Evaluation of patients' satisfaction of cervical ripening using dinoprostone by either intravaginal gel or pessary: an open-label, randomized, prospective study.

OBJECTIVE: To evaluate patient satisfaction of cervical ripening using dinoprostone (PGE2) by either intravaginal gel or pessary. STUDY DESIGN: A group of 173 nulliparous women requiring cervical ripening were recruited in the study and randomized to receive either intravaginal gel (Prepidil, Upjohn, Milan, Italy [group A]) or intravaginal pessary (Propess, Ferring Pharmaceuticals, Malmö, Sweden [group B]). Before administration of PGE2 and after delivery, the patients answered a questionnaire investigating the anxiety and discomfort caused by cervical ripening. RESULTS: Of the group, 22 women did not adequately complete the questionnaire; therefore 151 women were included in the study. Before cervical ripening, anxiety and discomfort did not significantly differ between the two study groups; more patients in group A than in group B declared they would have preferred the other form of application. The intensity of pain experienced during the application of PGE2 was higher in group B than in group A. For the future opportunity to choose the application necessary for cervical ripening, more patients in group B than in group A would change the form of application. CONCLUSION: Patient satisfaction with the two forms of treatment appears to be equally good. The application of the intravaginal pessary causes more discomfort than the vaginal gel.

Loss of sympathetic nerve fibers in intestinal endometriosis.

This study analyzed by immunofluorescence staining the sympathetic innervation in the bowel adjacent to the endometriotic lesion and in the healthy tissue at the border of the resected specimen. Sympathetic nerve fibers are significantly reduced in the mucosal and muscular layer near the endometriotic lesions; in contrast, sensory nerve fiber density is not altered in the area near the endometriotic lesions.

Crosstalk between decidual NK and CD14+ myelomonocytic cells results in induction of Tregs and immunosuppression.

Regulatory T cells (Tregs) are thought to play a major role in pregnancy by inhibiting the maternal immune system and preventing fetal rejection. In decidual tissues, NK cells (dNK) reside in close contact with particular myelomonocytic CD14(+) (dCD14(+)) cells. Here we show that the interaction between dNK and dCD14(+) cells results in induction of Tregs. The interaction is mediated by soluble factors as shown by transwell experiments, and the prominent role of IFN-gamma is revealed by the effect of a neutralizing monoclonal antibody. Following interaction with dNK cells, dCD14(+) cells express indoleamine 2,3-dioxygenase (IDO), which, in turn, induces Tregs. Notably, unlike peripheral blood NK (pNK) cells, dNK cells are resistant to inhibition by the IDO metabolite L-kynurenine. "Conditioned" dCD14(+) cells also may induce Tregs through transforming growth factor-beta (TGF-beta) production or CTLA-4-mediated interactions, as indicated by the effect of specific neutralizing Abs. Remarkably, only the interaction between dNK and dCD14(+) cells results in Treg induction, whereas other coculture combinations involving either NK or CD14(+) cells isolated from peripheral blood are ineffective. Our study provides interesting clues to understanding how the crosstalk between decidual NK and CD14(+) cells may initiate a process that leads to Treg induction and immunosuppression. Along this line, it is conceivable that an impaired function of these cells may result in pregnancy failure.

Letrozole and norethisterone acetate in colorectal endometriosis.

OBJECTIVE: Up to now limited attention has been given to the medical treatment of bowel endometriosis. This study evaluates the efficacy of aromatase inhibitors and norethisterone acetate in treating pain and gastrointestinal symptoms caused by bowel endometriosis. STUDY DESIGN: This prospective pilot study included six women with colorectal endometriosis; all women had intestinal nodules infiltrating at least the muscularis propria of the bowel and did not have a stenosis of the bowel lumen >60%; the patients suffered from pain and intestinal symptoms. The study subjects received letrozole (2.5 mg/day) and norethisterone acetate (2.5 mg/day) continuously for 6 months. The presence and intensity of symptoms were evaluated before starting the treatment, and after 3 and 6 months of treatment. RESULTS: The double-drug regimen improved pain, non-menstrual pelvic pain, deep dyspareunia, dyschezia, symptoms mimicking diarrhoea-predominant irritable bowel syndrome, intestinal cramping, abdominal bloating and passage of mucus in the stools, and 67% of the patients declared that the treatment improved their gastrointestinal symptoms. CONCLUSIONS: The administration of letrozole and norethisterone acetate reduces pain and gastrointestinal symptoms of women with colorectal endometriosis, particularly when patients suffer from symptoms mimicking diarrhoea-predominant irritable bowel syndrome.

