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.

Steroidogenic activity of liposomal methylated resveratrol analog 3,4,5,4'-tetramethoxystilbene (DMU-212) in human luteinized granulosa cells in a primary three-dimensional in vitro model.

PURPOSE: Steroid hormone secretion is one of the key functions of granulosa cells (GCs). Resveratrol is a natural polyphenol, known for its beneficial health effects, such as improving reproductive health. However, its application is limited due to poor bioavailability. The methoxy derivative of resveratrol (DMU-212) was demonstrated to be more lipophilic, and therefore of greater bioavailability. However, since the addition of methoxy groups to the stilbene scaffold was found to make the molecule insoluble in water, DMU-212 was loaded into liposomes. This study aimed to evaluate how the liposomal formulation of DMU-212 (lipDMU-212) alters estradiol and progesterone secretion of human ovarian GCs in a primary three-dimensional cell culture model. METHODS: DMU-212-loaded liposomes were prepared by thin film hydration followed by extrusion. Cell viability was measured after exposure of GCs spheroids to the liposomal formulation of DMU-212 using CellTiter-Glo® 3D Cell Viability Assay. The secretion of estradiol and progesterone was determined using commercial ELISA kits. RT-qPCR was conducted to analyze the expression of steroidogenesis-related genes. Finally, the western blot technique was used to analyze the effect of lipDMU-212 and FSH treatments on CYP11A1 and HSD3B1 protein levels. RESULTS: lipDMU-212 was found to significantly increase estradiol and progesterone secretion in a dose-dependent manner by enhancing the expression of CYP11A1, HSD3B1, StAR, CYP17A1, CYP19A1, and HSD17B1 genes. We have also shown that lipDMU-212, used alone and in combination with FSH, significantly increased the expression of the HSD3B1 and CYP11A1 proteins in GCs. Furthermore, our study suggests that lipDMU-212 increases FSH activity. CONCLUSIONS: This is the first study to describe the steroidogenic activity of liposomal formulation of DMU-212, possibly through increasing the StAR and CYP19A1 expression. These findings suggest that lipDMU-212 might have a beneficial effect in the treatment of disorders related to estrogen deficiency and hyperandrogenism, such as PCOS.

Cardiovascular Function in Different Phases of the Menstrual Cycle in Healthy Women of Reproductive Age.

Background: Sex hormones influence the cardiovascular (CV) function in women. However, it is uncertain whether their physiological variation related to the regular menstrual cycle affects the CV system. We studied changes in the hemodynamic profile and body's water content and their relation to sex hormone concentration in healthy women during the menstrual cycle. Material and methods: Forty-five adult women were examined during the early follicular, late follicular, and mid-luteal phases of the same menstrual cycle. The hemodynamic profile was estimated non-invasively by cardiac impedance while water content was estimated by total body impedance. Results were compared with repeated measures ANOVA with post-test, if applicable. Results: There were no significant changes in most hemodynamic and water content parameters between the menstrual cycle phases in healthy women. Left ventricular ejection time differed significantly among phases of the menstrual cycle, with shorter values in the mid-luteal phase (308.4 vs. 313.52 ms, p < 0.05) compared to the late follicular phase. However, the clinical relevance of such small differences is negligible. Conclusions: Changes in sex hormones during the physiological menstrual cycle appear to have no considerable effect on healthy women's hemodynamic function and water accumulation.

Endocrine Disrupting Chemicals in Polycystic Ovary Syndrome: The Relevant Role of the Theca and Granulosa Cells in the Pathogenesis of the Ovarian Dysfunction.

Polycystic ovary syndrome (PCOS) is the most common heterogeneous endocrine disorder among women of reproductive age. The pathogenesis of PCOS remains elusive; however, there is evidence suggesting the potential contribution of genetic interactions or predispositions combined with environmental factors. Among these, endocrine disrupting chemicals (EDCs) have been proposed to potentially contribute to the etiology of PCOS. Granulosa and theca cells are known to cooperate to maintain ovarian function, and any disturbance can lead to endocrine disorders, such as PCOS. This article provides a review of the recent knowledge on PCOS pathophysiology, the role of granulosa and theca cells in PCOS pathogenesis, and the evidence linking exposure to EDCs with reproductive disorders such as PCOS.

Expression Profile of New Gene Markers and Signaling Pathways Involved in Immunological Processes in Human Cumulus-Oophorus Cells.

