The role of microbiota in the management of genitourinary syndrome of menopause.

It is estimated that the 25-50% of women who are reaching menopause every year report symptoms related to the genitourinary syndrome of menopause (GSM). The symptoms are not due simply to lack of estrogen. One possible contributing cause of symptoms is the vaginal microbiota. The vaginal microbiota is a dynamic entity and plays a critical role in the pathogenic interplay of postmenopausal changes. Treatment of this syndrome depends on the severity and type of the symptoms and on the preferences and expectations of women. As there are many treatment options, therapy should be individualized. While new evidence on the role of Lactobacilli in premenopause is emerging, the role of Lactobacilli is still unclear in GSM and the impact of microbiota on vaginal health remains conflictual. However, some reports show promising data on the effect of probiotic therapy in menopause. In the literature there are few studies and small population samples on the role of an exclusive therapy with Lactobacilli and further data will be mandatory. Studies involving large numbers of patients and different intervention periods will be necessary to obtain evidence of the preventive and curative role of vaginal probiotics.

Evidence-based mixture containing Lactobacillus strains and lactoferrin to prevent recurrent bacterial vaginosis: a double blind, placebo controlled, randomised clinical trial.

Bacterial vaginosis (BV) is the most common cause of vaginal discomfort in women. It is characterised by abnormal vaginal microbiota with a depletion of lactobacilli and predominance of anaerobic microorganisms, mainly Gardnerella vaginalis and Atopobium vaginae. Although antibiotics represent an effective therapeutic option in the short-term, recurrent infections still remain a serious problem. Nowadays, evidence exists about the efficacy of probiotics for the management of BV. The aim of the current double blind, randomised clinical trial was to assess the efficacy of a probiotic mixture, including Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001, in combination with bovine lactoferrin, as adjuvant therapy to metronidazole in women with recurrent BV. In particular, normalisation of Nugent score, remission of symptoms and recurrences during a six-months follow-up were assessed. 48 adult women received metronidazole (500 mg twice daily) for 7 days and randomly assigned to take simultaneously either probiotics plus lactoferrin or placebo (2 capsules/day for 5 days followed by 1 capsule/day for 10 consecutive days; induction phase). The verum or placebo administration (1 capsule/day for 10 consecutive days) was repeated each month (maintenance phase) during the six months of follow-up starting the first day of menstrual cycle since the menstrual blood increases the vaginal pH and contributes to increase the risk of recurrences. The results showed that symptoms (vaginal discharge and itching), Nugent score and recurrence rate were significantly improved by probiotics mixture in association with lactoferrin. This alternative approach may represent a safe and effective remedy for the restoration of healthy vaginal microbiota in preventing recurrent BV.

The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis.

To evaluate the efficacy of an association of N-acetyl cystein, alpha-lipoic acid, and bromelain (NAC/LA/Br) in the treatment of endometriosis we set up a new in vivo murine model. We explored the anti-inflammatory and proapoptotic effect of this combination on human endometriotic endothelial cells (EECs) and on endothelial cells isolated from normal uterus (UtMECs). We implanted fragments of human endometriotic cysts intraperitoneally into SCID mice to evaluate the efficacy of NAC/LA/Br treatment. UtMECs and EECs, untreated or treated with NAC/LA/Br, were activated with the proinflammatory stimulus TNF-α and their response in terms of VCAM1 expression was evaluated. The proapoptotic effect of higher doses of NAC/LA/Br on UtMECs and EECs was measured with a fluorogenic substrate for activated caspases 3 and 7. The preincubation of EECs with NAC/LA/Br prior to cell stimulation with TNF-α prevents the upregulation of the expression of the inflammatory "marker" VCAM1. Furthermore NAC/LA/Br were able to induce EEC, but not UtMEC, apoptosis. Finally, the novel mouse model allowed us to demonstrate that mice treated with NAC/LA/Br presented a lower number of cysts, smaller in size, compared to untreated mice. Our findings suggest that these dietary supplements may have potential therapeutic uses in the treatment of chronic inflammatory diseases like endometriosis.

Intrapartum fetal heart rate monitoring interpretation in labour: a critical appraisal.

