Uterine prolapse associated with bladder exstrophy: surgical management and subsequent pregnancy.

Congenital bladder exstrophy affects 1 in 125,000 to 250,000 females. Consisting of absence of the anterior abdominal wall with exposure of the ureteral orifices, failure of pubic symphysis fusion, and deficient anterior pelvic diaphragm musculature, bladder exstrophy is frequently associated with genital prolapse. Pregnancy may be complicated by recurrent urinary tract infections, preterm labor, mild procidentia, and malpresentation. Due to the rarity of the condition, there is a corresponding scarcity of obstetric literature regarding management during pregnancy. We report the case of a young woman with surgically repaired bladder exstrophy who developed genital prolapse. The uterus was suspended using a sacral colpopexy utilizing a Gore-Tex graft. Subsequently, the patient became pregnant and delivered a healthy male infant at 35 weeks' gestation via cesarean section (without recurrence of the genital prolapse postpartum). Sacral colpopexy to correct genital prolapse associated with bladder exstrophy may preserve fertility in young patients.

Increased heterogeneity of chromosome 17 aneuploidy in endometriosis.

OBJECTIVE: Endometriosis is a complex gynecologic disorder that may display features similar to malignancy, including aggressive growth and localized invasion of the myometrium or spread to various organs outside the uterus. Molecular studies of cancer have demonstrated that genomic instability involving chromosome 17 plays a role in the development and progression of various tumor types. These involve gain and/or loss, deletions, and mutations of candidate tumor suppressor genes (eg, BRCA1 and p53 ) on chromosome 17. STUDY DESIGN: We used a 2-color fluorescence in situ hybridization method for analysis of endometriotic and normal archival tissue. Centromere-specific and locus-specific p53 probes localized to chromosome 17 were selected to study 8 patients with late-stage (severe) endometriosis. Single cells localized to endometriotic lesions or normal endometrial glands were analyzed and identified as normal or abnormal on the basis of the distribution of fluorescence in situ hybridization signals. RESULTS: Overall, chromosome 17 aneuploidy was significantly greater (P <.05) in the endometriosis specimens (mean of 65%) than in normal endometrial cells (mean of 25%). No significant difference (P =.1071) in the distribution of fluorescence in situ hybridization signals was observed among the 5 normal endometrial specimens. However, significant differences (P <. 0001) were observed between the 8 endometriosis tissue specimens. CONCLUSION: We found increased heterogeneity of chromosome 17 aneuploidy in endometriosis. These findings support a multistep pathway involving somatic genetic alterations in the development and progression of this common disease.

Historical prospective cohort study of the recurrence of pain after discontinuation of treatment with danazol or a gonadotropin-releasing hormone agonist.

OBJECTIVE: To determine the duration of time to the recurrence of pain attributable to endometriosis after the discontinuation of treatment with danazol or a GnRH agonist (GnRH-a) in patients who have had a satisfactory response to the treatment. DESIGN: Retrospective study. SETTING: Nine academic medical centers in three countries. PATIENT(S): Three hundred twenty-seven women with diagnosed and staged endometriosis who were treated with at least 6 months of danazol or a GnRH-a and who experienced significant pain relief with therapy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Duration of pain relief after completion of treatment as determined by a patient-initiated report of pain recurrence or increase in pain severity requiring intervention. RESULT(S): The median time to the recurrence of pain was 6.1 months for patients treated with danazol and 5.2 months for patients treated with a GnRH-a. CONCLUSION(S): Although there was a lack of uniformity in treatment effects across sites, the analyses have taken into account major covariant effects. The time to the recurrence of endometriosis-associated pain after danazol treatment was slightly longer than that after GnRH-a treatment.

Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicine's revised classification of endometriosis.

OBJECTIVE: To estimate the empirical relationship between the revised American Society for Reproductive Medicine's classification of endometriosis and pregnancy rates after treatment. DESIGN: Retrospective analysis. PATIENT(S): Patients seen by four practicing physicians. INTERVENTION(S): Medical and/or surgical therapy for endometriosis. MAIN OUTCOME MEASURE(S): Pregnancy defined as ongoing or delivered. RESULT(S): There were no significant differences in pregnancy rates across stages of endometriosis. There was a slight decline in pregnancy rates among patients with Stage IV endometriosis, but statistical significance was not achieved. CONCLUSION(S): The use of an arbitrary weighted system for assigning scores to individual categories of disease, or for computing a total score, has limited the overall effectiveness of the classification system to predict pregnancy.

