Thomas G. Stovall

Single-dose methotrexate: An expanded clinical trial

OBJECTIVE Our purpose was to report an expanded clinical trial with a nonlaparoscopic approach to ectopic pregnancy diagnosis combined with single-dose intramuscular methotrexate treatment. STUDY DESIGN A prospective cohort of 120 women with an ectopic pregnancy < or = 3.5 cm in greatest dimension was enrolled. RESULTS Patients had a mean age of 26.1 +/- 6.2 years, a mean gravidity of 3.2 +/- 1.6, and a mean parity of 0.97 +/- 1.0. The mean human chorionic gonadotropin titer before treatment initiation was 3950 +/- 1193 mIU/ml. Transvaginal ultrasonography visualized cardiac activity in 14 (11.7%) patients, with an ectopic mass visualized in 113 (94.2%). The mean time to resolution in the 113 (94.2%) subjects successfully treated was 35.5 +/- 11.8 days. Four (3.3%) patients required a second methotrexate dose on day 7. No biochemical or clinical side effects occurred. Posttreatment hysterosalpingograms demonstrated tubal patency on the ipsilateral side in 51 of 62 (82.3%) patients. Of those attempting pregnancy, 79.6% were pregnant, 87.2% intrauterine and 12.8% ectopic. The mean time to achieve pregnancy was 3.2 +/- 1.1 months. CONCLUSIONS This regimen requires minimal laboratory follow-up and eliminates leukovorin recovery, making it the regimen of choice for medical treatment of unruptured ectopic pregnancy.

Predictors of Success of Methotrexate Treatment in Women with Tubal Ectopic Pregnancies

BACKGROUND The use of methotrexate for the treatment of women with tubal ectopic pregnancies is now common practice. However, the clinical and hormonal determinants of the success of this treatment are not known. METHODS We studied 350 women with tubal ectopic pregnancies who were treated with methotrexate intramuscularly according to a single-dose protocol. Pretreatment serum concentrations of human chorionic gonadotropin and progesterone, the size and volume of the gestational mass, fetal cardiac activity, and the presence of fluid (presumably blood) in the peritoneal cavity were correlated with the efficacy of therapy, as defined by resolution of the ectopic pregnancy without the need for surgical intervention. RESULTS There was no relation between the womens age or parity, the size or volume of the conceptus, or the presence of fluid in the peritoneal cavity and the efficacy of treatment. Among the 320 women in whom treatment was successful (91 percent), the mean (+/-SD) serum chorionic gonadotropin and progesterone concentrations were 4019+/-6362 mIU per milliliter and 6.9+/-6.7 ng per milliliter (21.9+/-21.3 nmol per liter), respectively, as compared with 13,420+/-16,590 mIU per milliliter and 10.2+/-5.5 ng per milliliter (32.4+/-17.5 nmol per liter) (P<0.001 and P=0.02) in the 30 women in whom treatment was not successful. Fetal cardiac activity was present in 12 percent of the successfully treated cases and 30 percent of those in which treatment was not successful (P=0.01). Regression analysis revealed the pretreatment serum chorionic gonadotropin concentration to be the only factor that contributed to the failure rate. CONCLUSIONS Among women with tubal ectopic pregnancies, a high serum chorionic gonadotropin concentration is the most important factor associated with failure of treatment with a single-dose methotrexate protocol.

Methods of and attitudes toward screening obstetrics and gynecology patients for domestic violence

OBJECTIVE Our purpose was to define screening behaviors of obstetrician-gynecologists and barriers to screening their patients for domestic violence. STUDY DESIGN A questionnaire was developed to collect information on current practices and attitudes regarding screening for domestic violence. A randomly selected sample of obstetrician-gynecologists was surveyed. Respondents were also asked to rank a series of 19 potential barriers that may affect screening. RESULTS Of 6568 physicians sampled, 962 (14.6%) returned questionnaires. Of the respondents, 77.6% were male and 22.4% were female. Male physicians were less likely to screen for domestic violence (25.9% vs. 18.9%). Thirty-four percent said that they had no training in abuse. Physicians indicating they had received training in abuse were more likely to screen for domestic violence. The lack of education was identified as the most common barrier physicians have to screening. The feeling that abuse was not a problem in their patients (46%), lack of time to deal with abuse (39.2%), and frustration that the physician cannot help the victim (34.2%) were other common barriers. CONCLUSION The majority of obstetrician-gynecologists do not screen their patients for current or past domestic violence. If universal screening is to become a reality, educational tools and training materials are needed to overcome physician barriers.