Electronic fetal monitoring (EFM) has been introduced in the obstetrics practice as a test to identify the first signs of fetal deterioration, allowing a prompt intervention to reduce neonatal morbidity and mortality. However, results from clinical trials fail to demonstrate a clear benefit with the use of EFM. No decrease in the incidence of cerebral palsy due to intrapartum asphyxia has been achieved and a significant increase in the rate of operative deliveries and in medico-legal litigations has been observed instead. Despite the lack of evidence supporting its safety and effectiveness, this method is routinely used in the clinical practice and periodical updated guidelines to standardize the method of interpretation and proper actions are proposed. However, limitations still exist and the unavoidable consequences are the increasing rate of caesarean delivery, partly due to a defensive attitude in medical choices, and medico-legal litigations for presumed inappropriate evaluation in case of perinatal adverse event. While Obstetrics Societies are trying to "fight" the rise in caesarean section rates, intrapartum EFM tracings are taken in the court proceedings as one of the main evidences in case of adverse event. The aim of this review is to discuss the limitations of guidelines dealing with intrapartum EFM and the pathophysiological basis to assess the suspicious tracings which represent the most observed and critical issue of EFM interpretation.

Lactobacillus plantarum P17630 for preventing Candida vaginitis recurrence: a retrospective comparative study.

BACKGROUND: Recurrence is a frequent complaint of patients with vulvovaginal candidiasis (VVC). Although the pathogenesis of VVC remains a controversial issue, disruption of the balance between the vaginal microbiota may facilitate overgrowth by Candida. Some probiotic bacterial strains can suppress Candida albicans; Lactobacillus plantarum P17630 is able to attach to vaginal epithelial cells and significantly reduce the adhesion of C. albicans. OBJECTIVE: To evaluate the effect of the application of Lactobacillus plantarum P17630 in restoring the vaginal microbiota and prevention of relapses among women with acute VVC undergoing conventional (azole) local and main therapy. METHODS: Retrospective comparative study. We recruited 89 women with a diagnosis of VVC, who were placed into two groups on the basis of reported treatment. The control group was treated with a daily dose of 2% clotrimazole vaginal cream at bedtime for 3 days, followed by vaginal application of a capsule containing lubricant once a day for 6 days and then once a week for another 4 weeks. The probiotic group was treated with the same azole-based protocol but followed by vaginal application of a capsule containing Lactobacillus plantarum P17630 (>108 CFU) once a day for 6 days and then once a week for another 4 weeks beginning the day following clotrimazole discontinuation. Clinical and diagnostic patterns were monitored for three months of follow-up. RESULTS: At the end of study the probiotic-treated women showed a statistically significant increase in Lactobacillus values "+++" (80% versus 40%, p<0.001) and a better subjective resolution of symptoms such as vaginal discomfort described as burning or itching (90% versus 67.5%, p<0.03). Among controls there was a non-significant increase at 3 months of recurrence of infection, but a significant increase of women with value of pH=5 or >5. CONCLUSION: Although the results of different studies are controversial, most have suggested use of probiotics in the prevention or treatment of VVC, and no adverse effects have been reported. Our data with L. plantarum P17630 (Gyno-Canesflor - Bayer) confirm the role of this specific strain as a potential empirical preventive agent for reducing vaginal discomfort after conventional treatment of acute VVC and shifting the vaginal milieu toward a predominance of lactobacilli with an improvement of the vaginal pH value.

Pelvic inflammatory disease (PID) from Chlamydia trachomatis versus PID from Neisseria gonorrhea: from clinical suspicion to therapy.

Pelvic inflammatory disease (PID) is the most significant complication of sexually transmitted infections in childbearing-age women and it represents an important public health problem because of its long-term sequelae (chronic pelvic pain, tubal infertility, ectopic pregnancy). Prior to the mid 1970s PID was considered a monoetiologic infection, due primarily to Neisseria gonorrhea. Now it is well documented as a polymicrobial process, with a great number of microrganisms involved. In addition to Neisseria gonorrhea and Chlamydia trachomatis, other vaginal microrganisms (anaerobes, Gardnerella vaginalis, Haemophilus influenzae, enteric Gram negative rods, Streptococco agalactie, Mycoplasma genitalium) also have been associated with PID. There is a wide variation in PID clinical features; the type and severity of symptoms vary by microbiologic etiology. Women who have chlamydial PID seem more likely than women who have gonococcal PID to be asymptomatic. Since clinical diagnosis is imprecise, the suspicion of PID should be confirmed by genital assessment for signs of inflammation or infection, blood test and imaging evaluation. Laparoscopic approach is considered the gold standard. According to the polymicrobial etiology of PID, antibiotic treatment must provide broad spectrum coverage of likely pathogens. Early administration of antibiotics is necessary to reduce the risk of long-term sequelae.

