Mifepristone in combination with methotrexate for the medical treatment of tubal pregnancy: a randomized, controlled trial

In the search for a more potent alternative to a single i.m. injection of methotrexate for ectopic pregnancy, a randomized trial was organized. The efficacy of a combination of methotrexate and mifepristone was compared with methotrexate alone in the treatment of unruptured tubal pregnancies. The diagnosis of an unruptured tubal pregnancy was confirmed laparoscopically in 50 patients during a 2 year period. Women were randomized to receive a single i.m. injection of 50 mg/m2 methotrexate alone or a single dose of 600 mg oral mifepristone in combination with the same dose of methotrexate. Both treatment protocols were successful in achieving the resolution of unruptured ectopic pregnancy (18/25 in the methotrexate group and 22/25 in the combination group) following the initial intervention. A second injection was needed in four (16%) cases in the methotrexate group and in one (4%) case in the combination group. Overall, a complete resolution was achieved in 22/25 and 23/25 cases respectively. Unruptured ectopic pregnancy resolved faster in women given the combination of methotrexate and mifepristone compared to women given methotrexate only (P = 0.01). The effect of the methotrexate and mifepristone combination was more pronounced in women with higher human chorionic gonadotrophin concentrations.     

Selective salpingography and tubal cannulation through hysteroscopy

In this paper the procedure of selective salpingography and tubal cannulation through hysteroscopy for diagnosis and treatment of fallopian tube obstruction at the interstitial portion was introduced. We combined hysteroscopic tubal cannulation with selective salpingography under fluoroscopic quidance in 28 infertile women with 49 obstructed interstitial portion of fallopian tubes diagnosed previously. After the procedures 27 tubes (55.1%) became patent in 16 cases. In 16 women with patent tubes followed up over 6 months after the procedures 5 intrauterine pregnancies occurred. This procedure is a safe and simple diagnostic method to identify fallopian tube obstruction at the interstitial portion and may alos serve as a therapeutic approach in some of these patients.     

Clinico-pathologic study of 285 cases of ectopic pregnancy in intrauterine devices-users and non-intrauterine devices-users

Two hundred eighty five cases of ectopic pregnancy in Beijing area from Jan. 1 to Dec. 31 1990 including 150 cases of intrauterine devices (IUD) and 135 cases of non-IUD users were studied. Clinico-pathological observation included the history of pelvic inflammatory disease, the site of ectopic pregnancy, the classification of previous tubal inflammation of the ectopic side and other pathologic lesions, the side of the corpus luteum of pregnancy and histology of endometrium, etc. Besides, using stereologic technique the cilia length and cilia density of endosalpinx were studied in 50 cases through image analysis system. Results showed that except for a significant higher frequency of ovarian pregnancy in IUD-users, there was no significant differences between the 2 groups. It indicated that the degree of injury of fallopian tubes and the factors causing the damage were similar in both groups. The authors concluded that IUD does not increase the risk of fallopian tube lesions.     

Insulin levels after portal and systemic insulin infusion differ in a dose-dependent fashion

BACKGROUND: Before the advent of the falloposcope, the endosalpinx usually evaded endoscopic evaluation. The healthy condition of the tubal epithelium and the patency of the tube are important for development and transportation of early stage embryos. METHODS: Twenty patients had tubal occlusion diagnosed by hysterosalpingography, including 10 cases of hydrosalpinx, five cases of interstitial occlusion and five cases of fimbrial occlusion. Falloposcopy with a linear everting catheter and laparoscopy were performed simultaneously to evaluate tubal lumens and peritubal conditions. RESULTS: An attempt was made to cannulate 30 fallopian tubes in 20 cases with a falloposcope, using a nonhysteroscopic transvaginal approach through a linear everting catheter. The success rate was 93% (28/30). In 15 cases of hydrosalpinx or fimbrial obstruction, 10 patients (67%) were considered to be suitable for in vitro fertilization because of flattened mucosa in the endosalpinx and endotubal adhesions. Normal mucosa was noted in only four patients (27%), who were advised to have tuboplasty. One patient (6%) had normal mucosa without tubal occlusion. In two of the five cases of interstitial occlusion, dye (methylene blue) could not pass the interstitial portion of the fallopian tube when chromopertubation was performed twice. This tubal obstruction was overcome with the linear everting catheter. One patient had the complication of an ampulla wall perforation. CONCLUSIONS: In patients with fallopian tube disease, falloposcopy is a useful technique for evaluating the endosalpinx and providing information for selecting further treatment. In some cases of interstitial occlusion, it may also have a therapeutic effect.     

