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Pelvic Pain in Gynecology

Nerve fibres in peritoneal endometriosis.
Tokushige N, Markham R, Russell P, Fraser IS
Hum Reprod. 2006 Sep 1;.

BACKGROUND: Endometriosis is a gynaecological disease that can be associated with severe pelvic pain; however, the mechanisms by which pain is generated remain unknown. METHODS: Peritoneal endometriotic lesions and normal peritoneum were prepared from women with and without endometriosis (n = 40 and 36, respectively). Specimens were also prepared from endosalpingiosis lesions (n = 9). These sections were stained immunohistochemically with antibodies against protein gene product 9.5, neurofilament (NF), nerve growth factor (NGF), NGF receptor p75 (NGFRp75), substance P (SP), calcitonin gene-related peptide (CGRP), acetylcholine (ACh) and tyrosine hydroxylase (TH) to demonstrate myelinated, unmyelinated, sensory, cholinergic and adrenergic nerve fibres. RESULTS: There were significantly more nerve fibres identified in peritoneal endometriotic lesions than in normal peritoneum (P < 0.001) or endosalpingiosis lesions (P < 0.001). These nerve fibres were SP, CGRP, ACh or TH immunoreac-tive. Many of these markers were co-localized. There was an intense NGF immunoreactivity near endometriotic glands, and NGFRp75 immunoreactive nerve fibres were present near endometriotic glands and blood vessels in the peritoneal endometriotic lesions. CONCLUSIONS: Peritoneal endometriotic lesions were innervated by sensory Ad, sensory C, cholinergic and adrenergic nerve fibres. These nerve fibres may play an important role in the mechanisms of pain generation in this condition.

[Chronic pelvic pain as a complication of cystourethropexy with tension free vaginal tape. Case report]
del Rosario J, Urena R, Manduley A, Cordoba L
Arch Esp Urol. 2006 Jun;59(5):533-5.

OBJECTIVE: To report an interesting case of a rare complication of cystourethropexy, as well as its precise diagnosis and results after treatment. METHODS: We reviewed the medical records of the patients as well as their operative report and she underwent outpatient follow-up for the following six months. We descriptively report the findings. RESULTS: It is the case of a female patient presenting a foreign body rejection of a suburethral tension free vaginal tape (TVT). She complained of severe pain in the immediate postoperative period, which led to retrieval of the tape in spite of a good continence result. CONCLUSIONS: Foreign body rejection is a rare complication of vaginal tapes; it is rarely taken into account but it should be present in any exclusion diagnosis because the possibility of tape retrieval is not always associated with recurrence of the incontinence.

Chronic pelvic pain and endometriosis in adolescents.
Solnik MJ
Curr Opin Obstet Gynecol. 2006 Oct;18(5):511-8.

PURPOSE OF REVIEW: This review will provide a detailed account of chronic pelvic pain and endometriosis, two conditions that frequently occur in adolescents. Current approaches used to evaluate and treat these patients will be addressed. RECENT FINDINGS: Although previous investigations have established relative rates of disease and basic treatment algorithms for endometriosis in adolescents, its pathogenesis is yet to be explained. Recent scientific works have focused on the interplay of specific genes and the role of host immune response. Despite such progress, we have not yet learned how to apply this knowledge to clinical use. Most innovative treatment strategies are based on algorithms generated primarily for adults, with only a small percentage focusing on adolescents. SUMMARY: Treating pain associated with endometriosis may be facilitated by early intervention. Future study should focus on identifying adolescents with progressive disease and introducing less invasive therapies that could reverse inflammatory pathways and minimize subsequent morbidity.

Tender Point Examination in Women With Vulvar Vestibulitis Syndrome.
Pukall CF, Baron M, Amsel R, Khalife S, Binik YM
Clin J Pain. 2006 Sep;22(7):601-609.

OBJECTIVES: To examine whether generalized pain sensitivity in women with vulvar vestibulitis syndrome (VVS) is increased, suggestive of altered pain processing at the level of the central nervous system, and to investigate pain history and other pain measures in women with VVS. METHODS: Sixteen women with VVS and 16 age-matched (+/-3 years) and oral contraceptive status-matched (yes or no) control women participated in this cross-sectional study. The TP examination, typically used in the diagnosis of FMS, consists of the palpation of 9 bilateral nonvulvar areas by a blinded rheumatologist and was the main measure of generalized sensitivity. Pain intensity and unpleasantness rating (0 to 10) were recorded after each palpation. In addition, nonvulvar pain history, pain interference, catastrophizing, and anxiety were assessed via questionnaires. RESULTS: Women with VVS had significantly more painful TPs than nonaffected women; they reported significantly higher pain intensity and unpleasantness ratings and displayed more pain behaviors than controls (P<0.05). Furthermore, VVS patients reported having experienced more pain problems and associated interference, they catastrophized more in response to vulvar and nonvulvar pain, and they had higher levels of trait anxiety than controls (P<0.05). DISCUSSION: These results are consistent with recent findings of generalized sensitivity and heightened responses to pain in women with VVS. These results suggest that the mechanisms involved in VVS may include those that are genital specific in addition to those that are more generalized, and possibly centrally mediated.

Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients.
Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG
Hum Reprod. 2006 Aug 26;.

BACKGROUND: The association between lesion type, disease stage and severity of pain was studied in a large group of women with endometriosis to verify whether endometrial implants at different sites determine specific complaints and to evaluate the validity of the current classification system in women with symptomatic disease. METHODS: A total of 1054 consecutive women with endometriosis undergoing first-line conservative or definitive surgery were included. Data on age at surgery, disease stage according to the revised American Fertility Society (AFS) classification, anatomical characteristics of endometriotic lesions, and type and severity of pain symptoms were collected and analysed by multiple logistic regression. RESULTS: Minimal endometriosis was present in 319 patients, mild in 139, moderate in 292 and severe in 304. A significant inverse relationship was demonstrated between age at surgery and moderate-to-severe dysmenorrhoea, dyspareunia and non-menstrual pain. A strong association was found between posterior cul-de-sac lesions and pain at intercourse [Wald chi (2) = 17.00, P = 0.0001; odds ratio (OR) = 2.64, 95% confidence interval (CI) = 1.68-4.24]. A correlation between endometriosis stage and severity of symptoms was observed only for dysmenorrhoea (Wald chi (2) = 5.14, P = 0.02) and non-menstrual pain (Wald chi (2) = 5.63, P = 0.018). However, the point estimates of ORs were very close to unity (respectively, 1.33, 95% CI = 1.04-1.71, and 1.01, 95% CI = 1.00-1.03). CONCLUSIONS: The association between endometriosis stage and severity of pelvic symptoms was marginal and inconsistent and could be demonstrated only with a major increase in study power.


