Prediction of location of a symptomatic early gestation based solely on clinical presentation.

OBJECTIVE: To evaluate three strategies for diagnosis of women at risk for ectopic pregnancy based on information collected at initial presentation. METHODS: Strength of association for risk factors, signs, and symptoms obtained at initial presentation of women with pain, bleeding, or both in a first-trimester pregnancy and a nondiagnostic ultrasound examination were calculated using a cohort of 2,026 women. Three models (logistic regression, a numeric scoring system, and a Classification and Regression Tree) were created to predict final outcome and tested on a second cohort of 1,634 women. Accuracy was assessed using 2x2 tables evaluating the decision of send home compared with do not send home (combination of monitor or intervene) and intervene compared with do not intervene (monitor or send home). Sensitivity, specificity, and predictive values were calculated. RESULTS: The ultimate diagnosis of women in the test population was 304 (18.6%) patients with an ectopic pregnancy, 834 (51.0%) with miscarriage, and 494 (30.2%) with an ongoing intrauterine pregnancy. A total of 95.9% of patients with ectopic pregnancy or miscarriage were correctly assigned to the strategy to monitor or intervene upon based on the scoring system, and 97.6% based on the Classification and Regression Tree. The specificity of the decision to send a patient home with a likely intrauterine pregnancy was greater than 95% for all three methods. The sensitivity of all strategies in the decision to intervene for an ectopic pregnancy was greater than 98%. CONCLUSION: A simplified scoring system based on five factors (age, ectopic history, bleeding, prior miscarriage, and human chorionic gonadotropin level) was as effective as a Classification and Regression Tree or logistic regression modes in predicting outcome of women at risk for ectopic pregnancy. Prediction of location of a symptomatic first-trimester pregnancy based on clinical symptoms and risk factors is possible, but must be used in conjunction with outpatient surveillance. LEVEL OF EVIDENCE: II.

Vaginal distribution of two volumes of the novel microbicide gel cellulose sulfate (2.5 and 3.5 mL).

This was a blinded crossover study to determine the in vivo distribution of 2.5 and 3.5 mL of 6% cellulose sulfate gel. This potential vaginal microbicide was mixed with dilute gadolinium chelate and inserted into the vagina. Magnetic resonance imaging was performed at baseline and repeated after 5, 20, 35 and 50 min with subjects either resting or ambulating between data acquisitions. Use of 2.5 mL with no ambulation gave low linear spread (53.1% of vaginal length) and surface contact (61.7%) at 50 min. Using 3.5 mL of gel with ambulation improved linear spread (84.5%) and surface contact (85.9%) of the gel in the same time interval without significant leakage. Most linear spreading took place in the first 5 min after insertion, although lateral spreading continued to increase with time especially when ambulation took place. Leakage and gel was not a significant problem at either volume.

In vivo assessment of NuvaRing placement.

NuvaRing, a combined contraceptive vaginal ring 54 mm in diameter, offers many advantages over oral contraceptives. To better delineate in vivo placement, we performed MRI to confirm its anatomical position. Two healthy users, one nulliparous and one parous, underwent a series of MRI: preinsertion, immediately postinsertion and after ambulation. Three-dimensional imaging of the human vagina demonstrates that in vivo, NuvaRing is located superior to the urogenital diaphragm (UGD), surrounding the cervix. The superior-most aspect of the ring lies behind (posterior) the cervix, at a level superior to the external os. The inferior aspect of the ring also lies in the vaginal canal above the UGD. The entire cervix rests inside the ring. The preambulation image in the nulliparous woman was the only exception. In this case, the upper portion of the ring was at the level of the lower-mid cervix and the lower aspect below the UGD. After ambulation, the ring moved cephalad and surrounded the cervix. In all instances, ambulation resulted in lower aspect of NuvaRing moving away from the introitus. In vivo, NuvaRing is compressed laterally forming a gentle oval in the anterior-posterior direction (5-7 mm longer than wide), an effect that is seen more in nulliparous women.

