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Pelvic Pain in Gynecology

COX-2 overexpression in peritoneal lesions is correlated with nonmenstrual chronic pelvic pain.
Buchweitz O, Staebler A, Wulfing P, Hauzman E, Greb R, Kiesel L
Eur J Obstet Gynecol Reprod Biol 2005 Nov 21;.

OBJECTIVE: To investigate cyclooxygenase (COX-2) expression within different endometriotic lesions and to assess whether these expression patterns correlate with clinical characteristics. DESIGN: Retrospective cross-sectional study. SETTING: University Hospital. PATIENTS: Seventy patients with histologically confirmed exclusively peritoneal (n=20), ovarian (n=19) or deep-infiltrating (n=31) endometriosis and a detailed medical history. INTERVENTION: Immunohistochemical analysis for COX-2 was performed on 108 endometriotic lesions. MEASUREMENTS AND MAIN RESULTS: COX-2 intensity, percentage of stained glandular endometriotic cells, and correlation of COX-2 expression with clinicopathological parameters. Semiquantitative COX-2 expression did not differ between distinct morphological types of endometriosis and showed no association with the menstrual cycle. Patients with peritoneal-only endometriosis suffering from moderate or severe chronic pelvic pain showed significantly more frequent COX-2 overexpression than asymptomatic patients or patients with minimal symptoms. In patients with exclusively ovarian or deep-infiltrating endometriosis no association between COX-2 expression and clinical parameters, such as chronic pelvic pain, dysmenorrhoea, dyspareunia, sterility, lower urinary tract symptoms or gastrointestinal symptoms was observed. CONCLUSION: Peritoneal endometriotic lesions with increased COX-2 expression have a special relevance for the development of chronic, nonmenstruation-associated, pelvic pain in endometriotic patients. These patients may benefit from therapy with COX-2 inhibitors.

Uterine innervation after hysterectomy for chronic pelvic pain with, and without, endometriosis.
Atwal G, du Plessis D, Armstrong G, Slade R, Quinn M
Am J Obstet Gynecol 2005 Nov;193(5):1650-5.

OBJECTIVE: Chronic pelvic pain is associated with a wide range of clinical conditions that include endometriosis. The precise cause, mechanisms of pain, and natural history are imprecise. Patterns of uterine innervation have been studied after hysterectomy for chronic pelvic pain with and without endometriosis. STUDY DESIGN: Tissue blocks were taken from the lower one half of the uterus after hysterectomy for advanced endometriosis (n = 16 specimens; group 1) and for chronic pelvic pain without endometriosis (n = 15 specimens; group 2). The control group consisted of uteri that were removed for painless gynecologic conditions (n = 25 specimens; group 3). Tissue sections from the lower one half of the uterus were stained with anti-S100 to demonstrate patterns of innervation, and nerve fiber profiles were counted by standardized techniques; qualitative differences were also recorded. RESULTS: In uteri from women with advanced endometriosis, there were increased numbers of nerve fiber profiles compared with control specimens (group 1 vs group 3; P = .0013, Mann Whitney U test). There were also increased numbers of nerve fiber profiles in uteri that were associated with chronic pelvic pain without endometriosis (group 2 vs group 3; P = .04, Mann Whitney U test). There were no differences in nerve fiber count in uteri from groups 1 and 2 (P = .35, Mann Whitney U test). Comparing both groups of uteri with controls (groups 1 and 2 vs 3) demonstrated marked differences in nerve fiber counts (P = .002, Mann Whitney U test). Two distinctive patterns of reinnervation that were observed: disruption of nerve bundles (collateral sprouting with microneuroma formation) and ingrowth around blood vessels (perivascular nerve fiber proliferation). There were increased numbers of microneuromas (groups 1 and 2 vs 3; P = .001, chi-squared test with Yates correction) and perivascular nerve fiber proliferation (groups 1 and 2 vs 3; P = .008, chi-squared test with Yates correction) in the myometrium in chronic pelvic pain with, and without, endometriosis compared with the control group. CONCLUSION: Nerve fiber proliferation and other features of reinnervation have been observed in the isthmic regions of uteri that were removed at hysterectomy for chronic pelvic pain with and without endometriosis. There were no quantitative differences between the groups with chronic pelvic pain and endometriosis. These observations provide an alternative explanation for the source of pain and other clinical symptoms in these clinical settings.

Peritoneal fluid leptin is associated with chronic pelvic pain but not infertility in endometriosis patients*
Bedaiwy MA, Falcone T, Goldberg JM, Sharma RK, Nelson DR, Agarwal A
Hum Reprod 2005 Nov 3;.

BACKGROUND: Leptin influences the proinflammatory immune responses and has angiogenic activity in vitro and in vivo. The objective of this study was to evaluate the peritoneal fluid levels of leptin in patients with endometriosis and idiopathic infertility and compare them with a control group of tubal ligation/reanastomosis patients. METHODS: In this observational, prospective controlled study, peritoneal fluid from 108 women was obtained while they underwent laparoscopy for pelvic pain, infertility, tubal ligation or sterilization reversal. We measured the concentration of leptin in the peritoneal fluid and compared the levels among women who were divided into groups according to their post-surgical diagnosis. Sixty patients were diagnosed with endometriosis, 10 with idiopathic infertility and 38 had undergone tubal ligation or reanastomosis (control group). RESULTS: Peritoneal fluid leptin was significantly higher in endometriosis 14.62 +/- 9.79 (mean +/- SD) ng/ml compared to idiopathic infertility [0.92 +/- 1.57 ng/ml (P = 0.0007)] and to controls [0.78 +/- 1.94 ng/ml (P < 0.0001)]. Leptin levels were positively correlated with the stage of endometriosis (r = 0.45; P = 0.03), and with pelvic pain in endometriosis patients (r = 0.49; P = 0.001). Peritoneal fluid leptin levels in patients with idiopathic infertility were comparable to controls. CONCLUSIONS: Higher levels of leptin were observed in peritoneal fluid of patients with endometriosis compared to those without the disease. These data suggest that the proinflammatory and neoangiogenic action of leptin may contribute to the pathogenesis of endometriosis. Moreover, leptin may play a role in endometriosis-associated pain.

High density of small nerve fibres in the functional layer of the endometrium in women with endometriosis.
Tokushige N, Markham R, Russell P, Fraser IS
Hum Reprod 2005 Oct 27;.

BACKGROUND: Endometriosis is a common gynaecological disease and is frequently associated with recurrent and serious pelvic pain such as dysmenorrhoea and dyspareunia, but the mechanisms by which these symptoms are generated are not well understood. METHODS: Histological sections of endometrial tissue were prepared from endometrial curettings and hysterectomies performed on women with endometriosis (n=25 and n=10, respectively) and without endometriosis (n=47 and n=35, respectively). These were stained immunohistochemically for the highly specific polyclonal rabbit anti-protein gene product 9.5 (PGP9.5) and monoclonal mouse anti-neurofilament protein (NF) to demonstrate both myelinated and unmyelinated nerve fibres. RESULTS: Small nerve fibres were identified throughout the basal and functional layers of the endometrium in all endometriosis patients, but were not seen in the functional layer of the endometrium in any of the women without endometriosis (P<0.001). NF-immunoreactive nerve fibres were present in the basal layer in all endometriosis patients but not in non-endometriosis patients, with one exception (P< 0.001). CONCLUSIONS: Small nerve fibres detected in the functional layer in all women with endome-triosis may have important implications for understanding the generation of pain in these patients. The presence of nerve fibres in an endometrial biopsy may be a novel surrogate marker of clinical endometriosis.

Excisional surgery versus ablative surgery for ovarian endometriomata: a Cochrane Review.
Hart R, Hickey M, Maouris P, Buckett W, Garry R
Hum Reprod 2005 Nov;20(11):3000-3007.

