therapeutic abortion or ectopic pregnancies. The ultrasound imaging of cervical ectopic pregnancy shows round gestational sac (GS) located below the level of internal ostium of uterus, empty uterine cavity and peritrophoblastic Doppler colour flow. There are no specific guidelines about the treatment of cervical pregnancy and only case reports are reported. The early diagnosis in asymptomatic cases has provided the feasibility for a conservative management of cervical pregnancy. Medical treatment with methotrexate (MTX) can be administered by systemic or local route under ultrasound guidance (Vela and Tulandi 2007). A non-conservative therapy such as hysterectomy is used when conservative strategies

failed or in case of massive haemorrhage and haemodynamic instability in order to preserve woman’s life. We present a case of cervical pregnancy at 7 weeks’ gestation resolved by two intra-muscular injection of MTX without any additional surgical modality.

Case presentation A 38-year-old nulliparous woman became pregnant by intra-cytoplasmic sperm injection (ICSI). She did not undergo any previous cervical or intra-uterine procedure. After the stimulation with clomiphene citrate she underwent an ICSI with single embryo transfer. Beta-human chorionic gonadotropin (BHCG) values were 153 mIU/ ml 15 days after the transfer, 2885 mIU/ml after 20 days and 9595 mIU/ml after 23 days. She was admitted to our Department at 7 weeks of pregnancy for severe pelvic pain without vaginal bleeding. Ultrasounds showed that the GS was implanted in the cervix 18 mm away from the inner uterine orifice. Trophoblast seemed to be well-vascularised and to invade myometrium in the anterior-right wall of the cervix (Figure 1). The patient was hospitalised and we administered an intra-muscular injection of MTX (50 mg/mq) at day 1. At day 7, we repeated a second dose of MTX because the BHCG levels had not declined to 15% from the initial value. Neither ultrasound-guided curettage nor evacuation were required. No side effects or toxicity occurred after treatment. We measured weekly BHCG levels and performed ultrasound monitoring until BHCG was undetectable 30 days after the first administration Ultrasound findings of ectopic pregnancy disappeared after 40 days. Nine months later patient underwent an ICSI obtainiga singleton successful term pregnancy delivered by a scheduled caesarean section at 39 weeks’ gestation for breech presentation. No maternal or neonatal complication occurred.

Discussion The case we report is timely because it describes a patient with cervical pregnancy treated by MTX therapy obtaining a successful term singleton pregnancy 2 years later. Conservative management of cervical ectopic pregnancy is the most favorable option in women desiring future childbearing. The use of MTX can help preserve the fertility potential in cervical pregnancy and its use will become increasingly frequent in the coming years due to the increase of ART. Many techniques are involved in the conservative management: (1) systemic MTX either

Figure 1. 3D imaging of cervical pregnancy: gestational sac containing yolk sac and unviable embryo implanted in the cervix. Trophoblast seemed to be well vascularized and to invade myometrium using colour Doppler.

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in single or multiple doses (Sherer et al. 2004); (2) single transvaginal ultrasound-guided intra-amniotic instillation of MTX plus folic acid p.o. (Hassiakos et al. 2005); (3) transvaginal ultrasound-guided aspiration in combination with systemic single-dose MTX (Andrés et al. 2012) and (4) transvaginal ultrasound-guided intra-amniotic and intra-chorionic instillation of MTX with additional intracardiac foetal injection of 2 mL of potassium chloride (KCl) in case of cardiac activity (Jeng et al. 2007). However, additional treatment modalities seem to be necessary in a large proportion of women with cervical pregnancies, due to the primary MTX treatment failure. Surgical or combined medical-surgical treatments are (1) angiographic embolisation of the cervical, uterine or internal iliac arteries followed by curettage or MTX; (2) laparoscopyassisted ligation of uterine or internal iliac arteries followed by curettage or MTX; (3) intra-amniotical MTX followed by subsequent curettage (Adabi et al. 2013); (4) combination of MTX and mifepristone followed by subsequent curettage (Heikinheimo et al. 2004) and (5) complete resection by operative hysteroscopy or laparoscopy-assisted uterine artery ligation combined with hysteroscopic local endocervical resection. Advanced gestational age, high serum BHCG levels and the presence of a viable embryo are associated with higher rates of treatment failures. In patients with cervical pregnancy without embryonic cardiac activity, there is no reason to use to ultrasound-guided injection; therefore, systemic treatment with MTX should be the best choice. Verma et al. report the largest study about cervical ectopic pregnancies (25 cases) and indicate that non-surgical management by systemic MTX, combined with foetal intra-cardiac KCl injection in case of viable embryo, is a successful option in the vast majority of patients, in order to avoid haemorrhage, other complications and to preserve fertility (Verma and Goharkhay 2009). Very few cases of successful term pregnancy obtained after a cervical pregnancy are reported in literature, due to the condition of subfertility of many patients who developed cervical pregnancy after ART and the few studies describing the incidence of following pregnancies. This case supports the hypothesis that the use of MTX does not have negative effects on their subsequent fertility treatment (Ohannessian et al. 2014).

Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

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Cervical ectopic pregnancy treated with systemic methotrexate and following successful term pregnancy: case report.

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