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PubMed2003

The medical management of ectopic pregnancy: a meta-analysis comparing "single dose" and "multidose" regimens.

OBJECTIVE: Medical management of an unruptured ectopic pregnancy with intramuscular methotrexate is common and cost-effective. Two treatment protocols, the "single dose" and the "multidose," have been advocated and independently reported in the medical literature. This analysis systematically compares the success and prevalence of side effects of these two regimens. DATA SOURCES: Published data on women with an ectopic pregnancy medically managed were identified using a MEDLINE search from 1966 to 2001 using key words and review of the references of each manuscript. METHODS OF STUDY SELECTION: Studies were selected based on dosing regimen, number of subjects, and study quality. Data regarding outcome, number of doses administered, side effects, and baseline characteristics were extracted. Data were summarized, and the associations of failed management and the presence of side effects with treatment protocol were calculated. Baseline serum chorionic gonadotropin values and the presence of embryonic fetal actively were controlled for with multivariable logistic regression. TABULATION, INTEGRATION, AND RESULTS: The overall success rate for women treated with methotrexate for an ectopic pregnancy was 89% (1181 of 1327). The single dose was much more commonly used. The use of single dose was associated with a significantly greater chance of failed medical management than the use of the multidose in both crude (odds ratio [OR] 1.71; 1.04, 2.82) and adjusted analyses (OR 4.74; 1.77, 12.62). The single-dose regimen was associated with fewer side effects (OR 0.44; 0.31, 0.63). Women who experienced side effects were more likely to have successful treatment regardless of regimen. CONCLUSION: The multidose regimen is more effective than the single-dose regimen.

Abortifacient Agents, Nonsteroidal↗
PubMed1999

Management of separation pain after single-dose methotrexate therapy for ectopic pregnancy.

OBJECTIVE: To evaluate the conservative management of pain after systemic methotrexate therapy for ectopic pregnancy; identify prognostic factors for success; and compare hCG resolution time for patients with and without pain. METHODS: A retrospective review of patients with ectopic pregnancy requiring evaluation for pain after receiving single-dose methotrexate therapy is performed. Results of hematocrits, ultrasound findings, hCG levels, time for hCG levels to reach less than 15 mIU/mL, and outcome were noted. RESULTS: Fifty-three patients with 64 episodes of pain were identified. Seven hospitalized patients required surgery during admission. Two previously hospitalized and one outpatient also ultimately underwent surgery. For hospitalized patients, there were no statistical differences between patients who did or did not undergo surgery during admission for any variable studied, including the presence of free peritoneal blood or rebound tenderness. However, comparison of hospitalized and nonhospitalized patients showed those with rebound tenderness were more likely to be admitted. Hospitalized patients not requiring surgery had shorter resolution time than nonhospitalized patients. For hospitalized and nonhospitalized patients, the median time from treatment to presentation for pain was 8 days. CONCLUSION: The occurrence of pain following methotrexate therapy for ectopic pregnancy should not be the sole indication for surgical intervention. The majority of stable patients with pain after methotrexate therapy, even with rebound or free peritoneal fluid, can be treated successfully without surgery, either in hospital with close observation for severe pain or as outpatients for patients with less severe pain.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

Cost-effectiveness of single-dose methotrexate compared with laparoscopic treatment of ectopic pregnancy.

OBJECTIVE: To evaluate the cost-effectiveness of treatment with intramuscular (IM) methotrexate compared with fallopian tube-sparing laparoscopy for small unruptured ectopic pregnancy. METHODS: A decision-analytic model accounting for varying resolution rates, complication rates, and cost estimates was built to compare the use of methotrexate with laparoscopy. Meta-analysis results of studies identified by a MEDLINE search for IM methotrexate resolution rates and tube-sparing laparoscopy resolution rates were used in model estimation. A similar process was used to generate model complication rates. Data on associated resource use were derived from established clinical guidelines. Estimates of 1998 costs incurred by provider organizations were calculated using data from a large managed care organization. RESULTS: The average methotrexate resolution rate among the studies included was 87% (range 75-90%). The average laparoscopy resolution rate was 91% (range 72-100%). Complication rates for methotrexate ranged from 0% to 22%, with an average of 10% for minor complications, and from 0% to 11% for serious complications, with an average of 7%. Complication rates for laparoscopy ranged from 0% to 8% for intraoperative complications, with an average of 2%, and from 0% to 15% for postoperative complications, with an average of 9%. Baseline model estimates indicated an average cost saving of more than $3000 per resolved ectopic pregnancy with methotrexate treatment compared with laparoscopy. Results of extensive sensitivity analyses supported the finding of a cost saving with methotrexate treatment. CONCLUSION: Single-dose methotrexate is a cost-saving, nonsurgical, fallopian tube-sparing treatment for ectopic pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMedDate not supplied

Ectopic pregnancy.

