The prevalence of endometriosis in women with chronic pelvic pain

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%.     

Three-dimensional in vitro culture of endometrial explants mimics the early stages of endometriosis

OBJECTIVE: To reproduce the earliest phases of endometriosis using a new in vitro model in which cells from a cultured endometrial fragment can proliferate, invade, reconstitute new endometrial-like tissue, and generate blood vessels. DESIGN: Experimental in vitro study. SETTING: A hospital-based academic research institute. PATIENT(S): Five normal ovulating women undergoing surgery for various benign gynecological indications. INTERVENTION(S): Endometrial samples obtained from the fundus of the uterine cavity were placed in a three-dimensional fibrin matrix culture system. MAIN OUTCOME MEASURE(S): Degree of proliferation of stromal cells and invasion of the fibrin matrix, gland, and stroma formation, vessel sprouting, and immunohistochemical characterization of various cellular components. RESULT(S): During the first week of culture, an endometrial cell outgrowth was observed from the original fragments in 120 of 144 wells (83.3%). Subsequently, cell outgrowths could be quantified in 132 (91.6%), 129 (89.5%), and 127 (88.1%) of the wells after 15, 60, and 90 days, respectively. An invasion of the matrix by the human endometrial cells led to the formation of tubular structures that coalesced into tissue, architecturally resembling endometrium and in which the glands were immunohistochemically positive for cytokeratin. New capillaries, immunohistochemically positive for CD31 and vimentin, sprouted from the endometrial outgrowths at the beginning of the fifth week of culture. CONCLUSION(S): These data show that cells from endometrial explants can proliferate and invade a fibrin matrix in vitro generating new glands, stroma, and vessels consistent with endometriosis. The three-dimensional fibrin matrix used in the present study provides an opportunity to observe the earliest biological events of endometriosis in a quantifiable way.     

Soluble c-Met expression in the peritoneal fluid and serum of patients with different stages of endometriosis

Introduction

Hepatocyte growth factor (HGF), also known as scatter factor, and its receptor c-Met have been shown to be implicated in endometriosis. HGF acts as a mitogen, motogen, and morphogen on endometrial epithelial cells. The expression of c-Met on human endometrial cells has been reported. Many proteins are proteolytically released from the surface by a process known as ectodomain shedding. The aim of this study was to determine the levels of soluble c-Met (s-cMet) in the peritoneal fluid (PF) and serum samples of patients with different stages of endometriosis.

Material and methods

39 PF and serum samples from normal healthy and 130 samples from different stages of patients with endometriosis (33 cases of stage I, 38 stage II, 30 stage III and 29 stage IV) were included in this study. Total protein concentration (TPC) and the level of s-cMet in the PF and serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay, respectively.

Results

No significant change in the TPC was seen in the serum and PF of patients with endometriosis when compared with normal controls. Results obtained demonstrated that all PF and serum samples presented s-cMet expression, whereas, starting from stages I to IV endometriosis, a significant increase of s-cMet expression was observed as compared to controls.

Conclusion

The results of this study show that a high expression of s-cMet is correlated with advanced stages of endometriosis. It is also concluded that the detection of serum and PF s-cMet may be useful in classifying endometriosis.     

Expression of inflammatory cytokines in serum and peritoneal fluid from patients with different stages of endometriosis

Objective: To investigate the level of inflammatory cytokines in endometriosis patients, and explore the relationship between IL-37 concentration and endometriosis stages.

Methods: Inflammatory cytokine concentrations from 27 patients with different stages of endometriosis and 52 controls without endometriosis were examined by ELISA. Then, the specificity and sensitivity of cytokines for distinguishing from controls and the different stages of endometriosis were analyzed using the ROC curve.

Results: The difference in serum concentrations of IL-37, IL-17A, IL-10, and IL-2 between the endometriosis and control groups was statistically significant (p?p?p?=?.0034), IL-10 concentrations in PF were significantly lower in the early-stages of endometriosis than in the more advanced groups (p?=?.0439), and IL-4 concentration in PF was significantly higher in more advanced endometriosis (p?=?.0228). The sensitivity and specificity of serum IL-37 for distinguishing endometriosis were 81.48% and 83.33%, respectively, and the cutoff concentration was 69.84?pg/ml. For IL-17A, the sensitivity and specificity were 96.30% and 100%, respectively, and the cutoff concentration was 57.54?pg/ml. For IL-10, the sensitivity and specificity was 92.59% and 100%, respectively, and the cutoff concentration was 3.301?pg/ml. For IL-2, the sensitivity and specificity were 74.07% and 93.75%, respectively, and the cutoff concentration was 1.813?pg/ml. For PF IL-2, the sensitivity and specificity were 29.73% and 100%, respectively, and the cutoff concentration was 1.06?pg/ml.

