Is the leptin/BMI ratio a reliable biomarker for endometriosis?

Background: The aim of this study was to analyze the concentration of leptin in peritoneal fluid and plasma and to assess their role as potential biomarkers in the diagnosis of endometriosis. Materials & methods: Leptin adjusted for BMI (leptin/BMI ratio) was measured using surface plasmon resonance imaging (SPRI) biosensors. Patients with suspected endometriosis were included in the study. Plasma was collected from 70 cases, and peritoneal fluid from 67 cases. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group and a control group (patients without endometriosis). Results: Leptin/BMI ratio in plasma did not differ between women with endometriosis and the control group (0.7159 ± 0.259 vs 0.6992 ± 0.273, p= 0,7988). No significant differences were observed in peritoneal leptin/BMI ratio levels in patients with and without endometriosis (0.6206 ± 0.258 vs 0.6215 ± 0.264, p= 0,9896). Plasma and peritoneal leptin/BMI ratios were significantly lower in women with endometriosis - related primary infertility compared to women with endometriosis without primary infertility (0.640 ± 0.502 vs 0.878 ± 0.623, p < 0.05). The difference was observed in case of primary infertility, but not in terms of the secondary one. No significant differences were noted between leptin/BMI ratio in the proliferative phase and the secretory phase (0.716 ± 0.252 vs 0.697 ± 0.288, p= 0,7785). Conclusion: The results of present study do not support the relevance of leptin concentration determination as a biomarker of the endometriosis. Due to the limited number of samples in the tested group, further studies are needed to confirm its role.

The SPRi determination of cathepsin L and S in plasma and peritoneal fluid of women with endometriosis.

PURPOSE: Endometriosis is a common disease with a complex pathomechanism and atypical symptoms, often leading to delayed diagnosis. Currently, the sole method for confirming the presence of the disease is through laparoscopy and histopathological examination of collected tissue. However, this invasive procedure carries potential risk and complications, necessitating the exploration of non-surgical diagnostic methods for endometriosis. This study aims to analyze peritoneal fluid and plasma samples for the expression of cathepsin L and cathepsin S to identify potential biomarkers for non-invasive diagnostic approaches to endometriosis. MATERIAL AND METHODS: In this cross-sectional study, plasma and peritoneal fluid samples were obtained during laparoscopy from 63 patients diagnosed with chronic pelvic pain or infertility. The study group consisted of women with confirmed endometriosis. The concentrations of cathepsins L and S were determined using an SPRi biosensor. RESULTS: The study did not reveal significant differences in the concentrations of cathepsin L and cathepsin S between the control group and the study group, both in peritoneal fluid and plasma. CONCLUSIONS: Based on the results of this study, it appears that cathepsins L and S are not suitable candidates as biomarkers for endometriosis.

Plasma and Peritoneal Fluid Annexin A2 Levels in Patients with Endometriosis.

Introduction: Endometriosis is an inflammatory-related reproductive age disease characterized by the presence of endometrial cells outside the uterine cavity. Current laboratory practice does not provide specific markers for detecting and assessing the advancement of endometriosis in either plasma or peritoneal fluid. The severity of disease is assessed in stages from I to IV based on the results of laparoscopic inspection. The protein annexin A2 (ANXA2) has been reported to be associated with inflammatory processes. Aim of the Study: The study aimed to investigate and compare ANXA2 protein concentration using the ELISA method in plasma and peritoneal fluid in a group of women with endometriosis compared to controls. Materials and Methods: Biological material was collected during a multicenter, cross-sectional study, which was conducted at eight departments during elective laparoscopy from 53 women with and 40 women without endometriosis. Patients were divided by endometriosis stage and infertility status, and then compared with subgroups. Analysis included the Chi-square test for categorical variables, Mann-Whitney U-test and two-sided Wilcoxon rank-sum test for continuous variables. Results: Women with endometriosis had significantly elevated plasma ANXA2 levels compared to women without endometriosis (mean concentrations 28.69 vs 19.61 ng/L, p=0.01). Differences in peritoneal fluid ANXA2 levels were statistically insignificant (mean concentrations of 23.7 vs 22.97 ng/L, p=0.06). Plasma concentrations in patients with stage III and IV endometriosis were significantly higher compared to controls (mean concentrations of 24.19 vs 19.71 ng/L, p=0.03). No such differences were observed in plasma when comparing stages I-II vs III-IV, and stages I-II vs controls (mean concentrations of 33.82 vs 24.19 ng/L, p=0.72 and 33.82 vs 19.71 ng/L, p=0.12, respectively). Comparison of samples from patients with or without infertility, primary or secondary infertility, endometriosis with or without infertility, and non-endometriosis with or without infertility showed no significant differences in the plasma nor in the peritoneal fluid concentrations. Conclusion: ANXA2 is possibly involved in the pathogenesis of endometriosis, especially in advanced stages. Due to the limited group of tested samples, further studies are needed to confirm its role.