BACKGROUND: The objective of this review was to determine which is the most effective technique for treating an ovarian endometrioma; excision or ablation. METHODS: A systematic review employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was undertaken. No randomized studies of the management of endometriomata by laparotomy were found. Two randomized studies of the laparoscopic management of ovarian endometriomata of >3 cm in size were included. RESULTS: Laparoscopic excision of the cyst wall of the endometrioma was associated with a reduced rate of recurrence of the endometrioma [odds ratio (OR) 0.41, confidence interval (CI) 0.18-0.93], reduced requirement for further surgery (OR 0.21, CI 0.05-0.79), reduced recurrence rate of the symptoms of dysmenorrhoea (OR 0.15, CI 0.06-0.38), dyspareunia (OR 0.08, CI 0.01-0.51) and non-menstrual pelvic pain (OR 0.10, CI 0.02-0.56). It was also associated with a subsequently increased rate of spontaneous pregnancy in women who had documented prior subfertility (OR 5.21, CI 2.04-13.29). CONCLUSIONS: There is some evidence that excisional surgery for endometriomata provides for a more favourable outcome than drainage and ablation, with regard to the recurrence of the endometrioma, recurrence of symptoms and subsequent spontaneous pregnancy in women who were previously subfertile. Consequently this should be the favoured surgical approach. However, we found no data to indicate the best surgical approach in women planning to undergo assisted reproductive techniques.

The effect of preemptive pudendal nerve blockade on pain after transvaginal pelvic reconstructive surgery.
Abramov Y, Sand PK, Gandhi S, Botros SM, Miller JJ, Koh EK, Goldberg RP
Obstet Gynecol 2005 Oct;106(4):782-8.

OBJECTIVE: To assess the effect of preemptive pudendal nerve blockade on pain and consumption of narcotic analgesia following transvaginal pelvic reconstructive surgery. METHODS: This was a randomized, double-blind, placebo-controlled trial. Patients undergoing transvaginal pelvic reconstructive surgery under general anesthesia were randomized to receive pudendal block with either bupivacaine 0.25% or placebo (normal saline 0.9%) immediately before surgery. All patients received postoperative intravenous hydromorphone patient-controlled analgesia. Patients were asked to report on their pain intensity 1, 3, 5, 7, 18, and 24 hours postoperatively, using a validated visual analog pain scale from 0-10. Main outcome measures included postoperative pain intensity and hydromorphone consumption. RESULTS: One hundred ten patients enrolled in the study, of whom 106 underwent randomization, and 102 received pudendal nerve blockade, 51 with bupivacaine and 51 with saline. Demographic and baseline clinical characteristics were not significantly different between the 2 patients groups. There were no significant differences in postoperative pain intensity (median scores: 1 hour, 4.0 versus 5.0; 3 hours, 3.0 versus 4.0; 7 hours, 2.0 versus 3.0; 18 hours, 3.0 versus 4.0), the consumption of hydromorphone (0-3 hours, 1.84 mg versus 1.77 mg; 4-7 hours, 1.19 mg versus 1.20 mg; 8-18 hours, 2.89 mg versus 2.35 mg), or mean hospital stay (39.6 versus 37.3 hours) between the bupivacaine and saline groups. CONCLUSION: Preemptive pudendal nerve blockade does not affect postoperative pain intensity or the consumption of narcotic analgesia after transvaginal pelvic reconstructive surgery. LEVEL OF EVIDENCE: I.

Efficacy of laparoscopic excision of visually diagnosed peritoneal endometriosis in the treatment of chronic pelvic pain.
Wykes CB, Clark TJ, Chakravati S, Mann CH, Gupta JK
Eur J Obstet Gynecol Reprod Biol 2005 Sep 14;.

OBJECTIVE: To determine the efficacy of laparoscopic excision of visually diagnosed endometriosis in the treatment of chronic pelvic pain. STUDY DESIGN: Sixty-two women with chronic pelvic pain and who underwent laparoscopic excision of visually diagnosed peritoneal lesions suggestive of endometriosis returned postal questionnaires. The main outcomes measures were change in pelvic pain symptoms measured on a continuous and ordinal scale and patient satisfaction following treatment. Secondary outcomes were quality of life, time off work and use of health service resources. RESULTS: 42/62 (68%) women with an average follow up time of 13 months (range 6-38 months) returned completed outcome questionnaires. The mean amount of pelvic pain was reduced following surgery compared to immediately prior to treatment, regardless of the nature of the pain (P<0.05). Overall, 67% (95% CI 50-80%) of women reported improvement in pain symptoms and 71% (95% CI 55-84%) were satisfied with the results of treatment. Satisfaction with treatment was comparable whether the visual diagnosis of peritoneal endometriosis was confirmed histologically or not (62% versus 64%, P=1.0). CONCLUSION: Laparoscopic excision of visually diagnosed endometriosis appears to be efficacious in the treatment of women with chronic pelvic pain. The launch of a long-term randomised controlled trial to confirm these provisional results is now required.

Insight into the treatment of vulvar pain: A survey of clinicians.
Updike GM, Wiesenfeld HC
Am J Obstet Gynecol 2005 Oct;193(4):1404-1409.

OBJECTIVE: The purpose of this investigation was to determine practice patterns among clinicians who frequently treat patients with vulvar pain syndromes. STUDY DESIGN: A cross-sectional survey was distributed to providers in the United States whose names were on a referral list of clinicians that care for women with vulvar pain (National Vulvodynia Association, Silver Springs, MD). The survey included 2 clinical vignettes. Clinicians were asked to report what treatments they would use to treat women with generalized vulvodynia and localized vulvodynia. Data were analyzed with descriptive statistics. A comparison of categoric data was accomplished with the Fisher's exact test. RESULTS: Surveys were mailed to 327 providers; 167 completed surveys were returned, for an overall response rate of 51%. The most commonly used treatment for vulvodynia was tricyclic antidepressants. There was no difference in the use of physical therapy, estrogens, injected or topical steroids, interferon, or laser therapy to treat generalized and localized vulvodynia. Respondents were more likely to use tricyclic antidepressants (P < .001), gabapentin (P < .001), and psychiatric care (P < .001) and less likely to use local anesthesia (P < .001) and vestibulectomy (P=.007) for the clinical scenario that represented generalized vulvodynia than they were for the scenario that represented localized vulvodynia. Most clinicians reported screening for vaginal infections, and many clinicians perform colposcopy and/or vulvar biopsy. Respondents recommend a variety of lifestyle modifications in the treatment of vulvodynia. CONCLUSION: Clinicians use a wide variety of treatments for vulvar pain and use different therapies for variants of vulvodynia.

Successful Treatment of Deep Dyspareunia and Primary Dysmenorrhea with Laparoscopic Uterosacral Nerve Ablation (LUNA) Procedure.
Juang CM, Yen MS, Horng HC, Yu HC, Chang CM, Yeh JY
Gynecol Obstet Invest 2005 Aug 17;61(1):1-3.

Deep dyspareunia, often described as pain resulting from pelvic thrusting during sexual intercourse, is relatively common and has many causes. To date, feasible surgical interventions for deep dyspareunia are very rare. The two procedures which have been mentioned in the literature for the treatment of deep dyspareunia were laparoscopic uterosacral ligament ablation (LUNA) and uterine ventrosuspension. We report the case of a young female patient, aged 32, gravida 3, parity 2, presenting with deep dyspareunia and primary dysmenorrhea for 4 years. She had both subjective and objective improvements for dyspareunia and primary dysmenorrhea following LUNA operation. Further large-scaled randomized controlled trial is mandatory to verify the surgical effect of LUNA operation for patients with deep dyspareunia.

Effects of intradermal foot and forearm capsaicin injections in normal and vulvodynia-afflicted women.
Foster DC, Dworkin RH, Wood RW
Pain 2005 Sep;117(1-2):128-36.

Cutaneous response to capsaicin has been used to assess central sensitization in pain research. This study compared the response to intradermal capsaicin in the forearm and foot of vulvar vestibulitis (vestibulodynia)-afflicted cases and controls. We hypothesized that cases will experience greater spontaneous pain, larger cutaneous areas of punctate hyperalgesia and dynamic allodynia, and greater vascular flow than controls. We also hypothesized enhanced post-injection pain in the foot compared to the forearm based on dermatome proximity of the foot and vulva. Methods. Ten vulvar vestibulitis syndrome (VVS) cases and 10 age and ethnically matched controls underwent two randomized, cross-over trials with intra-dermal injections of capsaicin or a saline placebo in the forearm and foot. Outcome measures included spontaneous pain level, surface area of punctate hyperalgesia, surface area of dynamic allodynia, cutaneous blood flow, regional skin temperature and vital signs. Results. VVS cases experienced greater spontaneous pain, punctate hyperalgesia and dynamic allodynia than pain-free controls. Within the VVS group, post-capsaicin spontaneous pain, punctate hyperalgesia and dynamic allodynia were similar in the forearm and foot. Post-capsaicin blood flow did not differ between cases and controls by anatomic site. Measures of depression and anxiety correlated with spontaneous pain intensity but did not correlate with measures of hyperalgesia, allodynia, or blood flow. VVS cases had higher resting pulse rates and lower resting systolic blood pressures than in controls. Conclusion. VVS patients show enhancement of post-capsaicin pain response extending far beyond the anatomic location of the primary complaint.

