Total antioxidant status of peritoneal fluid in infertile women

OBJECTIVE: To determine whether impairment of the antioxidant systems of peritoneal fluid might be a factor responsible for infertility. STUDY DESIGN: Total antioxidant status was measured in peritoneal fluid obtained from 18 infertile women suffering from minimal or mild endometriosis, 23 patients with unexplained infertility, 12 women with tubal infertility and 13 fertile women. RESULTS: Total antioxidant status was significantly lower in peritoneal fluid from women with unexplained infertility (0.49+/-0.21 mmol/l) compared to both fertile patients (0.67+/-0.24 mmol/l, P=0.02) and women with tubal infertility (0.76+/-0.26 mmol/l, P=0.001). Peritoneal fluid total antioxidant status did not differ significantly between patients with endometriosis (0.61+/-0.2 mmol/l), tubal infertility and the fertile group (P>0.05). CONCLUSIONS: Our results suggest that low antioxidant status in peritoneal fluid may play a role in the pathogenesis of infertility.     

Antizona and antisperm antibodies in women with endometriosis and/or infertility

OBJECTIVE: To measure the levels of antigamete antibodies in serum and peritoneal fluid of women with endometriosis and/or infertility. DESIGN: Antibody activity against human sperm and porcine oocytes was analyzed in selected subgroups of women. SETTING: Clinic of reproduction. PATIENT(S): Women with endometriosis and/or infertility. INTERVENTION(S): No treatment was implemented before peritoneal fluid and blood sample collection. MAIN OUTCOME MEASURE(S): Quantitative ELISA. RESULT(S): Four groups of women (n = 98) were analyzed for the presence of antizona and antisperm antibodies: infertile with endometriosis (n = 30), idiopathic infertility (n = 28), fertile with endometriosis (n = 20), and healthy fertile controls (n = 20). Antibodies were analyzed simultaneously in serum and peritoneal fluid. No statistically significant differences in antibody levels were detected in serum samples among the analyzed groups. The median values for antizona and antisperm antibodies in peritoneal fluid were significantly higher in women with idiopathic infertility than in the control group. In women with unexplained infertility, a high degree of correlation (Spearman) was found between the presence of antizona antibodies in peritoneal fluid and serum (r = 0.579). A positive predictive value of 80% was calculated for the presence of antizona antibodies (>5 ng/oocyte) in the peritoneal fluid of patients with infertility. CONCLUSION(S): Antizona antibodies locally produced in the peritoneal fluid have diagnostic value for infertility status; however, they cannot be treated as a marker or prognostic factor for minimal endometriosis and/or its treatment.     

Total antioxidant status and activity of an extracellular superoxide dismutase in peritoneal fluid and plasma from women with unexplained infertility

OBJECTIVES: To evaluate the activity of an extracellular superoxide dismutase (EC SOD) and total antioxidant status in peritoneal fluid (PF) and plasma from women with unexplained infertility (UI). MATERIALS AND METHODS: PF and plasma samples were collected from 10 women with UI and 10 patients with tubal infertility (reference group). TAS was measured using Randox diagnostic reagent system. The activity of EC SOD was estimated using Calbiochem assay kit. RESULTS: TAS was significantly lower in PF from women with UI. Plasma TAS did not differ significantly between the groups. Peritoneal TAS was significantly lower compared to plasma TAS and there was a positive correlation between PF and plasma total antioxidant status. Activity of EC SOD did not differ significantly between the groups in either PF and plasma samples. CONCLUSIONS: These data demonstrate that low antioxidant status of PF but not that of blood may be responsible for idiopathic infertility. The activity of EC SOD doesn't appear to play a role in UI.     