Distribution of a 3.5-mL (1.0%) C31G vaginal gel using magnetic resonance imaging.

C31G (Savvy) has been developed as a topical vaginal microbicide with broad-spectrum antibacterial and antiviral properties. The objective of this study was to evaluate the distribution of a 1.0% concentration of (3.5 mL) C31G vaginal gel in the human pelvis using magnetic resonance imaging (MRI). Gel delivery with a standard applicator was primarily to the upper vagina and was well tolerated. Vaginal mucosal coverage at 18 min was excellent with 92% linear coverage and 75% surface contact coverage of the vagina. The upper vagina was almost completely covered and gel was also noted in the lower vagina. Coverage 6 h after application was substantially decreased, with 60% of maximal linear coverage and 41% surface contact. There was a very minimal coverage of the vaginal mucosa noted 24 h following insertion. Simulated intercourse resulted in relatively little change in overall distribution at all three time points. Repeat application of the gel may be necessary if intercourse has not occurred within the first few hours after initial insertion.

Hormone pattern after misoprostol administration for a nonviable first-trimester gestation.

OBJECTIVE: To evaluate serial hormone concentrations in subjects treated with vaginally administered misoprostol for early pregnancy failure. DESIGN: As part of a randomized clinical trial, serum was collected on treatment days 1, 3, 8, and 15. SETTING: Multicenter clinical trial. PATIENT(S): Women with a nonviable first-trimester pregnancy. INTERVENTION(S): Serum concentrations of human chorionic gonadotropin (hCG), progesterone, and sex hormone binding globulin (SHBG) were evaluated. MAIN OUTCOME MEASURE(S): A logistic regression model was constructed to assess the associations of percent and complete expulsion of the gestational sac and/or successful management. RESULT(S): The percent change from the day of treatment until the first follow-up visit was predictive for complete expulsion for progesterone (P) (P<.005) and hCG (P<.005), but not for SHBG. The actual value was not significantly associated with complete expulsion or successful management. A decrease (day 1-3) of 79% for both hCG and P was associated with a 90% probability of complete passage of the gestational sac. A 90% probability of successful management was noted if P decreased by 78% on day 3 or 59% on day 7, or hCG decreased by 74% on day 3 or 78% on day 7 compared with pretreatment values. CONCLUSION(S): Percent change, but not absolute change, in serial hormone values are strongly associated with both the complete expulsion of the gestational sac with one dose of misoprostol and ultimate success.

Magnetic resonance imaging to determine the distribution of a vaginal gel: before, during, and after both simulated and real intercourse.

To provide effective contraception and protection against sexually transmitted disease, vaginal gels should maximally cover the cervical os and the vaginal epithelium before, during and after intercourse. To non-invasively monitor the intravaginal distribution of an applied intravaginal gel, we performed high-resolution magnetic resonance imaging (MRI) of the female pelvis before, during and after both real and simulated sexual intercourse. We sought to determine whether simulated intercourse with a plastic phallus could be used as a surrogate for real intercourse for such experiments. Dilute gadolinium chelate solution was mixed with Gynol-II gel and introduced intravaginally to volunteer female human subjects using a conventional applicator. MRI was performed at 1.5 Tesla with a surface coil. Imaging of the female pelvis was performed: (1) immediately after insertion of the gel; (2) during real intercourse with a male partner (2 subjects) or simulated intercourse with a plastic phallus (4 subjects); and (3) after completion of real or simulated intercourse. Subjects were studied after application of both 3 mL and 5 mL of vaginal gel. Measurements of gel thickness covering the vaginal mucosa were made digitally using electronic calipers. The bolus of gel is initially located in the upper vaginal canal, superior to the urogenital diaphragm. Both real and simulated intercourse dramatically increases the spread of gel to the lower vagina. The cervix appears to be adequately covered with gel both before and after intercourse. Increasing the volume of the gel increases initial vaginal mucosal coverage but also increases leakage from the introitus. No statistically significant differences in vaginal mucosal coverage were found between patients having undergone real vs. simulated intercourse, or on post-intercourse scans of 3 mL versus 5 mL. MRI is a sensitive, reproducible means of tracking the spread of intravaginal medications.