Ectopic pregnancy is an important cause of morbidity and mortality worldwide. Use of transvaginal ultrasonography and quantitative measurement of the beta subunit of human chorionic gonadotropin (beta-hCG) has led to a reduction in the need for diagnostic laparoscopy. Furthermore, with earlier diagnosis, medical therapy with methotrexate can be offered and surgery avoided in some women, though the best regimen remains unclear. In the surgical management of ectopic pregnancy, the benefits of salpingectomy over salpingostomy are uncertain. Although there have been advances in the management of ectopic pregnancy there are still questions to be answered.

Female↗
PubMed1995

A cost-effectiveness study of a randomised trial of laparoscopy versus laparotomy for ectopic pregnancy.

We compared the cost-effectiveness of therapeutic laparoscopy and open laparotomy for treatment of laparoscopically diagnosed ectopic pregnancy. Clinical outcomes of ectopic pregnancy treatment were based on results of a randomised trial done between 1987 and 1989 at Sahlgrenska University Hospital (Göteborg, Sweden). We estimated costs for inpatient and follow-up care of ectopic pregnancy by the two methods. Observed resource use (eg, procedure duration) was multiplied by 1992 estimates of resource unit cost (eg, cost per minute of laparoscopy time), based on detailed internal cost accounting data from Huddinge University Hospital. By specified criteria, the initial procedure eliminated trophoblastic activity without major complications in 81% (95% CI: 68-90) of 52 laparoscopy patients, versus 95% (85-99) of 57 laparotomy patients. Residual trophoblast or complications were successfully treated in all remaining patients. Mean simulated costs (standard error) for the overall laparoscopy strategy were 28,058 (1780) Swedish kronor versus 32,699 (1080) kronor for laparotomy (p = 0.03). In the baseline simulation and most sensitivity analyses, laparoscopy produced final outcomes equivalent to those of laparotomy at lower costs. As laparoscopic outcomes improve, this newer approach should become increasingly preferable.

Cost-Benefit Analysis↗
PubMed1998

Immunohistochemical identification of the receptor for urokinase plasminogen activator associated with fibrin deposition in normal and ectopic human placenta.

The receptor for urokinase plasminogen activator (uPAR) is a key molecule in cell surface-directed plasminogen activation. uPAR binds urokinase plasminogen activator (uPA) and thereby focuses plasminogen activation on the cell surface. Plasmin dissolves fibrin deposits and facilitates cell migration during tissue repair processes by degrading the extracellular matrix. During human implantation and placental development, plasmin is considered important for both trophoblast migration/invasion and for fibrin surveillance. This study examined the expression of uPAR in normal and ectopic human placentae by immunohistochemistry. In first and third trimester normal placentae as well as in tubal ectopic placental tissues, a high uPAR expression was seen in the trophoblast associated with deposits of fibrin-type fibrinoid. Extravillous trophoblast of the basal plate, of the cell islands, and of the cell columns was also positive for uPAR in the first trimester whereas at term the expression of the protein was decreased. Moreover, uPAR immunostaining was observed in decidual cells throughout normal gestation and in endometrial tissues of patients with ectopic pregnancies. These findings suggest that uPAR participates in placental development and in trophoblast invasion particularly in the first trimester of pregnancy and that uPAR is involved in repair mechanisms of the trophoblast and fibrin surveillance.

Adult↗
PubMed1990

Serous culdocentesis in ectopic pregnancy: a report of two cases caused by coexistent corpus luteum cysts.

Two cases of women with large-volume serous culdocentesis results are presented. Both patients ultimately had ectopic pregnancies diagnosed surgically, and aspiration into coexistent corpus luteum cysts caused the "false-negative" culdocentesis results. The accuracy of culdocentesis and its continued role in the workup of the patient with possible ectopic pregnancy is reviewed. Because the corpus luteum is a cystic structure present in all pregnancies during the first seven weeks, cyst aspiration is always a possibility and should be suspected when large amounts of serous fluid are obtained by culdocentesis. Such results should be considered nondiagnostic and do not exclude a coexistent ectopic pregnancy.

Adult↗
PubMed1984

Ovarian ectopic pregnancy.