Conclusions: IL-37, IL-17A, IL-10, and IL-2 may play a significant role in immune response in endometriosis. IL-37 levels may be used as a diagnostic marker for endometriosis.     

Peritoneal fluid prostaglandins in various stages of the menstrual cycle: role in infertile patients with endometriosis

Thirty-nine patients with pelvic endometriosis and 45 patients with no evidence of endometriosis were entered in this study. The mean age was 29 years for each group. The volume of peritoneal fluid showed an increase towards the end of the cycle in both groups. Although the volume was higher in the endometriosis group than the control group, the difference between them was not significant. The concentration of prostaglandins F2 alpha and E2 was higher in patients with endometriosis than in the control group. The difference was significant (P less than 0.05) during days 9-16 and 17-24 for both prostaglandins, and during days 1-8 for prostaglandin F 2 alpha only. The high concentration of prostaglandins in the periovulatory and early luteal phases of the cycle may have adverse effects on tubo-ovarian function in endometriosis patients. Prostaglandin studies in peritoneal fluid are of significance during days 9-24 of the cycle when the effect of regurgitated menstrual fluid in the early phase of days 1-8 may be avoided.     

The prevalence of endometriosis among African-American and African-indigenous women

Endometriosis is gynaecological disorder, characterized by the growth of endometrial tissue outside the uterine cavity. It is the most common cause of pelvic pain and occurs in 20-25% of women with infertility. Although Sampson first described endometriosis in 1927, studies on the prevalence of endometriosis among African women are still lacking. The current thinking is that endometriosis rarely affects women from the African origin. However, in African-American women in the USA, endometriosis is one of the commonest indications for major gynaecological surgery and hysterectomy, and is associated with long hospital stay and high hospital charges. There is also some evidence that endometriosis is more commonly found in African-American patients from private practice than in African-American patients treated in public hospitals. The prevalence of endometriosis in African-indigenous women with infertility seems low, possibly due to a different life style (early pregnancy, increased risk for PID and blocked Fallopian tubes) and due to lack of laparascopic facilities and specific training of African gynecologists to diagnose ascites caused by endometriosis appear to be more frequently observed in African-indigenous of African-American women than in women with other ethnic backgrounds.     

Luteinized unruptured follicle in the early stages of endometriosis as a cause of unexplained infertility.

OBJECTIVE: We attempted to clarify the relationship between luteinized unruptured follicle, which occurs in the early stages of endometriosis, and unexplained infertility. STUDY DESIGN: Seventy patients who had unexplained infertility were reviewed. RESULTS: Laparoscopic examination showed that 47 patients (67%) had endometriosis; of these, 40 (85%) had minimal or mild disease. The incidence of luteinized unruptured follicle was higher (p < 0.05) in patients who had endometriosis (35%/patient and 25%/cycle) compared with patients who did not have endometriosis (11%/patient and 7%/cycle). Degenerated oocyte cumuli were collected in 6 (43%) of 14 luteinized unruptured follicles diagnosed by transvaginal ultrasound. CONCLUSIONS: These results show that luteinized unruptured follicle is common in patients who have mild or minimal endometriosis and that it may be one of the causes of endometriosis-associated infertility. Transvaginal ultrasound-guided follicular puncture of luteinized unruptured follicle during the mid luteal phase may be useful in establishing a definitive diagnosis of luteinized unruptured follicle.     

The role of fertility preservation in patients with endometriosis

Patients affected with severe endometriosis are at significant risk for ovarian tissue damage, which may lead to infertility, reduced response to ovarian stimulation, and occasionally, premature ovarian failure. The risk for a compromised ovarian reserve in young patients is especially high following repeated surgical intervention and in the presence of bilateral endometriomas. In many cases, enhanced loss of ovarian reserve may also result from the damaging effect of the pathologic process on follicle reservoir even without surgical interventions. Women diagnosed with severe endometriosis and those designated for extensive ovarian surgical intervention are frequently not planning to conceive. In light of recent advances in fertility preservation techniques (FPT), such as oocytes and ovarian tissue freezing, as well as their increasing success rates, we critically evaluate the options for FPT in patients suffering from endometriosis. Personalized counseling should be offered to all patients with endometriosis taking into account age, extent of ovarian involvement, current ovarian reserve, previous and impending surgeries for endometriosis, along with current success rates and possible risks associated with FPT.     

