Haim Abramovici

Activated protein C resistance (factor V Leiden) associated with thrombosis in pregnancy

OBJECTIVE Our purpose was to evaluate activated protein C resistance phenotype and genotype among patients with thrombosis during pregnancy and the puerperium. STUDY DESIGN This observational study was conducted prospectively during a 2-year period (July 1993 to June 1995) in a preselected population. All patients admitted to our high-risk pregnancy unit with a diagnosis of deep vein thrombosis, pulmonary emboli, transient ischemic attack, and cerebrovascular accident during pregnancy and the puerperium were included. Prothrombin time, partial thromboplastin time, fibrinogen levels, protein C, protein S, antithrombin III, functional test for activated protein C resistance, and factor V Leiden mutation by polymerase chain reaction were performed on each patient. RESULTS Fifteen patients were included. Seven (46.6%) patients were positive for activated protein C resistance (factor V Leiden). All other coagulation studies were negative for all patients. All patients with activated protein C resistance had a venous thrombotic event, deep vein thrombosis, or pulmonary emboli, and only one had a cerebrovascular accident on the basis of sagittal sinus thrombosis. Only two of the activated protein C resistance-negative patients had venous thrombosis (pulmonary emboli). The remaining six patients had transient ischemic attacks or cerebrovascular accidents. For the subgroup with venous thrombosis during pregnancy and the puerperium, the incidence of activated protein C resistance (factor V Leiden) was 78%. CONCLUSION This study demonstrates the incidence of factor V Leiden in a selected population in whom thrombotic events developed during pregnancy and the puerperium. This small-scale study provides justification for a large cohort study that will identify women with factor V Leiden and determine their risk for thrombosis during pregnancy and the puerperium. We believe that factor V Leiden should be evaluated in conjunction with thrombotic events in the pregnant woman.

Polymorphism for mutation of cytosine to thymine at location 677 in the methylenetetrahydrofolate reductase gene is associated with recurrent early fetal loss

OBJECTIVE This study was undertaken to determine whether a cytosine to thymine mutation at nucleotide 677 in the gene encoding for methylenetetrahydrofolate reductase is associated with particular subtypes of recurrent unexplained spontaneous abortion. STUDY DESIGN The prevalences of cytosine to thymine mutation at nucleotide 677 in the gene encoding for methylenetetrahydrofolate reductase among 41 patients with recurrent unexplained spontaneous abortions and among 18 healthy control subjects were determined with polymerase chain reaction. RESULTS Homozygosity and heterozygosity for the cytosine to thymine mutation at nucleotide 677 in the gene encoding for methylenetetrahydrofolate reductase were observed at nonsignificantly different rates among patients and control subjects (9% and 48% versus 22% and 38%, respectively, P <.95). Among patients with recurrent unexplained spontaneous abortions both homozygosity and heterozygosity were associated with significantly increased prevalence of recurrent early fetal loss rather than with repeated anembryonic gestations (P <.0001). CONCLUSION The observation that polymorphism for the cytosine to thymine mutation at nucleotide 677 in the gene encoding for methylenetetrahydrofolate reductase is associated with repeated early fetal losses rather than with anembryonic gestations strengthens the argument for the role of hypercoagulability and abnormal uteroplacental vasculature in recurrent spontaneous abortion.

Predicting the outcome of surgical treatment of vulvar vestibulitis

Objective To identify predictive factors for success or failure of perineoplasty for severe vulvar vestibulitis. Methods Seventy-nine women with severe vulvar vestibulitis underwent perineoplasty by a single surgeon during 1992–1994. Sixty (76%) who experienced a complete response were compared with 19 (24%) who had an incomplete response. Using univariate and then multivariate (logistic regression) analysis, the two groups were compared with regard to preoperative demographic, social, and medical variables, as well as physical findings in the vestibule. Results The complete- and incomplete-response groups were similar in all comparisons except for constant vulvar pain of vestibular origin (in addition to dyspareunia) and the presence of symptoms since first coitus. On multiple logistic regression, these characteristics had odds ratios (and 95% confidence intervals) of 4.97 (1.49, 16.63) and 5.83 (1.74, 19.55), respectively. Conclusion An incomplete response to perineoplasty may be anticipated in women with vulvar vestibulitis associated with dyspareunia since their first episode of inter-course and in those with associated persistent vulvar pain. Treatment approaches other than surgery should be considered for such patients.