Ectopic pregnancy in women who use intrauterine contraceptive devices]

This study analyzes occurrence of ectopic pregnancies in women using intrauterine contraceptive devices. During a 5-year period, 1990-1994, 524 women with ectopic pregnancies underwent surgery at our Clinic, while 22 (4.2%) had intrauterine devices. At admission most patients had signs of heavy intraabdominal bleeding, so in 77.27% cases the diagnosis was made by punction of the Douglas area, and only in 9.09% by laparoscopy, that is other methods for early detection of diseases. Rupture of the fallopian tube occurred in 50% of patients, tubal abortions in 36.36% and ovarian pregnancies in 13.64%, whereas 18 salpingectomies and 4 adnexectomies were performed. Late diagnosis and impossibility of performing conservative operations on fallopian tubes are the consequence of disregarding the possibility of getting pregnant by the users of intrauterine devices themselves, as well as by physicians whose help is asked for after symptoms appear.     

Recovery of cytomegalovirus and herpes simplex virus from upper and lower genital tract specimens obtained from women with pelvic inflammatory disease

Lower genital tract specimens and endometrial biopsies from 147 women with pelvic inflammatory disease (PID) and surgical specimens (fallopian tubes, ovaries, or both) from 22 women with PID and 37 women without PID were cultured for cytomegalovirus (CMV) and herpes simplex virus (HSV), as well as for organisms commonly associated with PID. CMV was isolated from 39 cervical or endometrial samples from 30 (20.4%) of 147 women with PID and from ovaries or fallopian tubes from 5 (22.7%) of 22 women with PID, but CMV was not recovered from surgical specimens obtained from 37 women undergoing surgery for tubal ligation, ectopic pregnancy, or other gynecologic conditions (P = .005). HSV was isolated from cervical samples obtained from 5 (3.4%) of 147 women with PID but not from any endometrial or surgical specimens. These data suggest that CMV, but not HSV, may contribute to the pathogenesis of PID in some patients.     

Threshold intrauterine perfusion pressures for intraperitoneal spill during hydrotubation and correlation with tubal adhesive disease

OBJECTIVE: To determine the minimum intrauterine perfusion pressure that will produce spill from the fallopian tubes into the peritoneal cavity and to correlate this pressure with the extent of tubal adhesive disease. DESIGN: Hydrotubation was performed at laparoscopy and intrauterine perfusion pressure was measured. The extent of peritubal and fimbrial adhesions was graded at laparoscopy. SETTING: Ambulatory surgery suites. PATIENTS: Ten patients with infertility and/or pelvic pain were enrolled in the study. Data from nine patients were analyzed. INTERVENTIONS: Measurement of intrauterine perfusion pressures. MAIN OUTCOME MEASURES: The minimum pressure that produced spill of dye from each fallopian tube and the correlation between extent of external tubal pathology and this threshold pressure. RESULTS: The median threshold pressure at which dye spilled from at least one fallopian tube was 100 mm Hg, and no spill occurred at pressures < 70 mm Hg. The threshold pressure was correlated negatively with the extent of tubal disease. CONCLUSIONS: Fluid with the same viscosity as hydrotubation dye will not spill into the peritoneal cavity through normal fallopian tubes until the intrauterine perfusion pressure exceeds 70 mm Hg. The threshold pressure is higher when tubal adhesive disease that can be visualized by laparoscopy is present.     

Variability of cutaneous lymphatic flow rates in melanoma patients

A woman with a small (6-mm gestational sac) interstitial pregnancy had complete resolution after medical therapy alone. A single cycle of methotrexate 50 mg/m2 was used as outpatient treatment without any operative procedure either for diagnosis or intervention. The guidelines that have evolved for selection of women for single dose methotrexate treatment for both intrauterine and tubal ectopic pregnancies may be applicable to interstitial ectopic pregnancy as well. A suggested framework for treatment decisions is presented.     