Use of MRI to determine the in vivo position of a silicone vaginal barrier contraceptive device.

This study was performed to determine the location of a silicone rubber vaginal barrier contraceptive device, the Lea's Shield, in vivo. Two women, one parous and one nulligravid, were enrolled in the study. Surface coil, multiplanar Magnetic Resonance Imaging (MRI) was performed immediately following insertion of the contraceptive device, and was repeated following 35-40 min of normal ambulation by the participant.The contraceptive device was markedly hypointense to pelvic structures on both T1 and T2 weighted images. Its position within the vagina and relationship to the cervix were readily identifiable on MR images. The device was located in the upper vagina and completely covered the cervix in both patients. The valve appeared closed, and there was no apparent pressure on the urethra. The position was not altered by ambulation. In conclusion, MRI was a reproducible and rapid means for noninvasively determining the intravaginal location and orientation of a barrier contraceptive device. After insertion, the Lea's Shield occupies the upper vagina and completely covers the cervix.

In vivo distribution of a vaginal gel: MRI evaluation of the effects of gel volume, time and simulated intercourse.

A microbicide is designed to coat the vaginal epithelium and prevent transmission of HIV. Complete coverage is desired for optimal protection. In vivo factors affecting coverage have not yet been studied. This randomized crossover trial evaluates the effect of gel volume and patient activity upon vaginal epithelial coating. Gynol II gel was mixed with a magnetic resonance imaging (MRI) contrast agent. Ten women self-inserted, on separate visits, 3 or 5 mL of gel and underwent serial MRI scanning both before and after simulated intercourse. Gel spread was dependent upon time and volume. There was modest spread during the first hour and greater spread 6 h after insertion. Five milliliters of gel resulted in statistically significantly greater coverage immediately following insertion, within the first 30 min and at 6 h after insertion. Simulated intercourse greatly enhances gel spread. After simulated intercourse, the distribution of the gel at each volume was similar. Less leakage of gel was reported with the smaller volume.

Prediction of outcome in women with symptomatic first-trimester pregnancy: focus on intrauterine rather than ectopic gestation.

OBJECTIVE: Symptoms of vaginal bleeding and abdominal pain are common in cases of ectopic pregnancy (EP), spontaneous abortions (SAB), and complications of an intrauterine pregnancy (IUP). It is important to determine if efforts should focus on differentiating EP from an IUP (IUP + SAB) or a viable IUP from a nonviable gestation (EP + SAB) in women at risk for EP. METHODS: This is a retrospective cohort study of women who presented with bleeding or pain or both during the first trimester of pregnancy. The cohort was divided into subjects diagnosed with IUP vs. (EP + SAB). The same cohort was then divided into subjects diagnosed with EP vs. (IUP + SAB). Logistic regression models based on risk factors for both outcomes (EP vs. [IUP + SAB] and IUP vs. [EP + SAB]) were obtained. ROC curves as well as Hosmer-Lemeshow goodness of fit and Akaike's information criterion (AIC) were used. RESULTS: Overall, 18.1% (n = 367) of the women were diagnosed with EP, 58.8% (n = 1192) were diagnosed with an SAB, and 23.1% (n = 467) had an ongoing IUP. The area under the ROC curve for the model IUP vs. (EP + SAB) was statistically greater than the model EP vs. (IUP + SAB), p < 0.001. AIC and Hosmer-Lemeshow goodness of fit confirmed the better accuracy of the model comparing IUP vs. (EP + SAB). CONCLUSIONS: Information collected at initial presentation from women at risk for EP to be used for building prediction rules should focus on differentiating a viable from a nonviable pregnancy rather than attempting to distinguish an extrauterine from an intrauterine pregnancy. However, this distinction should not affect current clinical care.