Etiology of cervical cancer: current concepts.

The data on the etiological factors presented here may enable us to suggest a synergism between the various factors associated with the pathogenesis of cervical cancer. Infection of the cervix by HPV 16/18 may result in persistence of viral DNA. The persistent HPV-DNA undergoes disruption at the E2 region, when integrated into the host genome. The transcriptional products E6 and E7 oncoproteins bind to and cause the degradation of p53 and Rb tumor-suppressor gene products. It is possible that, at that point, other cofactors may be involved in the progression toward a precancerous or cancerous condition. Those cofactors may include cigarette smoking, by introducing co-carcinogens to the tissue or by suppressing the local or systemic immune resistance similar to the effect of depressed immune resistance seen in AIDS or immunosuppression of transplant patients; hormones, by enhancing growth of HPV and transformation of HPV infected cells; low serum vitamin levels leading to decreased tissue resistance; or other infections causing local inflammation and the production of free radicals. CIN develops, leading eventually to cervical cancer.

Cessation of gonadotropin-releasing hormone analogue (GnRH-a) upon down-regulation versus conventional long GnRH-a protocol in poor responders undergoing in vitro fertilization

OBJECTIVE To determine whether a controlled ovarian hyperstimulation (COH) regimen that involves GnRH agonist (GnRH-a) discontinuation before administration of gonadotropins would benefit poor responders. DESIGN A prospective, randomized controlled trial. SETTING Hospital-based IVF Unit. PATIENT(S) Sixty-three patients with previous poor response to COH and/or high basal FSH level (> or =9 mIU/mL) undergoing 78 IVF-ET cycles. INTERVENTION(S) In both groups, administration of GnRH-a was started in the midluteal phase. Whereas in the study group (40 cycles), it ended before administration of gonadotropins, in controls (38 cycles) GnRH-a treatment was continued throughout the follicular phase. MAIN OUTCOME MEASURE(S) Ovarian stimulation patterns and IVF outcome. RESULT(S) A significantly higher cancellation rate was noted in the study group than in the controls (22.5% versus 5%, respectively). The new and control regimens resulted in similar stimulation characteristics and clinical pregnancy rates (11% versus 10.3%, respectively). In 13 patients with a basal FSH level that was not persistently high, the new regimen resulted in a significantly higher number of retrieved oocytes compared with the standard protocol (7.6+/-1.03 versus 4.0+/-0.68, respectively). CONCLUSION(S) Whereas for most low responders, the new COH regimen offers no further advantage, future prospective studies may demonstrate whether it can confer a benefit for a subset of patients with a basal FSH level that is not persistently high.

Perineoplasty compared with vestibuloplasty for severe vulvar vestibulitis

Objective To evaluate the efficacy of vestibuloplasty (vestibular undercutting without excision) to treat severe vulvar vestibulitis.

A randomized comparison of prostaglandin E2 oxytocin, and the double-balloon device in inducing labor