Serum adiponectin concentrations are decreased in women with endometriosis.
Takemura Y, Osuga Y, Harada M, Hirata T, Koga K, Morimoto C, Hirota Y, Yoshino O, Yano T, Taketani Y
Hum Reprod 2005 Jul 29;.

BACKGROUND: Adiponectin is a pleiotropic cytokine originally discovered as an adipocyte-specific gene product. Serum adiponectin concentrations have been reported to be low in women with endometrial cancer, breast cancer and uterine leiomyoma, suggesting possible involvement of adiponectin in these estrogen-related diseases. We thus addressed the relevance of adiponectin to endometriosis, an estrogen-dependent disease, in the present study. METHODS: Women with (n = 48) and without (n = 30) endometriosis undergoing laparoscopy were recruited in this study. Blood samples were collected, and serum adiponectin concentrations were measured using a specific enzyme-linked immunosorbent assay. The relationship between laparoscopic findings and serum adiponectin concentrations was analysed. RESULTS: The adiponectin concentrations in the serum of the women with endometriosis (median, 13.1 microg/ml; interquartile range, 10.2-16.7) were significantly lower than those of the women without endometriosis (15.9 microg/ml, 13.5-19.5; P = 0.008). A significant negative correlation was found between serum adiponectin concentrations and both endometriosis scores (R = - 0.307, P = 0.006) and adhesion scores (R = - 0.254, P = 0.026) of the revised American Society for Reproductive Medicine classification of endometriosis. CONCLUSIONS: The present findings suggest that adiponectin is implicated in the pathophysiology of endometriosis.

GnRH II as a possible cytostatic regulator in the development of endometriosis.
Morimoto C, Osuga Y, Yano T, Takemura Y, Harada M, Hirata T, Hirota Y, Yoshino O, Koga K, Kugu K, Taketani Y
Hum Reprod 2005 Jul 21;.

BACKGROUND: GnRH II is the second form of GnRH and is widely distributed in peripheral tissues of the female reproductive tract as well as in the central nervous system. In the present study, we studied the possible implication of GnRH II in endometriosis. METHODS: Effects of GnRH II on 5-bromo-2'-deoxyuridine (BrdU) uptake by cultured endometriotic stromal cells were examined. Effects of GnRH II on interleukin (IL)-1beta-induced expression of cyclooxygenase (COX)-2 and IL-8 were also studied. mRNA levels of GnRH I, GnRH II, type I GnRH receptor and type II GnRH receptor were determined by real-time quantitative RT-PCR in endometrial tissues of women with or without endometriosis and in endometriotic tissues. RESULTS: GnRH II dose-dependently suppressed BrdU uptake by endometrial stromal cells. Treatment with IL-1beta markedly increased mRNA levels of COX-2 and IL-8 in endometrial stromal cells and IL-8 protein secretion by these cells, while these increments were significantly suppressed by supplementation with GnRH II. The mRNA levels of GnRH II were lower in endometrial and endometriotic tissues of women with endometriosis than in endometrial tissues of women without endometriosis, both in the proliferative phase and the secretory phase. In addition, as for GnRH I, type I GnRH receptor and type II GnRH receptor, the mRNA levels were lower in endometrial tissues of women with endometriosis than in those without endometriosis in the secretory phase. CONCLUSIONS: In the light of the demonstrated antiproliferative and anti-inflammatory effects of GnRH II on endometrial stromal cells, the lower expression of GnRH II in eutopic and ectopic endometrium of women with endometriosis suggests that endogenous GnRH II-mediated cytostatic regulation may be impaired in the development of endometriosis.

Vulvar disease: a pelvic floor pain disorder?
Kennedy CM, Nygaard IE, Saftlas A, Burns TL, Torner JC, Galask RP
Am J Obstet Gynecol 2005 Jun;192(6):1829-34; discussion 1834-5.

OBJECTIVE: The purpose of this study was to compare the rates of painful bladder syndrome and functional bowel disorders in women with vulvar disease and control subjects. STUDY DESIGN: In this cross-sectional survey, a questionnaire that contained validated outcome measures was administered to women who were seeking care in a vulvar disease clinic and in general gynecology clinics. RESULTS: Women who were seen at a vulvar disease clinic were 2.18 (95% CI, 1.19, 3.97) times more likely to have painful bladder syndrome and 2.13 (95% CI, 1.35, 3.35) times more likely to have functional bowel disorders than general gynecology clinic control subjects after multivariable analyses. CONCLUSION: Painful bladder syndrome and functional bowel disorders are more prevalent in women who are seen at a vulvar disease clinic than gynecology clinics control subjects. These associations may reflect a common origin for these disorders in certain women. These findings lay the groundwork for future research to investigate a potential "pelvic floor pain disorder," which is a disease entity that would combine the diagnostic criteria for vulvar, bladder, and bowel pain disorders.

Outcomes and treatment options in rectovaginal endometriosis.
Emmanuel KR, Davis C
Curr Opin Obstet Gynecol 2005 Aug;17(4):399-402.

PURPOSE OF REVIEW: This review aims to explore the recent literature surrounding the role of colorectal surgery in rectovaginal endometriosis. RECENT FINDINGS: Recent findings would suggest that excision of a portion of the rectum along with complete excision of surrounding endometriosis is beneficial in terms of improvement in quality of life and recurrence of disease. However, further randomized controlled trials are needed to clarify this finding. SUMMARY: The optimal management of women with deeply infiltrating rectovaginal endometriosis remains a challenge to physicians involved in this disease process. The choice between medical and surgical treatments is not clearly defined, and neither is the role of adjunctive medical therapy prior to or following surgery. It is only when these questions have been asked in the context of well conducted clinical trials, with good outcome data, can the answers be given.

Efficacy of Functional Electrical Stimulation-Biofeedback with Sexual Cognitive-Behavioral Therapy as Treatment of Vaginismus.
Seo JT, Choe JH, Lee WS, Kim KH
Urology 2005 Jun 29;.

OBJECTIVES: To report 12 cases of vaginismus that were successfully treated with functional electrical stimulation (FES)-biofeedback with sexual cognitive-behavioral therapy (SCBT) to determine the efficacy of FES-biofeedback with SCBT as a standard therapy for vaginismus. Vaginismus is an involuntary spasm of the musculature of the outer third of the vagina that leads to impossible vaginal penetration, causing personal distress. Various therapeutic approaches, both physiologic and psychological, have been considered. METHODS: Twelve women with vaginismus referred from a checkup outpatient clinic participated in this study. The patients enrolled in this study had vaginismus according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders. The patients were assessed before and after treatment with gynecologic examinations and structured interviews pertaining to sexual function and psychological adjustment. After the diagnosis of vaginismus, we conducted weekly pelvic floor muscle relaxation using FES-biofeedback. Once the patients became tolerable to vaginal manipulation, the eight-stage SCBT (eight-stage gradual desensitization described by Kaplan using vaginal self-dilation with fingers and vaginal probe insertion) was added for 8 weeks. RESULTS: After 8 weeks of treatment, all 12 couples had completed the program, had become tolerable to vaginal insertion of larger size probes, and could achieve satisfactory vaginal intercourse. CONCLUSIONS: FES-biofeedback with SCBT is an effective aid for patients with vaginismus to learn muscle control. Therefore, it may increase the success rate of treatment of vaginismus.

Capsaicin for the treatment of vulvar vestibulitis.
Steinberg AC, Oyama IA, Rejba AE, Kellogg-Spadt S, Whitmore KE.
Am J Obstet Gynecol 2005 May;192(5):1549-53.

