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Michal Zygarowicz,1,* Joanna Kacperczyk-Bartnik,2,3,* Janusz Sierdzinski,4 Cezary Wojtyla,5,6 Piotr Pierzynski,5,6 Grzegorz Manka,7 Mariusz Kiecka,7 Robert Z Spaczynski,8 Piotr Piekarski,9 Beata Banaszewska,10 Artur Jakimiuk,11,12 Tadeusz Issat,13 Wojciech Rokita14,15 ,† Jakub Mlodawski,14,15 Maria Szubert,3,16,17 Piotr Sieroszewski,16,18 Grzegorz Raba,19,20 Kamil Szczupak,19,20 Tomasz Kluz,21 Marek Kluza,21 Michal Lipa,3,22 Damian Warzecha,5,22 Miroslaw Wielgos,23,24 Ewa Koc-Zorawska,25,26 Marcin Zorawski,26,27 Piotr Laudanski5,6,28 1Students’ Scientific Group Affiliated to the Department of Obstetrics, Gynecology and Gynecological Oncology, Medical University of Warsaw, Warsaw, Poland; 2II Department of Obstetrics and Gynaecology, Medical University of Warsaw, Warsaw, Poland; 3Club 35. Polish Society of Gynecologists and Obstetricians, Wrocław, Poland; 4Department of Medical Informatics and Telemedicine, Medical University of Warsaw, Warsaw, Poland; 5OVIklinika Infertility Center, Warsaw, Poland; 6Women’s Health Research Institute, Calisia University, Kalisz, Poland; 7Angelius Provita Hospital, Katowice, Poland; 8Center for Gynecology, Obstetrics and Infertility Treatment Pastelova, Poznan, Poland; 9Division of Infertility and Reproductive Endocrinology, Department of Gynecology, Obstetrics and Gynecological Oncology, Poznan University of Medical Sciences, Poznan, Poland; 10Chair and Department of Laboratory Diagnostics, Poznan University of Medical Sciences, Poznan, Poland; 11Department of Obstetrics and Gynecology, Central Clinical Hospital of the Ministry of Interior, Warsaw, Poland; 12Center of Reproductive Health, Institute of Mother and Child in Warsaw, Warsaw, Poland; 13Department of Obstetrics and Gynecology, Institute of Mother and Child in Warsaw, Warsaw, Poland; 14Collegium Medicum Jan Kochanowski University in Kielce, Kielce, Poland; 15Clinic of Obstetrics and Gynecology, Provincial Combined Hospital in Kielce, Kielce, Poland; 16Department of Gynecology and Obstetrics Medical University of Lodz, Lodz, Poland; 17Department of Surgical Gynecology and Oncology, Medical University of Lodz, Lodz, Poland; 18Department of Fetal Medicine and Gynecology, Medical University of Lodz, Lodz, Poland; 19Clinic of Obstetrics and Gynecology, Provincial Hospital, Przemysl, Poland; 20Department of Obstetrics and Gynecology, University of Rzeszow, Rzeszow, Poland; 21Department of Gynecology, Gynecology Oncology and Obstetrics, Institute of Medical Sciences, Medical College of Rzeszow University, Rzeszow, Poland; 22Department of Obstetrics and Gynaecology, Warsaw Southern Hospital, Warsaw, Poland; 23Premium Medical, Warsaw, Poland; 24Faculty of Medicine, Lazarski University, Warsaw, Poland; 25II Department of Nephrology, Hypertension and Internal Medicine with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland; 26The Academy of Applied Medical and Social Sciences, Elbląg, Poland; 27Department of Cardiology, Lipidology and Internal Medicine with Cardiac Intensive Care Unit, Medical University of Bialystok, Bialystok, Poland; 28Department of Obstetrics, Gynecology and Gynecological Oncology, Medical University of Warsaw, Warsaw, Poland*These authors contributed equally to this work†Professor Wojciech Rokita passed away on March 18, 2020Correspondence: Piotr Laudanski, Department of Obstetrics, Gynecology and Gynecological Oncology, Medical University of Warsaw, Kondratowicza Street 8, Warsaw, 03-242, Poland, Tel +48 22 326 53 80, Email piotr.laudanski@wum.edu.plIntroduction: 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.Keywords: annexin A2, endometriosis, infertility