[Proteomic applications in gynecology-obstetrics]. / Applicazioni della proteomica in ambito ginecologico-ostetrico.

Proteomics has recently emerged as a powerful approach both for discovering biomarkers as well as for understanding the physiopathology of unclear gynecological-obstetrical disorders. Currently, several biological fluids and fetal tissues were successfully tested, including maternal plasma, amniotic fluid, cervical-vaginal fluid, urine, saliva, placental trophoblast, amnio-chorionic membranes and cord blood. The potential of proteomics on the polycystic ovary syndrome (PCOS) involves biomarkers discovery for a more accurate diagnosis of the syndrome and identification, within the patients with PCOS, those who respond more easily to treatment and those who will be at increased risk for future metabolic complications. The proteomic approach applied to patients with endometriosis would allow not only a non-invasive early diagnosis, but also a staging of the disease and a prediction of infertility risk. Proteomics also involves oncological field, in order to discover biomarkers that allow early diagnosis and prognosis of female genital malignancies. In addition to this, proteomics could be used to understand and predict obstetrical complications such as recurrent spontaneous abortion, preterm birth and preeclampsia. However, further studies are needed on a larger cohort of patients to introduce these biomarkers in clinical practice.

Mannose-binding lectin is produced by vaginal epithelial cells and its level in the vaginal fluid is influenced by progesterone.

Mannose-binding lectin (MBL) is a recognition molecule of the complement (C) system and binds to carbohydrate ligands present on a wide range of pathogenic bacteria, viruses, fungi, and parasites. MBL has been detected in the cervico-vaginal cavity where it can provide a first-line defence against infectious agents colonizing the lower tract of the reproductive system. Analysis of the cervico-vaginal lavage (CVL) obtained from 11 normal cycling women at different phases of the menstrual cycle revealed increased levels of MBL in the secretive phase. Part of this MBL derives from the circulation as indicated by the presence of transferrin in CVL tested as a marker of vascular and tissue permeability. The local synthesis of MBL is suggested by the finding that its level is substantially higher than that of transferrin in the secretive phase. The contribution of endometrium is negligible since the MBL level did not change before and after hysterectomy. RT-PCR and in situ RT-PCR analysis showed that the vaginal tissue, and in particular the basal layer of the epithelium, is a source of MBL which binds to the basal membrane and to cells of the outer layers of the epithelium. In conclusion, we have shown that MBL detected in CVL derives both from plasma as result of transudation and from local synthesis and its level is progesterone dependent increasing in the secretive phase of the menstrual cycle.

Aetiology of preterm labour: bacterial vaginosis.

Bacterial vaginosis (BV) is a common condition characterised by a polymicrobial disorder, with an overgrowth of several anaerobic or facultative bacteria and with a reduction or absence of lactobacillus colonisation. The prevalence of BV ranges from 4 to 64%, depending on the racial, geographic and clinical characteristics of the study population. In asymptomatic women, the prevalence varies from 12 to 25%, and similar percentages are observed in pregnant women. Although BV is associated with several adverse outcomes, such as upper genital tract infections, pelvic inflammatory disease, endometritis, preterm birth and low birthweight, many basic questions regarding the pathogenesis of BV remain unanswered. Mucosal immune system activation may represent a critical determinant of adverse consequences associated with BV. An unequal risk for BV acquisition and\or recurrence could derive from different mucosal immune host abilities and\or capability of invading microbes to produce factors that inactivate the local immune response. BV is associated with a two-fold increased risk of preterm birth, with the greatest risk when BV is present before 16 weeks of gestation (odds ratio = 7.55). This may indicate a critical period during early gestation when BV-related organisms can gain access to the upper genital tract and set the stage for spontaneous preterm labour later in gestation. The results of treatment trials for pregnant women with BV have been heterogeneous, with anywhere from an 80% reduction to a two-fold increase in preterm birth among women who received treatment. For this reason, in current clinical practice significant controversy surrounds determining not only who and when to screen but also who and how to treat. Recent evidence shows that individual genetic backgrounds can affect chemokine production. This is an interesting area for future research and could lead to trials of treatment only for women genetically predisposed to preterm birth.

