Endometriosis: Radionuclide migration through the genital tract in infertile women with endometriosis

The migration of radionuclide through the genital tract wasobserved, comparing 20 patients with endometriosis and infertilitywith a control group of 23 infertile patients who had a normalpelvis. All patients had patent tubes at laparoscopy and chromopertubation,performed in both groups for the investigation of infertilityand to diagnose the presence and extent of endometriosis. Aradionuclide tubal test, using human albumin microspheres labelledwith 99m-technetium (^99mTc) was subsequently undertaken to observethe extent of genital tract migration of radionuclide to uterus,Fallopian tube and peritoneal cavity. The results show thatradionuclide migration to the peritoneal cavity was impairedin patients with endometriosis, compared with the control group(30 versus 83%, respectively; P < 0.001). There was no relationshipbetween migration and the severity of endometriosis. We concludethat impaired tubal function may be a cause of infertility insome patients with endometriosis.     

Differences in time to natural conception between women with unexplained infertility and infertile women with minor endometriosis

BACKGROUND: Opinion remains divided as to whether finding endometriotic lesions in the absence of adhesions has an adverse effect on the likelihood of conception. METHODS: This was a retrospective study of 192 fully investigated infertile couples, followed up for up to 3 years following laparoscopy. Women studied were ovulating, <40 old years and their partners had normal sperm parameters. All 117 women with unexplained infertility and 75 with minimal/mild endometriosis without adhesive disease were managed conservatively. RESULTS: Women with endometriosis were found to have a lower probability of pregnancy compared with women with unexplained infertility (36% versus 55%; P<0.05). Other factors adversely associated with pregnancy were primary infertility, smoking and longer duration (>3 years) of infertility. However, the effects of duration of infertility and primary infertility were not observed to be statistically significant for women with endometriosis. CONCLUSIONS: The findings, although undertaken in a select population undergoing laparoscopy, suggest the likelihood of pregnancy is reduced in infertile women with minimal/mild endometriosis compared with those infertile women with a normal pelvis. Duration of infertility and a previous history of pregnancy are important in predicting the likelihood of pregnancy in women with no obvious cause for their infertility (unexplained), whilst the relationship may be more complex in women with minor endometriosis     

Transvaginal hydrolaparoscopy compared with laparoscopy for the evaluation of infertile women: a prospective comparative blind study

Standard diagnostic laparoscopy is considered the gold standard to investigate tubo-peritoneal infertility. It requires general anaesthesia and full operative facilities. Due to the risk of complications, laparoscopy is frequently postponed to the final stage of infertility evaluation or even after treatment trials have failed. Transvaginal hydrolaparoscopy (THL) is based on vaginal access using a needle puncture technique and saline for distention. THL can be performed on an outpatient basis under local anaesthesia. However, little data exist concerning the accuracy of THL in comparison with laparoscopy. We conducted a prospective comparative blind trial to assess the feasibility and accuracy of THL compared with diagnostic laparoscopy in infertile women. Sixty women were assigned to undergo THL immediately prior to laparoscopy. Different operators evaluated the findings of the two procedures. In order to evaluate the accuracy of THL, findings in terms of tubal pathology, endometriosis and adhesions were analysed. The success rate of accessing the pouch of Douglas was 90.2%. Complication rate was 1.6%. THL diagnosis was correlated with that of laparoscopy in 92.3% of cases. In cases of abnormal findings by THL, there were no normal laparoscopies. Our pilot study suggests that THL is a safe and reproducible method. Retroverted uterus should be considered as a relative contraindication to THL. When a complete evaluation by THL is available, it is a highly accurate technique in comparison with the laparoscopy.     

Endometriosis: Effect of peritoneal fluid from infertile women with endometriosis on ionophore-stimulated acrosome loss

