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Objective: To evaluate the safety and acceptability of a novel dosing regimen of methotrexate to treat ectopic pregnancy. Design: Prospective study. Setting: Three academic medical centers. Patient(s): One hundred one patients with ectopic pregnancy who elected to have medical therapy. Intervention(s): Intramuscular methotrexate 50 mg/m2 was administered on days 0 and 4; additional doses of methotrexate were given on day 7 and/or day 11 if hCG levels did not decrease by 15% during the follow-up period. Main Outcome Measure(s): Adverse events, acceptability, and resolution of pregnancy without surgical treatment. Result(s): With this protocol, 87% of patients were treated successfully. Of those protocols that were considered failures, only 3% of patients experienced rupture of ectopic pregnancy. Treatment was well-tolerated; most side effects were reported as mild and transient. Ninety-one percent of the 61.5% of patients who responded to the satisfaction questionnaire reported satisfaction with this regimen. Conclusion(s): This “2-dose” protocol minimizes the number of injections and surveillance visits, compared with the “multiple dose” regimen, and methotrexate is administered more frequently than with the “single dose” regimen. The protocol may optimize the balance between convenience and efficacy. In a limited number of women, no safety concerns were noted with up to 4 doses of methotrexate in a 2-week period without leucovorin rescue. [Copyright &y& Elsevier]

: ObjectiveTo compare signs and symptoms between patients with recurrent and single ectopic pregnancies.: DesignCase-control study.: SettingUniversity medical center.: Patient(s)Three hundred six women with single ectopic pregnancies and 61 women with recurrent ectopic pregnancies.: Intervention(s)None.: Main outcome measure(s)Risk factors, historical factors, and findings at presentation that may predispose to recurrent ectopic pregnancy.: Result(s)The risk of recurrent ectopic pregnancy was increased with a history of surgery, history of live birth, and history of spontaneous miscarriage and not with a history of gonorrhea, chlamydia, pelvic inflammatory disease, Caesarean section, or pregnancy termination. Patients with a recurrent ectopic pregnancy had a nonsignificant trend toward higher initial hCG values. The majority of ultrasounds in both groups were nondiagnostic on presentation. The patients with recurrent ectopic pregnancy were less likely to have bleeding on initial presentation, though both groups had similar complaints of pain.: Conclusion(s)Secondary prevention of ectopic pregnancy is problematic because of the paucity of risk factors that can be modified to diminish the odds of recurrence. Clinicians'' ability to both diagnose and counsel patients at risk for recurrent ectopic pregnancy can be optimized by awareness of the clinical features of this condition. [Copyright &y& Elsevier]

: ObjectiveThe diagnosis of ectopic pregnancy (EP) is often confirmed at presentation (acute), but often requires serial β-hCG levels to confirm the diagnosis (chronic). The purpose of this study is to analyze whether these clinical presentations represent a spectrum of disease.: DesignThe retrospective cohort study of 452 patients diagnosed with EP at the University of Pennsylvania in the years 1990–1999.: SettingUniversity of Pennsylvania, Philadelphia, Pennsylvania.: Patient(s)Four hundred fifty-two patients diagnosed with EP. Patients diagnosed with EP were divided into two groups according to the time of diagnosis.: Main outcome measure(s)A total of 37 parameters were examined including historic and demographic factors, findings at presentation, and treatment and outcome variables.: Result(s)The two groups were similar in terms of historic EP risk factors. Multivariable analysis demonstrates that women with a chronic presentation were less likely to have received fertility medications (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.06–0.84), less likely to present with pain (OR 0.29; 95% CI 0.12–0.71), have a lower β-hCG level at presentation (9,849 mIU/mL ± 16,726 vs. 1,787 mIU/mL ± 4,717), lower chance of rupture (OR 0.19; 95% CI 0.05–0.73), and less frequently have blood type 0.: Conclusion(s)Women diagnosed with ectopic pregnancy can be categorized into two groups, those with an acute presentation and those with a chronic presentation. Differences in risk factors, presentation, and outcome may reflect differences in trophoblast viability or invasive potential. [Copyright &y& Elsevier]