The function of the immune system extends from defense against external pathogens to the recognition and elimination of mutated or dying cells, aiding elimination of malignant potential and/or maintaining homeostasis. The many cell types of the immune system secrete a broad range of factors to enable cellular signaling that is vital to physiological processes. Additionally, in the ovary, follicular selection and maturation, as well as ovulation, are directly regulated by the nearby immune cells. Additionally, ovulation and rupture of the follicle have been observed to resemble a local inflammatory response. Cells of the cumulus-oocyte complex (COC) show evolving gene expression profiles throughout the oocytes' lifespan, including genes associated with immunological processes. Analysis of these genes allows the identification of useful molecular markers, as well as highlighting gene functions and interactions in these cells. Cumulus cells were obtained from hormonally stimulated patients undergoing an in vitro fertilization procedure and studied under long-term culture conditions. The microarray technique made it possible to compare the level of CCs' gene expression on the 1st, 7th, 15th and 30th day of cultivation. Additionally, RNA microarray analysis was performed to map gene expression in these cells, associated with immunological processes and associated cytokine signaling. Subsequently, the use of DAVID software allowed us to identify the "defense response to other organism", "defense response", "defense response to virus", "cytokine secretion", "cytokine production" and "cytokine-mediated signaling pathway" GO BP terms, as well as allowing further analysis of the most differentially expressed genes associated with these processes. Of the 122 genes involved, 121 were upregulated and only one was downregulated. The seven most upregulated genes related to the abovementioned terms were ANXA3, IFIT1, HLA-DPA1, MX1, KRT8, HLA-DRA and KRT18. Therefore, genes involved in immunological defense processes are upregulated in CC cultures and could serve as useful molecular markers of growth and development in the COC, as well as the proliferation of granulosa and cumulus cells.

Human Granulosa Cells-Stemness Properties, Molecular Cross-Talk and Follicular Angiogenesis.

The ovarian follicle is the basic functional unit of the ovary, comprising theca cells and granulosa cells (GCs). Two different types of GCs, mural GCs and cumulus cells (CCs), serve different functions during folliculogenesis. Mural GCs produce oestrogen during the follicular phase and progesterone after ovulation, while CCs surround the oocyte tightly and form the cumulus oophurus and corona radiata inner cell layer. CCs are also engaged in bi-directional metabolite exchange with the oocyte, as they form gap-junctions, which are crucial for both the oocyte's proper maturation and GC proliferation. However, the function of both GCs and CCs is dependent on proper follicular angiogenesis. Aside from participating in complex molecular interplay with the oocyte, the ovarian follicular cells exhibit stem-like properties, characteristic of mesenchymal stem cells (MSCs). Both GCs and CCs remain under the influence of various miRNAs, and some of them may contribute to polycystic ovary syndrome (PCOS) or premature ovarian insufficiency (POI) occurrence. Considering increasing female fertility problems worldwide, it is of interest to develop new strategies enhancing assisted reproductive techniques. Therefore, it is important to carefully consider GCs as ovarian stem cells in terms of the cellular features and molecular pathways involved in their development and interactions as well as outline their possible application in translational medicine.

Assisted reproductive medicine in Poland, 2013-2016: Polish Society of Reproductive Medicine and Embryology (PTMRiE) and Fertility and Sterility Special Interest Group of the Polish Society of Gynaecologists and Obstetricians (SPiN PTGiP) report.

OBJECTIVES: The purpose of this publication is to present data on the results and complications associated with infertility treatment using assisted reproductive technology (ART) and intrauterine insemination (IUI) in Poland between 2013 and 2016. MATERIAL AND METHODS: The report was prepared by the Polish Society of Reproductive Medicine and Embryology (PTMRiE) and the Fertility and Sterility Special Interest Group of the Polish Society of Gynaecologists and Obstetrics (SPiN PTGiP) as a part of the European IVF Monitoring program (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). Reporting was voluntary and the data was not subject to external control. The report presents the availability and structure of infertility treatment services, the number of procedures, their effectiveness and complications. RESULTS: Between 2013 and 2016, a total of 106,718 treatment cycles using ART [64,413 classical in vitro fertilization and in vitro fertilization with intracytoplasmic sperm injection (IVF + ICSI), 36,041 frozen embryo replacements (FER)] and 51,405 IUI were recorded. The clinical pregnancy rates per embryo transfer in IVF, ICSI and FER were 38.3%, 38.1% and 32.4%, respectively. The effectiveness of IUI with husband/partner's semen (IUI-H) was 11.1% and with donor semen (IUI-D) 16.7%. Multiple delivery rates were 11.3% and 6.2% in IVF + ICSI and IUI, respectively. The most common complication was the ovarian hyperstimulation syndrome (OHSS) (0.34%). CONCLUSIONS: PTMRiE and SPiN PTGiP report is the only national study documenting Polish reproductive medicine. The results of infertility treatment effectiveness in Poland are comparable with the European data, complications are less frequent than in other countries. The low percentage of multiple pregnancies, and so perinatal complications, is especially valuable. However, due to the lack of a central database and register, the possibility of external control and monitoring of pregnancies and births is limited. Thus, a fully reliable assessment of the treatment quality in our country is not possible.