We present the case of a 27-year-old woman with left lower quadrant pain, tenderness, and rebound tenderness. Culdocentesis demonstrated non-clotting blood, and exploratory laparotomy showed an ovarian ectopic pregnancy. A wedge resection of the ovary was accomplished and the patient recovered completely. Ovarian ectopic pregnancy is an uncommon presentation of ectopic pregnancy.

Adult↗
PubMed1986

Performance of a new enzyme-linked immunoassay urine pregnancy test for the detection of ectopic gestation.

An enzyme-linked immunoassay urine pregnancy test was used on a group of patients suspected of having an ectopic pregnancy. Patients were seen in the county hospital emergency department and had the urine test correlated with a serum beta-hCG level determined by radioimmunoassay. There were 884 patients with urine ICON-serum beta-hCG correlations. The ICON was positive in each of the 247 patients whose serum value was over 50 mIU/mL, and was negative in each of the 619 patients whose serum level was below 5 mIU/mL. Eighteen patients had a serum level between 10 and 50 mIU/mL and the ICON was positive in 13. The five patients with a low serum beta-hCG level and a negative ICON had dilute urine when tested. Using a modified testing procedure, each of these produced a positive ICON. Of the 27 patients with an ectopic pregnancy the urine ICON was positive in 26. The urine ICON is an improved assay for hCG in patients suspected of having an ectopic pregnancy, and is ideally suited for ED use.

Chorionic Gonadotropin↗
PubMed2001

Non-invasive management of patients with suspected ectopic pregnancy: a survey among Dutch gynaecologists.

OBJECTIVE: To investigate if implementation of a non-invasive diagnostic work up of patients with suspected ectopic pregnancy, involving transvaginal sonography and serum human chorionic gonadotrophin (hCG) measurement decreases the likelihood of performing diagnostic laparoscopies. STUDY DESIGN: We interviewed 27 Dutch gynaecologists using 16 structured case summaries in a fractional factorial design. Each case summary concerned a hypothetical patient with suspected ectopic pregnancy. For each case presentation, the gynaecologists were asked for their inclination to perform laparoscopy. RESULTS: There were substantial differences in the degree to which data from a non-invasive work-up influenced the decision to perform a laparoscopy. Some gynaecologists would perform laparoscopy in all 16 patients at the first visit, whereas others would initially admit none of them. CONCLUSION: Dutch gynaecologists seem to be familiar with a non-invasive diagnostic approach in women with suspected ectopic pregnancy. However, there are considerable differences in management approach probably due to individual variability in weighing the risks and benefits of expectant management.

Chorionic Gonadotropin↗
PubMed2002

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 50mg/m(2) 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.

Abortifacient Agents, Nonsteroidal↗
PubMed1996

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.

Adult↗
PubMed1998

A 6-year clinical trial of methotrexate therapy in the treatment of ectopic pregnancy.

OBJECTIVE: Our aim was to assess the efficiency of methotrexate therapy for unruptured ectopic pregnancy. STUDY DESIGN: From November 1990 to December 1996, 60 patients diagnosed with unruptured ectopic pregnancies were treated by the Departamento de Ginecología y Obstetricia at the Hospital Virgen Macarena of Seville. Of these, 14 patients received an intrasacular injection of 15 mg of methotrexate, 45 were given an intramuscular dose of 50 mg/m2 and only one received the drug by both routes. RESULTS: Forty-six patients (76.7%) responded successfully to treatment. Of these, 10 had been given the drug intrasacularly (10/15, 66.7%), while 36 had received the drug intramuscularly (36/46, 78.3%). Twenty patients (33.3%) had minor side effects, the most frequent being mild abdominal pain. Falling levels of leukocytes on the third day after initiation of treatment may serve as a fairly accurate criterion to predict the patient's response to the treatment. CONCLUSION: Our data support the use of methotrexate therapy as a reliable alternative to surgical intervention in the treatment of unruptured ectopic pregnancy. Intramuscular administration, without laparoscopy, appears to be the most convenient route as it is easily implemented and has comparatively few complications.

Abortifacient Agents, Nonsteroidal↗
PubMed2004

[Medical treatment of ectopic pregnancy: a randomized clinical trial comparing metotrexate-mifepristone and methotrexate-placebo].