Bacterial vaginosis and biomarkers of oxidative stress in amniotic fluid

Objective: In this study we tried to determine if the activities of the primary antioxidant enzymes are detectable in amniotic fluid and if they can be used as early biomarkers of complications in pregnancy connected with bacterial vaginosis. Methods: This was a prospective study in which amniotic fluid was taken between 16 and 19 weeks of gestation. 161 pregnant women were divided into two groups: study group—patients with the treated local infection and control group—healthy pregnant women. Levels of reduced glutathione, and the activities of glutathione peroxidase, glutathione reductase, glutathione S-transpherase, xanthine oxidase, superoxide dismutase and lipid peroxidation were determined spectrophotometrically in amniotic fluid samples. Results: Concentration of malonyldialdehide (product of lipid peroxidation) varied greatly between investigated groups. Xanthine oxidase and superoxide dismutase activities, though very low, were present in amniotic fluid samples. Also, enzymes of glutathione cycle and reduced glutathione concentrations were detectable and showed certain variations. Conclusion: Although, biomarkers of antioxidant activity are present in the amniotic fluid, they are not differrent between women with and without bacterial vaginosis.     

Increased nitric oxide in peritoneal fluid from women with idiopathic infertility and endometriosis.

OBJECTIVE: To verify whether nitric oxide in peritoneal fluid is associated with endometriosis and infertility. STUDY DESIGN: Twenty-five women with idiopathic infertility and 38 with endometriosis were recruited, and 18 cases of uterine myomata and 2 cases of ovarian cyst served as controls. Peritoneal fluid samples were aspirated from the pouch of Douglas during laparoscopy or laparotomy. Metabolites of nitric oxide (nitrite and nitrate) in peritoneal fluid were determined by a method using nitrate reductase and the Griess reaction. RESULTS: Peritoneal concentrations of nitrate/nitrite in both infertile women (42.02 +/- 12.98 mmol/L) and patients with endometriosis (41.75 +/- 16.42 mmol/L) were significantly higher than that in controls (33.96 +/- 13.07, P < .05 for both). No significant difference in peritoneal nitrate/nitrite level was found between infertile women and patients with endometriosis (P > .5). Peritoneal levels of nitrate/nitrite were comparable among patients with endometriosis at different stages (P > .5). Patients with endometriosis had more peritoneal fluid than controls and idiopathic infertile women, while controls and idiopathic infertile women had comparable amounts of peritoneal fluid. CONCLUSION: An increased peritoneal level of nitric oxide is a common alteration in endometriosis, endometriosis-associated infertility and idiopathic infertility and may be associated with the pathogenesis of these diseases.     

Malonyldialdehyde and total antioxidant status in the peritoneal fluid of infertile women]

OBJECTIVE: To estimate the concentration of malonyldialdehyde (MDA) and total antioxidant status in the peritoneal fluid (PF) of patients with unexplained infertility (UI) and infertile women with minimal and mild endometriosis. MATERIALS AND METHODS: PF was obtained during laparoscopy from 8 women with UI, 12 infertile women with endometriosis (I degree and II degrees rAFS) and 10 women with benign noninflammatory ovarian tumours. All laparoscopies were performed in the follicular phase of the cycle. MDA concentration was measured according to Ledwozyw method, TAS was measured spectrophotometrically using RANDOX diagnostic reagent system. RESULTS: We found significantly higher concentration of MDA in PF from both patients with UI (p = 0.03) and with endometriosis (p = 0.046) compared to the control group. TAS was significantly (p = 0.027) higher in PF of women with UI but did not differ significantly (p = 0.49) between patients with endometriosis and controls. CONCLUSIONS: Our results show that an imbalance between lipid peroxides and the antioxidant system in PF environment may be one of the main factors responsible for the UI. In the group with endometriosis a marginally significant difference in MDA levels, no significant differences in TAS and data from the literature, suggest that accelerated lipid peroxidation in PF doesn't appear to play a role in the endometriosis associated infertility.     