miRNA Expression Profiles in Ovarian Endometriosis and Two Types of Ovarian Cancer-Endometriosis-Associated Ovarian Cancer and High-Grade Ovarian Cancer.

Endometriosis-associated ovarian cancer (EOC) consisting of endometrioid cancer and clear-cell ovarian cancer could be promoted by many factors. miRNAs, which are small, non-coding molecules of RNA, are among them. The aim of this study was to detect miRNAs connected with the malignant transformation of endometriosis. FFPE (formalin-fixed, paraffin-embedded) samples of 135 patients operated on for endometriosis and different types of ovarian cancer (EOC and HGSOC-high-grade serous ovarian cancer) were studied. Healthy ovarian tissue was used as a control group. From the expression panel of 754 miRNAs, 7 were chosen for further tests according to their ROC (receiver operating characteristic) curves: miR-1-3p, miR-125b-1-3p, miR-31-3p, miR-200b-3p, miR-502-5p, miR-503-5p and miR-548d-5p. Furthermore, other potentially important clinical data were analysed, which included age, BMI, Ca-125 concentration, miscarriages and deliveries and concomitant diseases such as hypertension, type 2 diabetes and smoking. Among the miRNAs, miR200b-3p had the lowest expression in neoplastic tissues. miR31-3p had the highest expression in women without any lesions in the ovaries. miR-502-5p and miR-548-5p did not differ between the studied groups. The examined miRNA panel generally distinguished significantly normal ovarian tissue and endometriosis, normal ovarian tissue and cancer, and endometriosis and cancer. The malignant transformation of endometriosis is dependent on different factors. miRNA changes are among them. The studied miRNA panel described well the differences between endometriosis and EOC but had no potential to differentiate types of ovarian cancer according to their origin. Therefore, examination of a broader miRNA panel is needed and might prove itself advantageous in clinical practice.

Evaluation of Proteasome and Immunoproteasome Levels in Plasma and Peritoneal Fluid in Patients with Endometriosis.

Endometriosis is a chronic disease in which the endometrium cells are located outside the uterine cavity. The aim of this study was to evaluate circulating 20S proteasome and 20S immunoproteasome levels in plasma and peritoneal fluid in women with and without endometriosis in order to assess their usefulness as biomarkers of disease. Concentrations were measured using surface plasmon resonance imaging biosensors. Patients with suspected endometriosis were included in the study-plasma was collected in 112 cases and peritoneal fluid in 75. Based on the presence of endometriosis lesions detected during laparoscopy, patients were divided into a study group (confirmed endometriosis) and a control group (patients without endometriosis). Proteasome and immunoproteasome levels in both the plasma (p = 0.174; p = 0.696, respectively) and the peritoneal fluid (p = 0.909; p = 0.284, respectively) did not differ between those groups. There was a statistically significant difference in the plasma proteasome levels between patients in the control group and those with mild (Stage I and II) endometriosis (p = 0.047) and in the plasma immunoproteasome levels in patients with ovarian cysts compared to those without (p = 0.017). The results of our study do not support the relevance of proteasome and immunoproteasome determination as biomarkers of the disease but suggest a potentially active role in the pathogenesis of endometriosis.

Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis.

