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Cervical pregnancy after in vitro fertilization and embryo transfer successfully treated with methotrexate and intracervical injection of vasopressin

2003; Informa; Volume: 83; Issue: 1 Linguagem: Inglês

10.1111/j.1600-0412.2004.0033b.x

1600-0412

Bih‐Chwen Hsieh, Yu‐Hung Lin, Lee‐Wen Huang, Jier‐Zen Chang, Kok‐Min Seow, Hun‐Shan Pan, Jiann‐Loung Hwang,

Gestational Trophoblastic Disease Studies

Cervical pregnancy is a rare condition associated with a high rate of maternal morbidity. If not detected and treated early, it may become an acute obstetric emergency (1–3). With the aid of high-resolution ultrasonography, this entity can be diagnosed at an earlier gestational age (4). Primary hysterectomy is no longer the initial therapy in any case of cervical pregnancy. However, management of this condition has not been standardized. For a woman who wants to preserve fertility, conservative treatment of cervical pregnancy using chemotherapy with methotrexate (MTX) is the most widely used modality (1–3). In this report, we describe a case of viable cervical pregnancy, which developed after in vitro fertilization and embryo transfer (IVF/ET). The case was successfully treated using a procedure combining intra-amniotic MTX and intracervical injection of a vasoconstricting agent to stop heavy bleeding. No surgical intervention or curettage was needed. The uterus and the patient's reproductive capability were preserved successfully. A 34-year-old woman with an 11-year history of unexplained primary infertility received IVF-ET at our clinic. She had previously been treated at another IVF center due to a long history of infertility but to no avail. Her past medical history was unremarkable and there was no previous surgical history. Her gynecologic history revealed no pelvic inflammatory disease, previous intrauterine procedure, or intrauterine devices. A hysterosalpingogram showed right side tubal obstruction at the proximal end. After ovulation induction with human menopausal gonadotrophin and gonadotropin-releasing hormone, 21 oocytes were retrieved by the transvaginal route, and 10 oocytes were fertilized. Because of the patient's strong desire for pregnancy, four embryos (two grade II embryos, one grade IV embryo that was an irregular blastomere, and one grade IV embryo that was a regular or irregular blastomere and had many fragments) were easily transferred to the uterus using a Wallace catheter under ultrasonographic guidance. Thirty-three days after embryo transfer, she visited our hospital due to irregular vaginal spotting. Her vital signs were stable. Pelvic examination revealed an enlarged and bluish barrel-shaped uterine cervix with minimal bleeding through the closed external os. The uterus was slightly enlarged and no adnexal masses were seen. Ultrasound examination showed an empty uterine cavity. The dilated cervix presented with an hourglass shape and a gestational sac containing fetal cardiac activity with a crown-rump length of 0.38 cm corresponding to a gestational age of 7 weeks was observed within the cervix (Fig. 1). Under the impression of cervical pregnancy, she was admitted for further evaluation. Beta-human chorionic gonodotropin (β-hCG) was 12920 mIu/mL and complete blood count, liver and renal function data were within normal limits. In order to preserve fertility, we offered the patient conservative treatment with MTX. The potential risks and alternative methods of management, including the possible need for a hysterectomy were explained and written informed consent for the procedure was obtained. After preparation of the abdomen with betadine solution, 5 mL of hemorrhagic amniotic fluid was aspirated with a 22-gauge needle under transabdominal ultrasound guidance, then 50 mg of MTX was injected into the gestational sac. After the procedure, the patient did not feel any discomfort. However, massive vaginal bleeding of about 1800 mL was noted the next day and her hemoglobin decreased to 6.6 g/dL. An immediate blood transfusion was given with 10 units of packed red cells and 4 units of fresh frozen plasma. But the bleeding remained continuous and heavy. Because of the patient's strong desire to preserve her childbearing function, cervical injection of 2 ampules of vasopressin diluted with 60 mL of saline was administered. The bleeding ceased dramatically and no uterine curettage or any other surgical intervention was needed. Vaginal gauze was placed into the cervix. On the following day after the vaginal gauze was removed, only a little oozing of coffee ground fluid was noted. Four days later, β-hCG had decreased to 667.03 mIu/mL and vital signs were stable. She was discharged and followed up at our clinics. Two weeks later β-hCG was 128.05 mIu/mL and it had decreased to nonpregnant status at 57 days after discharge. Her menstrual cycle resumed again 10 days later. Initial longitudinal sonogram of the uterus shows cervical gestation occupying the dilated endocervical canal. The uterine corpus is normal in size with an empty endometrium. Cervical pregnancy is an uncommon and dangerous form of ectopic pregnancy. The incidence of cervical pregnancy is not known but it is estimated to vary from 1/1000 to 1/50000 (1) and probably accounts for < 1% of ectopic pregnancy (4). Ginsburg et al. (5) illustrated a high risk for cervical pregnancy in IVF patients (3.7% vs. 0.01–0.006% in spontaneous conception). The diagnosis of cervical pregnancy is frequently delayed and is often made intraoperatively in the presence of extensive hemorrhage, necessitating an emergency hysterectomy in about 50% of cases (1–3). The availability of ultrasonography has