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., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Uterine fibroids are the most common noncancerous tumors in women of childbearing age. This review was developed to evaluate the current role of gonadotropin-releasing hormone (GnRH) agonists and antagonists in the therapy of symptomatic uterine fibroids., Areas Covered: There is a great need for alternative methods for surgical treatment of uterine fibroids. Hormonal therapy remains the first-line treatment option for most patients. GnRH analogs (agonists and antagonists) modulate the pulsatile release of GnRH. This review summarizes the available literature concerning pharmacologic principles underlying the mechanism of action of GnRH and its analogs, as well as individual therapeutic applications to which these drugs have been applied., Expert Opinion: In many cases, it is possible to try to treat uterine fibroids pharmacologically. Both groups of GnRH analogs are used in therapy, agonists instead as a preparation for surgery, and antagonists as a drug for long-term use. It is essential to develop this path further and look for at least long-term-release systems or new methods of administering these drugs. It is also important from the patient's perspective to search for possible drugs that may have an additive effect of decreasing side effects when combined with GnRH analogs.

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.

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 Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D 3 ) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

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.

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.

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.

Purpose: Despite considerable advances in recently developed combined oral contraceptives (COCs), resulting in lower rates of adverse events while maintaining contraceptive efficacy, there is interest in further innovation., Materials and Methods: Estetrol (E4), a native oestrogen, and progestin drospirenone (DRSP) were combined in a new COC. A European expert panel reviewed the pharmacology, efficacy, and safety and tolerability of this combination. Their findings are presented as a narrative review., Results: E4 15 mg/DRSP 3 mg in a 24/4 regimen provided effective contraception with good cycle control, characterised by a predictable regular bleeding pattern and minimal unscheduled bleeding, together with a good safety profile. The combination was associated with high user satisfaction, well-being, and minimal changes in body weight. The effects on endocrine and metabolic parameters were limited, and the combination was found to have a limited impact on liver function and lipid and carbohydrate metabolism. Moreover, its effect on several haemostatic parameters was lower than that of comparators containing ethinyl oestradiol (EE) 20 µg/DRSP 3 mg and EE 30 µg/levonorgestrel 150 µg., Conclusion: E4 15 mg/DRSP 3 mg provides safe and effective contraception, with high user satisfaction and predictable bleeding. Further research will evaluate the long-term safety of the COC.

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.

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.

Polycystic ovary syndrome (PCOS) is the most commonly diagnosed endocrine disorder in women of reproductive age, affecting approximately 5-8% of females in this group. It is characterized by hyperandrogenism, abnormal periods (rare periods or amenorrhea) and polycystic ovaries visualized through ultrasonography. The etiopathogenesis of polycystic ovary syndrome has not been elucidated in detail. There are numerous hypotheses on this subject which tend to complement one another. The most widely recognized hypothesis is that the development of PCOS is due to insulin resistance and hyperinsulinemia, which subsequently lead to hyperandrogenism. On the basis of an as of yet relatively small number of studies, an increased prevalence of various psychiatric disorders can be observed in women with PCOS. These include: depression, generalized anxiety disorder, personality disorders, social phobia, obsessive-compulsive disorder, attention deficit hyperactivity disorder (ADHD), and eating disorders. Bipolar affective disorder, schizophrenia and other psychotic disorders have also been reported in women with PCOS more often than in the general population. The higher prevalence of psychiatric disorders in patients with PCOS, especially depression and anxiety disorders, may be due to both hyperandrogenism and the resulting somatic symptoms. These symptoms can undoubtedly be stigmatizing for women and lower their quality of life. This article is intended to provide an overview of the literature regarding mental disorders associated with polycystic ovary syndrome and to present own research on depression and sexual dysfunction in this group.