Marked elevation of macrophage migration inhibitory factor in the peritoneal fluid of women with endometriosis

OBJECTIVE: To evaluate the presence of macrophage migration inhibitory factor (MIF) in the peritoneal fluid of normal fertile women and patients with endometriosis and its growth-promoting activity toward human endothelial cells. DESIGN: Retrospective study using ELISA to measure peritoneal fluid MIF, and [3H]-thymidine incorporation into the DNA of human endothelial cells to assess its mitogenic activity. SETTING: Gynecology clinic and human reproduction research laboratory. PATIENT(S): Thirty-six healthy women and 57 women with endometriosis. INTERVENTION(S): Peritoneal fluid samples were obtained at laparoscopy. MAIN OUTCOME MEASURE(S): Macrophage migration inhibitory factor concentrations in the peritoneal fluid samples and [3H]-thymidine incorporation into the DNA of human microvascular endothelial cells to assess proliferation. RESULT(S): This study demonstrated the presence of MIF in the peritoneal fluid and a 238% increase of MIF levels in women with endometriosis as compared with healthy women. Both fertile and infertile women with endometriosis had significantly higher MIF concentrations than did fertile women with normal gynecological status, but the difference was more significant in infertile endometriosis patients. Anti-MIF antibody significantly inhibited proliferation of human microvascular endothelial cells in response to peritoneal fluids from healthy women and women with endometriosis stages I-II and III-IV, as assessed by [3H]-thymidine incorporation. CONCLUSION(S): This study revealed the presence of MIF in the peritoneal fluid and its increased levels in endometriosis and suggests that MIF may be involved in endometriosis-associated infertility and angiogenesis.     

Reactive oxygen species as an inducing factor of neoplasms of female reproductive organs

AIM: In our study we measured selenium concentration in the blood of women with diagnosed cancer and benign tumors. The results were compared with healthy women. Some other parameters of the antioxidant system in all studied groups were also investigated, namely, activity of glutatione peroxidase, superoxide dismutase, as well as the levels of glutathione and malondialdehyde. MATERIAL AND METHODS: All parameters were determined in peripheral blood of (a) 47 women with diagnosed cancer (b) 46 women with diagnosed benign tumors, and (c) 20 healthy women (control group). Statistical analysis of the results was performed using "Statistica" software. RESULTS: Our results showed lower selenium concentration in the whole blood and plasma of cancer and benign tumor patients as compared to healthy women. An activity of glutathione peroxidase in erythrocytes and plasma were also lower in both patients' groups than in the control group. Statistical analysis of data revealed a positive correlation between selenium concentration and glutathione peroxidase activity in plasma. Lower activity of superoxide dismutase and increased concentration of malondialdehyde was noted in plasma of cancer patients as compared to healthy women. CONCLUSIONS: 1. A status of antioxidant systems plays an important role in carcinogenesis. 2. The antioxidant system of the women suffering from cancer is deficient. 3. A capacity of that system depends greatly on the concentration of antioxidants and activity of antioxidant enzymes, among them glutathione peroxidase.     

Inducible nitric oxide synthase expression by peritoneal macrophages in endometriosis-associated infertility.

OBJECTIVE: Determine whether peritoneal macrophages from women with endometriosis-associated infertility express more inducible nitric oxide synthase (NOS2) and produce more NO than fertile controls. DESIGN: Unblinded clinical study. PATIENT(S): Nine infertile women with endometriosis and nine normal fertile women undergoing laparoscopy.Intervention(s): Peritoneal fluid and macrophages were collected. Cells were also cultured with the NOS2 inducers interferon-alpha (IFN-alpha) or IFN-gamma plus lipopolysaccharide (LPS). MAIN OUTCOME MEASURE(S): Peritoneal fluid NO levels, peritoneal macrophage NOS activity, and peritoneal macrophage NOS2 protein expression. RESULT(S): NOS enzyme activity was higher in peritoneal macrophages from endometriosis patients. Immunoblots demonstrated NOS2 protein only in peritoneal macrophages from women with endometriosis. Peritoneal fluid NO concentration was similar in the two groups, but total peritoneal fluid NO content was higher in endometriosis patients. After 3 days' culture, peritoneal macrophages from women with endometriosis produced more NO in response to IFN-alpha or IFN-gamma plus LPS than controls. CONCLUSION(S): Peritoneal macrophages from women with endometriosis-associated infertility express higher levels of NOS2, have higher NOS enzyme activity, and produce more NO in response to immune stimulation in vitro. As high levels of NO adversely affect sperm, embryos, implantation, and oviductal function, reducing peritoneal fluid NO production or blocking NO effects may improve fertility in women with endometriosis.     