A multicenter randomized comparison of laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy in abdominal hysterectomy candidates.

Objective To compare intraoperative and postoperative outcomes between laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy among patients who are not eligible for vaginal hysterectomy. Methods Study subjects were randomly assigned to undergo laparoscopically assisted vaginal hysterectomy or standard abdominal hysterectomy. Intraoperative and post-operative management was similar for each group. Surgical characteristics, complications, length of hospital stay, charges, and convalescence were analyzed. Results Sixty-five women at three institutions underwent laparoscopically assisted vaginal hysterectomy (n = 34) or abdominal hysterectomy (n = 31). Three patients in the laparoscopic group required conversion to abdominal hysterectomy. Mean operating time was significantly longer for laparoscopically assisted vaginal hysterectomy (179.8 versus 146.0 minutes). There were no differences in blood loss or incidence of intraoperative complications. There was a higher incidence of wound complications in the abdominal hysterectomy group, but no significant difference in the frequency of postoperative complications. Laparoscopically assisted vaginal hysterectomy required a significantly shorter mean hospital stay (2.1 days) and convalescence (28.0 days) than abdominal hysterectomy (4.1 days and 38.0 days, respectively). There were no significant differences in mean hospital charges between the study groups (laparoscopic

Outpatient chemotherapy of unruptured ectopic pregnancy

8161, abdominal

Emergency department diagnosis of ectopic pregnancy

6974). Conclusion Except for operating time, there are no differences between laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy regarding intraoperative characteristics among abdominal hysterectomy candidates. Postoperatively, laparoscopically assisted vaginal hysterectomy requires a shorter hospital stay and convalescence. Hospital charges are similar between the procedures. A larger number of cases will help determine the indications for laparoscopically assisted vaginal hysterectomy.

Single serum progesterone as a screen for ectopic pregnancy: exchanging specificity and sensitivity to obtain optimal test performance *

This report describes an individualized, reduced dose, methotrexate (MTX) and citrovorum factor (CF) treatment regimen for outpatient management of unruptured ectopic pregnancy (EP). One hundred sixteen laparoscopically documented EPs, the majority (90%) of whom were symptomatic, were diagnosed from an Emergency Department population. Eighty of 116 (69%) were unruptured, 37 (46.3%) of whom were eligible for MTX-CF chemotherapy. One patient refused chemotherapy. Thirty-four of the 36 (94.4%) patients treated with MTX-CF had complete resolution of their ectopics, whereas 2 experienced rupture after chemotherapy, 1 of them 23 days after MTX initiation. While there were no major chemotherapy-related side effects, 3 of the 36 (8.3%) patients experienced minor side effects. The authors conclude that: (1) individualized dosing of outpatient MTX-CF chemotherapy for symptomatic EP can be safely managed, even in an indigent population; (2) rupture can occur up to 23 days after chemotherapy initiation; (3) fetal cardiac activity is an absolute contraindication to chemotherapy; (4) chemotherapy in patients with symptoms is of limited value because the disease is too far advanced; therefore, it is essential that the diagnosis of EP be established before symptom onset; and (5) chemotherapy offers no significant immediate advantages to outpatient laparoscopic surgery. However, increasingly reliable nonlaparoscopic diagnosis will soon give wider application to this approach.

GnRH agonist and iron versus placebo and iron in the anemic patient before surgery for leiomyomas : a randomized controlled trial

STUDY OBJECTIVES To assess the accuracy of the history and physical examination as compared to the addition of serum progesterone screening for ectopic pregnancy in women presenting to the emergency department. DESIGN Prospective, consecutive case series, N = 2,157. SETTING ED of the Regional Medical Center at Memphis, a publicly subsidized, 450-bed acute care hospital staffed by residents and faculty of the University of Tennessee, Memphis. TYPE OF PARTICIPANTS All ED patients with a positive urine pregnancy test treated between January 1 and December 31, 1988. INTERVENTIONS Screening history, physical examination, and serum progesterone (P) and quantitative human chorionic gonadotropin (hCG) titer. MEASUREMENTS All discharged patients were given follow-up appointments within two weeks; those found to have a P less than 25 ng/mL were called to return for repeat hCG and transvaginal ultrasound. MAIN RESULTS One hundred sixty-one of 2,157 patients (7.5%) with a positive urine pregnancy test were found to have an ectopic pregnancy. All but five had a P of less than 25 ng/mL (sensitivity, 97%); four of these were admitted for immediate surgery because of symptoms. Overall, the ED physician detected 89 of 161 ectopics (55.3%) on initial presentation, 53 (60%) of which were ruptured at the time of surgery. Seventy-two patients (44.7%) who were discharged but later found to have an ectopic pregnancy had benign clinical presentations, including 41 with vaginal bleeding. There were no statistically significant differences in the presenting symptoms of patients with unruptured ectopics compared with normal intrauterine pregnancies. All but one of the 72 discharged patients were noted the following day to have a progesterone of less than 25 ng/mL and contacted to return. Eight of these were found to have a ruptured ectopic at the time of surgery. Only 91 of 161 patients (56.5%) with ectopic pregnancy acknowledged one or more clinical risk factors on follow-up questioning. CONCLUSION The standard history and physical examination, including those performed by gynecologic specialists, are insufficiently sensitive for early detection of unruptured ectopic pregnancy. EDs with a high incidence of ectopic pregnancy should strongly consider implementation of a universal progesterone screening program to decrease unnecessary patient morbidity and the risk of mortality from undiagnosed ectopic pregnancy.