Identification of a meiotically expressed carbohydrate antigen in ovarian carcinoma: II. Association with proteins in tumors and peritoneal fluid.

A monoclonal antibody developed against a meiotically expressed porcine oocyte carbohydrate antigen has been shown to recognize an antigen in ovarian surface epithelial cells (OSE) of numerous mammalian species, including the non-human primate and the human (1). Although most of the ovarian surface epithelial cells are lost during aging in the human, a few cells may remain in ovarian crypts. Because the majority of ovarian carcinomas are thought to be derived from the OSE cells in aging women the PS1 antibody has been used to evaluate ovarian tumors. The secretory origin of this carbohydrate antigen in meiotic cells prompted further analyses of peritoneal fluid collected from gynecological surgery patients including those diagnosed with ovarian cancer. The present study demonstrates that ovarian tumor proteins separated on SDS PAGE include an antigen having a heterogeneous molecular weight (> 100 kDa) typical of glycosylated proteins. Additional studies show that peritoneal fluid from 19 patients not having cancer contain PS1 associated glycoproteins. However, of 14 cancer patients, only one had detectable levels of the carbohydrate antigen. These observations suggest that either the secretion of this glycoprotein is altered in ovarian carcinoma or that glycosidases or other proteolytic enzymes are involved in the degradation of these glycoproteins.

Sex hormones regulate ABR latency.

In an effort to characterize more completely the influence of sex hormones on auditory brainstem response (ABR) latency, we evaluated the ABRs of normal male and female subjects and women with previously diagnosed endocrinologic syndromes. We describe ABR latency results from the following subjects: five normal males, nine normally cycling females on no hormonal therapy, nine females using oral contraceptive pills, five females with premature ovarian failure (POF) undergoing cyclic estrogen-progesterone replacement therapy, and five hyperandrogenized females with polycystic ovarian disease (PCOD) treated with the gonadotropin-releasing hormone agonist, Lupron depot, to suppress ovarian steroid production. All subjects were between 23 and 40 years of age. Serum levels of estradiol, progesterone, testosterone, prolactic, and gonadotropins (lutienizing hormone and follicle stimulating hormone) were measured to document the hormonal status of each of the subjects at the time of the ABR evaluation. Normal cycling females and females with POF underwent ABR testing during different phases of the same cycle. Male subjects and females using birth control pills were studied four times in the same month at 1-week intervals. Females with PCOD were also studied four times; baseline and then at 2-week intervals after the initiation of Lupron depot therapy. Increased ABR wave V peak latencies were found to be associated with elevated levels of estrogen or testosterone. We have previously reported a lengthening of ABR wave V peak latencies coincident with peak estrogen levels during the female cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance improves in hyperandrogenic women treated with Lupron.

OBJECTIVE: To examine if changes in insulin sensitivity and glucose effectiveness in women with polycystic ovarian disease (PCOD) occurred after ovarian androgen suppression with a GnRH agonist, leuprolide acetate (LA, Lupron; TAP Pharmaceuticals, Deerfield, IL) using the minimal model method. DESIGN: Twelve patients with PCOD were tested in the untreated state (baseline) and after 6 weeks of LA treatment. Subjects were divided into two groups based on the degree of impairment of their baseline insulin sensitivity index (SI; (min-1) (microU/mL-1): mild insulin resistance (SI > 1) or severe insulin resistance (SI < 1). RESULTS: In all patients, serum T was significantly decreased from elevated baseline levels to normal female concentrations after 6 weeks of LA therapy. Insulin sensitivity in PCOD patients with mild insulin resistance significantly improved from baseline after 6 weeks of LA therapy, whereas no change in SI on LA therapy was seen in PCOD women with severe insulin resistance. Glucose utilization independent of increased insulin secretion did not change as a function of LA treatment in either group. CONCLUSION: These findings indicate a significant improvement in SI in mildly insulin-resistant women with PCOD after suppression of ovarian function with LA treatment.

Surgical treatment and adjunct therapy of endometriosis.