Antioxidant enzymes in women with endometrial polyps: relation with sex hormones

Objective

To investigate whether antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase) and lipid hydroperoxide levels in patients with endometrial polyps are influenced by the changes in sex hormones (estradiol, progesterone, FSH, and LH) during the menstrual cycle and in postmenopause.

Study design

The material consisted of blood and endometrial tissue specimens from women diagnosed with endometrial polyps. Patients were divided into groups depending on the phase of the menstrual cycle – follicular or luteal – and the postmenopause. The activities of antioxidant enzymes and the lipid hydroperoxide levels were compared among the phases and a linear regression model was used to evaluate the associations between hormones and antioxidant/oxidant variables.

Results

In the blood of examined women, a significant difference in superoxide dismutase activity and lipid hydroperoxide levels was recorded among the phases. There was also a positive correlation between the estradiol concentration and superoxide dismutase. In polyp tissue, we recorded a phase-related difference in superoxide dismutase and glutathione peroxidase activities as well as in the lipid hydroperoxide levels. A negative correlation was observed between FSH/LH and glutathione peroxidase, and between LH and superoxide dismutase.

Conclusion

Antioxidant enzymes and lipid hydroperoxide levels in patients with endometrial polyps are influenced by the changes in sex hormones during the menstrual cycle and after the menopause, pointing to a role of the observed relationship in polyp etiology.     

Indices of oxidative stress in eutopic and ectopic endometria of women with endometriosis

This study was designed to determine the activities of superoxide dismutase and glutathione peroxidase and some of the lipid peroxidation indices (malondialdehyde and total sulfhydryl groups) in eutopic and ectopic endometria of patients with endometriosis. Ectopic endometrial tissues (ovarian cysts; n = 22) were obtained laparoscopically during the preovulatory period. Statistical analyses were made using the Wilcoxon signed-rank test. The levels of malondialdehyde and total sulfhydryl groups were similar in the eutopic and ectopic endometria, whereas the superoxide dismutase activity was found to be significantly higher in the latter (1,893 +/- 780 vs. 3,512 +/- 1,502 U/g protein; p = 0.002). Although the glutathione peroxidase activity was slightly lower in the ectopic than in the eutopic tissues, the difference was not found to be statistically significant. The malondialdehyde levels were positively correlated with the plasma 17beta-estradiol concentrations in the ectopic endometria (r = 0.683, p = 0.001). No such correlation was seen in the eutopic tissue. It is suggested that various factors, such as cytokines released by activated macrophages in the peritoneal fluid and 17beta-estradiol itself synthesized by the ovaries, may locally affect the oxidant status of ectopic endometria.     

Lipoperoxidation and antioxidant enzymes activity in pregnancy complicated with hypertension

Objective: To assess maternal circulating levels of lipid peroxidation breakdown products and antioxidant enzymes activity in pregnancies complicated with hypertension. Study design: Ten women with uncomplicated pregnancies and nine women with hypertension antedating pregnancy were prospectively sampled. Eight women, who had developed preeclampsia, were also cross-sectionally included. Twenty healthy non pregnant volunteers were the control group. Thiobarbituric acid reactive substances (TBA-RS), as lipid peroxidation products, and the activity of catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD), as antioxidant enzymes, were assayed in red blood cell hemolysates. A prooxidant/antioxidant (P/A) ratio (TBA-RS/CAT + GPX + SOD) was determined from the mean value of the volunteers. Results: In women with chronic hypertension, TBA-RS levels were higher than those in normal pregnant women, whereas antioxidant enzymes activities were either stable or decreased. Therefore the P/A ratio was progressively lower in the second and third trimester. Similar results were found in patients with preeclampsia. Conclusions: Normal gestation induces an increase of lipid peroxidation products, whereas antioxidant activity seems stable. In pregnancies complicated by chronic hypertension, a deficiency of the oxidative system balance is detectable, which consistently progresses in the second and third trimester, strongly suggesting a failure of the protective mechanisms.     