The effect of peritoneal fluid (PF) from endometriosis patientswas studied in spontaneous and stimulus-induced (Ca-ionophore;A23187) acrosome reactions. PF samples were obtained from 21infertile women with endometriosis and five normal women (controls).Sperm acrosomes were examined by staining with Pisum sativumagglutinin labelled with fluorescein isothiocyanate. The incidenceof spontaneous acrosome reaction after 1 and 6 h of incubation(6.7 ± 1.6 and 6.9 ± 1.4 respectively) was significantly(P < 0.001) lower when the incubation was performed withPF from endometriosis patients in comparison with spermatozoaincubated in PF from the control group (12.8 ± 1.1 and12.8 ± 0.8). Similarly, the incidence of A23187-inducedacrosome reaction after 1 and 6 h of incubation (19.8 ±2.7 and 20.0 ± 2.4) was significantly (P < 0.001)lower when spermatozoa were incubated with PF from endometriosispatients in comparison with spermatozoa incubated with PF fromthe control group (34.6 ± 9.8 and 34.4 ± 1.1).The incidence of A23187-inducible acrosome reaction was alsosignificantly (P < 0.001) lower when the incubation was performedwith PF from endometriosis patients (13.1 ± 2.8 and 13.1± 2.4) when compared with that from the control group(21.8 ± 2.6 and 21.6 ± 1.5). No relationship wasfound between the stage of endometriosis and the incidence ofacrosome loss. In conclusion, the PF from endometriosis patientsdecreased both spontaneous and stimulus-induced acrosome reaction.This may represent a mechanism for the detrimental effect ofthe PF from endometriosis patients on the spermatozoa-oocyteinteraction and partially explain the aetiology of infertilityin patients with endometriosis.     

Medical treatment of mild endometriosis in infertile women: analysis of a failure

The easy access to the pelvis of infertile women by laparoscopy favours early diagnosis of endometriosis in an increasing number of subjects with minimal and mild disease. These initial forms have been associated with and considered as the cause of infertility despite the absence of relevant scientific evidence. Various hormone therapies, some with severe side-effects and high costs, have been used by numerous authors. However, no study comparing medically treated with untreated women has ever shown any drug to be more effective than expectant management. The possible explanations of treatment failures are reviewed.     

An association of IgG anti-laminin-1 autoantibodies with endometriosis in infertile patients

BACKGROUND: Laminin-1, a multifunctional glycoprotein of the basement membrane, is thought to be important in embryogenesis, embryonic implantation, and placentation. We recently showed that serum IgG anti-laminin-1 autoantibodies (auto-Abs) are associated with recurrent first-trimester miscarriages. The present study assessed the clinical significance of anti-laminin-1 Abs with infertility, accompanied with or without endometriosis. METHODS: Sixty-eight infertile patients who underwent laparoscopy or laparotomy and 39 healthy non-pregnant women were tested for IgG anti-laminin-1 Abs. The association between the Abs and endometriosis was analysed. The presence of laminin-1 mRNA was detected in endometriotic lesions. RESULTS: Twenty infertile patients were positive for anti-laminin-1 Abs. The Ab levels in those patients were significantly higher than those in healthy non-pregnant women (P = 0.0005). The presence of the Abs was significantly associated with endometriosis in those patients (P = 0.0096). The Abs recognized a particular domain, i.e., the laminin-alpha1 chain G domain. mRNA encoding laminin-alpha1, -beta1, and -gamma1 chains was expressed in 90% of endometriotic lesions. CONCLUSIONS: IgG anti-laminin-1 Abs were significantly associated with endometriosis in infertile patients. The Abs might be clinically important in the development of autoimmune-mediated reproductive failures and the assessment of the Abs may provide a novel non-invasive diagnosis of endometriosis.     

The risk of cancer and the role of parity among women with endometriosis

BACKGROUND: Several epidemiological studies have shown an increased cancer risk among women with endometriosis, especially ovarian cancer. Infertility and nulliparity are also known risk factors for different types of cancer. The aim of this study is to investigate cancer risk among women with endometriosis, stratifying for parity. METHODS: Women discharged from a hospital, with the diagnosis of endometriosis from 1969 to 2002, were identified using the National Swedish Inpatient Register. Data were linked to the National Swedish Cancer Register to identify cases of cancer and to the Swedish Multi-Generation Register to calculate parity and age at first birth. Standardized incidence ratios (SIR) were calculated. RESULTS: A total of 63,630 women entered the study. To exclude cancers already present at the time of endometriosis diagnosis, the first year of follow-up was excluded, leaving a number of 3,822 cases of cancer. There was no increased overall risk of cancer (SIR 1.01) among women with endometriosis. Endometriosis was associated with elevated risks for endocrine tumours (SIR 1.38), ovarian cancer (SIR 1.37), renal cancer (SIR 1.36), thyroid cancer (SIR 1.33), brain tumours (SIR 1.27), malignant melanoma (SIR 1.23) and breast cancer (SIR 1.08), as well as a reduced risk for cervical cancer (SIR 0.71). There were no significant differences between nulliparous and parous women with endometriosis regarding cancer risk for any of the cancer types. There was a non-significant decrease in risk of ovarian cancer with increasing parity for women with endometriosis. CONCLUSIONS: Women with endometriosis have an increased risk for several malignancies. The increased risks do not seem to be related to parity.     