Nonsurgical diagnosis and treatment of tubal pregnancy

OBJECTIVE To investigate the diagnostic accuracy of screening serum P in diagnosis of ectopic pregnancy (EP) and to identify a cutoff value that provides the best compromise between test sensitivity and specificity. DESIGN Retrospective analysis. SETTING University hospital. INTERVENTIONS Observation only. PATIENTS First trimester pregnant women at risk for EP. MAIN OUTCOME MEASURE Single P measurements were obtained from 3,674 pregnancies with outcomes defined as EP, viable intrauterine pregnancy (IUP), and spontaneous abortion (SAB). Diagnostic accuracy of the test was analyzed by generating receiver operating characteristic (ROC) curves, which quantify the ability of the test to distinguish EP and SAB from IUP. RESULTS Diagnostic accuracy for EP versus IUP was 88.7% +/- 0.1% (mean +/- SEM); for SAB versus IUP, 93.8% +/- 0.4%; and for SAB + EP versus IUP, 92.8% +/- 0.4%. Diagnostic accuracy for SAB versus EP was only 39.4% +/- 0.2%. In the interval of 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L), P missed 5.3% of the EPs and incorrectly included 84.3% of the viable IUPs; in the interval of 20.0 to 24.9 ng/mL (63.6 to 79.2 nmol/L), sensitivity improved in that only 3.5% of the EPs were missed but 88.8% of viable IUPs were included incorrectly. A cutoff value of > or = 17.5 ng/mL (55.7 nmol/L), the median point of the 15.0 to 19.9 ng/mL (47.7 to 63.3 nmol/L) interval, missed only 35 of 423 (8.3%) total EPs in the study. CONCLUSION Analysis of ROC curves demonstrates that single serum P has high diagnostic accuracy for differentiating accidents of pregnancy (SAB and EP) from viable IUP, both individually (SAB versus IUP and EP versus IUP) and collectively (SAB + EP versus IUP); it cannot efficiently discriminate SAB versus EP. We conclude that for P > or = 17.5 ng/mL (55.7 nmol/L), patients thought to be at risk for EP may be followed reasonably without ultrasound or further invasive diagnostic studies.

Reproductive performance after methotrexate treatment of ectopic pregnancy

Objective To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas. Methods This was a phase III, stratified, randomized, double-blind, placebo-controlled, parallel-group, 12-week multicenter study. Enrolled patients had hemoglobin levels of 10.2 g/dL or less and/or hematocrit values of 30% or less. Patients were entered into one of two strata based on their pre-study hematocrit level: stratum A, hematocrit less than or equal to 28%, and stratum B, hematocrit greater than 28%. Patients within each stratum were randomized to one of three treatment arms: leuprolide acetate depot 7.5 mg, leuprolide acetate depot 3.75 mg, or placebo. All patients received iron orally. Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36% or greater. Results Three hundred nine patients were entered into the study, of whom 265 were evaluated. Using our response criteria, a significantly greater number of patients in both leuprolide acetate groups (combined strata) responded to therapy than did those in the placebo group: 74% in each leuprolide acetate group versus 46% in the placebo group (P < .001). Gonadotropin-releasing hormone agonist-treated patients had a significant reduction in uterine and myoma volume when compared with the placebo group (P < .01). Hot flashes and vaginitis were reported significantly more often (P < .001) in the leuprolide acetate-treated groups than in the placebo group. Conclusion Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas, in reducing uterinemyoma volume, and in alleviating bleeding and other leiomyoma-related symptoms.