BACKGROUND: Medical treatment of ectopic pregnancy is widespread. To increase the efficacy of methotrexate, combination with mifepristone has been proposed. METHODS: We performed a large prospective multicentre double-blind sequential randomized trial in order to compare the efficacy of methotrexate and mifepristone (600 mg given orally) versus methotrexate and placebo. RESULTS: Two hundred twelve ectopic pregnancies were randomized. There was no significant difference in the initial characteristics between the 2 groups. There was no significant difference in the success rate of medical treatment between the methotrexate-mifepristone (n=113) and the methotrexate-placebo group (n=99): 79.6% (90/113) vs 74.2% (72/97) respectively, RR [95% CI]: 1.07 [0.92-1.25], p=0.41. However, there was a quantitative interaction between progesterone level and effect of treatment: when progesterone level was 10 ng/l, the efficacy of the combination of mifepristone and methotrexate was significantly higher than the combination of methotrexate and placebo, with a 83.3% success rate (15/18) vs 38.5% (5/13) respectively. CONCLUSION: Our study failed to demonstrate any benefit of the addition of mifepristone to methotrexate. By contrast, the quantitative interaction between treatment effect and base line serum progesterone suggested that this combination could be reserved to ectopic pregnancies associated with high serum progesterone concentrations.

Abortifacient Agents, Nonsteroidal↗
PubMed2005

[Ectopic pregnancy with etonogestrel contraceptive implant (Implanon): first case].

We describe the first case of ectopic pregnancy occurring in a patient with an etonogestrel contraceptive implant (Implanon). There was no factor predisposing to a failure of the technique (implant in place for less than 2 years and normal BMI). In addition there was no risk factor for an ectopic location of the pregnancy. We discuss the role of the micro progestative in the location of the pregnancy. This case report emphasizes the fact that ectopic pregnancy should not be ruled out in women taking this contraception, however efficient it is otherwise.

Contraceptive Agents, Female↗
PubMed1988

Ectopic hormone production.

Current understanding of the phenomenon of ectopic hormone production is largely based on a histopathological and immunocytochemical analysis of peptide hormone secreting tumours arising in non-endocrine tissues. Recent advances in the study of gene regulation show that the tissue-specific expression of genes is a highly sophisticated process and is unlikely to be disturbed by a spontaneous event such as point mutation in DNA. Study of several genes for frequently found ectopic hormones, i.e. prop-opiomelanocortin, vasopressin/neurophysin II, gastrin-releasing peptide, parathyroid hormone-related peptide, calcitonin gene-related peptide and beta-chorionic gonadotropin, suggests they are transcribed as they would be in their natural cell of origin. It is argued therefore that these data are compatible with the concept that the tumour cell of origin was capable of expressing these peptides, if only in a minor or transient manner. In one example, the ectopic ACTH syndrome, it is also necessary to explain the non-suppression of this gene's expression by elevated levels of glucocorticoids. Recent work suggests that this may result from physically present, but biologically inactive glucocorticoid receptors, a phenomenon that has occasionally been noted in hormonally inactive tumour tissue and cell lines.

Calcitonin↗
PubMed1994

Endoscopic management of ectopic pregnancy.

The rationale for the conservative management of ectopic pregnancy is the preservation of reproductive potential. Removal of trophoblast through a linear incision (salpingotomy) can be easily performed by endoscopy. The injection of vasopressin into the broad ligament is required in less than 10% of cases and its routine use is not recommended because of the risk of severe side-effects. The techniques in cases of isthmic or cornual tubal pregnancy are also described. Other alternatives such as expectant management, methotrexate, RU 486 and prostaglandins have also recently been proposed. Although methotrexate therapy has been demonstrated to be effective in cases of unruptured tubal pregnancy, further studies are needed to determine whether or not this medical therapy is a safer option than laparoscopic surgery and to compare the subsequent intrauterine and recurrent ectopic pregnancy rates. Endoscopic salpingotomy is an efficacious procedure. Indeed, residual trophoblast is found in only 5% of cases after this surgical procedure. In these cases of persistent trophoblast, methotrexate is proposed as the medical approach of choice. Evaluation of the postoperative fertility after linear salpingotomy demonstrates an intrauterine pregnancy rate of 63% and a recurrent ectopic pregnancy rate of 8%. In conclusion, endoscopic management of tubal pregnancy is a safe and efficacious therapy. The contraindications are relative and depend essentially on the surgeon's experience.

Female↗
PubMed2004

Ectopic pregnancy in an inguinal herniorrhaphy scar.

An ectopic pregnancy may occur in unusual sites. In the following case, an ectopic pregnancy was discovered in the first trimester within an inguinal herniorrhaphy scar from an inguinal herniorrhaphy performed about 20 years previously. Early diagnosis of the ectopic pregnancy by sonography enabled laparoscopic management and preservation of the woman's fertility.

Adult↗