Combined intrauterine and extrauterine gestation

This is the report of a patient, that had without using any assisted reproduction technology (ART) the rare event of a heterotopic pregnancy. After verifying the intrauterine pregnancy by ultrasound, the ectopic tubal pregnancy (EP) was detected at an emergency abdominal surgery as the cause of an intraabdominal hemorrhage. After removal the further pregnancy was uncomplicated. Received: 14 April 2000 / Accepted: 31 July 2000     

Ruptured extrauterine pregnancy

Extrauterine pregnancies contribute substantially to maternal mortality in all parts of the world. The most common cause of these deaths is massive bleeding after rupture of the ectopic pregnancy. The advent of transvaginal ultrasonography in early pregnancy and the use of quantitative measurement of the β-unit of human chorionic gonadotropin have revolutionized the management of this condition. These diagnostic modalities allow its early detection and, in many cases, treatment before rupture occurs. There is an ever increasing body of evidence supporting expectant, medical, and surgical management of ectopic pregnancy according to certain criteria. The indications and criteria for the different management options are described in the literature and in clear guidelines from institutions such as the Royal College of Obstetricians and Gynaecologists. Methotrexate, in a single dose protocol, is widely used in the medical management of ectopic pregnancy. Surgical therapy can be either laparoscopic or via laparotomy. Be that as it may, ruptured ectopic pregnancy will continue to present as a gynecologic emergency requiring prompt and appropriate care. Resuscitation of these patients should be an organized, systematic, and rapid process with the ultimate goal of getting them to the operating theatre in the best possible hemodynamic status. The aim of surgery should be to stop active bleeding by the most expedient method. The use of autotransfusion is well established in cardiac surgery, vascular surgery, orthopedic surgery, and trauma. Using autologous blood should be considered also in the treatment of ruptured extrauterine pregnancy when faced with massive bleeding and a need for transfusion. Advanced abdominal pregnancy is a rare condition with high perinatal and maternal morbidity and mortality. Placental management at delivery remains a dilemma. The risk of massive bleeding upon removal must be balanced against the risk of infection and other complications during the long time needed for resorption of the placenta if left in situ. Despite a reduction in maternal mortality due to ectopic pregnancy in the developed world during the preceding period, it would appear that no further inroads have been made in the last two decades. In developing countries, the problem is far greater, and problems with resources and infrastructure persist. It remains a challenge to all practitioners caring for women to apply available resources and use the published evidence-based guidelines to manage these women effectively and safely.     

Single-dose methotrexate for the treatment of unruptured ectopic pregnancy

Objective The objective of this study was to review our experience with single dose intramuscular methotrexate (MTX) for the treatment of ectopic pregnancy and to evaluate major confounding factors that relate to the success of therapy.Patients and methods The selection criteria were patients who had a stable hemodynamic status and an ectopic gestational mass of <4 cm. on ultrasound. Patients were not excluded from MTX therapy either by a baseline serum -hCG titer or by the presence of fetal cardiac activity demonstrated on ultrasonography. Thirty- four of 86 patients diagnosed with ectopic pregnancy and treated with single-dose MTX between July 1999 and November 2001 were reviewed retrospectively.Results The mean pre-treatment -hCG level was 2,490±2,912 mIU/ml. Twenty-two patients (73.3%) were successfully treated with a single-dose of MTX. Eight patients (26.6%) required a second dose 1 week after the first injection and 2 patients received three doses. Thirty of the 34 patients (88%) were successfully treated with MTX. The mean pre-treatment -hCG level was significantly lower in patients who were successfully treated with MTX than in patients who failed MTX therapy (1,932±2,361 mIU/ml vs. 6,955±2,690 mIU/ml respectively, p<0.05). The mean pre-treatment serum -hCG level was higher in patients who had a second MTX injection as compared to patients who were successfully treated with a single injection of MTX (3,272±3,551 mIU/ml vs. 1,280±2,273 mIU/ml respectively, p>0.05). The mean time to resolution of -hCG was 26.5 days (10 to 37 days) with MTX. All 3 patients who failed medical therapy had -hCG level >4,000 mIU/ml and 2 of them had positive fetal cardiac activity.Conclusion In conclusion, this study showed that medical treatment of ectopic pregnancy with systemic single-dose methotrexate seems to be an option for some patients with unruptured tubal pregnancy.     