Hyperoxaluria in women with vulvar vestibulitis syndrome.
Greenstein A, Militscher I, Chen J, Matzkin H, Lessing JB, Abramov L
J Reprod Med. 2006 Jun;51(6):500-2.

OBJECTIVE: To determine whether evaluation and treatment of hyperoxaluria in vulvar vestibulitis syndrome (VVS) is justified. STUDY DESIGN: Forty women (mean age, 24.5 years; range, 18-35) diagnosed with VVS at a sex therapy clinic participated. Diagnosis of VVS relied upon Friedrich's criteria: (1) severe vulvar vestibular pain upon touch or attempted vaginal entry, (2) tenderness to pressure localized within the vulvar vestibule, and (3) physical findings confined to vulvar erythema of various degrees. Oxalate was measured in 24-hour urine samples. Women with hyperoxaluria (urine oxalate >50 mg/24 h) were placed on a low-oxalate diet and oral calcium citrate as single therapy and reevaluated 3 months later. RESULTS: Hyperoxaluria was diagnosed in 7 women (17.5%), of whom 1 demonstrated an objective improvement and could have pain-free vaginal intercourse following treatment, yielding a 2.5% benefit from the evaluation and treatment of hyperoxaluria. CONCLUSION: There is no justification for evaluation and treatment of hyperoxaluria in women with VVS due to its low yield and economic burden.

Vulvodynia: a state-of-the-art consensus on definitions, diagnosis and management.
Bachmann GA, Rosen R, Pinn VW, Utian WH, Ayers C, Basson R, Binik YM, Brown C, Foster DC, Gibbons JM Jr, Goldstein I, Graziottin A, Haefner HK, Harlow BL, Spadt SK, Leiblum SR, Masheb RM, Reed BD, Sobel JD, Veasley C, W
esselmann U, Witkin SS
J Reprod Med. 2006 Jun;51(6):447-56.
Vulvodynia is a chronic pain syndrome affecting up to 18% of the female population. Despite its high prevalence and associated distress, the etiology, diagnosis and clinical management of the disorder have not been clearly delineated. This "white paper" describes the findings and recommendations of a consensus conference panel based on a comprehensive review of the published literature on vulvodynia in addition to expert presentations on research findings and clinical management approaches. The consensus panel also identified key topics and issues forfurther research, including the role of inflammatory mechanisms and genetic factors and psychosexual contributors.


Prognosis of women with pelvic pain during pregnancy: a long-term follow-up study.
Rost CC, Jacqueline J, Kaiser A, Verhagen AP, Koes BW
Acta Obstet Gynecol Scand. 2006;85(7):771-7.

Study design. A follow-up study of women with pelvic pain during pregnancy. Objectives. To evaluate prognostic factors for pelvic pain. Methods. Out of a cohort of 870 pelvic pain patients, 598 women, who delivered less than 42 months prior to the follow-up measurement, were selected for follow-up. Results. Data of 430 women were available for analysis with a mean follow-up duration of 18 months postpartum. Forty-three women still experienced moderate or severe pain and were seriously hindered in more than one activity. At intake symptomatic women experienced a higher overall severity of complaints, more walking deficiencies, and mentioned prepregnancy back pain more often and reported labor lasting longer than 18 h 2.5 times more often than asymptomatic women. Explained variance of these factors is small. Conclusions. Mean 18 months postpartum a small group had moderate or severe pain. Prepregnancy back pain, severity of complaints, and number of walking deficiencies at primary referral as well as duration of labor showed a significant relation with symptoms.

Endometriosis and assisted reproduction: the role for reproductive surgery?
De Hondt A, Meuleman C, Tomassetti C, Peeraer K, D'hooghe TM
Curr Opin Obstet Gynecol. 2006 Aug;18(4):374-379.

PURPOSE OF REVIEW: The aim of this review paper is to discuss the relationship between endometriosis and assisted reproductive technology. More specifically, the following clinically relevant issues will be discussed. (1) Does the presence of endometriosis affect the outcome of assisted reproductive technology? (2) Does surgical treatment for endometriosis prior to or after assisted reproductive technology treatment affect the outcome of assisted reproductive technology? (3) Is assisted reproductive technology a risk factor for the recurrence of endometriosis after medical or surgical therapy? RECENT FINDINGS: The review is based on recently published review papers/meta-analyses or international guidelines as published by the European Society of Human Reproduction or the American Society of Reproductive Medicine, updated with a selective review of recent papers searching PubMed with the key words 'Endometriosis', 'Assisted Reproduction', 'IVF', 'IUI' and 'Reproductive Surgery'. SUMMARY: At the end of this review, a practical proposal for the clinical management of women with endometriosis-associated subfertility is proposed, based on our own experience.

Genetic Polymorphism in the Fibrinolytic System and Endometriosis.
Bedaiwy MA, Falcone T, Mascha EJ, Casper RF
Obstet Gynecol. 2006 Jul;108(1):162-168.