allowed cervical pregnancy to be treated at an early gestational age and conservative methods have replaced hysterectomy as the preferred management (3). The etiology of cervical pregnancy remains unclear, but reported predisposing factors include anatomical anomalies, myomas, synechiae, and previous cervical interventions resulting in damage to the endocervical mucosa (1,4,6). It seems logical that one or more of the above factors in association with cervical stenosis may trap an embryo in the cervix and cause cervical implantation (7). Transport of the fertilized ovum that is too rapid or the presence of an endometrium that is too immature to accept the fertilized ovum may also cause cervical pregnancy (1). Ginsburg et al. (5) proposed that reflux of the embryos into the cervix after transfer or trauma to the cervix during ET are two possible contributing factors to cervical pregnancy and that identification and awareness of any previous damage to the endometrium, which may increase the incidence of cervical pregnancy, is therefore important. Cervical manipulation and misplacement of embryos have been implicated as risk factors for cervical pregnancy (8). There are several reports regarding cervical pregnancy related to assisted reproductive techniques (5,9–11). In all of these cases the patients had previous uterine or tubal pathology. Our patient had no previous intervention of the uterus, with obstruction of the right tube being the only pathological finding. This case illustrates that even with correct placement of the catheter tip and absence of known endometrial damage, cervical pregnancy can still occur. In this case, four embryos were transferred under the informed consent of the patient who strongly desired pregnancy despite a possible increased risk of ectopic implantation due to transfer of a larger number of embryos. Several forms of treatment have been reported, including nonsurgical and surgical methods. Ushakov et al. (4) reviewed the many variations in surgical treatment, such as cervical cerclage after evacuation, ligation of the internal iliac arteries or cervical branch of the uterine arteries and placement of a Foley catheter for compression, and embolization of the uterine artery under angiographic control (4). Among the nonsurgical methods, the folinic acid antagonist (MTX) is the most popular agent. Dall et al. (12) reported that MTX seems to stop invasion of trophoblastic tissue and that a hysterectomy could be avoided in 50% of cases when MTX is used in combination with other therapeutic methods. Kaplan et al. (13) reported a good outcome in a patient treated with injection of MTX into the amniotic sac after aspiration of amniotic fluid. Some authors have reported that MTX treatment is more likely to be successful under the following circumstances: earlier gestational ages, smaller cervical size, absence of fetal cardiac activity and lowβ-hCG (14,15). Other reports have suggested that parenteral MTX should not be used in treating cases with fetal cardiac activity because of the high failure rate. The main advantage of administration of MTX directly into the amniotic sac compared with parenteral administration are its greater effectiveness, shorter treatment time, reduced dosage, and absence of side-effects and toxicity (13,15,16) such as G-I irritation, myelosupression, and hepatic irritation (4). In our patient, fetal cardiac activity was present and the β-hCG level was high. We used intra-amniotic instillation of MTX as the initial treatment. Nevertheless, intractable bleeding developed. The bleeding could have been the result of trophoblast-decidua shedding from the uninvolutional and atonic cervix because of the effect of MTX or due to tissue necrosis and sloughing (17). In our patient, intracervical injection of diluted vasopressin dramatically decreased the bleeding. Vasopressin is a neurohypophyseal hormone that can cause vasospasm. It is used in gynecologic surgery such as myomectomy, dilation, evacuation and curettage and hysteroscopy, for the prevention and control of acute hemorrhage or excessive blood loss (18). The cervix itself is comprised mostly of fibrous connective tissue with only 15% smooth muscle (19). No contractile myometrium is present within the cervix, so hemorrhage resulting from the disruption of a cervical implantation should not be expected to have a good response to methergin or the local injection of prostaglandin (20). The advantage of vasopressin over other vasoconstrictors includes its short half-life (10–20 min), minimal side-effects and its ability to cause active contraction of the smooth muscle of the GI tract, uterus and all components of the vascular bed (18). When treating patients with IVF, it is important to be aware of any previous potential trauma of the uterine cavity, which increases the risk of cervical pregnancy. Treatment of cervical pregnancy depends upon the timing of diagnosis and desire to preserve future fertility (21). There are no consensus guidelines for treatment. Even with conservative management one must recognize the danger of hemorrhage. Patient should be counseled concerning the possible need for a hysterectomy. The conservative treatment of intra-amniotic MTX can avoid the adverse effects of systemic MTX, but when profound bleeding develops, intracervical injection of vasopressin, which is a vasoconstrictor, can cease the bleeding without any surgical intervention or curettage. This method may be a useful alternative for treating cervical pregnancy. Hun-Shaun Pan Department of Obstetrics and Gynecology Shin Kong Wu Ho-Su Memorial Hospital No 95 Wen Chang Road Shin Lin District Taipei Taiwan e-mail: m004407 @ms.skh.org.tw