OBJECTIVE: The purpose of this study was to evaluate the use of local capsaicin cream as an effective treatment for patients with documented vulvar vestibulitis syndrome. STUDY DESIGN: A retrospective chart review was performed for patients who received a diagnosis of vulvar vestibulitis syndrome that was treated with capsaicin. Patients performed local application of capsaicin 0.025% cream for 20 minutes daily for 12 weeks. A comparison was made between the pre- and posttreatment Kaufman touch test to evaluate discomfort. The Marinoff dyspareunia scale was also used to assess pre- and posttreatment. RESULTS: The sum of the Kaufman touch test scores before the treatment (13.2 +/- 4.9) compared with the scores after treatment (4.8 +/- 3.8) was statistically improved (P < .001). A significant improvement was also observed at each individual site (P < .001). The Marinoff dyspareunia scale also showed a significant improvement (P < .001). CONCLUSION: Vulvar vestibulitis syndrome that is treated with capsaicin significantly decreases discomfort and allows for more frequent sexual relations.

Vulvar vestibulitis syndrome: A review.
Farage MA, Galask RP.
Eur J Obstet Gynecol Reprod Biol 2005 May 28;.

Vulvar vestibulitis syndrome (VVS) is a perplexing disease involving pain limited to the vulvar vestibule without objective clinical findings to explain the symptoms. The condition impairs sexual function and creates significant psychological distress. Its cause is unknown, and few randomized studies exist on the efficacy of interventions. This article reviews disease characteristics, possible etiologies, and approaches to management.

Body mass index in endometriosis.
Ferrero S, Anserini P, Remorgida V, Ragni N.
Eur J Obstet Gynecol Reprod Biol 2005 Jun 8;.

OBJECTIVE: Previous studies did not establish a clear correlation between the presence of endometriosis and the values of body mass index (BMI). STUDY DESIGN: The BMI of 366 women with endometriosis was compared to that of 248 controls undergoing laparoscopy because of benign gynaecological conditions. Significant differences at univariate analyses were confirmed by using Analysis of covariance (ANCOVA) to control for potential confounding variables. RESULTS: BMI was significantly lower in women with endometriosis than in controls (p<0.001); this difference was confirmed when the analysis was restricted to subjects with normal BMI (18.50-24.99kg/m(2)) (p=0.002). 4.8% of control subjects and no woman with endometriosis were obese. No significant difference was observed in the BMI of women with mild (revised classification of the American Fertility Society, rAFS I-II) and severe endometriosis (rAFS III-IV). CONCLUSION: Women with endometriosis have lower BMI and are less frequently obese than control subjects. Further studies should investigate the physiopathological basis of decreased BMI in women with endometriosis.

Intravaginal electrical stimulation for the treatment of chronic pelvic pain.
de Oliveira Bernardes N, Bahamondes L.
J Reprod Med 2005 Apr;50(4):267-72.

OBJECTIVE: To evaluate the efficacy of intravaginal electrical stimulation in women with chronic pelvic pain (CPP). STUDY DESIGN: Between May 2002 and February 2004, 24 women with CPP with no apparent cause were evaluated. They underwent 10 sessions of intravaginal electrical stimulation. A program for measuring chronic diffuse pain, with a frequency of 8 Hz, variation in intensity and frequency, pulse length of 1 msec, and adjustment to the bearable intensity of each individual patient (in milliamps) was utilized. Treatment consisted of 30-minute applications, 2 or 3 times per week, and the pain was evaluated using a visual analog scale before and after each session and immediately after completion of the total treatment. The women were asked to evaluate the pain 2 weeks, 4 weeks and 7 months following the end of treatment. RESULTS: Intravaginal electrical stimulation was effective in alleviating pain in women with CPP, as evaluated at the end of treatment and 2 weeks, 4 weeks and 7 months after completion of treatment (p<0.05). There were significantly fewer complaints of dyspareunia following treatment (p = 0.0005). CONCLUSION: Intravaginal electrical stimulation is effective in the alleviation of pain in women with CPP.

Value of endorectal ultrasonography for diagnosing rectovaginal septal endometriosis infiltrating the rectum.
Delpy R, Barthet M, Gasmi M, Berdah S, Shojai R, Desjeux A, Boubli L, Grimaud JC
Endoscopy 2005 Apr;37(4):357-61.

BACKGROUND AND STUDY AIMS: Rectovaginal septal endometriosis (RVSE) can pose serious therapeutic problems when there is infiltration of the rectal septum (which occurs in approximately half of the cases). The aim of this study was to assess the value of endoscopic ultrasonography in diagnosing rectal wall involvement by pelvic endometriosis. PATIENTS AND METHODS: A prospective study was carried out from May 1998 to March 2003 at a single hospital center. The 30 patients included in the study presented with suspected RVSE and underwent systematic anorectal endoscopic ultrasonographic exploration prior to the surgical intervention. The endoscopic ultrasonography was carried out under general anesthesia with a 7.5-MHz miniprobe equipped with a distal balloon. RESULTS: The anorectal endoscopic ultrasonographic examination (EUS) showed the presence of endometriosis in the rectovaginal septum in 26 patients (88 %), in the uterosacral ligaments in 10 patients (33 %), and in the ovaries in two patients (6 %). At EUS, the nodules were infiltrating the rectal wall in 17 patients (56 %). The surgical exploration demonstrated endometriosis in the rectovaginal septum in 26 cases, the uterosacral ligaments in 22 cases, and the ovaries in 16 cases. The rectal wall was completely infiltrated in 12 cases and only partly in four cases, and intestinal tract resection was required in 10 cases. The sensitivity, specificity, and positive and negative predictive value of anorectal endoscopic ultrasonography as a means of diagnosing endometriosis of the rectovaginal septum and infiltration of the rectal wall were found to be 96 %, 100 %, 100 % and 83 %, and 92 %, 66 %, 64 % and 92 %, respectively; and the diagnostic accuracy was at 96 % and 80 %, respectively. The sensitivity for detecting nodules in the uterosacral ligaments or in the ovaries was 42 % and 14 %, respectively, leading to diagnostic accuracy rates of 56 % and 53 %. CONCLUSIONS: In terms of its sensitivity and its negative predictive value, anorectal endoscopic ultrasonography is a very effective means of detecting endometriosis of the rectovaginal septum and assessing possible infiltration of the rectal wall. However, this method is not as accurate for nodules located far from the EUS probe, as is the case with the uterosacral ligaments and ovaries.

Laparoscopic stripping of endometriomas: a randomized trial on different surgical techniques. Part II: pathological results.
Muzii L, Bellati F, Bianchi A, Palaia I, Manci N, Zullo MA, Angioli R, Panici PB
Hum Reprod 2005 Apr 28;.

BACKGROUND: The stripping technique for endometriomas excision has been reported to be associated with follicular loss. The objective of this trial was to evaluate the presence and nature of ovarian tissue adjacent to the endometrioma cyst wall obtained by stripping with different techniques. METHODS: Forty-eight patients with ovarian endometrioma were enrolled in two consecutive independent randomized trials. Two different techniques were analysed at the initial adhesion site (circular excision and subsequent stripping versus immediate stripping). Two different techniques were analysed at the ovarian hilus (stripping versus coagulation and cutting). Histology analysis was performed in three portions of the cyst wall (initial adhesion site, intermediate part of the specimen, ovarian hilus). RESULTS: Recognizable ovarian tissue was inadvertently excised together with the endometrioma cyst wall in most cases. At initial adhesion sites more ovarian tissue was removed with the circular excision technique (<0.001). No significant difference in quality of ovarian tissue (number and type of follicles) was found between specimens obtained with different surgical techniques at the initial or at the final part of the procedure. At the initial adhesion site and at the intermediate part of the cyst wall, the ovarian tissue removed along with the endometrioma wall was mainly constituted by tissue with no follicles or only primordial follicles (60% and 48% of the specimens from the initial part with both techniques, and from the intermediate part, respectively, had no follicles or only primordial follicles). Close to the ovarian hilus the ovarian tissue removed along with the endometrioma wall mostly consisted of tissue which contained primary and secondary follicles (69% of the cases, combining the two groups). CONCLUSIONS: Ovarian tissue is inadvertently excised together with the endometrioma wall in most cases. The excised tissue is at normal functional development stages only near the ovarian hilus. The different techniques used do not influence significantly the quality of the resected tissue.