The control of the radiochemical purity of compounds labelled with 113MIn using the method of thin-layer chromatography

A woman with two intrauterine pregnancies after two ectopic tubal pregnancies is presented. The first operation removed the left Fallopian tube (on 4 November 1970), while during the recurrent ectopic pregnancy, plastic surgery was applied in the remaining right tube (24 October 1972) with the enucleation of the fertilized egg after Prochownik's method. The patient became pregnant 3 months after the operation and had spontaneous abortion, with a fetus two-and-a half months old; the second time she became pregnant 17 months after the operation and gave birth to a female live-born, 26 days before the term, weighing 2,900 g and 49 cm high. The authors conclude that best results are obtained when the plastic surgery made in the fallopian tube is as small as possible and when postoperative instillation of the tubes is applied.     

The role of scientific societies

Ectopic pregnancy is one of the most common and dangerous complications of the early pregnancy period. Until now diagnosis has been late because major symptoms occur after tubal rupture and so only demolitive surgery has been possible. At present, with the appearance of ultrasound in obstetrics an earlier diagnosis of this pathology can be made before tubal rupture so medical treatment has become possible. We treated a series of twelve patients with early ectopic pregnancy (9 tubal and 3 with no localized site of implantation) with intramuscular 0.5 mg/kg methotrexate and oral 0.1 mg/kg of folic acid (Citrovorum Factor) on alternate days, in the attempt to reduce hospitalization and obtain more effective and safer medical management. We observed a fall in serum beta-HCG levels after one cycle of treatment in 11 out of 12 patients and after two cycles of therapy in the remaining case. Minimal side-effects were observed in four cases. Three pregnancies occurred after treatment before the advised interval time and ended in blighted ovum. Methotrexate systemic therapy can be considered an elective treatment and a sufficiently safe management in early unruptured ectopic pregnancy when a good clinical selection of patients is performed.     

Systemic methotrexate therapy versus laparoscopic salpingostomy in tubal pregnancy. Part II. Patient preferences for systemic methotrexate

OBJECTIVE: To investigate patient preferences for systemic methotrexate therapy relative to laparoscopic salpingostomy in the treatment of tubal pregnancy. DESIGN: Preference assessment in controlled clinical study. SETTING: Four hospitals and one infertility clinic. PATIENT(S): Forty patients who had been treated for tubal pregnancy and 40 nonpregnant controls. INTERVENTION(S): Preference for methotrexate therapy relative to salpingostomy was established during an interview. Two scenarios were offered for methotrexate therapy: one with and one without preceding diagnostic laparoscopy. Hypothetical tubal patency rates after methotrexate therapy were varied in both scenarios until patients switched in their initial preference. MAIN OUTCOME MEASURE(S): Preference for systemic methotrexate therapy. RESULT(S): Only a few patients switched in their initial preference when the tubal patency rate after systemic methotrexate therapy was varied. Most preferred methotrexate therapy without an increase in the tubal patency rate in a scenario without preceding diagnostic laparoscopy. A small group never opted for methotrexate therapy even when it would guarantee a 100% tubal patency rate. CONCLUSION(S): Systemic methotrexate therapy would be preferred by most patients as part of a completely nonsurgical management strategy. Tubal patency was a decisive factor for treatment preference in a minority of patients only.     

Hystero-salpingo scintigraphy: a routine investigation in sterile women?

Based on the spontaneous migration of radioactive tracer from the posterior vaginal fornix to the ovaries and peritoneal cavity, several attempts were made to assess hystero-salpingo scintigraphy (HSS). The low acceptance rate by sterile women of routine investigation of tubal function may be due to a fear of radiation exposure and unpleasant examination procedures. Our protocol for HSS adopts a low dose of radioactive tracer (0.2-0.3 mCi), a defined mode of application (between the external and internal os of the cervical canal) and a short imaging time (60 min). From 1990 to 1992, we investigated 60 fallopian tubes in 32 sterile women by HSS, hystero-salpingography (HSG) and/or chromopertubation during laparoscopy (LPSC). The results of HSG and HSS corresponded in 15 of 49 fallopian tubes, LPSC and HSS in 9 of 24. None of the 32 patients had become pregnant naturally during the average observation period of 17 months. Two patients became pregnant after in-vitro fertilization. HSS, performed according to our protocol, causes less pain and results in a lower dose of radiation than HSG (about 50%). It is well accepted by patients and is easy to perform. As an investigation of tubal function, HSS may serve as an additional examination technique in cases of presumed tubal sterility.     