Lipid peroxides, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in peritoneal fluid from infertile women with minimal and mild endometriosis

OBJECTIVES: To assess the concentrations of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and lipid peroxides (the marker of free radicals activity) in peritoneal fluid (PF) of infertile women with minimal and mild endometriosis. MATERIALS AND METHODS: 19 women were studied, including 9 infertile women with minimal or mild endometriosis and 10 patients with tubal occlusion (the reference group). Lipid peroxides (malonyldialdehyde and 4-hydroxynonenal), TNF-alpha and IFN-gamma concentrations were measured in the PF using commercially available kits. RESULTS: Concentration of IFN-gamma was detectable in PF of 7 (77.8%) women with endometriosis and in PF from 3 (30%) patients with tubal occlusion. Neither TNF-alpha or lipid peroxides PF concentration differed significantly (p < 0.05) between the groups. In the group with endometriosis we have found a positive correlation (R = 0.77, p = 0.04) between the concentrations of TNF-alpha and IFN-gamma. CONCLUSIONS: Our results suggest that oxidative stress in the PF doesn't appear to play a role in endometriosis-associated infertility.     

Lipid peroxidation in the peritoneal fluid of infertile women with peritoneal endometriosis

OBJECTIVE: To assess the level of lipid peroxidation in the peritoneal fluid of infertile women with peritoneal endometriosis and of fertile disease-free controls. STUDY DESIGN: Level of lipid peroxidation (malondialdeyde, malondialdeyde with copper addition, and cholest-3,5-dien-7-one) was measured in the peritoneal fluid obtained from 21 women with endometriosis-related infertility and from 21 fertile women having tubal ligation. RESULTS:: The level of lipid peroxidation did not differ significantly (P > 0.05) according to the stage of endometriosis. The level of lipid peroxidation (malondialdeyde, malondialdeyde with the addition of copper, and cholest-3,5-dien-7-one) did not differ significantly (P > 0.05) between patients with endometriosis-related infertility (0.07 nmol/ml, 0.34 nmol/ml, 0.24 microg/ml, respectively) and disease-free controls (0.04 nmol/ml, 0.21 nmol/ml, 0.25 microg/ml, respectively). CONCLUSION: The level of lipid peroxidation did not differ between women with endometriosis-related infertility and fertile disease-free controls, suggesting that increased reactive oxygen species may not be one of the factors responsible for compromised fertility in patients with endometriosis.     

Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women

Free radical reactions are involved in processes connected with aging. Estradiol acts as antioxidant and free radical scavenger ,but the mechanism of this action remains unknown. Estradiol has a hydroxyphenolic structure and may donate hydrogen atoms to lipid peroxyradicals to terminate chain reactions. There are a few reports concerning the influence of estradiol on natural antioxidant enzyme activity ,such as superoxide dismutase (SOD) ,glutathione peroxidase (GSH-Px) and catalase (CAT). The aim of this study was to estimate the relationship between the levels of estradiol and lipid peroxide (LPO) ,a marker of membrane lipid peroxidation ,and the correlation between estradiol and erythrocyte SOD and GSH-Px activity. The study included 13 premenopausal and 13 postmenopausal healthy women. Serum levels of estradiol, follicle-stimulating hormone (FSH) and LPO ,and erythrocyte SOD and GSH-Px activity were estimated in all subjects. Premenopausal women revealed significantly higher estradiol levels and lower LPO concentrations, as well as significantly higher GSH-Px activity than the postmenopausal group. SOD activity did not differ between the two groups. There was a negative correlation between serum estradiol and LPO levels as well as a positive correlation between estradiol and GSH-Px activity. These results support the hypothesis that estradiol exerts its antioxidant action not only through its chemical structure but probably also through its influence on natural cellular antioxidant enzyme activity.     

Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women.

Free radical reactions are involved in processes connected with aging. Estradiol acts as antioxidant and free radical scavenger, but the mechanism of this action remains unknown. Estradiol has a hydroxyphenolic structure and may donate hydrogen atoms to lipid peroxyradicals to terminate chain reactions. There are a few reports concerning the influence of estradiol on natural antioxidant enzyme activity, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). The aim of this study was to estimate the relationship between the levels of estradiol and lipid peroxide (LPO), a marker of membrane lipid peroxidation, and the correlation between estradiol and erythrocyte SOD and GSH-Px activity. The study included 13 premenopausal and 13 postmenopausal healthy women. Serum levels of estradiol, follicle-stimulating hormone (FSH) and LPO, and erythrocyte SOD and GSH-Px activity were estimated in all subjects. Premenopausal women revealed significantly higher estradiol levels and lower LPO concentrations, as well as significantly higher GSH-Px activity than the postmenopausal group. SOD activity did not differ between the two groups. There was a negative correlation between serum estradiol and LPO levels as well as a positive correlation between estradiol and GSH-Px activity. These results support the hypothesis that estradiol exerts its antioxidant action not only through its chemical structure but probably also through its influence on natural cellular antioxidant enzyme activity.     

Systemic oxidative stress as a possible mechanism underlying the pathogenesis of mild endometriosis-related infertility

Research questionDoes systemic oxidative stress occur during the early follicular phase of the menstrual cycle in infertile women with minimal (stage I) or mild (stage II) endometriosis? Are serum oxidative stress markers during the early follicular phase of the menstrual cycle good predictors of successful gestation in these women who undergo ovarian stimulation for intracytoplasmic sperm injection (ICSI)?Materials and methodsA pilot study (prospective case-control study) was conducted in a University Hospital. Serum samples were obtained during the early follicular phase of the natural cycle preceding ovarian stimulation for ICSI of infertile women (with and without stage I and II endometriosis, the latter having male factor infertility). Total hydroperoxides (FOX1), malondialdehyde, advanced oxidation protein products, reduced glutathione, superoxide dismutase, total antioxidant capacity (TAC), 8-hydroxy-2’-deoxyguanosine (8OHdG) and vitamin E were analysed in serum from 35 women with stage I or II endometriosis and 60 control women. The accuracy of oxidative stress markers for predicting clinical pregnancy and live births was determined by receiver operator characteristic curves.ResultsWomen with stage I and II endometriosis showed lower serum 8OHdG concentrations (16.02 ng/ml) compared with the control group (22.08 ng/ml). The best predictor for clinical pregnancy and live births was TAC, whereas FOX1 was the best predictor of clinical pregnancy in the control group.ConclusionsInfertile women with stage I and II endometriosis present systemic oxidative stress during the early follicular phase of the menstrual cycle. Some oxidative stress markers were good predictors of clinical pregnancy and live births after ICSI. Serum TAC was predictive of clinical pregnancy and live births after ICSI in women with stage I or II endometriosis.     

Oxidative stress in diabetic pregnancy: SOD, CAT and GSH-Px activity and lipid peroxidation products.