OBJECTIVE: Although most women experience retrograde menses during their reproductive life, endometriosis develops only in a small percentage. We hypothesized that persistence of a fibrin matrix in peritoneal pockets, as a result of hypofibrinolysis, could allow menstrually deposited endometrial fragments to initiate endometriosis. Fibrinolysis is modulated by several factors, and polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) gene are considered to be one of the important determinants. The objective of this study was to evaluate PAI-1 genotypes in a group of women with or without endometriosis. METHODS: In 118 women (75 with laparoscopically confirmed endometriosis and 43 controls), genomic DNA was extracted from blood and the PAI-1 promoter genotype was determined by polymerase chain reaction amplification of DNA using specific primers for the 4G or 5G allele followed by gel electrophoresis. A portion of the polymerase chain reaction product was purified and sequenced to confirm the gel electrophoresis results. RESULTS: Endometriosis was more likely in patients with 4G/5G (odds ratio 38; 95% confidence interval [CI] 6-229) or 4G/4G (odds ratio 441; 95% CI 53-3,694) compared with 5G/5G PAI-1 genotype. Fifty-two of 75 women with endometriosis (69 %, 95% CI 58-79%) had the 4G/4G genotype compared with only 5 of 43 (12%; 95% CI 4-25%) controls. In contrast, the 5G/5G genotype associated with normal fibrinolysis was found in 2 of 75 (3%; 95% CI 0-9%) women with endometriosis compared with 24 of 43 (56%; 95% CI 40-71%) controls. CONCLUSION: Hypofibrinolysis, associated with the 4G allele of the PAI-1 gene, was found significantly more often in women with endometriosis compared with controls. Persistence of fibrin matrix could support the initiation of endometriotic lesions in the peritoneal cavity, explaining why some women with retrograde menstruation develop endometriosis while others do not. LEVEL OF EVIDENCE: II-2.


Apoptosis pattern in human endometrium in women with pelvic endometriosis.
Szymanowski K
Eur J Obstet Gynecol Reprod Biol. 2006 May 12;.

OBJECTIVE: In the present study we aimed to describe apoptosis patterns in eutopic endometrium in women suffering from endometriosis in order to assess its value as a marker of early forms of endometriosis, and also to try to answer whether endometriosis is caused by changes within the eutopic endometrium or whether endometriotic lesions change the characteristics of eutopic endometrium. STUDY DESIGN: The study was performed on 125 women treated in Division of Reproduction. In 52 patients peritoneal endometriosis was diagnosed (I(0)-23; II(0)-29). Seventy-three patients in whom no endometriotic foci could be found at laparoscopy were qualified as the control group. Endometrial biopsy 7-9 days after ovulation was taken for assessment of apoptosis (TUNEL) and routine histology. RESULTS: Apoptosis indices in the eutopic endometrium of women with endometriosis were lower compared to women without endometriosis. In the endometrial glands apoptosis indices were 2.94+/-1.66 versus 5.23+/-2.06 (p<0.01) in the group of women with and without endometriosis, respectively. In the endometrial stroma apoptosis indices were estimated at 2.04+/-1.72 in women with endometriosis and 4.12+/-1.62 in the control group (p<0.01). CONCLUSIONS: The observed changes could support the hypothesis of the different properties of eutopic endometrium in endometriotic women as a causing factor of peritoneal endometriosis.

Distension of painful structures in the treatment for chronic pelvic pain in women.
Heyman J, Ohrvik J, Leppert J
Acta Obstet Gynecol Scand. 2006;85(5):599-603

BACKGROUND: There is a lack of established treatment for Chronic pelvic pain (CPP), defined as acyclic pain of at least six months duration. We decided to study the pain-alleviating effects of stretching on defined structures in women with CPP, and the treatment's impact on quality of life variables. DESIGN OF STUDY: An open, randomized study. SETTING: Primary Health Care Centre, Kolback, Sweden. METHODS: Fifty women, median age 33 years (range 19-54), complaining of CPP for a median duration of 25.5 months (range 6-264) were randomly assigned to either a treatment or a control group. A short questionnaire containing 17 questions was administered before randomization and two to three weeks after a second treatment of distension of pelvic structures. Visual analog scales were used for questions concerning intensity of pain and quality of life. Five-point scales were used for questions dealing with duration and frequency of pain. RESULTS: Intensity, frequency and duration of pelvic pain, painful intercourse, lower back pain, sleep disturbance, sleep quality, mental fatigue, depression, mood and anger improved significantly more in the treatment group than in the control group. Treatment proved more effective than counseling as reflected by self-rating scales: pain intensity (OR 18.37, 95% CI 3.39-99.64) and pain during intercourse (OR 8.59, 95% CI 1.57-46.68). CONCLUSION: In this open, randomized study, distension of painful pelvic structures in women with CPP resulted in significant relief of pain and improvement in quality of life measures.

Endoscopic treatment of deep infiltrating endometriosis (DIE) involving the bladder and rectosigmoid colon.
Langebrekke A, Istre O, Busund B, Johannessen HO, Qvigstad E
Acta Obstet Gynecol Scand. 2006;85(6):712-5.

Background. To study the feasibility, complications and symptom relief of laparoscopic treatment in patients with deep infiltrating endometriosis. Methods. From January 2004 to March 2005, 24 patients with deep infiltrating endometriosis were treated with laparoscopic techniques. Preoperative symptoms, staging, involvement of the disease, and surgical procedures were recorded. Operating time and perioperative complications were also registered, as well as follow-up of the patients. Results. The surgical treatment was individualized with removal of deep infiltrating endometriosis in all 24 patients, additional bladder resection in five patients and colorectal resection in eight patients. In two cases laparoconversion was performed, and one patient had a temporary loop ileostomy. We observed no major peri- or postoperative complications. Median operating time was 3.4 h (range 1.4-8.0 h). All patients with bladder involvement were relieved of their urinary dysfunction, while all except three patients were successfully treated for their pain problems, and also these three patients had symptom relief. Conclusions. Patients with deep infiltrating endometriosis represent a challenge to surgical procedures. Our results show that radical laparoscopic surgery including colorectal and bladder resection is feasible, safe, and effective in almost all patients.

Musculoskeletal pain and menopausal status.
Dugan SA, Powell LH, Kravitz HM, Everson Rose SA, Karavolos K, Luborsky J
Clin J Pain. 2006 May;22(4):325-31.