Ectopic pregnancy--changing trends

This study is an attempt to have an overall view of the changing trends in the clinical presentation, diagnostic modalities and management of ectopic pregnancy over a period of three and a half decades. The incidence of ectopic pregnancy was one in 368 during the 15-year period from 1959-1973 (group A) and has increased to one in 160 during the latter part of the study period from 1988-1993 (group B). Medical termination of pregnancy, abortion, intra-uterine contraceptive device and previous tubal ligation were the important risk factors recently (group B). Unruptured tubal pregnancy was diagnosed in 9.8% (group B) as compared to only 3% in group A. However, as most of the patients came to the hospital with disturbed pregnancy, the use of ultrasonography and urine gravindex test was helpful in only 14% in the latter part of the study. The characteristic clinical features like pain abdomen with amenorrhoea, vaginal bleeding and positive culdocentesis were the most reliable diagnostic criteria in both the groups. There is an increasing trend towards conserving the tubes and methotrexate use recently.     

Pelviscopic surgery in gynaecology (author's transl)

Surgery of the fallopian tubes has today developed into pelviscopic surgery. The development of suitable instruments such as the tube set, a new endocoagulation method were prerequisites for this development. Operative therapeutic pelviscopic surgery is a development past laparotomy. It is now possible to treat adhesions in the abdomen with this method, to coagulate and divide fallopian tubes for sterilization, to aspirate ovarian cysts and resect walls of ovarian cysts, to coagulate endometriosis and to perform salpingolysis and salpingostomy. In selected cases ovariectomy and myomectomy are possible through the pelviscope. Tables and statistics on 3300 pelviscopies are presented. The indications are discussed. The use of pelviscopy following previous laparotomy (1831 cases) is discussed. The complication rate was 1.10% without death, without injury to large vessels, without embolic phenomenon. The operative risk is therefore less than that of laparotomy. The operative therapeutic pelviscopy can replace the classical laparotomy in about 25% of the cases. For the operation of tubal infertility, a laparotomy is eliminated in about 80% of the cases.     

Injection of 5-fluorouracil in the treatment of tubal pregnancy through salpingo-catheter under hysteroscopy

Seventeen women with unruptured tubal pregnancy were given 5-FU through salpingo-catheter under hysteroscopy. In one case the injection failed because the tube opening could not be found. The success rate of salpingo-catheterization was 94.12% (16/17). The cure rate for the tubal pregnancies was 88.24% (15/17). 12 cases received injection once and 3 cases twice. The dose of 5-FU per injection was 250 mg in 10 ml solution. Serum beta-hCG test became negative in 7 to 14 days after the treatment, and signs and symptoms disappeared. Salpingography were done in 8 cases after 2 to 3 months, and all the diseased tubes were found patient. There was little side effects due to this treatment, which is more effective, convenient and less traumatic than injecting 5-FU to the affected site through laparoscopy or systemic administration. It may turn out to be an effective, simple, safe and acceptable new method for treating early tubal pregnancy.     

Ectopic bone formation in a child with a head injury: complete regression after immobilisation

OBJECTIVE: To study the correlation between microsurgical tubal reversal after tubal sterilization and ectopic pregnancy. METHODS: 1029 women who underwent microsurgical tubal reversal were followed up. The causes of ectopic pregnancy were analysed and discussed. RESULTS: 960 intrauterine pregnanciess and 12 ectopic pregnancies occurred. The 12 ectopic pregnancies were all tubal ones, among which 2 had intrauterine pregnancies. The rate of ectopic pregnancy in the 1029 women was 1.17%, and in the pregnant cases was 1.23%. The ratio of intrauterine pregnancy to ectopic pregnancy was 1:80. The rates of ectopic pregnancy in the 1st, 2nd year and 2 years later after tubal reversal were not significantly different respectively among the tubal reversal and among the pregnant cases. The rates of ectopic pregnancy in the 1st and 2nd 6 months after tubal reversal were not statistically different. The early tubal hydrapertubation could only increase the chance of ectopic pregnancy. The sterilization method, reversal mode, and interval between sterilization and reversal were not related to the ectopic pegnancy. CONCLUSION: When the lesion in the sterilized position is completely removed, the sutures being through the tubal mucosa and the early tubal hydrapertubation not carried out, the chance of ectopic pregnancy can not be increased after tubal reversal. The contraception 6 months after tubal reversal is not related to ectopic pregnancy.     

