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.

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.

Personalized embryo transfer (pET) guided by endometrial receptivity (ER) assessment - a possibility to increase effectiveness of IVF procedures. Review of available methods.

The continuous development of assisted reproductive techniques (ART) implies the search for solutions that could increase the effectiveness ofavailable methods. In the context of in vitro fertilization (IVF), a significant proportion of failures are due to unsuccessful embryo transfers. At this stage the most important issue is proper dialogue between implanting embryo and the maternal endometrium. Therefore, it seems justified to assess endometrial receptivity (ER), defined as the tissue's ability to accept an embryo to attach and invade into the mucosa. Window of implantation (WOI), is a certain period in which implantation of the properly developed embryo is possible. The cause of endometrial receptivity disorders is believed to be the disturbed expression of cytokines and endometrial surface proteins, the presence of which has been proven in commonly diagnosed diseases such as endometriosis or chronic endometritis. Despite many years of research on endometrial receptivity, the area of ​​diagnostic methods enabling clinical monitoring of ER still remains undeveloped. The aim of this study is to review the utility of selected markers and the available methods of ER assessment, ranging from noninvasive ultrasound, through endometrial fluid analysis, to genomic studies based on endometrial biopsy, in order to increase the effectiveness of IVF. Such an approach could potentially be a significant step towards personalizing medical procedures especially in patients diagnosed with repeated implantation failure (RIF).

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.

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.

Factors Associated with Uptake of Effective and Ineffective Contraceptives among Polish Women during the First Period of the COVID-19 Pandemic.

The COVID-19 pandemic has burdened the healthcare system and influenced individuals' health-related choices. The aim of the study was to estimate the prevalence and to identify the correlates of the use of more and less effective contraceptive methods among Poles in the initial period of the COVID-19 pandemic. The cross-sectional online study was conducted among the representative sample of 642 female respondents aged 18-49. Three groups of contraception choices (only effective methods-42.2%, mixed effective and ineffective methods-26.8%, none-31.0%) were distinguished and 11 potential determinants were considered. One in ten women declared having difficulty in accessing contraception during the first months of the pandemic. A multinomial logistic regression model explained 48.7% of the variation in contraceptive method choice. Both effective and ineffective methods were more often declared by young women, and less often in case of lower education, planning children or subjective no need for contraception. In addition, factors that reduced the chance of effective contraception were poor financial situation, already having children and a relatively higher degree of religiosity. The study confirmed that a significant share of Polish women do not opt for effective methods of contraception. Their choices had strong demographic, social and cultural determinants.

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.

How to avoid drug resistance during treatment and prevention of urinary tract infections.

Urinary tract infections (UTIs), defined as the presence of bacteria above the bladder sphincter, are among the most common infectious diseases. They remain a significant cause of antibiotic prescription worldwide. The incidence is much higher among women, especially of reproductive age, than among men. If the infection occurs at least 3 times a year or twice within 6 months, it is classified as recurrent urinary tract infection (rUTI). Among the causal pathogens, the vast majority are Gram-negative bacteria, the most common of which is Escherichia coli. Recommended treatment regimens differ depending on the diagnosed disease entity and the patient's clinical situation. Empirical antibiotic therapy is most often used. The first-line treatment in patients with acute simple cystitis include nitrofurantoin, trimethoprim-sulfamethoxazole, or fosfomycin. Beta-lactams and fluoroquinolones should be considered as a second-line agent. In particular cases (pregnancy or rUTIs) targeted treatment, based on the results of urine culture and antibiogram, is implemented. During pregnancy recommended treatment includes administration of cephalosporins (e.g. cefuroxime) or nitrofurantoin. In patients with uncomplicated pyelonephritis fluoroquinolones should be considered as the first-line regimen. In the case of rUTIs, there are no uniform guidelines for prophylactic management. Repeated administration of antibiotics due to infections leads to a growing problem of drug resistance. Most recommendations suggest not to use antibiotic prophylaxis routinely. Growing evidence favours non-antibiotic prophylaxis regimens for recurrent UTIs. Until now only one product - oral immunostimulant OM-89 - has been sufficiently investigated. Wider implementation of immunoprophylaxis in the future may reduce possible side effects of inappropriate antibiotic consumption.

Infertility in Female and Male Solid Organ Recipients - From Diagnosis to Treatment: An Up-To-Date Review of the Literature.