OBJECTIVES: The authors examined whether self-reported menopausal status is associated with musculoskeletal pain in a multiethnic population of community-dwelling middle-aged women after considering sociodemographics, medical factors, smoking, depression, and body mass index using a cross-sectional study design. METHODS: Participants were 2218 women from the Study of Women's Health Across the Nation assessed at the time of their third annual follow-up exam. Two dependent variables were derived from a factor analysis of survey questions about pain. These 2 outcomes were Aches and Pains, derived from 5 of 6 pain symptom questions and Consultation for Low Back Pain, derived from 1 question. RESULTS: Prevalence of aches and pains was high, with 1 in 6 women reporting daily symptoms. Compared with premenopausal women, those who were early perimenopausal (P=0.002), late perimenopausal (P=0.002), or postmenopausal (P<0.0001) reported significantly more aches and pains in age-adjusted analysis. With complete risk factor adjustment, postmenopausal women still reported significantly greater pain symptoms (P=0.03) than did premenopausal women. Menopausal status was marginally related to consulting a healthcare provider for back pain. DISCUSSION: This study demonstrates an association between pain and self-reported menopausal status, with postmenopausal women experiencing greater pain symptoms than premenopausal women.
Curr Opin Obstet Gynecol. 2006 Jun;18(3):333-337.

A conceptual model for the pathophysiology of vulvar vestibulitis syndrome.
Zolnoum D, Hartmann K, Lamvu G, As-Sanie S, Maixner W, Steege J
Obstet Gynecol Surv. 2006 Jun;61(6):395-401; quiz 423.

Vulvar vestibulitis syndrome (vestibulitis), the most common type of chronic vulvovaginal pain, impairs the psychologic, physical, and reproductive health of approximately 10% of women at some point in their lives. Research on the pathophysiology of vestibulitis suggests abnormalities in 3 interdependent systems: vestibular mucosa, pelvic floor muscles, and central nervous system pain regulatory pathways. To date, causes and relative contributions of these abnormalities to the development and maintenance of vestibulitis remain poorly understood. Research consistently supports the conceptualization of vestibulitis as a chronic pain disorder-akin to fibromyalgia, irritable bowel disorder, and temporomandibular disorder (TMD)-that is far more complex than vestibular hypersensitivity alone. Nevertheless, the clinical diagnosis of vestibulitis continues to rely on subjective report of pain during intercourse and vestibular sensitivity on clinical examination after exclusion of other gynecologic disorders. We propose that current diagnostic criteria, which are based on highly subjective patient and clinician measures, are not sufficient to describe and properly classify the heterogeneous clinical presentations of this disorder. To inform clinical care or research, we must be able to objectively characterize women with vestibulitis. This narrative review critically appraises current conceptualization of vestibulitis and presents a context for studying vestibulitis as a chronic pain disorder, emphasizing the need for objective assessment of clinical features. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state that vulvar vestibulitis is common; recall that the disorder has three major pathophysiological pathways and that understanding of these pathways is important in selecting treatment options, and explain that the clinician must attempt to properly classify the clinical presentations of the disorder.


Atherosclerosis in women with endometriosis.
Pretta S, Remorgida V, Abbamonte LH, Anserini P, Ragni N, Del Sette M, Gandolfo C, Ferrero S
Eur J Obstet Gynecol Reprod Biol. 2006 May 6;.

OBJECTIVE: This study aims to determine whether women with endometriosis have greater subclinical atherosclerosis than the general population. STUDY DESIGN: This case-control study included 66 women with endometriosis and 66 controls matched for age and body mass index. All subjects were >/=35 years old. Exclusion criteria were obesity, diabetes, hypertension, hyperlipidemia, renal or metabolic diseases. Before laparoscopy, all patients underwent a measurement of intima-media thickness (IMT) and distensibility coefficient (DC) on the common carotid artery. In addition, blood samples were taken to determine the levels of lipids, fibrinogen, C-reactive protein, homocysteine, fasting glycemia, antithrombin III, plasminogen, protein C, protein S, and activated protein C resistance. RESULTS: All the biochemical parameters evaluated had similar levels in the two study groups. IMT was similar in women with endometriosis and in controls both on left (p=0.330) and right (p=0.648) carotid artery. Similarly, no significant difference was observed in the DC between women with endometriosis and controls both on left (p=0.539) and right (p=0.178) carotid artery. No significant difference was observed in IMT and DC between women with mild and severe endometriosis. CONCLUSION: Women with endometriosis do not have more subclinical atherosclerosis than the general population.

Mensendieck somatocognitive therapy as treatment approach to chronic pelvic pain: results of a randomized controlled intervention study.
Haugstad GK, Haugstad TS, Kirste UM, Leganger S, Klemmetsen I, Malt UF
Am J Obstet Gynecol. 2006 May;194(5):1303-10. Epub 2006 Apr 21.

OBJECTIVE: The etiology of chronic pelvic pain is disputed and multifactorial. We studied the effect of Mensendieck somatocognitive therapy aimed at reducing physical pain by changing posture, movement and respiration patterns combined with standard gynecological treatment. STUDY DESIGN: Women with chronic pelvic pain unexplained by pelvic pathology were randomized into 2 groups: (1) standard gynecological treatment and (2) gynecological treatment plus somatocognitive therapy. A Mensendieck test of motor function (posture, movement, gait, sitting posture, respiration) and a visual analogue score of pain were obtained before and after the 90-day treatment period. RESULTS: The test results of patients treated by standard gynecological measures were unchanged (nonsignificant). By contrast, the patients receiving somatocognitive therapy in addition improved scores by 25% to 60% for all motor functions (P < .01, largest improvement for respiration, up from average 2.98 [SEM 0.30] to 4.72 [0.37]), and pain scores reduced by 50% (down from 5.60 [0.40] to 2.89 [0.40], P < .01). CONCLUSION: Mensendieck somatocognitive therapy combined with standard gynecological care improved pain experience and motor functions of women with chronic pelvic pain better than gynecological treatment alone.