氨甲喋呤单次静脉注射治疗异位妊娠63例分析

探讨氨甲喋呤单次静脉注射治疗异位妊娠的效果和适应证。方法对６３例患者随机分成Ａ、Ｂ两组。Ａ组３１例采用ＭＴＸ１００ｍｇ加生理盐水２０ｍｌ静注,不用甲酰四氨叶酸解毒。Ｂ组３２例应用同剂量ＭＴＸ后１２－２４小时内用ＣＦ１０－１２ｍｇ解毒。定期测血β－ｈＣＧ直至正常。     

Comparison of multidose and single-dose methotrexate protocols for the treatment of ectopic pregnancy

OBJECTIVE: The purpose of this study was to compare success rates of 643 patients who had ectopic pregnancy from the same database who were treated with multidose or single-dose methotrexate protocols. STUDY DESIGN: We compared demographics, gestational age, serum human chorionic gonadotropin, progesterone levels, ectopic sac size and volume, overall ectopic mass size and volume, ectopic cardiac activity, history of ectopic pregnancy, number of treatment days, methotrexate doses, and outcome in consecutive patients with ectopic pregnancy who were treated with methotrexate. RESULTS: Success rates were comparable between patients with multidose and single-dose therapy (95% vs 90%, respectively) as were human chorionic gonadotropin and progesterone levels, history of ectopic pregnancy (21.4% vs 21.7%, respectively), number of treatment days, gestational age, ectopic size, ectopic volume, and ectopic mass volume. Patients who received single-dose therapy were significantly heavier (146 vs 159 pounds), had greater ectopic cardiac activity (3.1% vs 10.3%), and received fewer methotrexate doses. CONCLUSION: This study suggests single-dose methotrexate therapy is as effective as multidose methotrexate therapy for the treatment of ectopic pregnancy.     

Transvaginal ultrasound-guided aspiration and instillation of hyperosmolar glucose for treatment of unruptured tubal heterotopic pregnancy

Objectives To report a case of tubal heterotopic pregnancy (HP) treated conservatively with transvaginal ultrasound-guided aspiration and instillation of hyperosmolar glucose. Methods Aspiration of the tubal ectopic pregnancy and hyperosmolar glucose instillation was performed with a 16-gauge needle under transvaginal ultrasound guidance. Results Unruptured tubal HP with positive cardiac activity was treated successfully without any further interventions, and intrauterine pregnancy has reached full-term without any complications. Conclusions Early diagnosis of this life-threatening condition is the key to its successful treatment. Transvaginal ultrasound-guided aspiration and hyperosmolar glucose injection can be safely performed for the treatment of unruptured tubal HP.     

Serial serum human chorionic gonadotropin (hCG) levels in ectopic pregnancy and first trimester miscarriage

Serial serum hCG levels were measured in 50 patients with a tubal ectopic pregnancy and 50 patients with spontaneous miscarriage of an intrauterine pregnancy. Serum samples were obtained at intervals of 3–5 d and more frequently if clinically indicated. The final diagnosis was confirmed by laparoscopy and/or dilatation and curettage. Data were analyzed using a linear regression model. Initial hCG concentrations ranged from 91 to 3,050 mIU/mL. Eighty percent of ectopic pregnancies and 35% of miscarriages were associated with rising hCG concentrations and no significant differences were noted in daily increments of hCG in the two groups (210 ± 30 mIU/mL/day for ectopic pregnancies versus 311 ± 55 mIU/mL/d for miscarriages). Twenty percent of ectopic pregnancies and 65% of miscarriages had falling hCG concentrations and significant differences were noted in the daily decrements of hCG for EP and AB (270 ± 52 mIU/mL/day for ectopic pregnancies versus 578 ± 28 mIU/mL/d for miscarriages (P≤ 0.05). Received: October 1999 / Accepted: 13 December 1999     

Evaluation of the relationship between endometrial thickness and failure of single-dose methotrexate in ectopic pregnancy

Objective: To test the hypothesis that endometrial stripe thicker than 12 mm increases treatment failure of single-dose methotrexate for the management of ectopic pregnancy. Study design: Seventy-three patients with ectopic pregnancy and measured pretreatment endometrial stripe were divided into two groups based on the endometrial stripe thickness (>12 mm or ≤12 mm). All patients were candidates for single-dose methotrexate treatment. Variables analyzed between the two groups were endometrial stripe thickness, initial beta human chorionic gonadotropin level (hCG), size of the ectopic mass, presence of fetal heart tones, previous ectopic pregnancy, and clinical outcomes. Results: Sixty patients had endometrial stripe thickness ≤12 mm and 13 patients >12 mm. The two groups were similar in initial hCG, size of ectopic mass, presence of fetal heart tones and rate of previous ectopic pregnancy. The failure rate was significantly higher in the group with endometrial stripe >12 mm compared to the group ≤ 12 mm (n=7, 53% vs. n=3, 5%, P<0.01). The endometrial stripe was significantly thicker in the group with endometrial stripe thickness >12 mm compared to the group ≤12 mm (mean ± SD, 17.64±5.82 mm vs. 7.69±2.82 mm, P<0.01). Conclusion: Endometrial stripe thicker than 12 mm increases the risk for treatment failure with single-dose methotrexate.     