Muscle Cell Morphogenesis, Structure, Development and Differentiation Processes Are Significantly Regulated during Human Ovarian Granulosa Cells In Vitro Cultivation.

Granulosa cells (GCs) have many functions and are fundamental for both folliculogenesis and oogenesis, releasing hormones and communicating directly with the oocyte. Long-term in vitro cultures of GCs show significant stem-like characteristics. In the current study, RNA of human ovarian granulosa cells was collected at 1, 7, 15 and 30 days of long-term in vitro culture. Understanding the process of differentiation of GCs towards different cell lineages, as well as the molecular pathways underlying these mechanisms, is fundamental to revealing other possible stemness markers of this type of cell. Identifying new markers of GC plasticity may help to understand the aetiology and recurrence of a wide variety of diseases and health conditions and reveal possible clinical applications of the ovarian tissue cells, affecting not only the reproductive ability but also sex hormone production. Granulosa cells were the subject of this study, as they are readily available as remnant material leftover after in vitro fertilisation procedures and exhibit significant stem-like characteristics in culture. The change in gene expression was investigated through a range of molecular and bioinformatic analyses. Expression microarrays were used, allowing the identification of groups of genes typical of specific cellular pathways. This candidate gene study focused on ontological groups associated with muscle cell morphogenesis, structure, development and differentiation, namely, "muscle cell development", "muscle cell differentiation", "muscle contraction", "muscle organ development", "muscle organ morphogenesis", "muscle structure development", "muscle system process" and "muscle tissue development". The results showed that the 10 most upregulated genes were keratin 19, oxytocin receptor, connective tissue growth factor, nexilin, myosin light chain kinase, cysteine and glycine-rich protein 3, caveolin 1, actin, activating transcription factor 3 and tropomyosin, while the 10 most downregulated consisted of epiregulin, prostaglandin-endoperoxide synthase 2, transforming growth factor, interleukin, collagen, 5-hydroxytryptmine, interleukin 4, phosphodiesterase, wingless-type MMTV integration site family and SRY-box 9. Moreover, ultrastructural observations showing heterogeneity of granulosa cell population are presented in the study. At least two morphologically different subpopulations were identified: large, light coloured and small, darker cells. The expression of genes belonging to the mentioned ontological groups suggest the potential ability of GCs to differentiate and proliferate toward muscle lineage, showing possible application in muscle regeneration and the treatment of different diseases.

The Stemness of Human Ovarian Granulosa Cells and the Role of Resveratrol in the Differentiation of MSCs-A Review Based on Cellular and Molecular Knowledge.

Ovarian Granulosa Cells (GCs) are known to proliferate in the developing follicle and undergo several biochemical processes during folliculogenesis. They represent a multipotent cell population that has been differentiated to neuronal cells, chondrocytes, and osteoblasts in vitro. However, progression and maturation of GCs are accompanied by a reduction in their stemness. In the developing follicle, GCs communicate with the oocyte bidirectionally via gap junctions. Together with neighboring theca cells, they play a crucial role in steroidogenesis, particularly the production of estradiol, as well as progesterone following luteinization. Many signaling pathways are known to be important throughout the follicle development, leading either towards luteinization and release of the oocyte, or follicular atresia and apoptosis. These signaling pathways include cAMP, PI3K, SMAD, Hedgehog (HH), Hippo and Notch, which act together in a complex manner to control the maturation of GCs through regulation of key genes, from the primordial follicle to the luteal phase. Small molecules such as resveratrol, a phytoalexin found in grapes, peanuts and other dietary constituents, may be able to activate/inhibit these signaling pathways and thereby control physiological properties of GCs. This article reviews the current knowledge about granulosa stem cells, the signaling pathways driving their development and maturation, as well as biological activities of resveratrol and its properties as a pro-differentiation agent.