Peritoneal fluid and serum levels of hepatocyte growth factor may predict the activity of endometriosis.
Khan KN, Masuzaki H, Fujishita A, Kitajima M, Hiraki K, Miura S, Sekine I, Ishimaru T
Acta Obstet Gynecol Scand. 2006;85(4):458-66.

BACKGROUND: The suitable parameter in PF as well as in serum that may predict the activity of endometriosis is not well described. Therefore, we tried to examine the peritoneal fluid (PF) and serum concentrations of hepatocyte growth factor (HGF) in different revised American Society of Reproductive Medicine (r-ASRM) staging and morphologic appearances of endometriosis in an attempt to determine whether HGF can be clinically useful to predict the activity of pelvic endometriosis. METHODS: Peritoneal fluid was collected from 137 women with endometriosis and 57 women without endometriosis during laparoscopy and blood sampling was collected from 37 women with endometriosis and 21 women without endometriosis before laparoscopy. The concentration of HGF in PF and serum was measured by enzyme-linked immunosorbent assay. The ability of isolated macrophages and stroma to secrete HGF in response to lipopolysaccharide (LPS) was evaluated. RESULTS: A significantly increased concentration of HGF in PF was found in women with endometriosis (1451.75 +/- 90.7 pg/mL) than that in non-endometriosis (1120.5 +/- 77.3 pg/mL, p < 0.01) without any remarkable difference in HGF levels between women with stage I-/II endometriosis and stage III-/IV endometriosis. When we distributed serum and PF levels of HGF according to different color appearances of endometriosis, we found a significantly higher serum and PF levels of HGF in women containing dominant red peritoneal lesions in pelvic cavity (740 +/- 109.3 pg/mL for serum; 1685 +/- 183.4 pg/mL for PF) than those having other pigmented lesions (649 +/- 79.5 pg/mL, p < 0.05 for serum; 1224 +/- 67.8 pg/mL, p < 0.05 for PF) or chocolate cysts (485 +/- 43.1 pg/mL, p < 0.05 for serum; 1118 +/- 83.1 pg/mL, p < 0.01 for PF). Exogenous stimulation with LPS significantly increased the production of HGF in the culture media by macrophages and stroma derived from women with endometriosis than that in women without endometriosis. CONCLUSIONS: These results suggest that women with early or advanced endometriosis as measured by r-ASRM scoring system are not associated with an increase in either serum or PF concentrations of HGF. Rather HGF levels in serum and PF were significantly increased in women harboring blood-filled red peritoneal lesions and may be clinically useful to predict the activity of pelvic endometriosis.

Validation of a test model of induced dysmenorrhea.
Liedman R, Skillern L, James I, McLeod A, Grant L, Akerlund M
Acta Obstet Gynecol Scand. 2006;85(4):451-7.

BACKGROUND: The myometrial hyperactivity and reduced uterine blood flow of primary dysmenorrhea is to a large extent caused by increased vasopressin secretion. A new therapeutic approach for this condition is to develop antagonists of uterine vasopressin V1a receptors. We studied a test model of vasopressin-induced dysmenorrhea in healthy, sterilized women and compared responses against those in dysmenorrheic subjects. METHODS: Eight women with primary dysmenorrhea and eight sterilized, healthy women participated in recordings of intrauterine pressure and experienced pain on days 1-2 of two menstruations. We tried to identify biochemical markers in plasma of uterine ischemia. Furthermore, the effects of repeated bolus injections of 10 pmol/kg b w of vasopressin or placebo on these parameters were assessed. RESULTS: The vasopressin injections caused statistically significant increases in the area under the intrauterine pressure curve (AUC) in both healthy volunteers and patients with dysmenorrhea, the overall responses being greater in healthy volunteers. The experienced pain measured by visual analog scale in individual dysmenorrheic subjects tended to show higher maximal post-dose scores for the vasopressin injections than for placebo. Maximum visual analog scale scores and maximum AUCs in individual subjects tended to be related. Mean creatine kinase MB levels were higher in women with dysmenorrhea than in healthy subjects both before and after vasopressin administration, the converse being observed for C-reactive protein levels. CONCLUSIONS: The present model appears to be useful for evaluating new drugs for the treatment of primary dysmenorrhea.

Clinical Aspects and Surgical Treatment of Urinary Tract Endometriosis: Our Experience with 31 Cases.
Antonelli A, Simeone C, Zani D, Sacconi T, Minini G, Canossi E, Cunico SC
Eur Urol. 2006 Apr 4;.

OBJECTIVES: To present and discuss clinical and surgical management of urologic endometriosis. METHODS: Retrospective review of a database on surgical patients with endometriosis. RESULTS: Thirty-one patients (incidence, 2.6%; mean age, 33.1 yr) were affected by urologic endometriosis (bladder, 12; ureter, 15; both, 4). Bladder endometriosis was revealed by symptoms related to menses and showed a typical endoscopic picture, whereas ureteral involvement had a nonspecific or silent symptomatology. All patients affected by bladder endometriosis and undergoing transurethral resection (2 cases) developed a bladder recurrence; a ureteral recurrence was observed in two of six patients submitted to laparoscopic ureterolysis and in one of two patients submitted to ureterectomy with ureteroureterostomy. Conversely, no relapses were observed among the 14 patients who had partial cystectomy or the 9 who had ureterectomy and ureterocystoneostomy. Finally, two patients underwent nephrectomy due to end-stage renal atrophy. CONCLUSIONS: Cystoscopy is advisable in women with pelvic endometriosis with lower urinary tract symptoms; the upper urinary tract should be evaluated in all patients with pelvic endometriosis to exclude asymptomatic ureteral involvement. Partial cystectomy gives the best results when used to treat bladder endometriosis. Ureterolysis can be successful only in case of limited ureteral involvement with no urinary obstruction, whereas terminal ureterectomy and ureterocystoneostomy should be preferred in case of obstructive ureteral endometriosis.