[Pregnancy in HIV-positive women: 6 years of activity of the Regional Reference Center]. / La gravidanza in donna HIV positiva: 6 anni di attività del Centro di Riferimento Regionale.

AIM: With this study, we wanted to evaluate HIV-positive pregnant mothers followed at the HIV Reference Center of Friuli Venezia Giulia and to describe obstetric treatment aimed at identifying vertical transmission factors and at undertaking a correct diagnostic-therapeutic approach to this patient group. The data include a large case series from the European Collaborative Study on HIV in Pregnancy, in which our facility is a collaborating center. METHODS: The protocol includes the administration of personalized antiretroviral therapy to seropositive patients at the first visit. An elective caesarean section is performed at 38 weeks gestation. Antiretroviral therapy is continued in the neonate. Breastfeeding is prohibited. RESULTS: From 1998 to 2002, 28 pregnant mothers with HIV infection were followed. Most patients came from out of region and had acquired the infection through heterosexual intercourse with a serodiscordant partner. In 1 in 3 patients, a diagnosis of seropositivity was made during pregnancy. One case of vertical transmission was observed. CONCLUSIONS: When appropriate prevention measures are instituted, the percentage of vertical transmission of infection can be reduced to less than 1% in Europe today. An important part of this effort is early screening for HIV infection in pregnancy. Other fundamental measures are the institution of antiretroviral therapy starting from the first weeks of pregnancy, monitoring of pregnancy at a tertiary reference center, intravenous administration of therapies before caesarean section, possibly not during labor and with the membrane intact. Equally important factors are neonatal therapy, adequate pediatric monitoring after the infant is born and discontinuation of breastfeeding.

Mannose binding lectin and C3 act as recognition molecules for infectious agents in the vagina.

In our study we examined the early complement components in patients with bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and in healthy controls. The levels of C1q, mannose-binding lectin (MBL) and C3 were measured by ELISA in the cervicovaginal lavage (CVL) from gynaecological patients and controls. No significant differences were observed in the levels of these proteins in the three study groups. Immunofluorescence analysis of the clue cells and Candida hyphae from BV and VVC patients for surface-bound complement components showed the presence of C3, while C1q was undetectable. MBL was revealed on clue cells but not on Candida. Binding of MBL to Candida, grown or cytocentrifuged from the CVL of VVC patients, was found to be pH dependent and occurred between pH 4.5 and pH 5.5. In conclusion, we demonstrated that MBL and C3 present in the vaginal cavity act as recognition molecules for infectious agents that colonize the cervicovaginal mucosa. Our finding that MBL, but not C1q, binds to bacteria and fungi in vagina suggests that the lectin and classical pathways of complement activation may play a different role in immune defence in the female genital tract.

Quantitative in situ detection of high-risk human papillomavirus in cytological specimens by SYBR Green I fluorescent labeling.

In this study we developed an in situ protocol for quantitative detection of high-risk human papillomavirus (HPV), based on direct in situ polymerase chain reaction (PCR) with SYBR Green I labeling and GeneAmp 5700 Sequence Detection System technology. This protocol was applied on cytological specimens of patients with cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). We performed direct in situ quantitative PCR on cell smears, uninfected human skin fibroblasts, Hela and Caski cells. After in situ amplification, slides were counterstained with propidium iodide and analyzed under a fluorescent microscope in order to localize high-risk HPV and verify preservation of morphology. After PCR optimization, we obtained the following results. The Hela cells showed values ranging from 15 to 33 copies of high-risk HPV per cell, the Caski cell line from 220 to 300 high-risk HPV copies per cell and the cell smear (both CIN and SCC) around 20-35 copies of high-risk HPV per cell. No high-risk HPV amplification was detected in uninfected human fibroblasts, healthy controls, non-amplification control, and non-specific primer control. A positive intranuclear high-risk HPV amplification was detected in cell smears from 20 patients with CIN and 10 with SCC. In conclusion, our in situ quantitative protocol for high-risk HPV detection on cell smears combines both quantitative data and in situ localization of the target, with preservation of morphology. For this reason it could be used as a rapid screening tool when both morphological and quantitative results are requested on the same slide.