Unusual complication of excision of pelvic endometriosis: pseudoaneurysm of the left uterine artery.

We report on a patient who had a pseudoaneurysm arising from the left uterine artery after surgical excision of deep endometriosis. The diagnosis was based on contrast-enhanced multidetector computed tomography angiography. Transfemoral selective catheterization and embolization of the left uterine artery determined a quick improvement of the symptoms.

Frozen section underestimates the need for surgical staging in endometrial cancer patients.

OBJECTIVE: To compare the risk status for lymph nodal metastasis at frozen section in endometrial cancer by applying a model based on tumor grade and myometrial involvement. STUDY DESIGN: A retrospective analysis was performed on 174 early-stage endometrial cancer patients on whom an intraoperative frozen section was requested. Patients were retrospectively divided into low, intermediate, and high risk for lymph nodal involvement based on tumor grade and myometrial invasion based on Gynecologic Oncology Group 33 data. Concordance of risk status at frozen and permanent sections was performed. RESULTS: Risk status at frozen and permanent sections were highly correlated (P < 0.01). Agreement between frozen and permanent sections was substantial (kappa = 0.625). In 16% of the cases, frozen section underestimated the risk when compared with permanent section. CONCLUSION: Relying on intraoperative frozen section of the uterus to assess risk status for lymph nodal involvement in early-stage endometrial cancer patients leads to suboptimal management in a substantial number of cases.

Uterine adenomyosis in persistence of dysmenorrhea after surgical excision of pelvic endometriosis and colorectal resection.

OBJECTIVE: To determine whether the presence of uterine adenomyosis may impair the amelioration of pain symptoms after laparoscopic excision of pelvic endometriosis combined with colorectal resection. STUDY DESIGN: This prospective study included 50 women with bowel endometriosis with or without uterine adenomyosis. Presence of uterine adenomyosis was investigated by magnetic resonance imaging. Patients underwent excision of pelvic endometriosis and colorectal resection; some patients with focal adenomyosis underwent uterine surgery. Pain symptoms and gastrointestinal complaints were evaluated before surgery and at 6, 12 and 18 months' follow-up. RESULTS: At 6-month follow-up, dysmenorrhea significantly improved in women without uterine adenomyosis and in those with adenomyosis that was excised at surgery; this improvement persisted at 18 months' followup. No significant improvement in dysmenorrhea was observed in women with adenomyosis not excised at surgery. Deep dyspareunia and chronic pelvic pain significantly improved at follow-up in all study groups. Most of gastrointestinal symptoms improved or disappeared at 6 months' follow-up; the improvement in gastrointestinal function persisted at 18 months' follow-up. CONCLUSION: Excision of pelvic endometriosis combined with bowel resection significantly improves chronic pelvic pain, dyspareunia and gastrointestinal symptoms; however, the presence of uterine adenomyosis may determine persistence of dysmenorrhea.

Pharmacological treatment of endometriosis: experience with aromatase inhibitors.

Current treatment of endometriosis is mainly based on surgery and ovarian suppressive agents. In the last 10 years, it has been demonstrated that aromatase P450, a key enzyme for estrogen biosynthesis, may have a pathogenic role in endometriosis because it is aberrantly expressed in endometriotic implants and in eutopic endometrium of women with endometriosis. Therefore, inhibition of aromatase activity may represent a new therapeutic option for endometriosis. Case reports and observational studies have shown that pain symptoms caused by endometriosis quickly improve after administration of aromatase inhibitors. Limited data are available on the long-term course of pain symptoms after completion of treatment with aromatase inhibitors; however, some recent studies suggest that symptoms may recur at short-term follow-up. A range of results are reported on the effects of aromatase inhibitors on endometriotic lesions, with some authors describing improvements and other authors reporting persistence of pelvic lesions at second-look laparoscopy after treatment. No severe adverse effect has been reported during treatment with aromatase inhibitors both in pre- and postmenopausal women. On the basis of the available data, administration of aromatase inhibitors should now be offered only to the small number of women who have severe pain despite previous surgical and hormonal therapies. Further research in the form of randomized controlled trials will be required before recommending the routine use of these agents.