The Prevalence of Endometriosis in Women with Chronic Pelvic Pain.
Guo SW, Wang Y
Gynecol Obstet Invest. 2006 Apr 28;62(3):121-130.

Background: The 2004 American College of Obstetrics and Gynecology clinical management guideline states that the prevalence of endometriosis is approximately 33% in women with chronic pelvic pain (CPP). This estimate came from a review showing that 28% of adult women with CPP were found to have endometriosis. The prevalence of 28% in adult women was arrived based on a compilation of 11 published studies. Yet even within the 11 studies, the reported prevalence of endometriosis varies wildly, ranging from 2 to 74%. Such an astounding variation or heterogeneity raises the question whether it is appropriate to use a single prevalence of endometriosis for all women with CPP. Methods: We sought to identify possible sources of heterogeneities in the estimation of prevalence of endometriosis in women with CPP. We included more studies that reported prevalence estimates than the review, and examined the effect of sample size and the year of publication on the heterogeneity. Results: The year of publication is positively associated with the prevalence estimate, which may indicate an increasing awareness of various appearances of endometriosis, or the prevalence of endometriosis may have increased among women with CPP. An alternative analysis with removal of four studies reporting highest prevalence estimates indicated that sample size is negatively associated with the prevalence estimates while the year of publication became only marginally significant. Conclusions: There are identifiable sources of heterogeneity in prevalence estimates, with the year of publication, sample size, and difference in evaluation of CPP being three apparent sources. Having a single prevalence estimate for all women with CPP may be too simplistic at best. The true prevalence is very likely to be higher than 33%. Copyright (c) 2006 S. Karger AG, Basel.

Adolescent endometriosis-related pelvic pain treated with acupuncture: two case reports.
Highfield ES, Laufer MR, Schnyer RN, Kerr CE, Thomas P, Wayne PM
J Altern Complement Med. 2006 Apr;12(3):317-22.

Background: Chronic pelvic pain in adolescents accounts for 10% of outpatient gynecology visits, and 70% of adolescent patients whose pelvic pain is unresponsive to initial therapy have endometriosis. To date, there has been no published research investigating the use of acupuncture for adolescents with chronic pelvic pain and/or endometriosis. Methods: This paper presents two case reports describing the impact of a course of acupuncture on adolescent girls with endometriosis-related chronic pelvic pain of more than 1 year. Results: Both patients, undergoing between 9 and 15 treatments over a 7- to 12-week period, experienced modest improvement in pain as measured by oral self-reports of pain on a scale from 1 to 10, as well as selfor family-reported improvement in headaches, nausea and fatigue. No adverse effects were reported. Conclusions: These case reports provide preliminary evidence that acupuncture may be an acceptable and safe adjunct treatment therapy for some adolescents with endometriosis-related pelvic pain refractory to standard antiendometriosis therapies. These observations suggest that a prospective, randomized controlled trial of the safety and efficacy of acupuncture for this population may be warranted.

Vulvodynia: diagnosis and management.
Reed BD
Am Fam Physician. 2006 Apr 1;73(7):1231-8.

The diagnosis of vulvodynia is made after taking a careful history, ruling out infectious or dermatologic abnormalities, and eliciting pain in response to light pressure on the labia, introitus, or hymenal remnants. Several treatment options have been used, although the evidence for many of these treatments is incomplete. Treatments include oral medications that decrease nerve hypersensitivity (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors, anticonvulsants), pelvic floor biofeedback, cognitive behavioral therapy, local treatments, and (rarely) surgery. Most women experience substantial improvement when one or more treatments are used.

Prevalence of pelvic musculoskeletal disorders in a female chronic pelvic pain clinic.
Tu FF, As-Sanie S, Steege JF
J Reprod Med. 2006 Mar;51(3):185-9.

OBJECTIVE: To determine the prevalence of 2 musculoskeletal pain disorders among women presenting to a referral chronic pelvic pain clinic. STUDY DESIGN: This was a retrospective, cross-sectional study of 987 women (aged 14-79) presenting for evaluation from 1993 to 2000 at a university-based gynecologic chronic pelvic pain clinic. RESULTS: At the initial visit, all women completed standardized interviews and underwent a pelvic examination. Single-digit palpation of the levator ani and piriformis muscles was performed intravaginally. Among these women, 212 of 955 (22%) had tenderness of the levator ani muscles, while 128 of 943 (14%) had tenderness of the piriformis muscle (pain score > 3 of 10 on a visual analogue scale). Both levator ani tenderness and piriformis tenderness were associated with a higher total number of pain sites, previous surgery for pelvic pain, Beck Depression Inventory score, McGill Pain Inventory score and pain worsened with bowel movements (p < 0.05). CONCLUSION: Piriformis and levator ani pain are present in a significant proportion of female chronic pelvic pain patients. Further research into the natural course, diagnosis and treatment of pelvic musculoskeletal pain is needed to determine its true contribution to chronic pain.


In situ methotrexate injection for treatment of recurrent endometriotic cysts.
Agostini A, De Lapparent T, Collette E, Capelle M, Cravello L, Blanc B
Eur J Obstet Gynecol Reprod Biol. 2006 Mar 9;.

OBJECTIVE: Ovarian endometrioma recurrence is frequent. Conventional treatment of ovarian endometrioma is by surgical cystectomy. We proposed an alternative medical treatment for recurrent ovarian endometrioma: cyst aspiration followed by in situ methotrexate injection. STUDY DESIGN: From January 2002 to May 2003, 14 patients with recurrent homolateral ovarian endometrioma underwent transvaginal ultrasound guided cyst puncture and aspiration followed by methotrexate injection, whilst under general anasthesia. Recurrence rate during follow up was evaluated. RESULTS: No complication was reported. After a mean follow up of 20+/-5 month (min: 13, max: 29), four recurrences were diagnosed (28.6%). Two asymptomatic recurrences were not treated and two painful recurrences underwent a second cyst drainage with methotrexate injection. CONCLUSIONS: In situ methotrexate injection is a simple, effective and an interesting alternative to surgical treatment in women with recurrent homolateral ovarian endometrioma.