Folliculogenesis and ovulation in infertile women with mild endometriosis

Twenty-one infertile women with laparoscopically documented minimal-mild endometriosis (AFS score 2-10) were studied during 27 cycles (six women had two cycles each) to investigate follicular development and ovulation. Of the 27 cycles studies, 24 (89%) appeared to be endocrinologically normal and ovulatory. Luteinized unruptured follicle (LUF) occurred in only one cycle (4%). One further patient exhibited abnormal endocrinology with evidence of premature ovulation over two (8%) consecutive cycles. This study indicates that the majority of women with minimal-mild endometriosis have endocrinologically normal menstrual cycles and that luteinized unruptured follicles occur infrequently.     

The risk of endometriosis and exposure to dioxins and polychlorinated biphenyls: a case-control study of infertile women

BACKGROUND: A case-control study was designed to determine the possible association between chronic exposure to dioxins and polychlorinated biphenyls (PCBs), and the occurrence of endometriosis. The study group consisted of 42 infertile endometriosis cases and 27 mechanical infertile controls, both groups attending one of the collaborating Centres for Reproductive Medicine, enrolled between 1996-1998. METHODS: Exposure assessment to dioxin-like compounds was determined through CALUX (chemical-activated luciferase gene expression)-bioassay to measure dioxin-like total toxic equivalents (dioxins and co-planar PCBs), whereas non-co-planar PCBs were determined through chemical analysis. RESULTS: No association was found between median dioxin-like total toxic equivalents (TEQ) and the occurrence of endometriosis in infertile women [cases (n = 34): 29; controls (n = 27): 24; NS]. When patients were subdivided based on an arbitrary cut-off value of 100 pg TEQ/g serum lipids, no statistically significant association between very high exposure to dioxin-like compounds and endometriosis was found [crude odds ratio (OR) = 4.33; confidence interval (CI) 0.49-38.19; NS]. After adjusting for body mass index, and alcohol consumption, the risk increased slightly to OR = 4.6 (CI 0.48-43.62; NS). There was no confounding by age, ovulatory dysfunction, caffeine intake, smoking or exposure to non-co-planar PCBs. CONCLUSIONS: The study results showed no statistically significant association between exposure to dioxin-like compounds and the occurrence of endometriosis in infertile women.     

Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study

The autopsy records between 1980 and 1995 of 399 female rhesusmonkeys (Macaca mulatta) at the Wisconsin Regional Primate ResearchCenter were examined. Spontaneous endometriosis was found in81 (20%) of the animals. The mean (±SD) ages at deathfor animals with and without endometriosis were 20.7±5.5(range 10-35) and 13.4±7.7 (range 4-37) years respectively.Many of the animals had been exposed to experimental procedures,including laparoscopies, hysterotomies and oestradiol implants,and these were examined as possible risk factors for endometriosis.Of the 81 affected animals, 62 were matched to unaffected controlsfor age at death (to within 1 year) and year of death (to within2 years) and the effect of various factors on the developmentof endometriosis was determined using conditional logistic regression.Exposure to three or more oestradiol implants or one or morehysterotomies were both significant risk factors, with estimatedrelative risks of 9.7 (95% confidence interval 2.5-37.2) and5.8 (95% confidence interval 1.6-20.2) respectively. Animalsthat had been exposed to one or more laparoscopies showed noincreased risk for developing endometriosis. These findingsprovide insight into the aetiology of the disease in women.     