GnRH analogue remarkably down-regulates inflammatory proteins in peritoneal fluid proteome of women with endometriosis.

OBJECTIVE: To determine the changes in the peritoneal fluid proteome of women with endometriosis determined by the administration of gonadotropin-releasing hormone analogues (GnRH-a). STUDY DESIGN: Peritoneal fluid samples were collected during laparoscopy from patients under GnRH-a and from women who did not receive any type of hormonal treatment in the 6 months before surgery. Samples were subjected to 2-D gel electrophoresis and compared by computerized analysis. Protein spots differentially expressed between the study groups were identified by liquid chromatography tandem mass spectrometry. RESULTS: More than 470 protein spots were analyzed. Several proteins with significant alterations were found. The down-regulated molecules were isoforms of alpha 2-HS glycoprotein, alpha 1-antitrypsin, S100-A8, haptoglobin alpha chain and vitamin D-binding protein. No protein spot had significantly higher expression in peritoneal fluid of women under GnRH-a than in untreated patients. CONCLUSION: Several inflammatory molecules present in peritoneal fluid are down-regulated during treatment with GnRH-a; administration of this drug reduces the inflammation in the peritoneal cavity.

Proteomic analysis of peritoneal fluid in fertile and infertile women with endometriosis.

OBJECTIVE: To evaluate the peritoneal fluid (PF) proteome of fertile and infertile women with endometriosis. STUDY DESIGN: PF samples were collected at laparoscopy from 26 fertile women and 26 infertile ones. Samples were subjected to 2-dimensional gel electrophoresis and compared by computerized analysis. Protein spots were identified by liquid chromatography tandem mass spectrometry. RESULTS: One isoform of immunoglobulin light chain spot was more frequently present in PF of infertile women than infertile patients. Nine protein spots had significantly higher expression in PF of infertile patients than infertile controls. They were 2 isoforms of serotransferrin, 1 isoform of complement C3, serum amyloid P-component, alpha-1-antitrypsin and clusterin; 3 protein spots remain unidentified. No protein spots had significantly lower expression in PF of infertile women with endometriosis than in PF of fertile controls. Complement C3 had higher PF levels in the luteal than in the follicular phase of the menstrual cycle in both infertile and fertile patients. CONCLUSION: Among women with endometriosis, those with infertility have aberrant expression of several PF proteins; most of these molecules are involved in the immune response.

Increased expression of one isoform of leucine-rich alpha-2-glycoprotein in peritoneal fluid of women with uterine leiomyomas.

OBJECTIVE: To compare the peritoneal fluid (PF) proteome of women with and without uterine leiomyomas. STUDY DESIGN: PF samples were collected at laparoscopy from 14 women with uterine leiomyomas and 14 patients without leiomyomas who underwent tubal sterilization. PF samples were subjected to two-dimensional gel electrophoresis, silver stained, digitally captured, and compared by computerised analysis. Protein spots with aberrant expression in PF of women with leiomyomas were identified by liquid chromatography tandem mass spectrometry. RESULTS: One isoform of leucine-rich alpha-2-glycoprotein (LRGm), one immunoglobulin light chain, and one unidentified protein (pI: 5.62; M(r): 51.1 kDa) had significantly higher expression in PF of women with leiomyomas. Two isoforms of fibrinogen gamma chain had decreased expression in PF of women with uterine leiomyomas. Following Bonferroni correction for multiple comparisons, the aberrant expressions of LRGm and of one isoform of fibrinogen gamma chain was confirmed. The expression of these molecules was not affected by the phase of the menstrual cycle. CONCLUSIONS: Uterine leiomyomas are associated with changes in proteins present within the peritoneal fluid. The physiopathological relevance of the increased expression of LRGm in PF of women with uterine leiomyomas remains unclear.

Fertility after bowel resection for endometriosis.