Increased ENA-78 in the follicular fluid of patients with endometriosis.
Wunder DM, Mueller MD, Birkhauser MH, Bersinger NA
Acta Obstet Gynecol Scand. 2006;85(3):336-42.

BACKGROUND: It is known that endometriosis is an inflammatory disease and those patients seem to have lower pregnancy rates. The aim of the study was to investigate the concentrations of chemokines and proinflammatory cytokines in the follicular fluid of patients with and without endometriosis. METHODS: Follicular aspiration, recovering follicular fluid during assisted reproductive treatment, follicular fluid storage and analysis of chemokines and proinflammatory cytokines were carried out. Tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, interleukin-15, leukemia inhibitory factor, epithelial neutrophil-activating peptide 78, regulated upon activation, normal T-cell expressed and secreted, and growth-regulated oncogene-alpha were analyzed in the follicular fluid and compared between women with (n =47) and without endometriosis (n = 279). RESULTS: The above cytokines were detected in the follicular fluid samples. Epithelial neutrophil-activating peptide 78 levels were significantly higher in follicular fluid from endometriosis patients than from controls (p = 0.008). Increases (to twice the control level) were also observed for tumor necrosis factor-alpha and for interleukin-6. CONCLUSIONS: Increased follicular fluid levels of epithelial neutrophil-activating peptide 78, tumor necrosis factor-alpha and interleukin-6 indicate that these cytokines may influence oocyte quality and fecundability of women with endometriosis by deteriorating the microenvironment in the human follicle.

Endometriosis in Patients with Chronic Pelvic Pain: Is Staging Predictive of the Efficacy of Laparoscopic Surgery in Pain Relief?
Milingos S, Protopapas A, Kallipolitis G, Drakakis P, Loutradis D, Liapi A, Antsaklis A
Gynecol Obst et Invest. 2006 Mar 15;62(1):48-54.

Background/Aims: Endometriosis is considered an important cause of chronic pelvic pain. Despite its high prevalence, controversy still exists regarding the true association between the extent of endometriosis and the severity of symptoms. We conducted this prospective study to investigate the association between the stage of endometriosis and type and severity of pain, and to evaluate the efficacy of laparoscopic surgery in pain relief. Methods: Ninety-five patients complaining of chronic pain were diagnosed with endometriosis and were treated with laparoscopic surgery. The severity of pain was assessed in patients with an endometriosis AFS (American Fertility Society) score less than 16 (group 1) and those with an AFS score greater than or equal to 16 (group 2), preoperatively and 6 months after surgery, using a visual pain scale. Any reduction in pain scores by 2 points or more was considered to be an improvement. Results: Dysmenorrhea and deep dyspareunia, were significantly more frequent in patients of group 2. Preoperative pain scores were significantly higher for dysmenorrhea (p = 0.0022) and deep dyspareunia (p < 0.0001) but not for non-menstrual pain in group 2. Deep dyspareunia was correlated with the presence of dense pelvic adhesions. After surgery, dysmenorrhea improved in 43% of cases in group 1, vs. 66% of cases in group 2 (p = 0.0037). For deep dyspareunia, improvement was reported by 33% in group 1, vs. 67% in group 2 (p = 0.074). Improvement in non-menstrual pain was not significantly different between the two groups (67% vs. 56%). Conclusions: Advanced endometriosis is more frequently related to dysmenorrhea and deep dypareunia in comparison to early disease. Laparoscopic surgery may offer relief or improvement in the majority of patients with endometriosis and chronic pelvic pain. Cases with advanced disease seem to benefit the most.

A Rare Case of Rectovaginal Endometriosis with Lymph Node Involvement.
Thomakos N, Rodolakis A, Vlachos G, Papaspirou I, Markaki S, Antsaklis A
Gynecol Obstet Invest. 2006 Mar 14;62(1):45-47.

A rare case of rectovaginal endometriosis with lymph node involvement is described in a 44-year-old patient. The presence of endometrial tissue in pelvic lymph nodes is rare and has been confirmed in the literature in subjects who underwent surgery for endometriosis. Involvement of pelvic lymph nodes by endometriosis seems unlikely to arise de novo and probably suggests lymphatic spread of the disease. Copyright (c) 2006 S. Karger AG, Basel.


Laparoscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without rectum involvement: surgical treatment and long-term follow-up.

Angioni S, Peiretti M, Zirone M, Palomba M, Mais V, Gomel V, Melis GB
Hum Reprod. 2006 Feb 22;.

BACKGROUND: The objective of the study is to evaluate the short- and long-term efficacy of complete laparoscopic excision of deep endometriosis, without rectum involvement, with the opening and partial excision of the posterior vaginal fornix. METHODS: Thirty-one patients were included in the study with symptomatic extensive disease including involvement of the cul-de-sac, rectovaginal space and posterior vaginal fornix without rectum involvement. Endoscopic surgery was performed with complete separation of rectovaginal space and in-block resection of the diseased tissue, opening and partial excision of the posterior vaginal fornix and vaginal closure either by laparoscopic or by vaginal route. Patients filled in questionnaires on pain before and 12, 24, 36, 48 and 60 months after surgical treatment. RESULTS: No intraoperative complications were observed; 65% were free of analgesic on post-operative day 2, 38% had total remission of chronic pain and 22% were improved; 38% had total remission of dysmenorrhoea and 22% were improved; 45% had total remission of dyspareunia and 25% were improved. Follow-up improvement of symptoms was statistically significant and was maintained for 5 years without recurrence of the disease or repeated surgery (P < 0.001). CONCLUSION: Complete surgical resection of deep infiltrative endometriosis with excision of the adjacent tissue of the posterior vaginal fornix improves quality of life with persistence of results for long time in patients not responsive to medical treatment.