An evaluation of the association between the concentrations of vitamin D-binding protein and lactoferrin in the plasma and peritoneal fluid may facilitate the elucidation of molecular mechanisms in endometriosis. Vitamin D-binding protein and lactoferrin concentrations were measured by ELISA in plasma and peritoneal fluid samples from 95 women with suspected endometriosis as classified by laparoscopy into groups with (n = 59) and without endometriosis (n = 36). There were no differences (p > 0.05) in the plasma and peritoneal fluid concentrations of vitamin D-binding protein and lactoferrin between women with and without endometriosis. In women with endometriosis, there was a significant correlation between plasma and peritoneal fluid vitamin D-binding protein concentrations (r = 0.821; p = 0.000), but there was no correlation between lactoferrin concentrations in those compartments (r = 0.049; p > 0.05). Furthermore, in endometriosis, lactoferrin was found to correlate poorly with vitamin D-binding protein (r= -0.236; p > 0.05) in plasma, while in the peritoneal fluid, the correlation between those proteins was significant (r = 0.399; p = 0.002). The characteristic properties of vitamin D-binding protein and lactoferrin and the associations between their plasma and peritoneal fluid concentrations found in women with endometriosis may provide a novel panel of markers to identify high-risk patients in need of further diagnostic measures.

How to Improve Non-Invasive Diagnosis of Endometriosis with Advanced Statistical Methods.

Background and Objectives: Endometriosis is one of the most common gynecological disorders in women of reproductive age. Causing pelvic pain and infertility, it is considered one of the most serious health problems, being responsible for work absences or productivity loss. Its diagnosis is often delayed because of the need for an invasive laparoscopic approach. Despite years of studies, no single marker for endometriosis has been discovered. The aim of this research was to find an algorithm based on symptoms and laboratory tests that could diagnose endometriosis in a non-invasive way. Materials and Methods: The research group consisted of 101 women hospitalized for diagnostic laparoscopy, among which 71 had confirmed endometriosis. Data on reproductive history were collected in detail. CA125 (cancer antigen-125) level and VEGF1(vascular endothelial growth factor 1) were tested in blood samples. Among the used statistical methods, the LASSO regression-a new important statistical tool eliminating the least useful features-was the only method to have significant results. Results: Out of 19 features based on results of LASSO, 7 variables were chosen: body mass index, age of menarche, cycle length, painful periods, information about using contraception, CA125, and VEGF1. After multivariate logistic regression with a backward strategy, the three most significant features were evaluated. The strongest impact on endometriosis prediction had information about painful periods, CA125 over 15 u/mL, and the lowest BMI, with a sensitivity of 0.8800 and a specificity of 0.8000, respectively. Conclusions: Advanced statistical methods are crucial when creating non-invasive tests for endometriosis. An algorithm based on three easy features, including painful menses, BMI level, and CA125 concentration could have an important place in the non-invasive diagnosis of endometriosis. If confirmed in a prospective study, implementing such an algorithm in populations with a high risk of endometriosis will allow us to cover patients suspected of endometriosis with proper treatment.

Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis.

STUDY QUESTION: Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls? SUMMARY ANSWER: This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients. WHAT IS KNOWN ALREADY: Various inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors. STUDY DESIGN, SIZE, DURATION: A multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: During laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays. MAIN RESULTS AND THE ROLE OF CHANCE: We observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P < 0.016 and adj. P < 0.026, respectively; logFC > 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P < 0.029), MAGEB4 (adj. P < 0.029), and TNIP2 (adj. P < 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance. LIMITATIONS, REASONS FOR CAUTION: Although this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results. WIDER IMPLICATIONS OF THE FINDINGS: Although endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The Influence of Lactoferrin in Plasma and Peritoneal Fluid on Iron Metabolism in Women with Endometriosis.

