Marian L. McCord

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.

Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate☆☆☆★

OBJECTIVES The objective of this study was to review the largest single series of ectopic pregnancies treated with single-dose methotrexate reported to date. STUDY DESIGN A review of 315 patients with unruptured ectopic pregnancies treated with single-dose methotrexate 50 mg/m2 from March 21, 1990, to March 1, 1997, was performed. RESULTS Overall 287 patients were successfully treated with methotrexate for a success rate of 90.1%. Six patients electively withdrew and requested surgery within 1 week of starting therapy. Excluding withdrawals the overall success rate was 92.9%. Ten patients with an ectopic pregnancy > 3.5 cm but < or = 4 cm in size were treated for a 90% success rate. Forty-four patients with positive ectopic cardiac activity were treated with an 87.5% success rate. CONCLUSIONS This large series indicates that single-dose intramuscular methotrexate for treatment of ectopic pregnancy is associated with an excellent overall success rate.

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

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.

The Effect of Nitrous Oxide and Carbon Dioxide Pneumoperitoneum on Operative and Postoperative Pain During Laparoscopic Sterilization Under Local Anesthesia

STUDY OBJECTIVE To compare carbon dioxide and nitrous oxide pneumoperitoneum with respect to intraoperative and postoperative pain during laparoscopic sterilization under local anesthesia. DESIGN Randomized, double-blind study of pain during surgery and at 15 minutes, 1 hour, and 24 hours postoperatively. SETTING Regional Medical Center, Memphis, Tennessee. PATIENTS Women scheduled for laparoscopic sterilization under local anesthesia. Interventions. Forty-nine patients were randomized to carbon dioxide and 56 to nitrous oxide pneumoperitoneum. MEASUREMENTS AND MAIN RESULTS Pain was assessed using a modified McGill pain questionnaire. Intraoperative pain was measured by the amount of supplemental narcotic required. Analgesic use in the recovery room and during the first 24 hours postoperatively was compared. Demographics for both groups were similar. The groups had no statistical differences in pain during surgery or at any of the postoperative time periods. Recovery room analgesia requirement was similar, but the nitrous oxide group used fewer pain tables (0.98 vs 0.42 tablets) in the first 24 hours. CONCLUSIONS There is no difference in intraoperative and postoperative pain between nitrous oxide and carbon dioxide pneumoperitoneum for laparoscopic sterilization when used in conjunction with a protocol such as ours.

Cervical cytology: A randomized comparison of four sampling methods

OBJECTIVE The purpose of this study was to compare smear quality and endocervical cell recovery of four cervical smear sampling devices. STUDY DESIGN Two thousand fifteen patients undergoing routine cervical smears at the University of Tennessee Obstetrics and Gynecology clinics were randomly assigned to a cotton swab-spatula, Cytobrush-spatula, Cervex-Brush, or Bayne Pap Brush. The cytopathology laboratory, blind to method, used specific criteria to grade smears as being optimal, adequate, marginal, or inadequate. Statistical analysis was by the chi 2 and analysis of variance tests. RESULTS No statistical differences occurred among the groups for nonpregnant patients. For pregnant patients smear quality was improved with both Cytobrush-spatula and Bayne Pap Brush versus cotton swab-spatula (p = 0.0301 and 0.0004, respectively); cotton swab-spatula had fewer endocervical cells than the Cytobrush-spatula (p = 0.0001), Cervex-Brush (p = 0.0288), and Bayne Pap Brush (p = 0.0081). CONCLUSIONS The cotton swab-spatula and Cytobrush-spatula appear to be the most effective screening methods for nonpregnant and pregnant patients, respectively.

Synthetic hygroscopic cervical dilator use in patients with unsatisfactory colposcopy.

Objective To assess the ability of a synthetic hygroscopic cervical dilator to make an unsatisfactory colposcopic examination satisfactory, thereby avoiding cervical conization. Materials From April 1991 to March 1993, 30 women with unsatisfactory colposcopic examinations underwent repeat colposcopy after a synthetic hygroscopic cervical dilator had been placed in the endocervical canal for approximately 2 hours. Results The reasons for initial unsatisfactory colposcopy in the 30 patients were squamocolumnar junction not seen in its entirety (18 patients, 60%), lesion not seen in its entirety (ten, 33%), and neither transformation zone nor lesion seen in their entirety (two, 7%). Complications were encountered in one patient from whom the dilator could not be removed completely. Of 29 patients undergoing repeat colposcopy, 23 (79%) had satisfactory examinations. In 15 of 30 patients, conization was avoided; it was required in six of 30 (20%) women for persistent unsatisfactory colposcopy (including the patient in whom the dilator broke) and in nine of 30 (30%) for other indications. Conclusion This experience suggests that a synthetic hygroscopic cervical dilator can be used in patients with an unsatisfactory colposcopy to achieve a satisfactory examination, thus avoiding cervical conization.