Around 20% to 30% of patients after solid organ transplantation are of reproductive age. The estimated rate of infertility in this group is slightly higher than in the general population. Choosing the optimal moment for pregnancy in transplanted patients plays a pivotal role, regardless of the method of conception. The first part of this article presents an up-to-date review of the problem of infertility in female and male solid organ recipients, with special attention to the influence of specific immunosuppressive drugs on semen parameters. The second part discusses the current knowledge regarding infertility treatment and the results of assisted reproductive techniques in this specific group of patients. Despite restoring gonadal functions after transplantation, the patients should be informed about possible negative effects of medications on fertility, course of pregnancy, and the fetus. Interdisciplinary care should always be provided for infertile graft recipients, especially women, as it ensures safety both for the graft and for the potential gestation. The process of infertility diagnosis and tools used for that purpose are the same in transplanted patients as in the general population. The treatment with assisted reproductive techniques is acceptable and gives favorable results as long as patients are managed rationally, with special attention paid to prevention of iatrogenic complications.

Should the patients with endometriosis be treated as a risk group of pregnancy complications? Single center experience and literature review and literature review.

OBJECTIVES: Multidirectional influence of endometriosis on fertility impairments is well known. Altered implantation and placentation among affected patients raised concerns regarding possible negative influence on the course of pregnancy. The primary objective of the study was to assess the course of gestation and the incidence of pregnancy complications among women with endometriosis. It also aimed to determine whether the method of conception might impact the primary results. MATERIAL AND METHODS: A single-center cohort study included 64 women with confirmed endometriosis and 296 healthy controls. Data concerning treatment of endometriosis related infertility, course of pregnancy and perinatal outcomes were evaluated. RESULTS: Patients with endometriosis were older than controls (33.6 +/- 4.2 y vs 31.8 +/- 4.6, p = 0.01) and more often gave birth for the first time (87.5% vs 43.9%, p = 0.001). The age at the time of first delivery was significantly higher within the study group (33.1 y +/- 4.1 vs 29.9 +/- 4.6, p < 0.001). In the study, 81.2% of patients with endometriosis had the diagnosis of infertility. Patients suffering from endometriosis were significantly more prone to spontaneous placental abruption during pregnancy and delivery (4.7 vs 0.3%, odds ratio = 14.5). Several complications occurred more often in endometriotic patients (gestational diabetes mellitus, small-for-gestational-age and anemia); however, without statistical significance. The risk of pregnancy complications was independent from stage of endometriosis and way of conception. The incidences of adverse neonatal outcomes (preterm delivery, low Apgar score, lower birth weight) were similar in both groups. CONCLUSIONS: Endometriosis may adversely affect perinatal outcomes, especially due to increased risk of placenta abruption and operative delivery. Stage of endometriosis and method of conception does not enhance these complications.

The Impact of Endometriosis on the Quality of Life and the Incidence of Depression-A Cohort Study.

The objective was to evaluate the quality of life and the incidence of depression among women suffering from endometriosis. Afterwards, the dependency between pelvic pain, its severity and stages of endometriosis were analyzed. The study protocol included women of reproductive ages with confirmed endometriosis. The stage of disease was conferred according to the ASRM (American Society of Reproductive Medicine) classification. Women fulfilled two questionnaires: "WERF EPHect Clinical Questionnaire" and self-prepared survey about fertility disorders. The study group comprised of 246 respondents. A total of 77.2% of women were symptomatic. The most common complaints were chronic pelvic pain (CPP, 71.1%), dysmenorrhea (69.0%) and dyspareunia (45.2%). Intensity of pain was independent from the stage of endometriosis. The incidence of infertility and the time to conceive increased with the stage of disease (stage 1-52.8%, 3.4 years; stage 2-66.7%, 4.1 years; stage 3-61.3%, 3.7 years; stage 4-96%, 6.1years; p = 0.02 and 0.03, respectively). The prevalence of depression was positively correlated with the beginning of dyspareunia (14.5 vs 19.6 years old., p = 0.002). CPP (OR(odds ratio) = 3.8, 95% CI 1.2-12.8, p = 0.04) and painful defecation (OR = 7.7, 95% CI 1.4-42.3, p = 0.01) increased the risk of depression. Symptoms related to endometriosis and severity of pain correlate with the prevalence of depression. Stage of endometriosis is significantly related to the prevalence of infertility.

Epidemiology, prevention and management of early postpartum hemorrhage - a systematic review.