The aim of this study was to investigate the relationship between lactoferrin and iron and its binding proteins in women with endometriosis by simultaneously measuring these parameters in plasma and peritoneal fluid. Ninety women were evaluated, of whom 57 were confirmed as having endometriosis. Lactoferrin was measured by ELISA, transferrin, ferritin and iron on a Cobas 8000 analyser. Lactoferrin and transferrin in peritoneal fluid were lower compared to plasma, in contrast to ferritin and iron. In plasma, lactoferrin showeds associations with iron and transferrin in endometriosis and with ferritin in the group without endometriosis. Lactoferrin in peritoneal fluid correlated with lactoferrin, iron and transferrin of plasma in patients without endometriosis. The ratio of lactoferrin concentration in peritoneal fluid to plasma differentiated stage I versus IV of endometriosis and was negatively correlated with the iron ratio in patients without endometriosis. The ferritin ratio differentiated women with and without endometriosis. The very high ferritin ratios, especially in advanced stages of endometriosis, suggest the protective involvement of this protein in peritoneal fluid and the loss of this role by lactoferrin. The results demonstrate the validity of assessing iron metabolism in women with endometriosis, which may be useful as a marker of the disease and its progression.

Plasma and Peritoneal Fluid Fibronectin and Collagen IV Levels as Potential Biomarkers of Endometriosis.

Laparoscopy as a diagnostic tool for patients with suspected endometriosis is associated with several potentially life-threatening complications. Therefore, it is imperative to identify reliable, non-invasive biomarkers of the disease. The aim of this study was to analyse the concentrations of fibronectin and type IV collagen in peritoneal fluid and plasma to assess their role as potential biomarkers in the diagnosis of endometriosis. Fibronectin and collagen IV protein levels were assessed by surface plasmon resonance imaging (SPRi) biosensors with the usage of monoclonal antibodies. All patients enrolled in the study were referred for laparoscopy for the diagnosis of infertility or chronic pelvic pain (n = 84). The study group included patients with endometriosis confirmed during surgery (n = 49). The concentration of fibronectin in the plasma (329.3 ± 98.5 mg/L) and peritoneal fluid (26.8 ± 11.1 µg/L) in women with endometriosis was significantly higher than in the control group (251.2 ± 84.0 mg/L, 7.0 ± 5.9 µg/L). Fibronectin levels were independent of endometriosis stage (p = 0.874, p = 0.469). No significant differences were observed in collagen IV levels (p = 0.385, p = 0.465). The presence of elevated levels of fibronectin may indicate abnormalities in cell-ECM signalling during the course of endometriosis, and may be a potential biomarker for early detection.

Plasma and Peritoneal Poly (ADP-Ribose) Polymerase Levels in Patients with Endometriosis.

The evidence of poly (ADP-ribose) polymerase (PARP) association with the immune response could be coherent with the immunological theory of endometriosis and suggests the possibility of a new research direction. The aim of the study was to evaluate the levels of PARP in plasma and peritoneal fluid of patients with and without endometriosis. It was a multicenter, cross-sectional study. Plasma and peritoneal fluid samples were collected from patients with and without endometriosis during planned laparoscopic procedures in eight clinical centers. In total, 84 samples of plasma and 84 samples of the peritoneal fluid were included in the final analyses. Double-antibody sandwich enzyme-linked immunosorbent assay was performed in order to assess levels of PARP in collected samples. No statistically significant differences regarding the detected levels of PARP in plasma and peritoneal fluid comparing patients with and without endometriosis were observed. Patients with a history of infertility had significantly higher plasma PARP concentrations (p = 0.04). We have not observed the potential role of PARP concentration levels in plasma nor peritoneal fluid as an endometriosis biomarker. We have determined an association between a higher plasma PARP concentration and a history of infertility.

Plasma and Peritoneal Fluid ZEB Levels in Patients with Endometriosis and Infertility.

Zinc finger E-box-binding homeobox 1 (ZEB1) and zinc finger E-box-binding homeobox 2 (ZEB2) are transcription factors that regulate epithelial−mesenchymal transformation (EMT). The aim of this study was to compare levels of ZEB1 and ZEB2 in the peritoneal fluid and plasma between patients with and without endometriosis in order to assess their utility in the diagnostic process. Plasma and peritoneal fluid samples were collected from 50 patients with and 48 without endometriosis during planned surgical procedures in eight clinical centers. Quantitative ZEB1 and ZEB2 levels analyses were performed using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in ZEB1 levels in any of the subanalyses nor any differences regarding ZEB2 levels between patients with and without endometriosis. Plasma ZEB2 levels were significantly higher among patients with infertility compared to fertile women (16.07 ± 12.70 ng/L vs. 12.07 ± 11.92 ng/L; p < 0.04). Both ZEB1 and ZEB2 do not seem to have a significant value in the initial diagnosis of endometriosis as a single marker. The differences in ZEB2 plasma levels between patients with and without infertility indicate the possibility of EMT dysregulation in the pathogenesis of adverse fertility outcomes.