Depression in women with endometriosis with and without chronic pelvic pain.
Lorencatto C, Petta CA, Navarro MJ, Bahamondes L, Matos A
Acta Obstet Gynecol Scand. 2006;85(1):88-92.

AIM: The aim of the study is to compare the prevalence of depression in women surgically diagnosed with endometriosis according to the presence or absence of pelvic pain. METHODS: This cross-sectional prospective study evaluated 100 women receiving care at the Outpatients' Clinic for Endometriosis, Department of Obstetrics and Gynecology, Universidade Estadual de Campinas (UNICAMP), Campinas, Sao Paulo, Brazil, equally divided into two groups: one suffering from chronic pelvic pain and the other pain-free. The Beck Depression Inventory was used in order to measure depression. RESULTS: Depression was detected in 86 and 38% of the women with and without chronic pelvic pain, respectively. Complaints of depression, such as somatic concerns, work inhibition, dissatisfaction, and sadness, were observed at a significantly higher rate in the group with pain. A sensation of failure was the only variable observed more frequently in the pain-free group. CONCLUSIONS: Depression is highly prevalent in women with endometriosis, especially those with pelvic pain. Careful evaluation can identify women with depression who may benefit from treatment.

Chronic vulvar and other gynecologic pain: prevalence and characteristics in a self-reported survey.
Bachmann GA, Rosen R, Arnold LD, Burd I, Rhoads GG, Leiblum SR, Avis N
J Reprod Med. 2006 Jan;51(1):3-9.

OBJECTIVE: To characterize and assess the prevalence of chronic gynecologic pain and, more specifically, chronic vulvar pain. STUDY DESIGN: A questionnaire was mailed to women aged 18-80 years who were ambulatory patients at an academic multidisciplinary practice. Quality of life, health history, obstetric and gynecologic history, and pain symptoms were assessed. RESULTS: Of the 4,872 surveys mailed to deliverable addresses, 36.8% were returned. The population was primarily Caucasian (83%), with an average age of 50.2 years. Approximately 4% of respondents reported a history of vulvar pain in the 6 months preceding the survey, and 17% reported other types of chronic gynecologic pain. Women reporting vulvar and nonvulvar pain were 2 times as likely as asymptomatic women to report a history of depression and vaginal infections, a poorer quality of life (p < 0.001) and greater stress. Dyspareunia and pain with daily activities were reported more frequently by women with vulvar pain than by women with non-vulvar gynecologic pain. CONCLUSION: The prevalence of vulvar pain in this study was lower than previously reported. Chronic gynecologic pain, and vulvar pain in particular, affects quality of life on both intimate and social levels. Self-reported stress and vaginal infections were the strongest correlates of chronic vulvar pain.

Decrease of pregnant women's pelvic pain after acupuncture: a randomized controlled single-blind study.
Lund I, Lundeberg T, Lonnberg L, Svensson E
Acta Obstet Gynecol Scand. 2006;85(1):12-9.

BACKGROUND: The efficacy of acupuncture on low-back and/or pelvic pain in late pregnancy is reviewed in few reports. Our aim was to evaluate the effects of two different acupuncture stimulation modes on pelvic pain intensity and some emotional symptoms due to the pain condition. METHODS: In a prospective randomized controlled single-blind study, pregnant women with pelvic pain, median gestational age 26 weeks (range 18-35), were given 10 acupuncture treatments. Needles were inserted subcutaneously over acupuncture points without further stimulation (superficial, n=22), or intramuscular and stimulated repeatedly until a perceived sensation of numbness, de qi, (deep, n=25). Self-reported pain intensity at rest and during daily activities was assessed on a visual analog scale. The variables pain, emotional reactions, and loss of energy were assessed according to the Nottingham Health Profile questionnaire. Changes in assessed variables were analyzed with a nonparametric statistical method allowing for analysis of systematic group changes separated from additional individual changes. RESULTS: After acupuncture stimulation, significant systematic group changes towards lower levels of pain intensity at rest and in daily activities as well as in rated emotional reaction and loss of energy were seen. The results also showed additional individual changes in most variables. In this study, no differences between the effects induced by the superficial and deep acupuncture stimulation modes were observed. CONCLUSION: Acupuncture stimulation that is individually designed may be a valuable treatment to ameliorate suffering in the condition of pelvic pain in late pregnancy.


The pains of endometriosis.
Berger RE
J Urol. 2006 Feb;175(2):573.

Surgical Treatment for the Vulvar Vestibulitis Syndrome.
Traas MA, Bekkers RL, Dony JM, Blom M, van Haren AW, Hendriks JC, Vierhout ME
Obstet Gynecol. 2006 Feb;107(2):256-262.

OBJECTIVE: To study the outcome and complications of surgical treatment for vulvar vestibulitis syndrome and to identify patient characteristics that may have influenced the outcome. METHODS: Relevant patient characteristics were extracted retrospectively from the medical records of 155 women aged 40 years or younger who had received surgical treatment for vulvar vestibulitis syndrome. To assess outcome and complications, 126 of these 155 women (81%) participated in a telephone interview, conducted 1 to 4 years after surgery. RESULTS: After surgery 93% of the patients could have sexual intercourse compared with 78% before surgery; this increase was statistically significant (Mantel-Haenszel odds ratio 3.43, 95% confidence interval [CI] 1.48-7.96). In 62% of the women (95% CI 53-70%), sexual intercourse was painless after surgery. Eighty-nine percent (95% CI 84-95%) would recommend surgical treatment to other women experiencing vulvar vestibulitis syndrome. There were no major complications. Decreased lubrication during sexual arousal was the most frequently reported adverse effect (24%, 95% CI 16-32%), followed by the development of a Bartholin's cyst (6%, 95% CI 2-10%). More of the women aged 30 years or younger reported that they could have sexual intercourse after surgery, and more of them would recommend surgical treatment to other patients than women aged 31 years or older. CONCLUSION: Surgical treatment for vulvar vestibulitis syndrome achieved high success rates with an acceptable rate of complications. Age of 30 years or younger was associated with a better outcome. LEVEL OF EVIDENCE: III.