New perspectives in antibiotic prophylaxis for obstetric and gynaecological surgery.

The goals of antibacterial prophylaxis during obstetric/gynaecological surgery are similar to those of prophylaxis during intra-abdominal surgery. The vaginal flora consists of many aerobic and anaerobic organisms, is dominated by peroxide-producing lactobacilli, and is non-pathogenic under normal conditions. Destabilization of the vaginal ecosystem, as in bacterial vaginosis (BV), causes a massive increase in the ratio of anaerobes to aerobes and is associated with a large increase in the risk of infection. The surgical procedures at most risk of postoperative infection are vaginal, abdominal and radical hysterectomy and caesarean section. Both the American College of Obstetricians and Gynecologists and the American Society of Health-System Pharmacists have recommended single-dose prophylactic protocols using a variety of agents (penicillins, cephalosporins and clindamycin). However, it remains doubtful whether prophylaxis is used widely. In Italy, such prophylaxis has proved less effective in women with BV. Accordingly, patients with confirmed BV are given topical clindamycin for 7 days leading up to surgery, in addition to the usual prophylactic regimen. Caesarean delivery carries a 5- to 20-fold greater risk of infection that normal vaginal delivery. A meta-analysis of 66 clinical studies has shown that any prophylactic regimen is effective in reducing postoperative complications. The use of prophylaxis in patients undergoing a low-risk caesarean section remain controversial.

Does amniotic fluid alpha-fetoprotein have diagnostic or prognostic value at the time of second midtrimester genetic amniocentesis?

In order to assess the usefulness of amniotic fluid alpha-fetoprotein (AFP) levels at the time of midtrimester genetic amniocentesis, 4,430 cases were retrospectively studied to compare the high, normal or low AFP values with the karyotype characteristics and fetal anatomy using ultrasound (US) scanning and confirmed by postnatal evaluation or necroscopy in the case of termination of pregnancy. All the cases presenting malformations were correctly diagnosed by US examinations. AFP levels over the 2nd standard deviation (SD) were found in 112 cases (2.52%) and below the 2nd SD in 11 cases (0.24%). The characteristics of these cases are presented and discussed. According to our results, it is concluded that routine assessment of AFP at the time of midtrimester genetic amniocentesis, if coupled with optimal US scanning, is no longer justified.

Quality of life assessment in patients who undergo sacral neuromodulation implantation for urge incontinence: an additional tool for evaluating outcome.

PURPOSE: We investigated the impact of sacral neuromodulation on quality of life and assessed the importance of quality of life for determining the success of sacral neuromodulation in patients with detrusor hyperactivity, including instability and hyperreflexia. We also compared it with parameters documented in a voiding diary. MATERIALS AND METHODS: From May 1998 to December 2000, 82 female and 31 male patients 17 to 79 years old (mean age 51.1) with urge incontinence (63), urgency/frequency (5), voiding disturbance (41) and pelvic pain (4) resistant to conservative treatment were enrolled in a national prospective registry after showing a positive response to percutaneous nerve evaluation testing. Of the patients 47 who were 32 to 79 years old (mean age 59.2) with urge incontinence due to detrusor instability and 16 who were 27 to 51 years old (mean age 51.5) with hyperreflexia were asked to complete a validated self-reporting incontinence domain specific quality of life questionnaire before, and 3, 6, 9, 12, 18, 24 and 36 months after implantation. RESULTS: Compared with baseline the quality of life index significantly improved at each followup, which strongly correlated with the decrease in the number of incontinence episodes. CONCLUSIONS: Evaluating quality of life may be an additional useful tool for assessing the results of sacral neuromodulation for urge incontinence. Our study confirms that sacral neuromodulation is effective therapy for urge incontinence that can have a positive effect on patient quality of life.

Short-term sacral nerve stimulation for functional anorectal and urinary disturbances: results in 40 patients: evaluation of a new option for anorectal functional disorders.