Objective: To validate recently characterized curves of hCG rise and fall that are seen in viable and nonviable pregnancies in a population of women who have pregnancies of unknown location. Design: Historical cohort study. Setting: University hospital. Patient(s): One thousand two hundred forty-nine women with symptomatic early pregnancies. Intervention(s): None. Main Outcome Measure(s): Comparison of observed hCG values to predicted hCG values; time to diagnosis of ectopic pregnancy; accuracy of diagnosis. Result(s): Of the 1,249 patients included in this study, 196 had ectopic pregnancy (EP); 261, intrauterine pregnancy (IUP); and 792, spontaneous abortion (SAB). By determining the rate of change in hCG values from two consecutive visits and comparing them with a minimal rise of 35% in 2 days (the bound that is defined by the 99.9% confidence interval [CI] for the rise of hCG in an IUP) or a minimal fall of 21%–35% (the bound that is defined by the 90% CI for the fall of hCG in an SAB), we were able to make the diagnosis of EP an average of 2.5 days sooner than by standard clinical practice. Only 12% of patients had an EP go undiagnosed by using these rules, because the curve of rise or fall of their hCG mimicked that of a non-EP gestation. Conclusion(s): Recently redefined curves of rise and fall in hCG for IUP and SAB are valid for clinical use on the basis of our application to this large cohort of patients. Using them can shorten the time needed to make the diagnosis of EP. Use of a more conservative cutoff for minimal rise in hCG, one as slow as 35% over 2 days, to characterize a potentially viable gestation would minimize potential interruption of a desired pregnancy. [Copyright &y& Elsevier]

Objective: To evaluate the association between ectopic pregnancy (EP) and clinical and historical factors among women presenting with pain and/or bleeding in early pregnancy. Design: Nested case–control study. Setting: University medical center. Patient(s): Women with symptomatic early pregnancies of unknown location presenting for care between January 1, 1990 and July 31, 1999. Intervention(s): None. Main Outcome Measure(s): Clinical and historical risk factors were compared between women with EP and women with ongoing intrauterine pregnancies or spontaneous abortions. Result(s): The following factors were associated with increased risk of EP: prior EP (odds ratio, 2.98 [95% confidence interval, 1.88–4.73] for one prior EP and 16.04 [5.39–47.72] for 2 or more), pelvic inflammatory disease history (1.5 [1.11–2.05]), pain at presentation (1.42 [1.06–1.92]), vaginal bleeding at presentation (1.42 [1.04–1.93]), and hCG of 501–2,000 mIU/mL (1.73 [1.24–2.42]). Age younger than 25 years (0.59 [0.41–0.85]) and a history of abortion were protective from EP (0.58 [0.38–0.90]). Prior nontubal pelvic surgery, past intrauterine device use, prior cesarean section, and current cervical infection demonstrated no association with EP. Conclusion(s): Evaluation of women with a symptomatic early pregnancy confirms and refutes some of the classical risk factors for EP. Prior EP is a strong risk factor, whereas pelvic inflammatory disease has an unexpected weak association. Previous abortion was found to have a negative association, whereas nontubal surgery, cesarean section, and a history of or concomitant cervical infection have no association. Knowledge of historical and clinical factors associated with EP may aid in early diagnosis. [Copyright &y& Elsevier]

Because lower initial hCG concentrations are associated with slower rates of decline in spontaneous abortions, the aim of this study was to provide a detailed description of the expected rates of hCG decline in patients presenting with very low initial hCG levels and who ultimately were confirmed to have spontaneous abortions. When initial levels lie between 50 and 500 mIU/mL, the slowest expected percentage decline ranges from 12% to 24% in 2 days and from 34% to 68% in 7 days. [Copyright &y& Elsevier]