Diabetic pregnancy is often complicated by a number of pathological conditions among which is increased oxidative stress. This study was conducted to investigate the parameters of oxidative stress in 90 patients divided into the three groups: pregnant women with Type 1 diabetes mellitus, healthy pregnant women and non-pregnant women. In pregnancy groups all parameters were followed in 1st, 2nd and 3rd trimester. Diabetic control was monitored by fasting blood glucose and glycosylated hemoglobin (HbA(1c)) and these values, as well as measured biochemical parameters (urea, creatinine, total cholesterol and uric acid), were appropriate throughout the study. The concentration of TBARS, as a measure of lipid peroxidation, and activity of antioxidant enzymes superoxide dismutase (Cu, Zn-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were investigated in hemolysate of erythrocytes. TBARS concentration increased significantly in pregnant women when compared with control group (non-pregnant women), as well as in pregnant diabetics compared with healthy pregnant women. The SOD activity was gradually increased in the group of normal pregnant women vs. non-pregnant group, but decreased significantly in the group of diabetic pregnant women. Catalase activity was significantly increased only in 3rd trimester diabetic pregnant women. Increased lipid peroxidation and reduced antioxidant status, despite good diabetic control, show that pregnant women are exposed to oxidative stress to a greater degree than controls.     

Women who are not exposed to spermatozoa and infertile women have similar rates of stage I endometriosis.

OBJECTIVE: To compare the prevalence of endometriosis and its different stages in infertile women and women not exposed to spermatozoa. DESIGN: Prospective study. SETTING: Artificial insemination donor program at a university hospital. PATIENT(S): One hundred fifty women unable to conceive because they had not been exposed to spermatozoa (134 with azoospermic partner, 10 with an HIV-positive partner, and 6 without a male partner). Controls were 750 women in infertile couples in which the male partner had normal sperm. INTERVENTION(S): Laparoscopy was systematically performed in a blinded manner in both groups as part of the infertility work-up. MAIN OUTCOME MEASURE(S): Diagnosis of endometriosis. RESULT(S): In unexposed women and controls, the prevalence of endometriosis was similar (32% and 34.5%). Rates of stage I disease were also similar in both groups (26% and 19.3%). There was a significant trend toward higher stages of endometriosis in infertile women (stage II disease, 3.3% vs. 5.7%; stage III disease, 1.3% vs. 3.1%; stage IV disease, 1.3% vs. 6.4%). Endometriosis was not associated with the few demographic characteristics that differed between groups. CONCLUSION(S): From an epidemiologic point of view, stage I endometriosis is not more common in infertile women than in unselected women. However, stage II to IV endometriosis was more frequent in infertile women. Whereas a relation between stage I endometriosis and infertility seems unlikely, the relation between stages II to IV endometriosis and infertility seems possible.     

Ovarian cancer risk associated with varying causes of infertility

OBJECTIVE: To evaluate the risk of ovarian cancer as related to underlying causes of infertility. DESIGN: Retrospective observational cohort study. SETTING: Five large reproductive endocrinology practices. PATIENT(S): A total of 12,193 women evaluated for infertility between 1965 and 1988. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ovarian cancer ascertained through 1999. RESULT(S): With 45 identified ovarian cancers, this cohort of infertility patients demonstrated a significantly higher rate of ovarian cancer than the general female population (standardized incidence ratio [SIR] = 1.98; 95% confidence interval [CI], 1.4-2.6). The risk was higher for patients with primary infertility (SIR = 2.73) than for those with secondary infertility (SIR = 1.44), and it was particularly high for patients who never subsequently conceived (SIR = 3.33). Women with endometriosis had the highest risk (SIR = 2.48; 95% CI, 1.3-4.2), with a further elevated risk among those with primary infertility (4.19, 2.0-7.7). Comparisons among the infertile women, which allowed calculation of rate ratios (RRs) after adjustment for multiple factors, also showed links with endometriosis. Compared with women with secondary infertility without endometriosis, patients with primary infertility and endometriosis had a RR of 2.72 (95% CI, 1.1-6.7). CONCLUSION(S): Determination of ovarian cancer risk should take into account the type of infertility (primary vs. secondary) and underlying causes. Further study of endometriosis may provide insights into ovarian carcinogenesis.