PURPOSE: There are several options in the treatment of fecal incontinence; it is often difficult to choose the most appropriate, adequate treatment. The consolidated experience gained in the urologic field suggests that sacral nerve stimulation may be a further option in the choice of treatment. The aim of our study was to evaluate the preliminary results of the peripheral nerve evaluation test obtained in a multicenter collaborative study on patients with defecatory and urinary disturbances. METHODS: Forty patients (9 males; mean age, 50.2; range, 26-79 years) underwent the peripheral nerve evaluation test, 28 (70 percent) for fecal incontinence and 12 (30 percent) for chronic constipation. Fourteen (35 percent) patients also had urinary incontinence; six had urge incontinence, two had stress incontinence, and six had retention incontinence. Associated diseases were scleroderma (2 patients), spinal injuries (4 patients), and syringomyelia (1 patient). All the patients underwent preliminary investigations with anorectal manometry, pudendal nerve terminal motor latency testing, anal ultrasound, defecography, and if required, urodynamic tests. The electrode for sacral nerve stimulation was positioned percutaneously under local anesthesia in the S2 (4), S3 (34), or S4 (1) foramen unilaterally (1 patient not accounted for because of no response to acute test), based on the best motor and subjective responses of paresthesia of the pelvic floor. Stimulation parameters were average amplitude, 2.8 (range, 1-6) V and average frequency, 15 to 25 Hz. RESULTS: The mean duration of the tests was 9.9 (range, 7-30) days; tests lasting fewer than seven days were not evaluated. There were four early displacements of the electrode. In 22 of the 25 evaluable patients with fecal incontinence, there was an improvement of symptoms (88 percent), and 11 (44 percent) were completely continent to liquid or solid stools, whereas in 7 symptoms were unchanged. Mean number of episodes of liquid or solid stool incontinence per week was 8.1 (range, 4-18) in the prestimulation period and 1.7 (range, 0-12) during the peripheral nerve evaluation test. (P = 0.001; Wilcoxon's signed-rank test). The most important manometric findings were: increase of maximum rest pressure (39.4 +/- 7.3 vs. 54.3 +/- 8.5 mmHg; P = 0.014, Wilcoxon's test) and maximum squeeze pressure (84.7 +/- 8.8 vs. 99.5 +/- 1.1 mmHg; P = 0.047), reduction of initial threshold (63.6 +/- 5.2 vs. 42.4 +/- 4.7 ml; P = 0.041) and urge sensation (123.8 +/- 0.6 vs. 78.3 +/- 8.9 ml; P = 0.05). An improvement was also found in patients with constipation, with reduction in difficulty emptying the rectum, with prestimulation at 7 (range, 2-21) episodes per week and end of peripheral nerve evaluation test at 2.1 (range, 0-6) episodes per week, P < 0.01) and in the number of unsuccessful visits to the toilet, which dropped from 29.2 (7-24) to 6.7 (0-28) per week (P = 0.01). The most important manometric findings in constipated patients were an increase in amplitude of maximum squeeze pressure during sacral nerve stimulation (prestimulation, 63 +/- 0 mm Hg; end of peripheral nerve evaluation test, 78 +/- 1 mm Hg; P = 0.009) and a reduction in rectal volume for urge threshold (prestimulation, 189 +/- 52 ml; end of peripheral nerve evaluation test, 139 +/- 45 ml; P = 0.004). CONCLUSIONS: In functional bowel disorders short-term sacral nerve stimulation seems to be a useful diagnostic tool to assess patients for a minor invasive therapy alternative to conventional surgical procedure.

Neuromodulation for fecal incontinence: outcome in 16 patients with definitive implant. The initial Italian Sacral Neurostimulation Group (GINS) experience.

