Resolution of acute cervical insufficiency after antibiotics in a case with amniotic fluid sludge.

Cervical insufficiency generally refers to a condition in which there is mid-trimester cervical dilatation or protruding chorioamniotic membranes in the absence of uterine contractions. Such condition is a risk factor for spontaneous mid-trimester abortion or early preterm birth, and is associated with adverse neonatal outcomes. Both intra-amniotic infection and inflammation ascertained by amniocentesis have been identified in patients with cervical insufficiency, and are poor prognostic factors. A subset of patients with intra-amniotic inflammation will have no demonstrable microorganisms detected via cultivation or molecular methods, and therefore represent cases of sterile intra-amniotic inflammation. Amniotic fluid sludge (free-floating hyperechogenic material within the amniotic fluid in close proximity to the uterine cervix) identified on sonography is a biomarker for intra-amniotic infection and inflammation. Recent evidence suggests that intra-amniotic infection, as well as sterile intra-amniotic inflammation can be treated successfully using antimicrobial agents. We report a unique case in which administration of antibiotics in the presence of mid-trimester cervical insufficiency, sterile intra-amniotic inflammation, and amniotic fluid sludge was associated with resolution of the cervical findings, as demonstrated on both sonographic and speculum examination. The patient successfully underwent elective cesarean delivery at 36-2/7 weeks of gestation. This case illustrates that antibiotic therapy may be effective despite the presence of several high-risk pregnancy conditions, and that successful outcome is possible.

Conservative management of cervical ectopic pregnancy: utility of uterine artery embolization.

OBJECTIVE: To evaluate the use of uterine artery embolization (UAE) in conjunction with methotrexate in the conservative treatment of cervical ectopic pregnancy (CEP). DESIGN: Case series. SETTING: Tertiary-care university hospital. PATIENT(S): Cases of CEP treated at Hutzel Women's Hospital between January 1997 and December 2008. INTERVENTION(S): Multidose methotrexate treatment with or without UAE and intra-amniotic potassium chloride injection (KCl). MAIN OUTCOME MEASURE(S): Beta-human chorionic gonadotropin level, vaginal bleeding, length of hospital stay, and future fecundity. RESULT(S): A retrospective analysis of 15 patients with CEP treated conservatively using methotrexate with leucovorin rescue (MTx/Leu) alone (group 1, five cases), with UAE as an adjunctive therapy (group 2, six cases), or also having received intra-amniotic KCl before UAE (group 3, four cases) is reported. There was no significant difference in age, parity, or gestational age among treatment groups. The median ß-hCG level on presentation was 9,606 mIU/mL for group 1, 26,516 mIU/mL for group 2, and 130,464 mIU/mL for group 3. The difference was found to be statistically significant. No patients developed complications from UAE. Of the 10 patients who underwent UAE, 2 subsequently had confirmed viable pregnancies. CONCLUSION(S): Uterine artery embolization with methotrexate is an option for minimally invasive intervention in the treatment of CEP.

Reasons for poststerilization hysterosalpingography noncompliance in a clinic population.

OBJECTIVE: Although hysterosalpingography (HSG) is required 12 weeks after hysteroscopic sterilization, HSG compliance in our clinic population is remarkably low. We were interested in determining the reason(s) for HSG noncompliance in this urban-based patient population. STUDY DESIGN: University Health Center patients who underwent hysteroscopic sterilization between January 1, 2006, and December 31, 2007, and who did not complete HSG were contacted by telephone to elicit the reason(s) for lack of follow-up. RESULTS: Fifty-two patients qualified for inclusion in this study. Consent was obtained from all 14 patients accessible by telephone. Of note, 63.5% of patient-provided phone numbers were not in service at the time contact was attempted (n = 33). Patient-reported reasons for HSG noncompliance included insurance issues (n = 5), failure to remember to schedule HSG (n = 4), HSG scheduling difficulties (n = 2),failure to be informed about the need for HSG (n = 2), and prolonged postoperative vaginal bleeding (n =1). CONCLUSION: Reasons for poststerilization HSG noncompliance varied. However, an insurance issue was the most frequently reported reason for noncompliance. not recalling the need to schedule HSG was another common reason for noncompliance. Approaches to increase compliance with poststerilization HSG are needed, particularly in an urban-based, clinic population.