Early Postpartum Hemorrhage (EPH) is one of the leading causes of postpartum mortality. It is defined as blood loss of at least 500 mL after vaginal or 1000 mL following cesarean delivery within 24 hours postpartum. The following paper includes literature review aimed to estimate the incidence and predictors of early postpartum hemorrhage (EPH). Available prevention and treatment methods were also assessed. The inclusion criteria for the study were met by 52 studies. The exact frequency of EPH in different populations varies from 1.2% to 12.5%. Maternal, pregnancy-associated, laborcorrelated and sociodemographic risk factors seem to be important predictors of EPH. In these cases appropriate prophylaxis should be considered. However, EPH may occur without previous risk factors. The main reason for EPH is uterine atony which contributes to up to 80% of cases of postpartum hemorrhage (PPH). Other common reasons for PPH include genital tract injuries, placenta accreta or coagulopathies. Interestingly, the majority of uterotonics seem to have a similar effect. However, carbetocin seems to be the most effective in certain situations. Appropriate diagnosis of EPH is the most important issue. The treatment should be causative. The first-line treatment should include uterotonics. Surgical interventions, if required, should be performed without delay, although preoperative uterine tamponade should be considered due to its high effectiveness. Medical staff training in medical simulation centers is an important factor that improves the outcomes of EPH treatment. It provides adaptation to hospital protocols, team work improvement, self-confidence building, more accurate blood loss evaluation and reduced perception of stress. The implementation of systematic trainings provides better outcomes in the future.

Blood pressure in postmenopausal women with a history of polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder at reproductive age, affecting 6-10% of females in this group. The aetiology of this syndrome is not fully understood. Genetics, endocrinology factors, and the influence of the environment are possible causes of this syndrome. PCOS is characterised by menstrual disorders, hyperandrogenism, and abnormalities in ovarian morphology as well as metabolic disorders. PCOS increases the risk of overweight and obesity, diabetes, endometrial cancer, and cardiovascular diseases such as hypertension along with all its long-term consequences. There are limited studies about cardiovascular disorders, especially hypertension, in postmenopausal women with a history of PCOS. The presented paper is an attempt to briefly summarise literature data concerning the influence of this disease on the incidence of hypertension and blood pressure control in postmenopausal women. Women with PCOS more often present features of metabolic syndrome and have increased cardiovascular risk factors including hypertension. The prevalence of hypertension is 2.5 times higher than in corresponding healthy peers. Furthermore, hyperandrogenaemia is associated with elevated blood pressure independent of the patient's age, insulin resistance, obesity, and dyslipidaemia. In view of this, these patients should be thoroughly screened for hypertensive disorders and educated about the lifestyle modifications that could prevent hypertension later in life.

Premature ovarian insufficiency as a variable feature of blepharophimosis, ptosis, and epicanthus inversus syndrome associated with c.223C > T p.(Leu75Phe) FOXL2 mutation: a case report.

BACKGROUND: FOXL2 gene mutations cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and may be associated with premature ovarian insufficiency (POI). Two types of BPES were described in the literature. BPES type 2 is a simple association of inherited developmental defects of the eyelid area, while in type 1 female patients additionally suffer from POI. The following case study is the first report of endocrine impairments typical for menopausal transition in young female with NG_012454.1:g.138665342G > A, c.223C > T p.(Leu75Phe), mutation in FOXL2 gene. This mutation has been reported in the literature before, however until now, it was never linked to BPES type 1. CASE PRESENTATION: An 18-year-old nulliparous woman suspected of secondary amenorrhea was referred to our Endocrinology Outpatient Clinic. Blood tests revealed decreased levels of AMH (anti-Mullerian hormone) and increased levels of gonadotropins, suggesting menopausal transition. Her past medical history was remarkable for several ophthalmic defects that has required surgical interventions. BPES syndrome had not been suspected before, although the patient had reported a similar phenotype occurring in her father, sister and half-sister. Venous blood samples were collected from the female proband and from her three family members. Whole-exome sequencing and deep amplicon sequencing were performed. A potential pathogenic variant in the FOXL2 gene was revealed. Namely, the c.223C > T p.(Leu75Phe) missense variant was detected. CONCLUSIONS: The authors found mutations, c.223C > T p.(Leu75Phe) in the FOXL2 gene in a young woman with hormonal disorders suggesting menopausal transition. These results indicate that the possibility of different phenotypes should be considered in patients with a similar genetic mutation.