The Role of Cadherin 12 (CDH12) in the Peritoneal Fluid among Patients with Endometriosis and Endometriosis-Related Infertility.

Cadherin 12 (CDH 12) can play a role in the pathogenesis of endometriosis. The aim of this study was to compare the levels of cadherin 12 in the peritoneal fluid between women with and without endometriosis. This was a multicenter cross-sectional study. Eighty-two patients undergoing laparoscopic procedures were enrolled in the study. Cadherin 12 concentrations were determined using the enzyme-linked immunosorbent assay. The level of statistical significance was set at p < 0.05. No differences in cadherin 12 concentrations between patients with and without endometriosis were observed (p = 0.4). Subgroup analyses showed that CDH 12 concentrations were significantly higher in patients with infertility or primary infertility and endometriosis in comparison with patients without endometriosis and without infertility or primary infertility (p = 0.02) and also higher in patients with stage I or II endometriosis and infertility or primary infertility than in patients without endometriosis and infertility or primary infertility (p = 0.03, p = 0.048, respectively). In total, CDH 12 levels were significantly higher in patients diagnosed with infertility or primary infertility (p = 0.0092, p = 0.009, respectively) than in fertile women. Cadherin 12 can possibly play a role in the pathogenesis of infertility, both in women with and without endometriosis.

Correlation between Endometriosis and Selected Allergic and Autoimmune Diseases and Eating Habits.

Background and Objectives: Endometriosis is a hormone-dependent chronic inflammatory disease with serious reproductive and general health consequences. It is viewed as a multifactorial problem, consisting of matters related to altered immunity and genetics. In this study, we determined the correlation between endometriosis and allergic and autoimmune diseases in patients at reproductive age. Materials and Methods: Online surveys distributed through websites related to gynecological problems. The questionnaire was composed of 63 single and multiple-choice questions concerning the course of endometriosis, diet, and allergic and autoimmune diseases. The obtained data were assessed using statistical tests. Results: 501 female patients (mean age 31.1 SD = 6.8) were included in the study. The control group (n = 155) consisted of healthy females, whereas the study group (n = 346) consisted of female patients with endometriosis; each group was subdivided according to allergy status. There were statistically significant differences between groups for the following: positive family history of endometriosis (p = 0.0002), onset of allergic symptoms (p = 0.0003), frequency and duration of abdominal pain (p = 0.00625), and defecation disorders (p = 0.0006). Asthma was less common in the study group (p = 0.00611). The group of patients with endometriosis and allergies had a high median of consumption of red meat (p = 0.0143), fish (p = 0.0016), and dairy products (p = 0.0001). Conclusions: Endometriosis did not affect autoimmune diseases and their courses. Patients with diagnosed endometriosis presented allergy symptoms much earlier than the healthy patients. The consumption of dietary products such as soya products, red meat, and alcohol had an influence on the occurrence of endometriosis.

miR 31-3p Has the Highest Expression in Cesarean Scar Endometriosis.