Conservative surgery at laparoscopy or laparotomy is effective against stage I-IV endometriosis to relieve pelvic pain and treat infertility. The subsequent average conception rate is 45-65%. Recurrence of endometriosis may occur, although pregnancy may delay this. Hysterectomy is indicated in severe disease, but the ovaries may be preserved if there is no evidence of active disease or significant periovarian adhesion. Combined surgery and pre- or postoperative medical therapy using gonadotropin releasing hormone agonists or danazol is recommended in young non-infertile women and those with extensive or severe disease.

Complexion changes in oral contraceptive users. Results from a phase IV multicenter trial evaluating the safety and efficacy of ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms.

An open-label, phase IV, multicenter survey of obstetrician-gynecologists was conducted to evaluate the efficacy and safety of a low-dose monophasic oral contraceptive, ethynodiol diacetate, 1 mg, with ethinyl estradiol, 35 micrograms. Surveys from 983 community-based physicians reported on 6,382 women. Most patients did not experience "clinically noticeable complexion changes" (5,695/6,382, or 89.2%). Of the 687 patients with complexion changes, nearly three-fourths reported an improvement (501/687, or 72.9%). A follow-up questionnaire was sent to 127 respondents (18.6%) who reported worsening of the complexion; 70% of the questionnaires were returned. Most complexion worsening was of slight degree (63%), reported by the patient and not the physician (84% vs. 16%), and experienced during the first two to three months (84%). Although the literature includes many references to skin condition "improvement" on oral contraceptives, this report of a descriptive study gives clinicians as estimate of the incidence and severity of complexion changes in actual use.

PIP: An open-label, phase IV, multicenter survey of obstetrician-gynecologists was conducted to investigate the efficacy and safety of a low-dose monophasic oral contraceptive (OC), ethynodiol diacetate, 1 mg, with ethinyl estradiol (EE), 35 mcg. Surveys from 983 community-based physicians reported on 6382 women, most of whom did not experience "clinically noticeable complexion changes" (5695/6382 or 89.2%). Of the 687 who did, nearly 3/4 reported an improvement (501/587 or 72.9%). A followup questionnaire was sent to 127 respondents (18.6%) who reported worsening of their complexions; 70% of the questionnaires were returned. Most had a slight degree of complexion worsening (63%) as reported by the patient and not the physician (84% vs 16%), and these changes were experienced during the 1st 2-3 months (84%). Although the literature includes many references to skin condition improvement while taking OCs, this report of a descriptive study gives clinicians an estimate of the incidence and severity of complexion changes during actual use. (author's modified).

Androgen responses to acutely increased endogenous insulin levels in hyperandrogenic and normal cycling women.

We examined androgen responses in hyperandrogenic (polycystic ovarian disease [PCOD]) and normal women after an acute endogenous insulin elevation. Standard intravenous glucose tolerance tests (IVGTTs), modified to include a tolbutamide injection 20 minutes after IVGTTs, were performed. Polycystic ovarian disease patients were studied in the untreated state, after 6 weeks of ovarian androgen suppression with leuprolide acetate, after a 6-week rest period, and after 6 weeks of antiandrogen therapy with spironolactone. Normal menstruating women were studied during the early follicular, midcycle, and luteal phases of a single cycle. An acute rise in insulin did not alter serum testosterone or androstenedione levels in PCOD or normal women. A significant rise in dehydroepiandrosterone sulfate after modified IVGTTs was found in both hyperandrogenic and normal cycling women. Although these results are not supportive of the theory that insulin acts on the ovary to stimulate androgen production, they may be because of the short time course of insulin elevation that occurs during an IVGTT.

The surgical management of endometriosis.

Surgical treatment is an important option in treatment of all stages of endometriosis. Surgical options of operative laparoscopy, lasers, laparotomy technique, and perioperative medical treatment are discussed in the contexts of both published literature and the authors' clinical experience.

Vulvovaginal sequelae of Stevens-Johnson syndrome and their management.

We describe a woman with Stevens-Johnson syndrome, a life-threatening form of erythema multiforme characterized by bullae formation, extensive mucosal damage, and systemic toxicity, and known to be triggered by various drugs, infections, ingestants, or contactants. Serious complications have been reported in most body systems, including cases of permanent damage to the urogenital tract. Three methods of surgical treatment for severe vaginal complications, depending on the degree of vaginal mucosal damage, are described, including the successful treatment of our patient, who had vaginal adenosis, endometriosis, and severe stenosis from this disease. Methods of therapy are presented for possible prevention of severe vaginal sequelae from Stevens-Johnson syndrome.