甲氨蝶呤联合米非司酮与中药宫外孕I号方治疗异位妊娠疗效的对比观察

目的观察比较甲氨蝶呤（MTX）联合米非司酮与配伍中药治疗有生育要求且未破裂型异位妊娠的临床疗效。方法：把入选的126例患者随机分为A、B两组,A组采用MTX联合米非司酮杀胚,B组采用MTX配伍中药保守治疗,比较两组临床疗效。结果在血β-HCG水平降至正常,治愈的时间及包块消失时间等方面比较,A组显著优于B组（P〈0．05）。而在治愈率、输卵管再通率、妊娠成功率等方面比较,两组差异无统计学意义（P〉0．05）。结论：MTX联合米非司酮可以缩短患者住院时间,见效快,值得临床推广。     

Cervical pregnancy treated with transvaginal ultrasound-guided intra-amniotic instillation of methotrexate

Aim Aim of the study was to investigate the efficacy of single transvaginal ultrasound-guided intraamniotic installation of methotrexate in the management of cervical pregnancy with concurrent review of the literature.Materials and methods Six patients with cervical pregnancy are included in the study. All patients were treated with single transvaginal ultrasound-guided intraamniotic installation of 70 mg of methotrexate plus folic acid p.o. The main presenting symptoms were mild to moderate vaginal bleeding and lower abdominal cramp-like pain, resembling the clinical presentation of a threatened abortion. The typical ultrasound findings were the absence of intrauterine gestational sac and the detection of a gestational sac within the cervical canal, invading the anterior or the posterior wall of the cervix and normal appearance of the adnexa, bilaterally. The hourglass-shaped cervix was not characteristic at 5 weeks of gestation but it was at 8 weeks of gestation.Discussion Ultrasound-guided intraamniotic installation of methotrexate in the management of cervical pregnancy appears to be an effective and safe method but the choice of the method should be depended on the gestational age of cervical pregnancy, the presence of active bleeding or not and its severity, the desire for preservation of future fertility, the presence of coexisting valuable intrauterine pregnancy and the experience of the physician in charge.     

Human chorionic gonadotropin patterns after a single dose of methotrexate for ectopic pregnancy

Objective: The great variability in human chorionic gonadotropin (HCG) levels after a single dose of methotrexate (MTX) for ectopic pregnancy makes it difficult to predict treatment failure. We describe different patterns of HCG levels. Study design: Fifty patients were injected i.m. with 50 mg/m² of MTX for an ectopic pregnancy. Venous blood samples for HCG detection were obtained on the day of treatment (day 0), day 3 and day 7 and weekly until values were undetectable. Patients were classified as: group 1, persistent pathology (n=11); group 2, complete resolution with a decrease of HCG levels at day 3 (n=30); group 3, complete resolution after a rise of HCG values at day 3 (n=9). Statistical analysis was performed using the Mann–Whitney non-parametric test with 95% confidence intervals. Results: Values of day 0 were similar for all the groups. HCG levels of group 3 decreased rapidly after day 3 and at day 7 they were significantly different from levels of group 1. Differences in HCG levels between groups 2 and 3 became indistinguishable from day 21. Conclusion: The observation of patients undergoing resolution after an initial increase of HCG levels justify an expectant management for 1 week in clinically stable patients. The strategy to separate HCG curves in patients undergoing resolution may shed light on the different clinical responses to therapy for ectopic pregnancies. However, the phenomenon of the immediate rise of HCG should be better investigated.     

Recurrent cornual pregnancy after heterotopic cornual pregnancy successfully treated with systemic methotrexate

This report concerns a recurrent spontaneous cornual pregnancy 2 years after selective feticide of a heterotopic cornual pregnancy which occurred after IVF for tubal pathology. The recurrent cornual pregnancy was treated successfully with systemic methotrexate. Assisted reproductive techniques, especially in patients with tubal pathology, and non-invasive management of cornual pregnancies may lead to a higher incidence of recurrence.     