腹腔镜治疗子宫内膜异位症合并不孕症的疗效分析

目的探讨腹腔镜治疗子宫内膜异位症合并不孕症的疗效分析。方法我院收治的子宫内膜异位症合并不孕患者110例,按照手术方法的不同,分为腹腔镜组和开腹组,两组各55例,观察两组手术时间、术中出血量、住院时间和术后并发症,检测高敏C反应蛋白（hs-CRP）和前白蛋白（PA）,随访半年妊娠率、1年妊娠率和1年内膜异位症复发率。结果腹腔镜组的手术时间、术中出血量、住院时间和术后并发症分别为（55.87±22.73）min、（43.37±12.72）ml、（4.76±1.06）d和7.27%,均较开腹组短或者减少,差异有统计学意义（P〈0.01）。两组半年妊娠率、1年妊娠率和子宫内膜异位症复发率接近,差异无统计学意义（P〉0.05）。手术后,两组的hs-CRP和PA水平均较术前明显升高或者下降,但开腹组的升高或降低水平更为明显,差异有统计学意义（P〈0.01）。结论腹腔镜治疗子宫内膜异位症具有手术创伤小,术后微炎症反应轻,恢复时间短等特点,是一种具有发展前景的新技术。     

Visible and non-visible endometriosis at laparoscopy in fertile and infertile women and in patients with chronic pelvic pain: a prospective study

In 100 consecutive patients who were undergoing laparoscopyfor infertility (group 1, n = 52), chronic pelvic pain (group2, n = 18) or tubal sterilization (group 3, n = 30, asymptomaticfertile women), peritoneal biopsies were taken from areas ofvisually normal peritoneum of uterosacral ligaments. Twenty-sixpatients in group 1 (50%), eight patients in group 2 (44.4%)and 13 patients in group 3 (43.3%), were found to have laparoscopicevidence of endometriosis elsewhere in the pelvis. The majorityof women (80.7% in group 1, 87.5% in group 2, and 100% in group3) had stage I disease. The incidence of the distinctive appearancesof the lesions was similar in the three groups of patients and7% of all women or 15% (7/47) of those patients having endometriosisat laparoscopy had only subtle (non-‘typical’) endometrioticperitoneal lesions. Uterosacral biopsies showed the presenceof endometriotic tissue in three cases (5.7%), two cases (11%)and three cases (10%) in groups 1, 2, and 3 respectively. Oneof the two patients in group 2 and two of the three patientsin group 3 had no evidence of endometriosis at laparoscopy;thus histological study revealed the presence of endometriosisin normal peritoneum hi 11 % (5/47) of patients having macroscopicendometriosis and hi 6% (3/53) of patients without endometriosisat laparoscopy. Previous oral contraceptive users were significantlyhigher among women having macroscopic and/or microscopic endometriosisthan among women without the condition. In conclusion, our prospectivestudy shows a high prevalence (45–50%) of endometriosis(including microscopic forms) in both patients with chronicpelvic pain and asymptomatic women (fertile and infertile),thus supporting the modern concept that in many women endometriosismay be a paraphysiological condition while probably only hisome patients small amounts of endometriosis are an ‘annoyance’with implications to their reproductive health and may producesymptoms (eg. pelvic pain) and therefore should be defined asa ‘dis-ease’. Previous use of oral contraceptivesmay increase the risk of developing endometriosis.     

Leukaemia inhibitory factor and interleukin 11 levels in uterine flushings of infertile patients with endometriosis

BACKGROUND: Exact aetiology of infertility in stage I/II endometriosis patients is not known. Interleukin 11 (IL-11) and leukaemia-inhibitory factor (LIF) are factors associated with implantation window in human eutopic endometrium. We decided to test whether there is an altered secretion of these factors, which could explain receptivity defect in patients with minimal endometriosis. METHODS: Uterine flushing and endometrial samples were collected 7-9 days after ovulation (implantation window) from infertile patients with stage I/II endometriosis (n = 14) and fertile, endometriosis-free controls (n = 21). IL-11 and LIF were assessed in uterine flushings in eutopic endometria in all patients by enzyme-linked immunosorbent assay (ELISA). In eutopic endometrium, semiquantitative RT-PCR was performed for LIF and IL-11 mRNA expressions. RESULTS: No statistically significant differences were found in uterine flushing in women with and without endometriosis with regard to IL-11 levels (0.0 pg/ml versus 0.0 pg/ml) and LIF (25.53 pg/ml versus 36.26 pg/ml). These results were confirmed by the results of RT-PCR, where there were also no differences between studied groups. CONCLUSIONS: There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic endometrium in infertile women with endometriosis.     

Is a long period without childbirth a risk factor for developing endometriosis?