PURPOSE: Sacral nerve modulation appears to offer a valid treatment option for some patients with fecal incontinence and functional defects of the internal anal sphincter or of the striated muscle. METHODS: Sixteen patients with fecal incontinence (4 males; mean age, 51.4 (range, 27-79) years) with intact or surgically repaired (n = 1) anal sphincter underwent permanent sacral nerve stimulation implant. Cause was traumatic in two patients, and associated disorders included scleroderma (2 patients) and spastic paraparesis (1 patient); eight (50 percent) of the patients also had urinary incontinence, and two (12.5 percent) had nonobstructive urinary retention. All patients were selected on the basis of positive findings from at least one peripheral nerve evaluation. The stimulating electrode was positioned in the S2 (1 patient), S3 (14 patients), or S4 (1 patient) sacral foramen. RESULTS: Mean follow-up was 15.5 (range, 3-45) months. Mean preimplant Williams score decreased from 4.1 +/- 0.9 (range, 2-5) to 1.25 +/- 0.5 (range, 1-2) (P = 0.01, Wilcoxon test), and the number of incontinence accidents for liquid or solid stool in 14 days decreased from 11.5 +/- 4.8 (range, 2-20) before implant to 0.6 +/- 0.9 (range, 0-2) at the last follow-up. Important manometric data were an increase in mean maximal pressure at rest of 37.7 +/- 14.9 mmHg (implantable pulse generator 49.1 +/- 18.7, P = 0.04) and in mean maximal pressure during squeeze (prestimulation 67.3 +/- 21.1 mmHg, implantable pulse generator 82.6 +/- 21.0, P = 0.09). CONCLUSIONS: Neuromodulation can be considered an option for fecal incontinence. However, an accurate clinical and instrumental evaluation and careful patient selection are required to optimize outcome.

Chronic sacral neuromodulation in patients with lower urinary tract symptoms: results from a national register.

PURPOSE: The Italian Register was created in February 1997 to collect the national results of sacral neuromodulation. All Italian centers at which sacral neuromodulation is performed were invited to participate in our study. We present the results from retrospective and prospective registers. MATERIALS AND METHODS: A total of 196 patients underwent permanent implantation of sacral neuromodulation and were enrolled in the Italian register. There were 18 males and 75 females in the retrospective, and 28 males and 75 females in the prospective studies. Student's t test was used to compare paired values, and the Wilcoxon rank sum and nonparametric tests were used when necessary. RESULTS: Mean incontinent episodes daily plus or minus standard deviation for patients with detrusor instability went from 5.4 +/- 3.9 to 1.1 +/- 1.6 (median 5 and 0, respectively) at 12-month followup (p <0.001). For idiopathic retention average residual volume decreased from 277 to 108 cc (median 287 and 80, respectively), and 50% of patients stopped catheterization and another 13% catheterized once daily at 1-year after implantation. With neurogenic voiding disturbances, the results fluctuated with time from a minimum of 33% to a maximum 66% of patients who did not catheterize at 6-month followup and 12 months after implantation, respectively. At 12-month followup, 50% of patients with hyperreflexia had less than 1 incontinent episode daily. The problem was completely solved in 66% of patients in the retention group. Of patients in the urge incontinent population 39% were completely dry and 23% had less than 1 incontinent episode daily. CONCLUSIONS: Sacral neuromodulation is effective therapy for treating lower urinary tract symptoms resistant to less invasive therapy.

Pregnancy in hyperprolactinemic infertile women treated with vaginal bromocriptine: report of two cases and review of the literature.

Vaginal bromocriptine has proven safe and effective in treating hyperprolactinemic women. However, there has been no long-term clinical assessment regarding the influence of daily vaginal bromocriptine administration on the ability to conceive. This article presents two cases of successful pregnancy resulting from this alternative treatment. An infertile woman with an empty sella and hyperprolactinemia was treated with vaginal bromocriptine because of intolerance to oral administration. Prolactin levels were quickly normalized and no side effects occurred. Repeated postcoital tests during treatment proved normal. Twelve months later, the patient conceived. The therapy was discontinued during pregnancy, without complications. Although bromocriptine treatment was not resumed after delivery, postpartum prolactin levels were lower than before treatment and magnetic resonance imaging revealed an unchanged empty sella. Another patient with infertility and pituitary microadenoma with intolerance to oral dopaminergic agonists received the same treatment. Prolactin quickly fell to within the normal range. Vaginal bromocriptine was well tolerated and postcoital test results were not impaired. Tumor regression occurred and 10 months later the patient conceived. Despite bromocriptine withdrawal, no significant complications occurred during pregnancy. It can therefore be concluded that a couple's fertility does not appear to be significantly affected by the persistent local presence of bromocriptine.