Estrogen and progesterone receptor expression in macrophages and regulation of hepatocyte growth factor by ovarian steroids in women with endometriosis.
Khan KN, Masuzaki H, Fujishita A, Kitajima M, Sekine I, Matsuyama T, Ishimaru T
Hum Reprod 2005 Apr 14;.

BACKGROUND: Information regarding macrophage-mediated regulation of hepatocyte growth factor (HGF) by ovarian steroid hormones in women with endometriosis is limited. Therefore, we investigated the regulation of HGF by steroid hormones in isolated macrophages and stromal cells derived from women with or without endometriosis. METHODS: We isolated CD68 immunoreactive adherent macrophages in vitro from 46 women with endometriosis and 30 women without endometriosis. Estrogen receptor (ER) and progesterone receptor (PR) expression in macrophages was demonstrated by immunohistochemistry and RT-PCR. Production of HGF in the culture media of basal and ovarian steroid-stimulated macrophages was examined by enzyme-linked immunosorbent assay. Expression of mRNA for HGF and its receptor, c-Met in macrophages and stromal cells in response to ovarian steroid was investigated by RT-PCR. The single and combined effect of HGF and estrogen on the growth of macrophages and stromal cells was analysed by bromodeoxyuridine (BrdU) incorporation. RESULTS: ER and PR were expressed in isolated macrophages and intact tissue at the protein and mRNA levels. Macrophages derived from women with endometriosis produced significantly higher concentration of HGF (352.2 +/- 4.9 pg/ml) in conditioned media after treatment with estradiol (10(-8) mol/l) than that of basal macrophages (221.5 +/- 32.8 pg/ml, P<0.05) or women without endometriosis (170.6 +/- 2.6 pg/ml, P<0.05). These effects were less evident after treatment with progesterone. Treatment with tamoxifen (10(-6) mol/l) reversed the production of HGF and other macromolecules. Secretion of HGF in response to ovarian steroids was further enhanced after activation with lipopolysaccharide. The mRNA expressions of HGF and its receptor, c-Met, were also detected in macrophages and stroma in response to estrogen, suggesting an autocrine regulation. HGF mRNA expression was higher in cells of women with endometriosis than non-endometriosis women. Bromodeoxyuridine incorporation indicated that exogenous stimulation with HGF and estrogen, either alone or in combination, significantly increased the cell proliferation of both endometrial stroma and macrophages compared to that of non-endometriosis or non-treated cells. CONCLUSION: These results suggest that besides other inflammatory mediators, ovarian steroids also participate in the production of HGF by peritoneal macrophages which may be involved in the growth of endometriosis either alone or in combination with estrogen.

Neural correlates of painful genital touch in women with vulvar vestibulitis syndrome.
Pukall CF, Strigo IA, Binik YM, Amsel R, Khalife S, Bushnell MC
Pain 2005 May;115(1-2):118-27.

Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre-menopausal women. Recent evidence points to the importance of the sensory component in VVS, particularly the heightened processing of tactile and pain sensation in the vulvar vestibule. The goal of the present study was to examine the neural basis of heightened sensitivity to touch (i.e. allodynia) in women with VVS. Using functional magnetic resonance imaging, we compared regions of neural activity in 14 women with VVS and 14 age- and contraceptive-matched control women in response to the application of mild and moderate pressure to the posterior portion of the vulvar vestibule. Intensity and unpleasantness ratings were recorded after each scan; these ratings were significantly higher for women with VVS than controls. All women with VVS described moderate pressure as painful and unpleasant, and 6 of the 14 women with VVS described mild pressure as painful and unpleasant. In contrast, none of the stimuli was painful for control women. Correspondingly, women with VVS showed more significant activations during pressure levels that they found to be either painful or non-painful than did controls during comparable pressure levels. During pressure described as painful by women with VVS, they had significantly higher activation levels in the insular and frontal cortical regions than did control women. These results suggest that women with VVS exhibit an augmentation of genital sensory processing, which is similar to that observed for a variety of syndromes causing hypersensitivity, including fibromyalgia, idiopathic back pain, irritable bowel syndrome, and neuropathic pain.

Successful treatment of Zoon's vulvitis with high potency topical steroid.
Botros SM, Dieterich M, Sand PK, Goldberg RP
Int Urogynecol J Pelvic Floor Dysfunct 2005 Apr 15;.

Zoon's vulvitis is a rare, chronic condition of the vulva that presents with burning, pruritus, and dysuria with characteristic lesions and histopathology. Several treatment options have been reported with limited success. A 63-year-old woman with Zoon's vulvitis diagnosed on histopathology was treated with clobetasol propionate 0.05%. Complete resolution of her symptoms and lesions occurred in less than 1 week. No recurrence of her symptoms has occurred after 9 months. Zoon's vulvitis may be successfully and expeditiously treated with high potency topical steroids.

Vitamin D Binding Protein in Endometriosis.
Ferrero S, Gillott DJ, Anserini P, Remorgida V, Price KM, Ragni N, Grudzinskas JG
J Soc Gynecol Investig 2005 May;12(4):272-277.

OBJECTIVE: Two-dimensional gel electrophoresis is a powerful method for identifying post-translationally modified molecules in biological fluids. We examined the presence and expression of vitamin D binding protein (DBP) in the peritoneal fluid (PF) and plasma (PL) of women with endometriosis. METHODS: PL and PF samples were obtained from 36 women with untreated mild endometriosis (revised classification of the American Fertility Society [rAFS] stage I-II), 52 women with untreated severe endometriosis (rAFS stage III-IV), 17 women with endometriosis treated with the oral contraceptive (OC), and 40 controls (infertility, n = 23; tubal sterilization, n = 12; pelvic pain, n = 5). PF and PL samples were analyzed by quantitative, high-resolution 2-dimensional gel electrophoresis. RESULTS: The expression of one DBP isoform (DBPE) in the PF of patients with untreated endometriosis was significantly lower than in the control group (P <.05). The levels of PF DBPE in patients with endometriosis using OC were significantly higher than in women with untreated endometriosis (P <.05). No significant difference was observed in PL DBPE expression between women with and without endometriosis, while it was significantly increased in patients with endometriosis using OC (P <.05). DBP expression was not correlated with the stage of endometriosis (rAFS classification) or the phase of the menstrual cycle. CONCLUSION: The decreased level of DBPE in the PF but not in PL of women with untreated endometriosis suggests that this molecule may be relevant in the pathogenesis of this disease.

Immunohistochemical Expression of p53, MDM2, and p21(Waf1) Oncoproteins in Endometriomas But Not Adenomyosis.
Goumenou A, Panayiotides I, Mahutte NG, Matalliotakis I, Fragouli Y, Arici A
J Soc Gynecol Investig 2005 May;12(4):263-6.

OBJECTIVE: p53, MDM2, and p21(Waf1) are oncoproteins that regulate the cell cycle. The purpose of this study was to examine the distribution of p53, MDM2, and p21(Waf1) oncoprotein expression in endometriomas and in adenomyosis. METHODS: Tissue samples from 25 women with pathologically confirmed endometriomas and 31 women with pathologically confirmed adenomyosis were analyzed. Expression of p53, MDM2, and p21(Waf1) oncoproteins was assessed by immunohistochemical nuclear staining. RESULTS: p53, MDM2, and p21(Waf1) expression were detected in 20%, 60%, and 80% of endometrioma tissue samples, respectively. All endometrioma tissue samples expressing p53 also tested positive for both MDM2 and p21(Waf1). MDM2 expression was significantly higher in the proliferative than in the secretory phase of the cycle. In contrast, all 31 adenomyosis tissue samples were negative for p53, MDM2, and p21(Waf1) expression. CONCLUSION: The expression of p53, MDM2, and p21(Waf1) suggests a role for these oncoproteins in the regulation of endometrioma cell growth, but not in adenomyosis.

Modified vulvar vestibulectomy: simple and effective surgery for the treatment of vulvar vestibulitis.
Lavy Y, Lev-Sagie A, Hamani Y, Zacut D, Ben-Chetrit A
Eur J Obstet Gynecol Reprod Biol 2005 May 1;120(1):91-5.