Post-Essure hysterosalpingography compliance in a clinic population.

STUDY OBJECTIVE: To determine the follow-up rate for post-Essure hysterosalpingography (HSG) in a non-study, general clinic population in an urban environment. DESIGN: Retrospective chart review (Canadian Task Force classification II-2). SETTING: University teaching hospital. PATIENTS: Eighty-three University Health Center (UHC) patients who underwent attempted placement of the Essure permanent birth control device at the ambulatory surgery center at Hutzel Women's Hospital from January 2003 through June 2007. INTERVENTION: Hysteroscopic placement of the Essure permanent birth control device. MEASUREMENTS AND MAIN RESULTS: Placement of the Essure permanent birth control device was attempted in 83 patients, of which 79 were successfully completed (95.2%). Of the 79 patients, 10 underwent post-Essure HSG (12.7%). HSG was performed 3 to 6 months after placement of the Essure device. Bilateral tubal occlusion was documented in all 10 patients. CONCLUSION: Despite preoperative and postoperative counseling, the follow-up rate for post-Essure HSG for this clinic population was only 12.7%. For those in whom HSG was performed, bilateral tubal occlusion was confirmed in all. Steps or approaches to promote compliance with postprocedural confirmation of tubal occlusion should be utilized to improve future follow-up rates.

Evaluation of RNA markers for early detection of cervical neoplasia in exfoliated cervical cells.

Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but their usefulness in routinely collected exfoliated cells remains uncertain. We used quantitative reverse transcription-PCR to evaluate expression of 40 candidate genes as markers for high-grade cervical intraepithelial neoplasia (CIN) in exfoliated cervical cells collected at the time of colposcopy. Samples from the 93 women with CIN3 or cancer were compared with those from 186 women without disease matched (1:2) for age, race, and high-risk human papillomavirus status. Normalized threshold cycles (C(t)) for each gene were analyzed by receiver operating characteristics to determine their diagnostic performance in a split sample validation approach. Six markers were confirmed by an area under the curve >0.6 in both sample sets: claudin 1 (0.75), minichromosome maintenance deficient 5 (0.71) and 7 (0.64), cell division cycle 6 homologue (0.71), antigen identified by monoclonal antibody Ki-67 (0.66), and SHC SH2-domain binding protein 1 (0.61). The sensitivity for individual markers was relatively low and a combination of five genes to a panel resulted in 60% sensitivity with 76% specificity, not positively increasing this performance. Although the results did not indicate superiority of RNA markers for cervical cancer screening, their performance in detecting disease in women referred for colposcopy suggests that the genes and pathways they highlight could be useful in alternative detection formats or in combination with other screening indicators.

Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women.

While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0, 95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*I transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.

Lycopene supplementation prevents the development of spontaneous smooth muscle tumors of the oviduct in Japanese quail.

Leiomyomas (fibroids) are benign tumors of the uterus affecting millions of women. Spontaneous leiomyomas of the oviduct are common tumors of the Japanese quail (Coturnix coturnix japonica), which makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Because dietary intake of lycopene has been associated with a reduced risk of a variety of human cancers, we investigated the effects of lycopene supplementation on the development of leiomyomas in the oviduct of Japanese quail. We also measured serum levels of oxidative stress markers [malondialdehyde (MDA) and homocysteine], lycopene, vitamins C, E, and A, and tissue biomarkers Bcl-2 and Bax expression. One hundred twenty quails (6 mo old) were assigned to 3 treatment groups consisting of 4 replicates of 10 birds in each group. Birds were fed either a basal diet (group C) or the basal diet supplemented with 100 mg (group L1) or 200 mg (group L2) of lycopene per kilogram of diet. The animals were sacrificed after 285 days and the tumors were identified. Lycopene supplementation decreased the number of leiomyomas compared with control subjects (P=0.056). The tumors in lycopene-fed birds were smaller than those found in control birds (P=0.01). There were no significant differences in the expression of tissue Bcl-2 and Bax among the study groups. Serum vitamins C, E, and A increased (P=0.01), whereas MDA and homocysteine concentrations decreased (P=0.01) with lycopene supplementation. No measurable lycopene could be detected in the serum of control birds, whereas a dose-dependent increase was observed in the serum of lycopene-supplemented birds. The results indicate that dietary supplementation with lycopene reduces the incidence and size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail. Clinical trials should be conducted to investigate the efficacy of lycopene supplementation in the prevention and treatment of uterine leiomyoma in humans.

Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III.

OBJECTIVE: The objective of this study was to determine an effective dose for all-trans retinoic acid (atRA) delivered with a cervical cap and sponge for 4 days to women with cervical intraepithelial neoplasia (CIN) II/III. METHODS: Study participants made up of 175 women with biopsy-proven CIN II/III were randomized to four consecutive days of atRA at one of three doses (0.16%, 0.28%, and 0.36%) or placebo. All subjects underwent a repeat colposcopy evaluation and biopsy of the cervix at 12 weeks. RESULTS: The study participants mean ages were 27.6 years. The racial distribution was 63% Caucasian, 27% African American, and 8% other. Among participants, 93% were human papillomavirus-positive at baseline with 68% positive for high-risk types. The disease response at 12 weeks to atRA or placebo was not significantly different (P = 0.49) among the four dose groups. Participants with CIN II at baseline were more likely to be free of disease at 12 weeks than participants with CIN III at baseline (P = 0.003). There were no reported systemic adverse events related to drug or placebo exposure and only mild local self-reported and clinician-detected toxicities. CONCLUSION: Lower concentrations of atRA applied with a cervical cap for 4 days were no more effective than placebo. However, the rate of histologic regression in biopsied CIN II/III patients was high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size.

Recruitment and retention of economically underserved women to a cervical cancer prevention trial.

This review contrasts the planned and actual recruitment and retention efforts for a cervical cancer prevention study within a predominantly underserved population. Recruitment was a primary obstacle to trial progression and multiple strategies to improve recruitment were implemented to meet objectives. The actual recruitment strategies were expansion to five geographically distinct clinical sites, use of nurse practitioners focused primarily on patient issues, extremely flexible study hours and location, honorariums, support for transportation and child care, and creativity in maintaining contact with study participants. With these strategies, 90% of eligible patients consented to participate in the study.

Estimation of time of fetal death in the second trimester by placental histopathological examination.

It has been suggested that certain placental histopathological changes may be useful in predicting the time of death in stillborn fetuses. We retrospectively evaluated 36 placentas from therapeutic terminations in which the time interval between fetal death and delivery was relatively short and well-documented to determine the earliest stillbirth-associated changes and the utility of placental examination in timing death in the second trimester. In each case, termination had been initiated by creating fetal asystole with intracardiac KCl injections. The gestational age ranged from 18-23 wk. The time from asystole to placental delivery range was 2.8-52.0 h. Placental groups were categorized by time intervals from asystole to delivery: I, <12 h [n = 4 (11%)]; II, 12-24 h [n = 15 (42%)]; III, 24-36 h [n = 14 (39%)]; IV, > 36 h [n = 3 (8%)]. Among eight histopathologic changes involving the umbilical cord or chorionic villi evaluated, only three were present in a significant number of cases and also appeared to be the result of stillbirth. Degeneration of cord vascular smooth muscle was present in 33% of umbilical cords in group I, but was seen in 100% of cords in groups II-IV; the extent of these changes increased significantly with increasing time intervals. Intravascular karyorrhexis was present in villous blood vessels in 75, 73, 64, and 100%, respectively, for groups I-IV. Villous blood vessel luminal abnormalities were seen in 25, 7, 21, and 67%, respectively, for groups I-IV. These findings indicate that these are the earliest morphological changes in stillbirth in second trimester placentas, but they cannot be used to accurately predict time of death in the relatively short time intervals evaluated in this study.