Increased prevalence of p53 overexpression from typical endometriosis to atypical endometriosis and ovarian cancer associated with endometriosis

OBJECTIVE: To evaluate the expression of p53, c-erb-B-2, MIB1 and Bcl-2 in normal endometrium, endometriosis, atypical endometriosis and ovarian cancer associated with endometriosis, looking for immunohistochemical markers that may help determine endometriosis with premalignant potential. STUDY DESIGN: Between 1948 and 1999, 410 epithelial ovarian cancers and 521 cases of endometriosis were surgically treated at Fundación Jiménez Díaz. Pathology reports and slides were reviewed. Four groups were defined: (1) endometriosis/cancer (n=17); (2) atypical endometriosis (n=6); (3) endometriosis (n=17); (4) endometrium (n=7). Tumors and controls were immunostained and evaluated for expression of p53, c-erb-B-2, MIB1 and Bcl-2. Statistical analysis was performed using Chi-square for linear trends, Fisher exact and Kruskal-Wallis tests. RESULTS: Of the 410 cancers, 17 (4.1%) had associated endometriosis and of the 521 endometriosis, 6 (1.2 %) had atypical changes. Fourteen of 17 (82.4%) cancers associated with endometriosis and all atypical endometriosis had p53 overexpression. Only 2 of 17 (11.8%) endometriosis and none of the endometriums had mutant p53 (P<0.01). We found a trend towards increased expression of MIB1 (0.073) in the cancer and atypical endometriosis groups, and no differences in expression of Bcl-2 or c-erb-B-2. The sensitivity and specificity of p53 as a marker for the diagnosis of atypical endometriosis and cancer associated with endometriosis were 87%; CI 95% (73.2-100%) and 92% (80.6-100%), respectively. When comparing all groups, the mean positive p53 and MIB1 cell count was statistically significant (P=0.01). CONCLUSIONS: Overexpression of p53 in atypical endometriosis and cancer associated with endometriosis is a common finding and may be used to identify endometriosis with premalignant potential.     

The prognostic implications of anaemia in the outcome of patients with early stages of uterine cervix carcinoma

 We studied the prognostic value of anaemia in the evolution of patients with early stages of uterine cervix cancer and treated with radical surgery. An observational study of 114 patients treated for cervical cancer at the ”La Fe” Maternity Hospital in Valencia (Spain) during the period 1971 to 1989. Survival analyses were carried out whereby both recurrence and mortality rates were considered. The level of haemoglobin influences the prognosis of the patients in the study presented, and explains a variation in the disease-free interval in correlation with that of tumour size. However, its influence on the survival interval proved to be somewhat less. Its predictive value is not diminished when associated with other important factors regarding the influence on patient evolution and is seen to be a protector variable against recurrence. Patients with haemoglobin levels of less than 13 gr/dl have a less favourable prognosis and this prognosis worsens still further when levels are lower than 12 gr/dl, which is more frequently the case in patients under 40 years of age and with a greater stromal invasion depth. The influence of haemoglobin levels is equally as important in its influence on prognosis and patient evolution as the volume of the tumour itself. The effect of this variable depends on both the clinical characteristics of the patients and the pathological characteristics of the tumour. Received: 17 October 2001 / Accepted: 28 December 2001     

Functional and phenotypic alterations in peritoneal macrophages from patients with early and advanced endometriosis