OBJECTIVE: To determine the pregnancy rate after bowel resection for rectosigmoid endometriosis. DESIGN: Prospective cohort study. SETTING: University hospital. PATIENT(S): Forty-six symptomatic women with bowel endometriosis requiring colorectal resection. INTERVENTION(S): Bowel resection by either laparoscopy or laparotomy. MAIN OUTCOME MEASURE(S): Pregnancy rate after surgery. RESULT(S): The pregnancy rate was higher in women who underwent bowel resection by laparoscopy (57.6%) than in those who underwent laparotomy (23.1%). No significant difference was observed in pregnancy rate and mode of conception between women with different fertility status before bowel resection. Women who conceived were significantly younger than those who did not conceive; only 26.7% of women aged > or =35 years conceived after bowel resection. Uterine adenomyosis was more frequently present in women who did not conceive than in those who conceived. Infertile women who conceived had a shorter length of infertility before surgery than those who did not conceive. CONCLUSION(S): Laparoscopic colorectal resection is less likely to impact negatively on fertility than the laparotomy approach. Previous laparotomies, age > or =35 years, uterine adenomyosis, and longer duration of infertility before surgery are associated with decreased pregnancy rate.

Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.

BACKGROUND: Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but the clinical impact of lymphadenectomy has not been addressed in randomized studies. We conducted a randomized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to standard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival. METHODS: From October 1, 1996, through March 31, 2006, 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were randomly assigned to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Patients' clinical data, pathological tumor characteristics, and operative and early postoperative data were recorded at discharge from hospital. Late postoperative complications, adjuvant therapy, and follow-up data were collected 6 months after surgery. Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis. All statistical tests were two-sided. RESULTS: The median number of lymph nodes removed was 30 (interquartile range = 22-42) in the pelvic systematic lymphadenectomy arm and 0 (interquartile range = 0-0) in the no-lymphadenectomy arm (P < .001). Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy (81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm, P = .001). Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm (13.3% vs 3.2%, difference = 10.1%, 95% confidence interval [CI] = 5.3% to 14.9%, P < .001). At a median follow-up of 49 months, 78 events (ie, recurrence or death) had been observed and 53 patients had died. The unadjusted risks for first event and death were similar between the two arms (hazard ratio [HR] for first event = 1.10, 95% CI = 0.70 to 1.71, P = .68, and HR for death = 1.20, 95% CI = 0.70 to 2.07, P = .50). The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms (81.0% and 85.9% in the lymphadenectomy arm and 81.7% and 90.0% in the no-lymphadenectomy arm, respectively). CONCLUSION: Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.

Peritoneal fluid proteome in women with different ASRM stages of endometriosis.

OBJECTIVE: Endometriosis has a wide range of severity but molecular factors associated with variable extension of the disease have not been widely investigated. The present study compares the peritoneal fluid (PF) proteome of 109 women with endometriosis and different disease stage as defined by the American Society for Reproductive Medicine (ASRM). METHODS: PF samples were subjected to two-dimensional gel electrophoresis; protein spots of interest were identified by liquid chromatography tandem mass spectrometry. RESULTS: Over 470 protein spots were analyzed. One isoform of haptoglobin alpha chain, alpha-1b-glycoprotein and one unknown protein had higher expression in PF of women with ASRM stage I-II endometriosis. Four isoforms of alpha1-antitrypsin, three isoforms of alpha-1b-glycoprotein, one isoform of S100-A8 and serotransferrin had higher expression in PF of women with ASRM stage III-IV disease. CONCLUSIONS: Several protein isoforms have different expression in PF of women with ASRM stage I-II endometriosis than in those with ASRM stage III-IV disease; most of these molecules are involved in inflammation and immune response.

Proteomics technologies in endometriosis.

Endometriosis is a common disorder that is associated with infertility and pelvic pain. Diagnosis is based on the visualization of endometriotic lesions during surgery as no reliable serum marker is currently available. The etiology of endometriosis is largely unknown. Over the last 20 years, several proteomics technologies have been used to research novel proteins with a potential etiological role in endometriosis, and to identify candidate serum markers for this condition. While some molecules identified by proteomics technologies may have a relevant role in the pathogenesis of endometriosis, the research of potential serum markers for this condition is still far from any clinical application. This review summarizes the state of the art and potential applications of proteomics in endometriosis research.

Deep dyspareunia: causes, treatments, and results.