OBJECTIVE: To evaluate the success of a simple modified vestibulectomy in treating vulvar vestibulitis. STUDY DESIGN: Fifty-nine patients with vulvar vestibulitis refractory to nonsurgical treatment underwent modified vestibulectomy. Response was defined as return to normal coitus and was graded as complete, partial or non-responsive. RESULTS: The postoperative follow-up period was 6 months-10 years. Thirty-nine (73.6%) patients reported complete response, 7 (13.2%) had partial response, and 7 (13.2%) were non-responsive to surgery. CONCLUSION: Surgery is an effective treatment for vulvar vestibulitis refractory to conservative treatment. Simple modified vestibulectomy is considerably less invasive, technically simpler and probably less time consuming. Postoperative results employing this surgical procedure are found to be in line with postoperative results reported by others who employ surgical methods that are more extensive.

A historical perspective on pregnancy-related low back and/or pelvic girdle pain.
Bastiaanssen JM, de Bie RA, Bastiaenen CH, Essed GG, van den Brandt PA
Eur J Obstet Gynecol Reprod Biol 2005 May 1;120(1):3-14.

The growing interest in pregnancy-related low back and/or pelvic girdle pain has invoked research projects to this subject. Although it seems a modern syndrome, historical articles show that pregnancy-related pelvic girdle pain (PPGP) was already known centuries ago. The purpose of the present article is to provide a summary review of performed studies on pregnancy-related pelvic girdle pain. Remarkably, these studies show large differences in results with regard to, for example, incidence rates and relevant etiologic factors of pregnancy-related pelvic girdle pain. These differences can be explained by the use of different definitions and descriptions of pregnancy-related pelvic girdle pain between studies. In conclusion, it is necessary to search for an evidence-based overall definition of pregnancy-related pelvic girdle pain in order to provide more knowledge about incidence rates, etiologic factors and other related subjects.

Oxidative stress and endometriosis.
Jackson LW, Schisterman EF, Dey-Rao R, Browne R, Armstrong D
Hum Reprod 2005 Apr 7;.

BACKGROUND: Little is known about the aetiology of endometriosis; however, in the presence of oxidative stress, reactive oxygen species might increase growth and adhesion of endometrial cells in the peritoneal cavity, leading to endometriosis and infertility. Within a study investigating persistent organic compounds and endometriosis, the authors evaluated the association between oxidative stress and endometriosis. METHODS: Women aged 18-40 years who were undergoing laparoscopy were contacted to participate in the study (n=100); 84 were eligible and agreed to be interviewed; 78 provided blood specimens. Four markers of oxidative stress and antioxidant status were measured in serum for 61 women. Multiple imputation of missing data was used to generate values for the missing oxidative stress data. RESULTS: Thirty-two women had visually confirmed endometriosis at laparoscopy while 52 did not, including 22 undergoing tubal ligation and 30 with idiopathic infertility. There was a weak association between thiobarbituric acid-reactive substances (nmol/ml) and endometriosis, after adjusting for age, body mass index, current smoking, hormone use in the past 12 months, gravidity, serum vitamin E, serum estradiol, and total serum lipids (beta=1.18; 95% CI-0.04, 2.39). CONCLUSIONS: These results suggest that oxidative stress might play a role in the development and progression of endometriosis, which should be evaluated in larger studies.

Laparoscopic stripping of endometriomas: a randomized trial on different surgical techniques. Part I: Clinical results.
Muzii L, Bellati F, Palaia I, Plotti F, Manci N, Zullo MA, Angioli R, Panici PB
Hum Reprod 2005 Mar 31;.

BACKGROUND: Laparoscopic surgery has become the gold-standard treatment for ovarian endometriomas. The objective of this trial was to evaluate different procedures for the laparoscopic excision of ovarian endometriomas with the stripping technique. METHODS: Forty-eight patients with ovarian endometrioma were enrolled in two consecutive independent randomized trials. Two different techniques were analysed at the initial adhesion site (circular excision and subsequent stripping versus immediate stripping). Two different techniques were analysed at the ovarian hilus (stripping versus coagulation and cutting). Operative time and technical difficulties were prospectively evaluated. Histological analysis was performed in three portions of the cyst wall and the results of the histologic study are reported separately. RESULTS: At the initial part of the stripping procedure, the technique of circular excision and subsequent stripping appeared to be more easily performed than the technique of direct stripping (P<0.01), although operative times were comparable between the two techniques. At the hilus, the two techniques utilized appeared to be comparable both for easiness of procedure and operating times. CONCLUSIONS: In this prospective, randomized study, different techniques used during the stripping procedure appeared to be comparable in terms of operative times and complications. One technique used at the beginning of the procedure (circular excision followed by stripping) was easier to perform.

Effects of acupuncture and stabilising exercises as adjunct to standard treatment in pregnant women with pelvic girdle pain: randomised single blind controlled trial.
Elden H, Ladfors L, Olsen MF, Ostgaard HC, Hagberg H
BMJ 2005 Apr 2;330(7494):761. Epub 2005 Mar 18.

OBJECTIVES: To compare the efficacy of standard treatment, standard treatment plus acupuncture, and standard treatment plus stabilising exercises for pelvic girdle pain during pregnancy. DESIGN: Randomised single blind controlled trial. Settings East Hospital, Gothenburg, and 27 maternity care centres in Sweden. PARTICIPANTS: 386 pregnant women with pelvic girdle pain. INTERVENTIONS: Treatment for six weeks with standard treatment (n = 130), standard treatment plus acupuncture (n = 125), or standard treatment plus stabilising exercises (n = 131). MAIN OUTCOME MEASURES: Primary outcome measure was pain (visual analogue scale); secondary outcome measure was assessment of severity of pelvic girdle pain by an independent examiner before and after treatment. RESULTS: After treatment the stabilising exercise group had less pain than the standard group in the morning (median difference = 9, 95% confidence interval 1.7 to 12.8; P = 0.0312) and in the evening (13, 2.7 to 17.5; P = 0.0245). The acupuncture group, in turn, had less pain in the evening than the stabilising exercise group (-14, -18.1 to -3.3; P = 0.0130). Furthermore, the acupuncture group had less pain than the standard treatment group in the morning (12, 5.9 to 17.3; P < 0.001) and in the evening (27, 13.3 to 29.5; P < 0.001). Attenuation of pelvic girdle pain as assessed by the independent examiner was greatest in the acupuncture group. CONCLUSION: Acupuncture and stabilising exercises constitute efficient complements to standard treatment for the management of pelvic girdle pain during pregnancy. Acupuncture was superior to stabilising exercises in this study.

Randomized clinical trial of a levonorgestrel-releasing intrauterine system and a depot GnRH analogue for the treatment of chronic pelvic pain in women with endometriosis.
Petta CA, Ferriani RA, Abrao MS, Hassan D, Rosa E Silva JC, Pdgaec S, Bahamondes L
Hum Reprod 2005 Mar 24;.

BACKGROUND: The objective of this multicentre randomized, controlled clinical trial was to compare the efficacy of a levonorgestrel-releasing intrauterine system (LNG-IUS) and a depot-GnRH-analogue in the control of endometriosis-related pain over a period of six months. METHODS: Eighty-two women, 18 to 40 years of age (mean 30 years), with endometriosis, dysmenorrhoea and/or CPP, were randomized using a computer-generated system of sealed envelopes into either LNG-IUS (n=39) or GnRH analogue (n=43) treatment groups at three university centres. Daily scores of endometriosis-associated CPP were evaluated using the Visual Analogue Scale (VAS), daily bleeding score was calculated from bleeding calendars, and improvement in quality of life was evaluated using the Psychological General Well-Being Index Questionnaire (PGWBI). The pain score diary was based on the VAS in which women recorded the occurrence and intensity of pain on a daily basis. A monthly score was calculated from the result of the sum of the daily scores divided by the number of days in each observation period. RESULTS: CPP decreased significantly from the first month throughout the six months of therapy with both forms of treatment and there was no difference between the groups (P>0.999). In both treatment groups, women with stage III and IV endometriosis showed a more rapid improvement in the VAS pain score than women with stage I and II of the disease (P<0.002). LNG-IUS users had a higher bleeding score than GnRH-analogue users at all time points of observation with 34% and 71% of patients in the LNG-IUS and GnRH-analogue groups, respectively, reporting no bleeding during the first treatment month, and 70% and 98% reporting no bleeding during the sixth month. No difference was observed between groups with reference to improvement in quality of life. CONCLUSIONS: Both, the LNG-IUS and the GnRH-analogue were effective in the treatment of CPP-associated endometriosis, although no differences were observed between the two treatments. Among the additional advantages of the LNG-IUS is the fact that it does not provoke hypoestrogenism and that it requires only one medical intervention for its introduction every 5 years. This device could therefore become the treatment of choice for CPP-associated endometriosis in women who do not wish to conceive.