Human Cumulus Cells in Long-Term In Vitro Culture Reflect Differential Expression Profile of Genes Responsible for Planned Cell Death and Aging-A Study of New Molecular Markers.

In the ovarian follicle, maturation of the oocyte increases in the presence of somatic cells called cumulus cells (CCs). These cells form a direct barrier between the oocyte and external environment. Thanks to bidirectional communication, they have a direct impact on the oocyte, its quality and development potential. Understanding the genetic profile of CCs appears to be important in elucidating the physiology of oocytes. Long-term in vitro culture of CCs collected from patients undergoing controlled ovarian stimulation during in vitro fertilization procedure was conducted. Using microarray expression analysis, transcript levels were assessed on day 1, 7, 15, and 30 of culture. Apoptosis and aging of CCs strictly influence oocyte quality and subsequently the outcome of assisted reproductive technologies (ART). Thus, particular attention was paid to the analysis of genes involved in programmed cell death, aging, and apoptosis. Due to the detailed level of expression analysis of each of the 133 analyzed genes, three groups were selected: first with significantly decreased expression during the culture; second with the statistically lowest increase in expression; and third with the highest significant increase in expression. COL3A1, SFRP4, CTGF, HTR2B, VCAM1, TNFRSF11B genes, belonging to the third group, were identified as potential carriers of information on oocyte quality.

The polycystic ovary syndrome: a position statement from the Polish Society of Endocrinology, the Polish Society of Gynaecologists and Obstetricians, and the Polish Society of Gynaecological Endocrinology.

Polycystic ovary syndrome (PCOS) diagnosis and therapy still arouse a lot of controversy. Each year brings new information, so, having collected the experience of three scientific societies, we present contemporary recommendations concerning PCOS diagnostics and treat-ment. In adult female diagnosis, we still use the Rotterdam criteria, which is two out of three of the follwing characteristics: a) ovulation abnormality, b) clinical or biochemical hyperandrogenism, and c) polycystic ovaries. In the case of teenagers, diagnostic criteria are as follows: menstruation disturbances two years after menarche and clinical or biochemical hyperandrogenism. The presence of polycysti-cally abnormal ovaries is not necessary. The consensus paper presents the threats resulting from imperfect diagnostic methods applied in PCOS (hyperandrogenism diagnostics, ultrasound examination of ovaries). Suggested therapy includes personalised schemes according to the dominant PCOS phenotype, i.e. metabolic, hyperandrogenic, or reproductive ones.

Effects of Resveratrol on Polycystic Ovary Syndrome: A Double-blind, Randomized, Placebo-controlled Trial.

CONTEXT: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Hyperandrogenism is the central feature of PCOS. Studies on isolated ovarian theca-interstitial cells suggest that resveratrol, a natural polyphenol, reduces androgen production. OBJECTIVE: This study was designed to evaluate endocrine and metabolic effects of resveratrol on PCOS. DESIGN AND SETTING: This was a randomized (1:1) double-blind, placebo-controlled trial that evaluated the effects of resveratrol over a period of 3 months in an academic hospital. PATIENTS AND OTHER PARTICIPANTS: Subjects with PCOS were identified according to the Rotterdam criteria. Thirty-four subjects were enrolled and 30 subjects completed the trial. Evaluations were performed at baseline and repeated after 3 months of treatment. INTERVENTION: Resveratrol (1,500 mg p.o.) or placebo were administered daily. MAIN OUTCOME MEASURE: Primary outcome was the change in the serum total T. RESULTS: Resveratrol treatment led to a significant decrease of total T by 23.1% (P = .01). In parallel, resveratrol induced a 22.2% decrease of dehydroepiandrosterone sulfate (P = .01), a decrease of fasting insulin level by 31.8% (P = .007) and an increase of the Insulin Sensitivity Index (Matsuda and DeFronzo) by 66.3% (P = .04). Levels of gonadotropins, the lipid profile as well as markers of inflammation and endothelial function were not significantly altered. CONCLUSIONS: Resveratrol significantly reduced ovarian and adrenal androgens. This effect may be, at least in part, related to an improvement of insulin sensitivity and a decline of insulin level.

[Selected legal aspects of the protection of the unborn child in the light of the draft amendment to the Polish Penal Code]. / Wybrane aspekty prawne ochrony dziecka poczetego w swietle projektu nowelizacji Kodeksu Karnego.