Endometriosis was found in 42 (20%) of 206 symptom-free, parous Norwegian women with a mean age of 37 years at the time of sterilization. Case-control analysis between the 42 women with endometriosis and the 164 without endometriosis revealed an increased risk of endometriosis with increasing number of years since the last childbirth. After 10 years without a birth, the odds ratio for endometriosis was 4.5 compared with the first 5 years after the last delivery. An increased risk of endometriosis with increasing age of the women could not be detected. If these findings from women with voluntary infertility are transferred to women with endometriosis associated with involuntary infertility, endometriosis could be a consequence of a long period without childbirth. This might explain why endometriosis is often diagnosed in infertile women.     

Usefulness of transvaginal hydrolaparoscopy in investigating infertile women with Chlamydia trachomatis infection

BACKGROUND: A new technique called transvaginal hydrolaparoscopy (THL) was recently developed for the exploration of the tubo-ovarian structures in infertile patients without obvious pelvic pathology. This study was performed to investigate the usefulness of THL to evaluate Chlamydia trachomatis tubal infertility. METHODS: Forty-one women with primary and secondary infertility participated in this study. Fourteen had past C. trachomatis infection. In 38 (92.7%) of the 41, access to the pouch of Douglas was obtained. In total, 71 (93.4%) out of 76 adnexa were clearly visualized. Thirty-seven patients were analysed and compared their tubal passages and peritubal adhesions using both hysterosalpingography (HSG) and THL. Twenty-four tubes from 14 patients with past C. trachomatis infection and 44 tubes from 23 patients without a history of C. trachomatis infection were compared. RESULTS: For the diagnosis of the tubal passage, there were no significant differences in the discrepancy rates between HSG and THL, in patients with and without past C. trachomatis infection. In 14 (58.3%) of the 24 tubes from patients with past C. trachomatis infection and in eight (18.2%) of the 44 tubes from patients without infection, peritubal adhesion was diagnosed only by THL. There was a significant difference in the discrepancy rates of the diagnosis of peritubal adhesion between HSG and THL in the two groups (P = 0.0007 ). CONCLUSIONS: These results suggest that C. trachomatis infection is highly associated with peritubal adhesion which is difficult to diagnose by HSG. Therefore, in C. trachomatis antibody-positive patients, exclusion of tubal pathology by THL or standard laparoscopy should be carried out to consider appropriate treatments. Although THL is not a substitute for laparoscopy, it can be proposed as a first line procedure in the early stages of the infertility investigation.     

腹腔镜手术联合GnRH-a类药物治疗子宫内膜异位症伴不孕的疗效观察

目的探讨腹腔镜术后联合GnRH-a治疗子宫内膜异位症伴不孕的疗效及与r-AFS分期的相关性分析。方法106例子宫内膜异位症伴不孕患者经腹腔镜卵巢子宫内膜异位囊肿剔除、异位灶烧灼、粘连分离、输卵管整形及通液等手术治疗，术中行子宫内膜异位症的r-AFS分期，Ⅰ期21例，Ⅱ期25例，Ⅲ期36例，Ⅳ期24例，Ⅰ、Ⅱ期为轻度组，Ⅲ、Ⅳ为重度组。轻、重度组再分单纯腹腔镜手术治疗组和联合GnRH-a治疗组，并行随访1年的临床疗效比较，分析各组的症状缓解率、年复发率和妊娠率等情况。结果轻度子宫内膜异位症组的单纯腹腔镜手术治疗组的症状缓解率、年复发率和妊娠率与联合GnRH-a治疗组差别无显著性。重度子宫内膜异位症组的单纯腹腔镜手术治疗组的症状缓解率与联合GnRH-a治疗组差别无显著性。但年复发率及妊娠率差别有显著性。结论重度子宫内膜异位症组的腹腔镜手术治疗后有必要加用药物巩固治疗，GnRH-a巩固治疗的疗效明显优于单纯腹腔镜手术治疗，术后联合GnRH-a药物治疗可降低年复发率和提高妊娠率。     

Lack of endometriosis in patients with repeated abortion

Laparoscopy was performed in 25 consecutive patients with twoor more (range 2-6, mean 2.8) histologicaDy documented firsttrimesterabortions in whom the well established causes for recurrentmiscarriages had been excluded. Endometriosis could not be diagnosedin any of the 25 women. Thus our results are against endometriosisas a cause of repeated abortion and do not support the routineinclusion of laparoscopy in the evaluation of the patient withrecurrent abortions     

Risk factors associated with asthma and rhinoconjunctivitis among Swedish farmers