A predictive model for endometriosis.
Wolfler MM, Nagele F, Kolbus A, Seidl S, Schneider B, Huber JC, Tschugguel W
Hum Reprod 2005 Mar 10;.

BACKGROUND: Aromatase is the key enzyme in the process of estrogen biosynthesis from the precursor androgen. Recently, aromatase has been found to be aberrantly expressed in eutopic endometrium of patients suffering from endometriosis. This finding has prompted speculation about the contribution of this enzyme to the prediction of this disease. METHODS: We prospectively aimed to evaluate whether endometrial biopsy, prior to laparoscopy in symptomatic women to screen for the presence of aromatase by real-time RT-PCR and immunohistochemistry, combined with select patients' characteristics, is of value to predict endometriosis. RESULTS: Of 48 consecutive symptomatic and eligible patients, 25 (52.1%) exhibited endometriosis and 23 (47.9%) were disease-free. A multiple logistic regression model revealed that 95.5% of patients whose eutopic endometrium was found to be positive for aromatase mRNA as well as immunohistochemically detected protein and who were additionally suffering from moderate to severe dysmenorrhoea (visual analogue scale score >4/10) exhibited endometriosis at laparoscopy. CONCLUSIONS: These findings provide direct evidence that screening for eutopic endometrial aromatase in combination with clinical data could be of discriminative value in the prediction of disease.

Surgical treatment of ureteral obstruction from endometriosis: our experience with thirteen cases.
Antonelli A, Simeone C, Frego E, Minini G, Bianchi U, Cunico SC
Int Urogynecol J Pelvic Floor Dysfunct 2004 Nov-Dec;15(6):407-12; discussion 412. Epub 2004 Jul 31.

Endometriosis is a biologically benign albeit aggressive pathology marked by high local recurrences. Ureteral involvement accounts for only a minority of cases (0.1-0.4%) with often non-specific symptoms at clinical presentation and difficult preoperative diagnosis. Thirteen cases of severe ureteral endometriosis (i.e. causing significant obstruction to the urinary flow) were observed and surgically treated, out of 17 ureteral units affected (three cases of bilateral involvement, one case of complete pyeloureteral duplicity). The initial symptomatology was acute and related to ureteral obstruction in eight cases, silent and non-specific in the other five; a presumptive diagnosis was made only for the seven patients (53.9%) with a positive medical history for pelvic (and in two cases also ureteral) endometriosis. Preoperative drainage of urine proved necessary for eight patients due to the complete functional exclusion of the excretory axis. One patient (7.7%) underwent nephrectomy due to renal atrophy. Segmental ureteral resection and termino-terminal anastomosis were performed in two patients, while seven patients underwent segmental ureterectomy and ureterocystoneostomy, with bladder psoas hitching in four cases and vesical flap according to Casati-Boari in one case. All three cases of bilateral involvement were treated by bilateral segmental ureterectomy and trans-uretero-uretero-cystoneostomy with bladder psoas hitching. Following histological examination, all patients were diagnosed with active ureteral endometriosis, which was found to be intrinsic in five cases (38.5%) and extrinsic in the other eight. One of the two patients that had undergone ureterectomy and termino-terminal anastomosis had to undergo ureteral resection and ureterocystoneostomy 22 months later due to relapsing endometriosis-induced stenosis. Conversely, no ureteral endometriosis relapses occurred in the remaining 12 patients within the mean follow-up time of 41.1 months (range 6-91). Ureteral endometriosis is marked by non-specific symptoms, making preoperative diagnosis often difficult. Therefore, an ultrasound or urographic examination of the urinary tract in case of pelvic endometriosis is absolutely essential. In our experience, terminal ureterectomy with ureterocystoneostomy has provided long-term favourable results as extended ureteral resection can be performed and continuity of the urinary tract can be restored without resorting to the distal pelvic ureter, which is often affected by the disease besides being more subject to relapses.

Where are the genes that cause endometriosis?
Simpson JL
J Soc Gynecol Investig 2005 Apr;12(3):143-4.

Three-year experience in outpatient microwave endometrial ablation.
Tawfeek S, Hayes T, Sharp N
Obstet Gynecol Surv 2005 Apr;60(4):234-5.

The authors present their experience with 117 women with therapy-resistant menorrhagia who underwent microwave endometrial ablation between April 2000 and March 2003. The procedures were performed on an outpatient basis under local anesthesia. Study criteria included at least 1 vaginal delivery, no previous vaginal surgery, no confounding medical problems, and normal weight. In addition, women with an anxious disposition, a history of mental illness, previous unwelcome sexual contact, or previous unpleasant obstetrical or gynecologic experience were not enrolled. The presence of a vaginal infection, intolerance of nonsteroidal antiinflammatory drugs, restricted hip or knee mobility, or a history of GnRH agonist therapy also prevented inclusion in the study.Anesthesia was delivered with the patient in the semirecumbent Lloyd-Davis position. First, the cervix was numbed with a small amount of local anesthetic placed in the anterior lip. Then, while grasping the cervix with a tenaculum, the operator injected a full 4 x 2.2-mL cartridge of citanest and octapressin (prilocaine 3% with felypressin) into the center of each 4 quadrants of the cervix, creating a ring block at the internal os. To provide postoperative analgesia, a second series of injections was administered using 20 mL of 0.25% bupivacaine or Chirocaine with a standard 20-mL syringe and 21-g needle. After completion of the ring block, the first of 2 initial soundings of the uterus was taken and checked against a sterile steel ruler. The cervix was then dilated with a no. 9 Hegar dilator and a second sounding made to confirm the length of the uterine cavity.The microwave applicator was introduced into the cavity through the cervix and inserted to the tip of the fundus. A series of graduations on the applicator shaft enabled confirmation of the depth of insertion. This depth was matched against the first 2 measurements.At this point, the patient was offered inhaled nitrous oxide/oxygen to lessen the pain associated with ablation. If this proved to be inadequate, 4 mg midazolam (Hypnoval-Roche) intravenously in conjunction with 0.4 mg alfentanil (Rapifen-Janssen) was administered using intravenous access established preoperatively.Ablation was performed by energizing the microwave applicator. After the temperature reached 60 degrees C (approximately 6 seconds), the uterine fundus and corneal areas were evenly heated with a gentle side-to-side motion. When a yellow mark appeared at the external os, the applicator was slowly withdrawn until the mark was totally visible, at which time the power was turned off. After microwave ablation, coagulated debris in the uterus was removed with suction aspiration using a 7-mm Cory curette.One patient was found to have a large fibroid polyp inside the uterine cavity and the procedure was abandoned. In the remaining 116 patients, the average time of treatment was 254 seconds (range, 103-573 seconds). The ring block was sufficient anesthesia for most patients (81%). Seven patients required inhalation analgesia, and 14 needed inhalation analgesia and intravenous sedation. Abdominal pain caused 3 patients to be admitted to the hospital overnight, and 3 additional patients were admitted for abdominal pain within 3 days of treatment. In 1 patient, a hysteroscopy was done to confirm cavity integrity. There were no intraoperative or postoperative complications.A follow-up questionnaire was sent to participants at 3 and 6 months. Almost 90% (88.6%) reported being satisfied with their treatment. Of the 12 patients who were dissatisfied, 5 women elected repeat treatment with microwave endometrial ablation. Repeat treatment was successful in only 1 woman. Eleven women underwent subsequent hysterectomy for continued pain and bleeding, including 4 women who underwent repeat treatment. A fifth patient had a hysterectomy within 3 days of initial treatment, and 6 were operated on within 2 years of treatment. There was a 90% satisfaction rate among these women. At follow up, 47 (41.2%) patients reported amenorrhea.

Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study.
Tsai YL, Hwang JL, Loo TC, Cheng WC, Chuang J, Seow KM
J Reprod Med 2004 Dec;49(12):955-9.

OBJECTIVE: To assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery. STUDY DESIGN: Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2). RESULTS: Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%). CONCLUSION: Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery.