Ectopic pregnancy

Ectopic pregnancy is a implantation occurring elsewhere than in the cavity of the uterus, whereas nintynine percent of extrauterine pregnancies occur in the fallopian tube. The incidence of extrauterine pregnancy has increased from 0.5% thirty years ago, to a present day 1–2%. The most frequent cause of tubal pregnancy is previous salpingitis. Mortality rates for tubal pregnancies used to be approximately 1.7% in the 1970 s but dropped to 0.3% in 1980 s. Diagnosis: Using transvaginal ultrasound it is possible to obtain positive evidence of an ectopic pregnancy at a very early stage. In cases of hCG titers>2000 IU/l, intrauterine pregnancy can be diagnosed with certainty. The most important differential diagnosis of ectopic pregnancy is early intrauterine pregnancy. Clinical management and therapy: Regardless of the therapeutic strategy selected by the physician, informing the patient is a major aspect of the management of ectopic pregnancy. If surgery is considered appropriate, the patient must be informed about the nature, side effects and complications of the procedure. However, it should be remembered that in some cases, the actual chances of cure first become apparent at surgery. In asymptomatic patients with a serum hCG titer <1000 IU/l that is falling, it is appropriate to wait and watch. In clinically stable patients with an unruptured tubal pregnancy and steady hCG levels, systemic treatment with methotrexate might also be considered. In unruptured tubal pregnancy with a hCG titer between 1000 and 2500, a further therapeutic alternative is intratubal injection of prostaglandins, hyperosmolar glucose of NaCl. Generally speaking, the currently widespread laparoscopic surgical treatment of the fallopian tube hardly influences the risk of recurrence. If the gestational mass is larger, the serum hCG titer higher than the approximate limit of 2500 mU/ml and/or the tube already ruptured, surgery is usually required. Prevention: The most effective prevention is to avoid tubal inflammation or, in cases of preexisting inflammation, to administer effective therapy. Received: December 1998 / Accepted: 25 May 1999     

异位妊娠药物治疗三种方法比较

目的　寻找一种简单、有效、成功率高又不影响生育功能的异位妊娠的药物治疗方法。方法　 94例患者分氨甲喋呤 (MTX)单次注射 (A组 ) ,单纯中药 (B组 )及MTX单次注射配合中药联合治疗 (C组 )进行比较。结果　C组较A、B两组能明显缩短血 β-hCG(绒毛膜促性腺激素 )降至正常范围的时间 ,减少住院日 ,提高治疗成功率(P <0 0 1)。结论　MTX单次注射配合中药治疗异位妊娠 ,疗效高 ,副作用小 ,可作为临床首选治疗方案     

Efficacy of methotrexate treatment in extrauterine pregnancies defined by stable or increasing human chorionic gonadotropin concentrations

OBJECTIVE: To evaluate the efficacy of methotrexate treatment in selected cases of extrauterine pregnancy (EUP) defined by stable or increasing hCG concentration. DESIGN: Prospective cohort study. SETTING: Gynecology department of the Lis Maternity Hospital. PATIENT(S): Fifty women with EUP diagnosed whenever an intrauterine gestational sac was not seen on transvaginal ultrasonography. INTERVENTION(S): Women received IM methotrexate at a dose of 50 mg/m(2) of body surface area. Failure of hCG levels to fall by >/=15% during any successive week resulted in repeated administration of methotrexate. Surgical intervention was performed for presumed tubal rupture. MAIN OUTCOME MEASURE(S): Serial hCG measurement was performed weekly until hCG concentration reached 15 mIU/mL. Success was defined as the achievement of hCG concentration of 25 mIU/mL without surgical intervention. Result(S): Forty-four women (88%) were successfully treated. The mean time from first methotrexate injection to success was 34 +/- 2.4 days. Women treated successfully and unsuccessfully differed significantly only with regard to serum hCG levels of 1,876 +/- 243 and 3,489 +/- 376 mIU/mL, respectively. When the initial hCG levels were lower or higher than 2,000 IU/L, the success rate was 97% and 74%, respectively (significant by Fisher's exact test). CONCLUSION(S): When methotrexate treatment is administrated in a selected group of EUP defined by stable or increasing hCG, it may fail more frequently (26%) when initial hCG levels are >2,000 mIU/mL.     

Tubal patency after clinical treatment of unruptured ectopic pregnancy.

OBJECTIVE: To evaluate tubal patency using hysterosalpingography after clinical treatment of tubal pregnancy. METHOD: Of 80 patients who underwent hysterosalpingography after clinical treatment of tubal pregnancy from April 1994 to February 2002, 30 were treated with a single 50 mg/m(2) dose of methotrexate intramuscularly (n=30) and 50 were followed up expectantly. RESULTS: Patency of the ipsilateral tube was 84% after methotrexate treatment and 78% after expectant management. In addition, contralateral tubal patency was 97% after methotrexate treatment and 92% after expectant management. There were no statistically significant differences between the groups. CONCLUSION: Findings from this study suggest similar tubal patency rates after methotrexate treatment and expectant management.