Successful conservative treatment of a 14‐week gestational age cervical pregnancy by primary local injection of single‐dose intra‐amniotic methotrexate and intracardiac potassium chloride feticide (2006)

Many surgical or medical conservative treatments were developed to avoid castrating hysterectomy, so that the patient's fertility could be preserved. These procedures were often combined with intra-muscular, intra-arterial, or intra-amniotic methotrexate (MTX) administration. Regardless of the described treatment, the gestational ages of all reported cases were early at 12 weeks or fewer of gestation. We report a case of cervical pregnancy with the most advanced gestational age in the English literature up to now, which was successfully treated with conservative medical management. A 31-year-old woman, gravida 5, para 4, with a history of three cesarean sections, was referred from a local obstetric clinic due to a viable cervical pregnancy. She complained of vaginal bleeding of several days duration. Calculations based on her last menstrual period yielded a gestational age of 14 weeks. Both her medical history and her gynecologic history were unremarkable. On examination, her vital signs were stable, and she was not in any acute distress. Her general physical examination was within normal limits. Pelvic examination revealed a mildly bulging cervix containing blood clots and no active bleeding from the cervical os. A urinary pregnancy test was positive. Transvaginal ultrasonographic examination showed a generally empty uterine cavity containing only a few blood clots and a fetus appropriately sized for the estimated gestational age (crown-rump length of 7.5 cm) located in the cervical canal (Fig. 1). Fetal cardiac activity could be seen. Serum β-human chorionic gonadotropin (hCG) concentrations were 32 085 mIU/ml (first reference preparation). After obtaining informed consent, which included discussing the potential risks, alternative methods of treatment, and the patient's strong desire to preserve uterus, we decided to perform transcervical feticide with MTX and potassium chloride (KCl) to arrest fetal viability. Prior to treatment, 1000 ml of whole blood was prepared for emergency surgery, should surgery and blood transfusion be necessary. Under general anesthesia, a 22-gauge needle was placed through the anterior cervical wall into the amniotic sac using transvaginal ultrasonographic guidance. One milliliter (40 mEq) of KCl was injected into the fetal heart to stop the fetal heartbeat, and the intra-amniotic fluid was partially aspirated followed by injection of 50 mg of MTX into the amniotic cavity and chorionic villi. The patient tolerated the procedure without any difficulty. The estimated blood loss was minimal, and she was transferred to the postoperation recovery room in stable condition. Her postoperative course was uneventful. Two days later, she was discharged in good condition. There was no vaginal bleeding or other adverse effect after the procedure. During the follow-up period, the serial changes of the uterus and cervix were monitored using transvaginal ultrasound. The cervix had no mass on the 53rd day after the operation. Serial serum β-hCG concentrations were measured weekly. β-Human chorionic gonadotropin became less than 10 mIU/ml on the 49th day after the operation. Vaginal spotting occurred intermittently. Complete blood count and liver and renal function did not change significantly. Menstruation resumed 2 months later. The patient spontaneously conceived another fetus 3 years later, but the pregnancy ended in idiopathic intra-uterine fetal death at 29 weeks of gestational age. During a recent 40-year period, although the maternal mortality rate of cervical pregnancy decreased from 45 to 0%, the hysterectomy rate was still as high as 15% 1. Several conservative treatment procedures have been suggested for the management of cervical pregnancy in an attempt to gain hemostasis and avoid hysterectomy, but they are not recommended beyond 12 weeks gestational age 2-6. One study demonstrated that for patients with cervical pregnancies, a gestational age of ≥9 weeks, serum β-hCG concentration of ≥10 000 mIU/ml, a crown-rump length ≥10 mm, and embryonic cardiac activity were associated with a significantly increased risk of an unsatisfactory result with primary MTX treatment 4. Nonetheless, that study also suggested that for a patient with a living cervical pregnancy, intra-cardiac injection of KCl, intra-amniotic instillation of MTX, or direct cardiac puncture to stop the embryonic cardiac activity is effective to decrease the potential risk of MTX treatment failure. Another study revealed that intra-amniotic injection with MTX, KCl, or a combination of these two agents provided the advantage of immediate fetal death and appeared to also enhance the effectiveness of aberrant trophoblast eradication 7. After systemic MTX injection, 29% of the patients had side-effects such as gastrointestinal upset, pharyngitis, somatitis, elevated serum liver enzyme activities, leukopenia, thrombocytopenia, conjunctivitis, and fever. However, none of the patients who underwent local injection reported any side-effect 8. Local MTX administration avoided the side-effects of systemic administration. In our case, this simple, local procedure was successful and supported their suggestions. We present a case of advanced gestational age (14 weeks) cervical pregnancy successfully treated with only primary local injection of intra-amniotic MTX and KCl feticide guided by ultrasonography, without any other additional procedures. To the best of our knowledge, this is the first report of a patient with such a gestational age cervical pregnancy treated with simple, conservative treatment. The patient had no massive vaginal bleeding requiring the need for control by any other procedure. The gestational sac resolved spontaneously without complication. We think the fetus became fetus papyraceus finally. We suggest that for a patient with a cervical pregnancy in the early second trimester, primary local injection of MTX combined with KCl feticide may be the conservative treatment of choice. Nonetheless, the clinician must be prepared to control severe, potentially life-threatening hemorrhage, should it occur. Our patient spontaneously conceived 3 years later, but unfortunately, the pregnancy ended in idiopathic, intra-uterine fetal death at 29 weeks of gestation. We do not know whether or not this condition was caused by our previous conservative treatment. But we did have several cases of live births after MTX local medical treatment for cervical pregnancy. There are reports of live births after treatment for cervical pregnancy, although no pregnancy occurred in patients whose cervical pregnancy was greater than 12–14 weeks gestational age 9. One study revealed that according to the observation of 11 patients experiencing cervical pregnancy, MTX local administration is not likely to increase the risk of fetal anomalies or spontaneous abortion of later conceptions 8. They suggested a minimum of 8 months of follow-up before attempting subsequent pregnancy following cervical pregnancy to ensure adequate functional recovery of the cervix. In conclusion, early diagnosis of cervical pregnancy makes conservative treatment possible and can preserve the patient's fertility. However, if an advanced or an early second trimester cervical pregnancy is encountered, conservative treatment, as in our case, may still be tried.