Vesical and vaginal recurrent endometriosis in postmenopause following estrogen replacement therapy.
Sesti F, Vettraino G, Pietropolli A, Marziali M, Piccione E
Eur J Obstet Gynecol Reprod Biol 2005 Feb 1;118(2):265-6.

Feasibility and clinical outcome of laparoscopic colorectal resection for endometriosis.
Darai E, Thomassin I, Barranger E, Detchev R, Cortez A, Houry S, Bazot M
Am J Obstet Gynecol 2005 Feb;192(2):394-400.

Objective This study was undertaken to evaluate the feasibility and complications of laparoscopic segmental colorectal resection for endometriosis and its efficacy on gynecologic and digestive symptoms. Study design After magnetic resonance imaging and rectal endoscopic sonographic evaluation of symptomatic colorectal endometriosis, 40 consecutive women requiring colorectal resection were included in this study. Symptom questionnaires were completed before and after the procedure. Perioperative complications and linear intensity scores for several gynecologic and digestive symptoms were recorded. Results Thirty-six women (90%) underwent laparoscopic segmental colorectal resection and 4 required laparoconversion. Major complications occurred in 4 cases (10%), including 3 rectovaginal fistulae and 1 pelvic abscess. Transient urinary dysfunction occurred in 7 women (17.5%). Median follow-up after colorectal resection was 15 months (3-22 months). Median overall preoperative and postoperative pain scores were 8 +/- 1 (range 4-10) and 2 +/- 2 (0-10), respectively ( P < .0001). Nonmenstrual pelvic pain ( P = .0001), dysmenorrhea ( P < .0001), dyspareunia ( P = .0001), and pain on defecation ( P < .0005) were improved by colorectal resection. Lower back pain and asthenia were not improved. Conclusion Our results suggest that laparoscopic segmental colorectal resection for endometriosis is feasible but carries a risk of major postoperative complications. Colorectal resection improved gynecologic and digestive symptoms, and the overall pain score.

Postpartum pelvic pain - the 'pelvic joint syndrome': a follow-up study with special reference to diagnostic methods.
Hansen A, Jensen DV, Larsen EC, Wilken-Jensen C, Kaae BE, Frolich S, Thomsen HS, Hansen TM
Acta Obstet Gynecol Scand 2005 Feb;84(2):170-6.

Background. The etiology of pelvic joint syndrome (PJS) is not fully clarified. As a consequence, there is a lack of diagnostic methods to confirm the diagnosis, which today is mainly based on medical history. Objective. The aim of this study was to examine women with PJS using various diagnostic methods. The hypothesis is that there are characteristics in this group of women that separate them from women who only suffer from pelvic pain during pregnancy and shortly after delivery, or healthy women. Methods. Fifty-eight women participated in this follow-up study - twenty-one with PJS, 17 women who suffered from pelvic pain during pregnancy and shortly after delivery, and 20 controls with no history of pregnancy-induced pelvic pain. Clinical examination, gynecologic examination, psychological tests, spine X-ray, magnetic resonance imaging (MRI), blood samples, and urine dipsticks were performed. Results. Clinical examination showed significant differences with regard to provocative tests and tenderness in the muscles and ligaments in the low back and the pelvis. Furthermore, psychological testing showed bad coping strategies when women with PJS were compared with those of the two control groups. However, no diagnostic method could explicitly differentiate between women with PJS and those of the two control groups. Thus, there was no significant difference in MRI, X-ray, blood or urine sample analysis. Conclusions. Women with PJS have positive provocative tests and ligament and muscular tenderness. Bad coping strategies might be an explanation why these women develop PJS.

Rectus abdominis endometriosis: a report of two cases.
Coeman V, Sciot R, Van Breuseghem I
Br J Radiol 2005 Jan;78(925):68-71.

Endometriosis is characterized by the presence of histological normal endometrial tissue outside the uterine cavity. Most frequently endometriosis occurs within the pelvis. Extrapelvic endometriosis is less common, but can involve nearly every organ. We present two patients in whom endometriosis was found in the rectus abdominis muscle and discuss the imaging findings and pathological correlation.

Posterior Cul-de-Sac Obliteration Associated with Endometriosis: MR Imaging Evaluation.
Kataoka ML, Togashi K, Yamaoka T, Koyama T, Ueda H, Kobayashi H, Rahman M, Higuchi T, Fujii S
Radiology 2005 Jan 21;.

PURPOSE: To retrospectively evaluate the accuracy of magnetic resonance (MR) imaging in depicting posterior cul-de-sac obliteration in patients with endometriosis. MATERIALS AND METHODS: Institutional review board approval was not required for this retrospective study, but informed consent was obtained from all patients. MR images obtained between January 1989 and December 2000 in 57 women (mean age, 39 years; age range, 26-52 years) with histologically confirmed endometriosis were retrospectively evaluated by four radiologists independently. All patients underwent laparotomy or laparoscopy less than 1 month after MR imaging. MR images were evaluated for the presence and location of endometrial implants and adhesions. MR images were also scored for the presence of five findings: retroflexed uterus, elevated posterior vaginal fornix, intestinal tethering or tethered appearance of rectum in direction of uterus, faint strands between uterus and intestine, and fibrotic plaque or nodule covering serosal surface of the uterus. Interobserver agreement for each of the five findings and for the overall diagnosis of cul-de-sac obliteration was calculated. Sensitivity, specificity, accuracy, positive and negative predictive values, and kappa statistics were determined. RESULTS: Laparotomy or laparoscopy revealed posterior cul-de-sac obliteration in 30 patients. Overall, the four radiologists had mean accuracies of 89.0% and 76.3% for diagnosing endometrial implants and adhesions, respectively, at MR imaging. Overall, the radiologists achieved mean sensitivity, specificity, accuracy, and positive and negative predictive values of 68.4%, 76.0%, 71.9%, 76.6%, and 68.5%, respectively, in diagnosing posterior cul-de-sac obliteration. The best accuracy (mean value, 64.5%) was obtained with the finding of fibrotic plaque in the uterine serosal surface. Readers agreed on the observations 63.2%-91.2% of the time. For the impression of the presence or absence of posterior cul-de-sac obliteration, interobserver agreement varied between substantial and moderate: Mean interobserver agreement was 78.4% (range, 70.2%-84.2%), and mean kappa was 0.57 (range, 0.40-0.67). Mean accuracy of MR imaging for diagnosing posterior cul-de-sac obliteration was 71.9%. CONCLUSION: These results suggest that use of the described MR imaging findings may enable diagnosis of posterior cul-de-sac obliteration. (c) RSNA, 2005.

Association between endometriosis and genetic polymorphisms of the estradiol-synthesizing enzyme genes HSD17B1 and CYP19.
Tsuchiya M, Nakao H, Katoh T, Sasaki H, Hiroshima M, Tanaka T, Matsunaga T, Hanaoka T, Tsugane S, Ikenoue T
Hum Reprod 2005 Jan 7;.

BACKGROUND: Endometriosis, an estrogen-dependent disease, is believed to be influenced by multiple genetic and environmental factors. Here, we evaluated whether the risk and severity of endometriosis are associated with polymorphisms in estradiol-synthesizing enzyme genes: the Ser312Gly polymorphism in 17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1) and the Arg264Cys polymorphism in cytochrome P450, subfamily XIX (CYP19). METHODS: All participants underwent diagnostic laparoscopy, and the stage of endometriosis was determined according to the Revised American Fertility Society classification. Of the 138 women enrolled, 59 had no endometriosis, 21 had stage I, 10 had stage II, 23 had stage III and 25 had stage IV. SNPs were discriminated by allele-specific oligonucleotide hybridization. RESULTS: Individuals having at least one A-allele (A/G or A/A genotype) of HSD17B1 showed a significantly increased risk of endometriosis (A/G genotype: adjusted OR, 3.06; 95%CI 1.21-7.74; A/A genotype: adjusted OR, 3.02; 95%CI 1.08-8.43). There was a significant trend associating A/G + A/A genotypes with severity of endometriosis (P for trend <0.01). No statistically significant association was found for the CYP19 polymorphism. CONCLUSIONS: Evidence for association between the Ser312Gly polymorphism in HSD17B1 and endometriosis was found in a Japanese population. The A-allele of HSD17B1 appears to confer higher risk for endometriosis.