Aim of the Paper: Comparison of conventional cytodiagnostics with molecular identification of DNA and mRNA HPV HR, immunocytochemical test for suppressor protein P16 and nuclear Ki 67 to detect cervical pathology screening of the division to LG SIL and HG SIL., Material: 630 Pap smears were taken from women with suspected cervical pathology were submitted for analysis, together with 558 smears for the presence of DNA HPV HR, 421 swabs for the presence of mRNA HPV HR, 86 swabs for the presence of suppressor protein P16 and nuclear Ki 67. In all of the women standard colposcopy with biopsy and endocervical abrasion were performed., Method: The study used a classic cytological smear taken on the slide, rated in accordance with TBS classification, colposcopy implemented in accordance with the guidelines of the International Federation of Cervical Pathology and Colposcopy from 2003, molecular diagnostic tests based on identifying DNA, mRNA HPV HR and immunocytochemistry diagnostic test--CINtecPLUS., Results: The sensitivity of Pap test identification of CIN 2+ was of 85% and specificity of 23%. Indicators PPV and NPV were respectively 39% and 72%. The accuracy of cytology reached a level of 46%. DNA HPV HR test obtained 91% sensitivity and 33% specificity of the diagnosis of CIN 2+. Its accuracy was 54%. The value of PPV and NPV for molecular diagnostics was respectively 43% and 87%. For mRNA HPV HR test sensitivity of the method was 79%, the specificity was 67%. CINTecPLUS test achieved 100% sensitivity and 67% specificity in the diagnosis of CIN 2+., Conclusions: 1. Conventional cytodiagnostics are inferior in terms of both sensitivity and specificity of molecular test for DNA, mRNA HPV HR and immunocytochemical test for detecting of LG SIL and HG SIL. 2. Immunocytochemical technique shows maximum sensitivity and high specificity of detection of actual precancerous stages--CIN 2+.

Objective: The aim of the study was to assess the diagnostic value of pap smears and detection of the p16 and Ki67 proteins in women with cervical intraepithelial neoplasia (CIN)., Materials and Method: 630 women, aged between 25 and 65, with abnormal pap smears were included into the study All patients had a control pap smear and in each case punch biopsy with endocervical curettage were performed under the control of a colposcope. The presence of p16 and Ki67 proteins was detected using the CINtecPlus test. The results of the research were statistically assessed., Results: Abnormal pap smears were found in 82.5% (520/630) of the studied women. In 40% (252/630) of the cases the LSIL changes were found. The recognition of ASC-US concerned 35.2% (222/630) of the patients, and pap smears with the HSIL result were found in 7.3% (46/630) of the women. In 17.5% (110/630) of the patients the result of the cytological examination was normal. Abnormal results of the pap smears were found significantly statistically more frequently (p<0,0001) in women with cervical intraepithelial neoplasia (CIN). The results of the CINtecPlus test were positive in 68,4% of women with CIN and in 33,3% of patients with normal cervix. In the group of women with precancerous lesions (HGSIL/CIN2+) the diagnostic accuracy of the pap smear was 41% for the cytological results ASC-US, 56% LSIL and 73% for detection of HSIL. Immunocytochemical detection of p16 and Ki67 proteins gained the highest accuracy (78%) in recognition of cervical precancerous lesions., Conclusion: 1. ASC-US and LSIL cytological recognition has low accuracy in the diagnosis of CIN2+ cervical changes. 2. Cytological recognition of HSIL has the highest accuracy in the diagnosis of CIN2+ changes. 3. Immunocytochemical detection of p16 and Ki67 proteins is more accurate in recognizing precancerous states and cervical cancer than cytological examination. 4. Immunocytochemical detection of the p16 and Ki67 proteins can be used to triage patients with atypical squamous cells of undetermined significance and low grade squamous intraepithelial lesions.