Micro-RNAs expression can vary between different forms of endometriosis, but data on miRNA expression in cesarean scar endometriosis is lacking. The present study is comprised of 30 patients with endometriosis in the cesarean scar (scar endometriosis, SE), 14 patients with deep infiltrating endometriosis (DIE), 47 patients with endometrioma (ovarian endometrial cyst, OE), and 33 patients with healthy ovarian tissue as the control group (CG). In the initial experiment to identify possible dysregulated miRNAs, the levels of 754 miRNAs in formalin-fixed paraffin-embedded tissue (FFPE) samples from OE, high-grade ovarian cancer, endometrioid ovarian cancer, and CG were measured. We identified seven potentially dysregulated miRNAs: miR-1-3p, miR-31-3p, miR-125b-1-3p, miR-200b-3p, miR-548d, miR-502, and miR-503. We then examined the expression profiles of each of these miRNAs individually in the SE, DIE, OE, and CG FFPE samples using RT-qPCR. miR-31-3p had significantly higher levels of expression and miR-125b-1-3p had significantly lower levels of expression in SE compared to the controls. Overall, the higher expression levels of miR-31-3p and the lower expression levels of miR-125b-1-3p are consistent with the benign nature of SE. Importantly, the results of the present study demonstrate the possibility of using miRNA to monitor the risk of malignant transformation of endometriosis tissue.

Adenomyosis as a Risk Factor for Myometrial or Endometrial Neoplasms-Review.

Adenomyosis is a common benign gynecological condition, defined as an extension of endometrial tissue into the myometrium. Some studies suggest that adenomyosis could be a favorable prediction factor associated with survival outcomes in endometrial cancer. The aim of our systematic review was to investigate the current knowledge regarding adenomyosis and a possible molecular mechanism of carcinogenesis in adenomyotic lesions. In addition, the long-term prognosis for patients with endometrial cancer and coexisting adenomyosis (and endometriosis) was a key point of the research. The current literature was reviewed by searching PubMed, using the following phrases: "adenomyosis and endometrial cancer" and "malignant transformation of adenomyosis". According to the literature, genetic mutations, epigenetic changes, and inactivation of specific tumor suppressor genes in adenomyosis are still poorly understood. Data regarding the influence of adenomyosis on survival outcomes in endometrial cancer seem to be contradictory and require further clinical and molecular investigation.

Endometriosis Stem Cells as a Possible Main Target for Carcinogenesis of Endometriosis-Associated Ovarian Cancer (EAOC).

Endometriosis is a serious recurrent disease impairing the quality of life and fertility, and being a risk for some histologic types of ovarian cancer defined as endometriosis-associated ovarian cancers (EAOC). The presence of stem cells in the endometriotic foci could account for the proliferative, migrative and angiogenic activity of the lesions. Their phenotype and sources have been described. The similarly disturbed expression of several genes, miRNAs, galectins and chaperones has been observed both in endometriotic lesions and in ovarian or endometrial cancer. The importance of stem cells for nascence and sustain of malignant tumors is commonly appreciated. Although the proposed mechanisms promoting carcinogenesis leading from endometriosis into the EAOC are not completely known, they have been discussed in several articles. However, the role of endometriosis stem cells (ESCs) has not been discussed in this context. Here, we postulate that ESCs may be a main target for the carcinogenesis of EAOC and present the possible sequence of events resulting finally in the development of EAOC.

Impact of Contraception on Uterine Fibroids.

Background and Objectives: Uterine fibroids develop in 25-40% of women of childbearing age; however, there are discrepancies resulting from population and socioeconomic differences. The pathogenesis of fibroids is not clear. The aim of the study was to assess the potential connection between the use of oral contraceptives and the occurrence of uterine fibroids in women of childbearing age. Materials and Methods: In this prospective, survey, case-control study, data were collected from Caucasian female patients (mean age = 30) using a questionnaire concerning the onset, duration and form of hormonal contraception, and medical and obstetrical history. The questionnaires were handed personally to hospitalized patients as well as distributed through Google forms on social media. Results: In a study group (n = 140) of patients using hormonal contraception, 37.8% of them were diagnosed with uterine fibroids, whereas among the patients not using hormonal contraception (n = 206), uterine fibroids were diagnosed in 59.6% of the patients. The most common hormonal contraception was two-component hormonal tablets used by 93.3% of the patients. Taking contraceptives was a uterine fibroids protective factor (OR = 0.4, p = 0.007). In the study group, 5.5% of the patients were pregnant and 60.42% were diagnosed with uterine fibroids (OR = 4.4, p < 0.000001). Conclusion: Contraception was found to be a protective factor for uterine fibroids among the women surveyed. The presented data confirm the theory about the hormonal dependence of uterine fibroids.