BACKGROUND: Earlier studies have shown a high prevalence of respiratory symptoms in farming communities and that storage mites constitute important allergens. We examined risk factors associated with asthma and rhinoconjunctivitis among Swedish farmers. METHODS: A population of 1015 small-scale dairy farmers was part of an epidemiologic survey. After selection based on symptom reports in a questionnaire, 461 of the farmers attended a medical examination, which comprised SPT, RAST analyses, and lung-function measurements. Risk factors for sensitization to different allergens, and development of asthma and rhinoconjunctivitis were assessed by multiple logistic regression. RESULTS: The prevalence of atopy was 26.7% among the farmers. For both asthma and rhinoconjunctivitis, sensitization to mites (OR = 5.8 vs. OR = 3.8) and pollens (OR = 10.3 vs. OR=5.8) was a significant risk factor. There was a significant relationship between sensitization to mites and working time (OR = 5.2). Environmental tobacco smoke and exposure to different animal species at the farm did not appear to affect the risk of allergen sensitization or respiratory symptoms. Farmers smoked less than the general population, but they more frequently had reduced FEV1. CONCLUSIONS: Allergen sensitization, especially to mites and pollens, was significantly associated with asthma and rhinoconjunctivitis in a farming community. The results point to allergen avoidance as a major goal for the prevention of occupational respiratory diseases among the farming population.     

Prolactin and growth hormone secretion after thyrotrophin-releasing hormone infusion and dopaminergic (DA2) blockade in infertile patients with minimal/mild endometriosis

BACKGROUND: The origin of infertility in patients with endometriosis without tubal occlusion has not yet been clearly defined. Several reports show an abnormal pituitary-ovarian axis in this group of patients. Moreover, prolactin (PRL) and growth hormone (GH) secretion is closely related to reproductive status. This study aimed to evaluate PRL and GH secretion after metoclopramide and thyrotrophin-releasing hormone (TRH) infusion in infertile patients with minimal/mild endometriosis. METHODS: A total of 64 women participated in the study: 33 fertile patients without endometriosis; 10 fertile patients with minimal/mild endometriosis; and 21 infertile patients with minimal/mild endometriosis. TRH or metoclopramide was administered randomly in two sequential menstrual cycles (cycle days 3-5). Serum PRL and GH secretion before and after dopaminergic type 2 (DA2) receptor blockade and TRH were compared. RESULTS: Higher serum PRL levels were observed in patients with endometriosis at baseline and after 15 and 30 min of TRH administration. Also, infertile patients with endometriosis had lower serum estradiol levels than fertile patients. Moreover, the dopaminergic blockade did not result in abnormal PRL or GH secretion. CONCLUSIONS: Decreased serum estradiol levels and altered PRL secretion after TRH administration in infertile patients with minimal/mild endometriosis are related to ovulatory dysfunction and infertility in this group of patients without tubal occlusion.     

Paracrine changes in the peritoneal environment of women with endometriosis

During the past decade, macrophage-derived substances such as prostanoids, cytokines, growth factors and angiogenic factors have been detected in the peritoneal fluid of women with endometriosis. In particular, growth-promoting and angiogenic factors are considered to be substantially involved in the pathogenesis of endometriosis. In this study, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta) and intercellular adhesion molecule 1 (ICAM-1), substances recently detected in the peritoneal fluid of women with endometriosis, were assessed with regard to their concentrations in different stages of endometriosis and changes of the peritoneal paracrine activity after medical treatment with a gonadotrophin releasing hormone agonist (GnRHa). Peritoneal fluid was obtained from patients with endometriosis during laparoscopy before and after a 4-month treatment with a GnRHa. VEGF, TGF-beta and ICAM-1 could be detected in all women presenting with various stages of active endometriosis. After GnRHa therapy, all patients showed significant decreases in mean concentrations of VEGF (194+/-77 pg/ml), TGF-beta (902+/-273 pg/ml) and ICAM-1 (157+/-52 ng/ml). Patients with stage III and IV endometriosis (according to the rAFS score) had much higher concentrations of VEGF and TGF-beta before treatment compared with those patients with mild endometriosis (rAFS stages I and II). The most striking decrease in concentration was for TGF-beta, from 902 pg/ml before to 273 pg/ml after therapy. These results indicate an important role for paracrine activity in the establishment and maintenance of endometriosis. Indeed, treatment with a GnRHa may reduce paracrine activity in the peritoneal cavity via hypo-oestrogenism and provide proof of successful therapy.