The effect of topical 20% benzocaine on pain during loop electrosurgical excision of the cervix

OBJECTIVE Our purpose was to evaluate the effect of cervical application of 20% benzocaine on the pain associated with subsequent cervical injection of local anesthetic and tissue excision during the loop electrosurgical excision procedure of the cervix. STUDY DESIGN Fifty consecutive women scheduled for loop electrosurgical excision were randomized by use of computer-generated numbers to receive cervical application of either 20% benzocaine or placebo gel in a double-blinded fashion. A visual analog scale was used to measure the pain associated with both cervical injection of local anesthetic and tissue excision. RESULTS Lower mean pain scores were associated with the use of benzocaine gel for both anesthetic injection and tissue excision, but these scores did not reach statistical significance in either group. CONCLUSION Preoperative cervical application of 20% benzocaine does not appear to reduce the pain associated with either subsequent local anesthetic injection or tissue excision during the loop electrosurgical excision procedure of the cervix.

Methotrexate Therapy for Ectopic Pregnancy in Adolescents

STUDY OBJECTIVE To determine the suitability and efficacy of methotrexate (MTX) therapy for adolescent patients with ectopic pregnancy. MATERIALS Patients with ectopic pregnancy were treated with methotrexate, 50 mg/m2 intramuscularly. Follow-up determinations of quantitative beta hCG levels were done on days 1, 4, and 7. They were then seen weekly until beta hCG levels were less than 15 mIU/ml. PARTICIPANTS Adolescents with ectopic pregnancy (55 patients) received MTX therapy and comprised the study group. They were compared with 186 adults similarly treated. The groups were compared for treatment outcome and for compliance with the rigid protocol requirements. MAIN OUTCOME MEASURES Treatment success was defined as a patient who required no surgical intervention and whose beta hCG levels declined to < 15 mIU/ml. RESULTS 85% of patients required no surgical intervention following MTX injection. Surgical intervention rates were slightly higher and success rates slightly lower for adolescent patients, but these differences were not statistically significant (p = .71). Although adult patients were more likely to have a perfect compliance rating, comparison of all compliance categories showed no significant differences (p = .17). CONCLUSIONS MTX therapy is satisfactory for adolescent patients. It is effective, and adolescent patients are able to comply with the requirements of a rigid protocol.

Aspiration and microscopy in the diagnosis of ectopic pregnancy

Objective: To compare Karman cannula aspiration followed by dissecting microscopy with suction curettage and permanent histology in obtaining and identifying chorionic villi. Methods: Karman cannula aspiration was performed before standard curettage for failed intrauterine pregnancies (N=22) or possible ectopic gestation (N=24). Dissection microscopy for chorionic villi was performed on aspirates before submission for permanent histology. Sensitivity, specificity, positive and negative predictive value of each method in obtaining and identifying villi was determined. Results: Overall, all methods were only moderately sensitive in detecting chorionic villi (50–76%). If failed intrauterine pregnancies were excluded, all methods had poor sensitivity (25–64%). However, if villi were detected, the positive predictive value of all methods was high (>80%). Conclusions: Karman cannula aspiration followed by dissecting microscope examination or permanent histology may offer an alternative to traditional curettage in the diagnosis of ectopic gestations. A larger trial to validate these findings seems justified.

Serum bupivacaine levels during laparoscopic sterilization using local anesthesia

STUDY OBJECTIVE To determine the serum levels of bupivacaine during laparoscopic sterilization when bupivacaine 0.5% without epinephrine is used as the sole local anesthetic agent. DESIGN Case series. SETTING Regional medical center and primary teaching hospital of Ob/Gyn Department of the University of Tennessee, Memphis. PATIENTS; Thirty women undergoing laparoscopic sterilization with bupivacaine for local anesthesia. INTERVENTIONS Venous serum bupivacaine levels were measured, with samples drawn at 45, 60, 90, and 120 minutes after injection in 25 patients. Five additional patients had sampling at 15 and 30 minutes as well as at the above times. MEASUREMENTS AND MAIN RESULTS The highest concentration of bupivacaine was detected at 15 minutes. The mean concentrations at 15, 30, 45, 60, and 120 minutes were 0.86, 0.74, 0.31, 0.27, 0.23, and 0.22 microg/ml, respectively. This is well below the level of serious toxicity. Only four patients received 2.5 mg/kg or greater of bupivacaine. In these patients, mean serum levels were 1.1, 1.0, 0.28, 0.43, 0.9, and 0.29 microg/ml, respectively. CONCLUSION Serum bupivacaine levels during sterilization using bupivacaine 0.5% without epinephrine for local anesthesia are well below the threshold for serious toxicity.