The association between imbalances in vaginal microflora and duration of pregnancy as well as selected maternal and neonatal parameters.

OBJECTIVES: Abnormal vaginal flora (AVF) is a result of excessive growth of some aerobic bacteria and fungi in relation to the scarce presence of Lactobacillus spp. It has been suggested that AVF is responsible for preterm birth and such neonatal conditions as infections or sepsis. The aim of the study was to assess the influence of excessive vaginal colonization with aerobic bacteria and fungi on the selected postnatal parameters of newborns, duration of pregnancy and length of hospitalisation of neonates. MATERIAL AND METHODS: Retrospective data of all 1057 patients who delivered between 01.2019 and 06.2019 in the Department of Perinatology of Medical University of Lodz was analyzed. Eight hundred nine patients were included in this retrospective study. The study group consisted of 396 patients with abundant growth of aerobic bacteria and fungi obtained between 26 and 42 weeks of gestation, while 413 patients with physiologic vaginal biocenosis constituted the control group. Two hundred forty-eight patients (23.46%) were excluded from the study due to incomplete data. RESULTS: Patients with abnormal vaginal flora (AVF) gave birth prematurely (9.09%) more often than patients with balanced microflora (5.31%), p = 0.038. Newborns of mothers with AVF obtained an Apgar score under four more frequently (1.21% vs 0%; p = 0.024). Eutrophic neonates were born less frequently in the study group (82.08% vs 88.65%; p = 0.025). Hospitalisation period was longer for children of mothers with AVF (mean of 6.30 ± 9.87 days) than those of mothers from the control group (mean of 5.06 ± 5.30), p = 0.025. Newborns of mothers with AVF developed perinatal infections more often (23.97% vs 15.94%; p = 0.004). Four infants died in the study group whereas no deaths were recorded in the control group (p = 0.045). The most prevalent pathogens were: Streptococcus agalactiae (GBS) 57.32%, Candida spp. 39.64%, Klebsiella spp. 9.85%, Staphylococcus aureus 7.32%. Signs of infection were more frequently recorded in newborns of mothers infected with Klebsiella spp. (35.90% vs 19.16%; p = 0.011). Premature birth was more prevalent in GBS carriers (11.81% vs 6.28%; p = 0.022). CONCLUSIONS: Abundant growth of aerobic bacteria in the 3rd trimester of gestation contributes to preterm birth, causes the development of infection signs in newborns, increases their mortality rate and prolongs hospitalisation period.

Adenomyosis and Infertility-Review of Medical and Surgical Approaches.

The aim of this review is to clarify the relative association between adenomyosis and infertility and the possible treatment for an infertile patient. Although adenomyosis is detected more often in women of late reproductive age, its influence on pregnancy rates is important, especially considering the tendency to delay pregnancy among women in developed countries. In this article, we present a critical analysis of the literature data concerning the impact of adenomyosis on fertility. The possible effects of treatment on the pregnancy rate will also be discussed. We conducted a literature search; publications from Pubmed, Embase and Cochrane databases published from 1982 to 2019 were retrieved using terms 'adenomyosis and infertility' and 'adenomyosis and pregnancy outcomes', extensively studied in the aspects of diagnosis, pathogenesis of infertility and possible treatment methods. Molecular studies have given deep insight into the pathogenesis of adenomyosis in the recent few years, but there is a huge discrepancy between in vitro studies and praxis. Oral contraceptive pills, anti-prostaglandins, oral or parenteral progestins, danazol and gonadotrophin-releasing hormone (GnRH) analogues have all been used to control menstrual pain and menorrhagia in women with adenomyosis, but they temporarily suppress the menstrual cycle. Additionally, endometrial ablation and hysterectomy used to alleviate pain caused by adenomyosis exclude pregnancy planning. The development of imaging techniques-ultrasound and MRI-enables the diagnosis of adenomyosis with very high accuracy nowadays, but the methods of treatment mentioned above have not given satisfactory results in women planning pregnancy. For these patients, the high-intensity-focused ultrasound method (HIFU) and combined treatment before assisted reproductive techniques can prove beneficial in adenomyosis patients.