Salpingitis isthmica nodosa: results of transcervical fluoroscopic catheter recanalization

OBJECTIVE: To investigate the role of transcervical tubal catheterization in diagnosis and treatment of proximal tubal obstruction associated with salpingitis isthmica nodosa. DESIGN: Retrospective case study. SETTING: University hospital and outpatient radiology practice. PATIENTS: Fifty-two women with proximal tubal obstruction associated with salpingitis isthmica nodosa. INTERVENTION: Selective salpingography and catheter recanalization using fluoroscopic guidance. MAIN OUTCOME MEASURES: The number of tubes visualized to the fimbria as a percentage of the tubes with proximal tubal obstruction on the initial hysterosalpingogram was determined as a measure of diagnostic efficacy. To evaluate the treatment potential of catheter recanalization, the patients were grouped according to tubal status at the conclusion of the procedure and subsequent pregnancies were evaluated. RESULTS: Forty-seven of 65 tubes (72%) with proximal tubal obstruction were recanalized successfully. Among the 19 women who were able to conceive only via a recanalized salpingitis isthmica nodosa tube, there were 6 live births (32%) and two tubal pregnancies (10%). CONCLUSION: Selective salpingography allows complete tubal diagnosis in almost three fourths of patients with proximal tubal obstruction and salpingitis isthmica nodosa. The radiographic diagnosis of salpingitis isthmica nodosa may be pressure dependent. Intrauterine pregnancies occur via recanalized salpingitis isthmica nodosa tubes, therefore catheter recanalization may be attempted before tubal microsurgery or IVF in patients with proximal tubal obstruction and associated salpingitis isthmica nodosa.     

Combining B-mode ultrasound with pulsed wave Doppler for the assessment of tubal patency

This study was conducted to determine whether the additional use of pulsed wave Doppler improves the diagnostic capacity in assessing tubal patency by hysterosalpingo contrast sonography (HyCoSy). A total of 210 women with a history of infertility were included in this study. HyCoSy was performed after intrauterine injection of Echovist 200. For the assessment of tubal patency B-mode scanning and pulsed wave Doppler ultrasound were performed in the proximal and distal tubal segments. With the combined sonographic procedure 297 tubes (74%) were rated patent, 35 (8%) incompletely obstructed and 70 (18%) completely obstructed. A total of 252 tubes were additionally examined by laparoscopy for reference purposes. Concordant results for both methods were found in 92% of tubes, nine had been rated false negative and 10 tubes appeared to have been rated false positive. The combined sonographic specificity was found to be 85% with a sensitivity of 95%. Peritubal adhesions detected by laparoscopy were found to be the reason for false positive sonographic results in 60% of cases. In conclusion, the combined B-mode and pulsed wave Doppler examination appears to be a non-invasive and low-cost test for the assessment of tubal patency, which should be performed during diagnostic work-up for infertility.     

Late complications after systemic methotrexate treatment of unruptured ectopic pregnancies: a report of three cases

BACKGROUND: The use of methotrexate (MTX) by systemic administration in the treatment of unruptured ectopic pregnancy has been reported as a safe and effective method. CASES: We report three cases (one hematosalpinx and two pelvic hematocoeles) of complications after the use of MTX in the treatment of unruptured ectopic pregnancies. All three cases came to our observation for pelvic pain, abnormal bleeding and a pelvic mass after an interval of 3-5 months, subsequent to the disappearance of symptoms and normalization of serum human chorionic gonadotropin beta-subunit (beta-hCG) levels. CONCLUSIONS: These findings suggest that: (a) such complications should be considered before selecting the mode of treatment for ectopic pregnancy; and (b) that an early ultrasonographic control should be performed after MTX treatment even when the decline in beta-hCG levels suggests a successful resolution. This would permit an early diagnosis of these late complications.