Intrasaccular methotrexate treatment of cervical pregnancies maintains fertility: a case series

Keywords:

• Ectopic pregnancy
• heterotopic pregnancy
• cervical pregnancy
• heterotopic cervical pregnancy
• fertility-sparing
• intrasaccular methotrexate

Introduction

Cervical ectopic pregnancy is the rarest form of ectopic pregnancy, accounting for less than 1% of all cases, but it is the most lethal form. Bleeding associated with these conditions is life-threatening and frequently requires hysterectomy. An early diagnosis can allow conservative treatment for fertility preservation (Stabile et al. 2020).

Heterotopic pregnancy is a simultaneous intrauterine pregnancy and at least one ectopic pregnancy. Its incidence is increased when assisted reproductive technologies are used (Schivardi et al. 2021).

We present three cases, a heterotopic pregnancy (intrauterine-cervical) and two cervical ectopic pregnancies successfully treated with an intrasaccular injection of methotrexate (MTX) as a fertility preservation procedure. All patients signed a written consent form for inclusion in this report.

Case 1

A 35-year-old nulliparous patient with a history of primary infertility. In vitro fertilization was performed with antagonist protocol. Two fresh day-3 embryos were transferred. The patient reported mild transvaginal bleeding for one week without additional symptoms. The ultrasound revealed an intrauterine gestational embryo corresponding to 6.2 weeks gestational age with a normal fetal heart rate. A second gestational sac of 11 mm in diameter was found in the cervix with a 4-mm crown-rump length embryo inside with a normal heart rate. Three days later, under epidural anaesthesia, the cervical gestational sac was punctured with ultrasound guidance, a millilitre of amniotic fluid was aspirated, and 100 mg of MTX were injected. No complications were observed. At 38.4 weeks of gestation, a c-section was performed, with no complications.

Case 2

A 28-year-old patient with a previous c- section presented to our clinic with a pregnancy of 7.1 weeks of gestation. She complained of moderate transvaginal bleeding with no other symptoms. A vaginal ultrasound was performed, a gestational sac was observed in the cervix with a 9-mm crown-rump length embryo inside with a normal fetal heart rate. The same approach was performed on this patient. No complications occurred. Control ultrasonography was performed, the gestational sac in the cervix was absent a week after the procedure.

Case 3

A 40-year-old nulliparous patient presented to our clinic due to a 2-year history of infertility. She underwent to an in vitro fertilization. Two fresh embryos were transferred on day 3. An ultrasound evaluation was made two weeks after a positive ß-hCG, which revealed an empty uterus; however, a gestational sac with a 5-mm crown-rump length embryo with normal fetal heart rate was found in the cervix. The same procedure was performed without complications. Follow-up ultrasound confirmed the absence of the gestational sac one week later.

A 4-11 MHz transvaginal transducer of a LOGIQ P3 ultrasound system (General Electric Healthcare, Chicago, IL, USA) was used for the described procedures. For aspiration and administration of intrasaccular methotrexate, a double-lumen oocyte puncture set with a valve (CCD Laboratory, Paris, France) was used.

Discussion

We present three cases of cervical ectopic pregnancy; one was a heterotopic pregnancy managed successfully with an intrasaccular injection of 100 mg of MTX in which fertility preservation was achieved without increasing the complication rate.

A history of intrauterine curettage, assisted reproductive technologies, the use of intrauterine devices, and caesarean section have been suggested as predisposing factors for cervical pregnancy (Dilday et al. 2021).

Its clinical presentation generally consists of painless transvaginal bleeding after a period of amenorrhoea and a soft and disproportionately enlarged cervix (Hosni et al. 2014).

Early pregnancy ultrasound has three main objectives: to confirm the number and location of the embryos, establish whether the embryo can develop beyond the first trimester, and assess the risk of ectopic pregnancy (Kirk et al. 2020). According to The European Society of Human Reproduction and Embryology (ESHRE) ectopic pregnancy classification, ours can be classified as uterine ectopic pregnancies and subclassified as cervical and complete.

Transvaginal ultrasound is the gold standard for an accurate diagnosis of a cervical ectopic pregnancy (Mangino et al. 2014).

There is no standard treatment for this pathology, but historically hysterectomy was performed. As an alternative, the use of MTX has been reported for the treatment of hemodynamic stable patients while maintaining fertility potential. In this regard, a combined approach of MTX administered intramuscularly and into the gestational sac has been described. Ozcivit et al. (2020), reported a negative gonadotropin test after 90 days of a 75 mg MTX dose, 45 mg injected into the gestational sac and 30 mg intramuscularly. A case series that included 5 patients (Elmokadem et al. 2019) reported a successful treatment rate of 80% with UAE and MTX intraarterial infusion. As for multiple MTX doses, Oleksik et al. (2021) reported two cases treated with two doses of intramuscular MTX (50 mg/m²) at 7-day intervals with subsequent UAE.

Similarly, Monteagudo et al. (2019) reported a case series successfully treated with methotrexate injected into the gestational sac in addition to 100 mg administrated intramuscularly and placement of a foley catheter with a double intracervical catheter.

An intrasaccular injection of a lower dose of methotrexate (50 mg) was reported by Yamaguchi et al. (2017). In 11 of the 15 procedures performed, the pathology was resolved. Three patients required an additional intrasaccular dose of methotrexate and one patient required uterine artery embolisation to resolve the condition.

In our report, a single intrasaccular dose of 100 mg of methotrexate was enough to resolve a cervical ectopic pregnancy without additional medical or surgical interventions. In contrast to intramuscular injection, local treatment with methotrexate can be used even in the presence of intrauterine pregnancy, blood dyscrasias, liver, kidney, gastric, or pulmonary disease (ACOG Practice Bulletin No. 193 2018). It offers a safe way to treat while preserving the patients’ reproductive potential.

In conclusion, management of cervical ectopic and heterotopic cervical pregnancy through intrasaccular injection of methotrexate is a safe and effective treatment with few adverse effects and complications. This report adds to the evidence that supports its use whilst preserving fertility.

Study registration/ethics committee approval

Due to the study nature, it was unnecessary to register it on the ethics committee.

Disclosure statement

No potential conflict of interest was reported by the author(s).