The aim of this study was to elucidate whether peritoneal macrophage (pMO) alterations are a generalized feature in all stages of endometriosis and the effect of hormonal treatment on this leukocyte population. For this purpose we quantified the number of pMO, the expression of HLA-DR antigen (pMO DR+), percentages of pMO that reduced nitro-blue tetrazolium (pMO NBT+), and interleukin-1 (IL-1) and prostaglandin E₂ (PGE₂) production by pMO from patients with early (stages I/II) and advanced (stages III/IV) endometriosis, we also analyzed some of these properties in pMO from patients which had been treated for 6 months with 800 mg/day of Danazol or gonadotropin releasing hormone agonist (GnRHa). We found that there were a significant increase of the pMO number in both types of patients, though the highest values were obtained in early endometriosis (p<0.001). Percentages of pMO DR+ were decreased in all patients (p<0.01) while percentages of pMO NBT+ were significantly increased. Production of IL-1 by early and advanced endometriosis pMO were considerably enhanced. PGE₂ release was not altered in early endometriosis pMO but, in advanced endometriosis, pMO PGE₂ levels were 100-fold higher than control values. In post-treatment patients, the number of pMO and percentage of pMO NBT+ were similar to early endometriosis patients, though the percentage of pMO DR+ was within the normal range. We conclude that the pMO population, as well as IL-1 and PGE₂ production, were altered in all stages of endometriosis, and that these changes could be involved in the pathogenesis of endometriosis and associated infertility. Hormonal treatments do not reverse the pMO changes. Received: 3 September 1997 / 29 December 1997     

Laparoscopic appendectomy in patients with endometriosis

STUDY OBJECTIVE: To report the frequency and spectrum of histologically proved diseases of the appendix in patients undergoing laparoscopic surgery for chronic pelvic pain in conjunction with endometriosis in a tertiary referral center. DESIGN: Patient database with retrospective chart review (Canadian Task Force classification II-3). SETTING: University ambulatory endoscopic surgery center-tertiary referral center. PATIENTS: Two hundred thirty-one women. INTERVENTIONS: Appendectomy during laparoscopic surgery for endometriosis. MEASUREMENTS AND MAIN RESULTS: We reviewed the medical records of 231 patients who underwent appendectomy during laparoscopic treatment of endometriosis performed from January 1994 through July 2004. Of the 231 patients with pelvic endometriosis, concomitant appendiceal pathology was present in 115. CONCLUSION: The appendix may be involved and may contribute to pelvic pain in patients with endometriosis.     

The role of in vitro fertilization in infertile patients with endometriosis

Thirty-nine cycles were studied in patients with a history of endometriosis who went through in vitro fertilization. In 15 cycles, there was no evidence of endometriosis; in 10 cycles, the patients had mild or moderate disease; in 14 cycles, severe or extensive endometriosis was found. The pregnancy rates per cycle were 33%, 60%, and 7%, respectively (groups I and II, no significant difference; groups II and III, P less than 0.01). The difference was due to the different number of oocytes aspirated at laparoscopy because of technical problems in the cases with severe and extensive disease. There was also a significant difference in the number of pregnancies per transferred cycles. There was no difference in the luteal phase in the three groups. The reproductive potential, which seemed to be similar in groups I and II, was severely impaired in the group with severe endometriosis.     

Infertility in patients with bowel endometriosis

The impact of bowel endometriosis on fertility is unclear, and the optimal management of patients who wish to conceive is not well-defined. Infertile patients with bowel endometriosis may either undergo surgery to enhance fertility or assisted reproductive technology (ART). It is necessary to consider that some complications may occur in patients undergoing ART because of the ovarian stimulation needed during these procedures. Interpretation of the available data on fertility outcomes after colorectal surgery for deep endometriosis is difficult as several studies do not distinguish patients with real infertility from those wishing to conceive without proven infertility and outcomes of complex surgery are operator-dependent. The effect of bowel surgery to increase the likelihood of spontaneous conception is yet to be established. Limited data are available on fertility outcomes after the removal of endometriotic nodules without the excision of bowel endometriotic implants.     

子宫内膜异位症不育患者的助孕治疗

子宫内膜异位症 (内异症 )发生在 10 %～ 15 %的育龄妇女 ,是妇科常见病。其发病机理尚不明确 ,很多学者从免疫角度进行研究 ,发现内异症局部变化的特点与不育的原因有关。内膜异位局部ＣＤ+3Ｔ淋巴细胞、ＣＤ+8杀伤 /抑制Ｔ细胞及ＣＤ+8/ＣＤ+4 辅助Ｔ细胞比值 ,以及ＣＤ+6 8巨噬细胞 ,均较在位内膜及正常子宫内膜为高[1] ;趋化因子ＲＡＮＴＥＳ (ｒｅｇｕｌａｔｅｄｕｐｏｎａｃｔｉｖａｔｉｏｎ ,ｎｏｒｍａｌＴｃｅｌｌｅｘｐｒｅｓｓｅｄａｎｄｓｅｃｒｅｔｅｄ)在内异症患者腹水中增多 ,可招募大量巨噬细胞和Ｔ淋巴细胞至腹腔中 ,与肿…