PURPOSE OF REVIEW: We critically review the causes and treatments of deep dyspareunia. RECENT FINDINGS: Endometriosis, pelvic congestion syndrome, and interstitial cystitis have been associated with deep dyspareunia. Although medical therapies may improve deep dyspareunia in women with endometriosis, laparoscopic excision of deep endometriotic lesions has been demonstrated to improve not only deep dyspareunia but also the quality of sex life. Deep dyspareunia related to the presence of pelvic congestion syndrome should be treated by pelvic vein embolization. Intravesical therapy may be effective in treating deep dyspareunia in women with interstitial cystitis. It remains unclear whether uterine myomas and adenomyosis are causes of deep dyspareunia. SUMMARY: Treatment of deep dyspareunia should be mainly directed to causative factors; however, clinicians should keep in mind that secondary sexual dysfunction can arise from organic pelvic pathology.

Myasthenia gravis during pregnancy.

Myasthenia gravis (MG) affects women in the second and third decades of life, overlapping with the childbearing years. During pregnancy, the course of this disease is unpredictable; worsening of symptoms occurs more likely during the first half of pregnancy and postpartum. MG can be well managed during pregnancy with relatively safe and effective therapies. Cesarean section is recommended only for obstetric reasons; epidural anesthesia is advised to reduce physical and emotional stress. Anticholinesterase drugs are the mainstay of treatment, when MG symptoms are not satisfactorily controlled, corticosteroids, azathioprine and in some cases cyclosporin A may be used. Life-threatening conditions (e.g., respiratory insufficiency) may occur during pregnancy; therefore, intensive check-ups by a gynecologist and a neurologist are necessary.

Hysterectomy and women satisfaction: total versus subtotal technique.

INTRODUCTION: The impact of different surgical procedures on women's satisfaction after hysterectomy is a topical issue. The aim of this study was to investigate the impact of sub-total and total hysterectomy on women's satisfaction, evaluated with questionnaire assessment of sexual activity, body image, and health status. MATERIALS AND METHODS: A prospective, randomized, non-blind study was conducted. In the study period of 3 years, 105 women were enrolled and completed the questionnaires [EuroQol (EQ-5D), body image scale (BIS), sexual activity questionnaire] 2 weeks before and 1 year after surgery. RESULTS: Both total and sub-total hysterectomy resulted with improvements in the women's sexual satisfaction (1 year after surgery), but no statistically significant differences were reached between the two groups. A highly significant difference (P < 0.001) in the perception of the body image between total and sub-total hysterectomy, at 1 year after surgery, was underlined. The health-related quality of life resulted significantly better in the "sub-total hysterectomy" group 1 year after surgery (P < 0.05). CONCLUSION: Considering these results, why should a total hysterectomy be performed, if the women's satisfaction seems to be higher using the sub-total technique? In our opinion, the woman undergoing hysterectomy for benign conditions must be counseled regarding the differences between the two techniques and, when possible, a choice must be offered to the woman.

Peritoneal fluid macrophages in endometriosis: correlation between the expression of estrogen receptors and inflammation.

OBJECTIVE: To investigate the expression of estrogen receptors (ERs) and inflammatory cytokines in macrophages obtained from peritoneal fluid (PF) of women with endometriosis. DESIGN: Comparative immunocytochemical study. SETTING: University hospital. PATIENT(S): Thirty women with endometriosis and 22 controls. INTERVENTION(S): The PF samples were collected at laparoscopy. MAIN OUTCOME MEASURE(S): The expression of ERalpha, ERbeta, differentiation markers (CD68, NCL-MACRO, HAM56), and inflammatory cytokines (interleukin [IL]-1beta, tumor necrosis factor-alpha [TNF-alpha], IL-6) in PF macrophages was determined. RESULT(S): The expression of CD68, NCL-MACRO, HAM56, TNFalpha, IL-6, and IL-1beta was significantly higher in PF macrophages obtained from women with endometriosis than in controls. The ERalpha and ERbeta had significantly higher expression in macrophages of women with endometriosis than in controls. A positive correlation was observed between the expression of ERalpha and ERbeta both in women with and without endometriosis. The ERalpha expression was positively correlated with the expression of inflammatory cytokines in women with endometriosis but not in controls; ERbeta expression was correlated to the expression of inflammatory cytokines in the both groups. CONCLUSION(S): There is a correlation between the expression of ERbeta and proinflammatory cytokines both in women with and without endometriosis. The expression of ERalpha correlates with cytokine production selectively in women with endometriosis but not in controls.