Objective To compare the efficacy of three methods for ripening and dilating the unfavorable cervix for induction of labor. Methods Pregnant women having an indication for induction of labor with a singleton vertex fetus, intact membranes, and Bishop score of no more than 4 were randomized to one of three induction methods: intravaginal prostaglandin (PG) E2, tablets (3 mg) followed by a second dose if labor did not start; continuous intravenous oxytocin drip; or the Atad Ripener Device, with inflation of both balloons and removal after 12 hours. For all patients, the cervix was assessed by the same investigator before induction and 12 hours later. Results Thirty subjects were included in the PGE2 group, 30 in the oxytocin group, and 35 in the Atad Ripener Device group. The postpartum course was comparable in all. The change in Bishop score in the PGE2 and Atad Ripener Device groups was significantly better than in the oxytocin group (median and range of 5 [0–9] and 5 [0–7], respectively, versus 2.5 [0–9]; P ≤ .01). Cervical dilation more than 3 cm was more frequent in the Atad Ripener Device group compared with both the PGE2 and oxytocin groups (85.7 versus 50 and 23.3%, respectively; P ≤ .01). The trial of induction failed in only two patients (5.7%) in the Atad Ripener Device group, compared with six (20%) in the PGE2 and 16 (53.3%) in the oxytocin groups (P ≤ .001). Mean (± standard deviation) induction-to-delivery interval was 21.3 ± 7.0 hours in the Atad Ripener Device group, 23.2 ± 12.5 hours in the PGE2 group, and 28.2 ± 14.7 hours in the oxytocin group. The success rate for vaginal delivery was significantly better in the Atad Ripener Device and PGE2 groups compared with the oxytocin group (77.1 and 70%, respectively, versus 26.7%; P ≤ .01). Conclusion The Atad Ripener Device had a significantly better success rate for cervical dilation and a lower failure rate than those for PGE2 and oxytocin. The PGE2 and Atad Ripener Device groups had better results than the oxytocin group in regard to Bishop score change and induction-to-delivery interval. The Atad Ripener Device may be a superior method for cervical ripening and labor induction in patients with unfavorable cervices.

The Classic Approach to Diagnosis of Vulvovaginitis: A Critical Analysis

OBJECTIVE To correlate the symptoms, signs and clinical diagnosis in women with vaginal discharge, based on the combined weight of the character of the vaginal discharge and bedside tests, with the laboratory diagnosis. METHODS Women presenting consecutively to the womens health center with vaginal discharge were interviewed and examined for assessment of the quantity and color of the discharge. One drop of the material was then examined for pH and the whiff test was done; a wet mount in saline and in 10% KOH was examined microscopically. The clinical diagnosis was based on the results of these assessments. Gram stain and cultures of the discharge were sent to the microbiology laboratory. RESULTS One hundred and fifty-three women with vaginal discharge with a clinical diagnosis of vulvovaginitis participated in the study. Fifty-five (35.9%) had normal flora and the other 98 (64.1%) had true infectious vulvovaginitis (kappa agreement = 18%). According to the laboratory, the principal infectious micro-organism causing the vulvovaginitis was Candida species. Candida infection was associated with pH levels of less than 4.5 (p < 0.0001, odds ratio = 4.74, 95% confidence interval: 2.35-9.5, positive predictive value 68.4%). The whiff test was positive in only a small percentage of bacterial vaginosis (BV) (p = not significant (NS)). Clue cells were documented in 53.3% of patients with a laboratory diagnosis of BV (p < 0.02, positive predictive value 26.7%). CONCLUSIONS The current approach to the diagnosis of vulvovaginitis should be further studied. The classical and time-consuming assessments were shown not to be reliable diagnostic measures.

Spontaneous fetal reduction in multiple gestations assessed by transvaginal ultrasound

Objective To assess the occurrence of disappearance of one or more of the fetuses in pregnancies which start as multiple gestation.

Vulvar vestibulitis: physical or psychosexual problem?

OBJECTIVE To examine whether vestibulitis has a physical or a psychosexual etiology. DATA SOURCES MEDLINE was searched to retrieve publications dating from January 1981 through June 1998 that evaluated the outcomes of surgical treatment and the psychosexual theory of the origin of vestibulitis. INTEGRATION: Articles were analyzed for methods of subject selection and surgery, surgical outcome, and length of follow-up. RESULTS A significant decrease in symptoms (complete responses + partial responses) was reported by 89% of 646 women who had perineoplasty for vulvar vestibulitis. Complete resolution of dyspareunia with surgical treatment was reported in 72% of 512 women whose cases were reviewed in studies in which complete responses and partial responses were evaluated separately. Women with vestibulitis did not differ from the normal population with respect to marital satisfaction, psychologic distress, or psychopathology. A suggestion that childhood sexual abuse caused vestibulitis has not been confirmed. The findings of somatization and shyness might be explained as results rather than causes of vulvar vestibulitis. CONCLUSION We do not agree that vestibulitis is a psychosexual problem and one that should not be treated surgically. A high rate of success can be achieved with proper surgical treatment.