Objectives: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and oligo-/anovulation and is associated with risk factors for cardiovascular disorders, such as insulin resistance and central adiposity. All these factors can lead to endothelial dysfunction and impaired coagulation processes. Metformin effectively treats hyperinsulinemia in women with PCOS. However, clinical trials assessing influence of metformin on endothelium and fibrinolysis are limited. Therefore, the objective of this study was to prospectively assess the effects of a 6-month metformin therapy on body mass index (BMI), insulin sensitivity and coagulation/fibrinolysis markers in hyperinsulinemic women with PCOS., Materials and Methods: Thirty hyperinsulinemic PCOS women (aged 26.0 +/- 3.7 [mean +/- SD]) without any additional disorders were included into the study. Metformin was administered at a dose of 1700 mg daily for 6 months. Serum plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA) concentrations and von Willebrand factor (vWf) levels were measured with specific assays, together with glucose and insulin concentrations. Insulin sensitivity index (ISI) and BMI were calculated., Results: All patients completed the study and no side effects were reported. BMI decreased significantly (by 8.5%, p < 0.0001). The metformin therapy improved insulin sensitivity as evidenced by an increase in ISI by 41.5% (p = 0.0005). A marked reduction in PAI-1 (by 26%, p < 0.005) concentrations was observed. No significant changes were noted for t-PA and vWf., Conclusions: Metformin administration decreases the circulating PAI-1 concentration and simultaneously improves insulin sensitivity and BMI in PCOS women with hyperinsulinemia. Long-term metformin administration may be a new prophylactic measure for the prevention of cardiovascular disorders in such patients.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 6-9% of women in reproductive age. It is characterized by hyperandrogenism, oligo- or anovulation and infertility PCOS is associated with important cardiovascular risk factors including: obesity dyslipidemia, systemic inflammation and endothelial dysfunction. Statins are well-tested medications reducing a broad range of cardiovascular risk factors. The primary mode of action of statins is inhibition of HMG-Co A reductase, a rate-limiting step of cholesterol synthesis. In recent randomized studies in PCOS women, statins have decreased testosterone level, improved menstrual cycle regularity and lipid profile.

Ovarian tumors complicating clinical course of pregnancy are rare (approximately 1 per 1000 deliveries). Conservative management, as well as surgical intervention could be associated with high risk for the mother and fetus. In this report we describe diagnosis and therapy of 26 years old primary gravida with 7 cm ovarian teratoma. Extensive ultrasound examination assessing localization and risk of malignancy of the tumor was done before operation. Laparoscopy was performed at 16 weeks gestation and no intra- and postoperative complications were observed. The outcome of the pregnancy was normal. Laparoscopic treatment of ovarian tumors during pregnancy, by experienced team, after appropriate diagnostic process, seems to be safe and effective.

Purpose: The aim of this study was to determine the incidence of abnormal LH/FSH ratio in women with polycystic ovary with normo- and hyperinsulinemia and to assess the influence of elevated LH/FSH ratio on selected endocrine and biochemical parameters., Material and Methods: One hundred nineteen polycystic ovary syndrome women in reproductive age hospitalized between 1996 and 2000 in Division of Infertility and Reproductive Endocrinology at Poznan University of Medical Sciences were selected for the study. In all selected women LH and FSH serum levels were determined and LH/FHS ratio was calculated. These groups became the subject of a detailed clinical, hormonal and metabolic analysis, which was performed between 6th and 10th day of a natural or induced menstrual period., Results: LH/FSH ratio greater than 2 was accepted as abnormal, and it was found in 54 women (45.4%; I group). Normal gonadotropin ratio was detected in 65 women (55%; group II). Statistically significant differences were noted between groups with normal and elevated LH/FSH ratio in the following parameters: BMI (body mass index), serum insulin, and LH levels. Further analysis revealed that the majority of women with elevated insulin concentrations belong to the group with normal LH/FSH ratio., Conclusions: LH/FSH ratio is not a characteristic attribute of all PCOS women: in the present study this abnormality was detected in a subpopulation smaller than 50%. Most of the PCOS women with normal gonadotropin ratio belong to a group of patients suffering from hyperinsulinemia and obesity. Patients with hyperinsulinemia and excess of LH constitute a selected and distinct subgroup with increased adrenal androgenic activity.