Criminal Law Codification Commission, acting at the Ministry of Justice prepared proposals for amendments in the Polish Penal Code, related to offenses against life and health that were presented to the public in 2013. The draft provides for the protection of the child in the prenatal stage, introducing a new category of the entity to be protected, which is "unborn child" and "unborn child able to live outside the mother's body". These regulations provide for mothers criminal liability and responsibility of the medical staff (a doctor), as well as the child's father to the extent in which he is obliged to take steps aimed at rescuing the fetus. It is doctor's responsibility to show particular care for human health and life since a doctor has special medical knowledge and that is regulated by art. 30 of the act on professions of doctor and dentist. The proposed rule changes were not brought before the legislature in the current term of the Sejm (2011-2015), but due to the development of medicine, including obstetrical ultrasound, which enables visualization of a child that moves in the womb and is treated as a separate entity with distinct personal features the grounds are given for the opinion that the issue of the legal status of the unborn child, particularly in the context of causing death of a child in the last phase before birth as a result of medical malpractice or other external factors will be back in the public discussion.

Decreased large-artery stiffness in midluteal phase of the menstrual cycle in healthy women of reproductive age.

OBJECTIVES: Sex hormones are specific factors contributing to the regulation of cardiovascular system. Studies on the effects of hormonal fluctuations during the menstrual cycle on hemodynamics and arterial stiffness in young women are limited and provide conflicting results. AIM: The aim of the study was to assess arterial stiffness, peripheral/central blood (pBP and cBP) and pulse (pPP and cPP) pressures throughout the single, natural menstrual cycle (early follicular [EFP], late follicular [LFP] and midluteal [LP] phase). MATERIALS AND METHODS: Forty two healthy regularly menstruating women (28.6±5.1 yrs of age; BMI 22.0±3.5 kg/m2) were evaluated during EFP (Estradiol [E], FSH, LH, PRL, TSH, Testosterone [T], DHEAS, and SHBG), LFP (E, FSH, LH) and LP (Progesterone, E, FSH, LH). Transvaginal ultrasound was performed to confirm ovulatory cycle. Resting radial and aortic BP were assessed noninvasively and continuously using tonometric measurement of peripheral PP wave-PPW (Colin BMP7000, Japan) and on-line reconstruction of central PPW (Sphygmocor Mx, Australia) at EFP, LFP and LP. ANOVA and Friedman test were used in statistical analysis. RESULTS: There were no significant differences in systolic/diastolic BP and PP both at the periphery and at ascending aorta throughout the menstrual cycle. Comparable observations of no interphasal differences were noted for peripheral Augmentation Index (AI). Central AI and augmentation pressure (AP) were significantly lower in LP than in LFP (by 4%; p<0.05 and by 37%; p<0.05, respectively). CONCLUSIONS: We demonstrated significant differences in mechanical properties of large arteries at the midluteal phase of natural menstrual cycle. We conclude that sex hormones may play role in the regulation of arterial stiffness in the reproductive age women.

[Assisted reproductive medicine in Poland, 2011--SPiN PTG report]. / Medycyna wspomaganego rozrodu w Polsce--raport za rok 2011 Sekcji Plodnosci i Nieplodnosci Polskiego Towarzystwa Ginekologicznego (SPiN PTG).

AIM: The aim of this report is to present data concerning results and complications related to infertility treatment using assisted reproductive technology (ART) and insemination (IUI) in Poland in 2011. MATERIALS AND METHODS: The report was prepared by the Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG), based on individual data provided by fertility clinics in Poland. Reporting was voluntary and the provided data was not subject to external control. The report presents the availability and the structure of infertility treatment services, the number of procedures performed, their effectiveness and the most common complications. MAIN RESULTS: In 2013, 33 Polish fertility clinics provided information to the SPiN PTG report, presenting data from the year 2011. The total number of reported treatment cycles using ART was 15,340 (incl. 10,011 IVF/ICSI procedures) and 15,627 IUI procedures. The rate of clinical pregnancies in terms of a cycle was 34.2% in case of IVF/ ICSI procedures and 13.4% in case of IUI. The prevalence of multiple births was 20.2% and 8.3% respectively in case of IVF/ICSI and IUI methods. The most frequent complication in the course of treatment using ART was ovarian hyperstimulation syndrome (OHSS). CONCLUSION: The SPiN PTG report allows to find out the average effectiveness and safety of assisted reproduction technologies and is currently the only proof of responsibility and due diligence of fertility centres in Poland. However due to the lack of a central register of fertility clinics, facultative participation in the report as well as incomplete information on pregnancy and delivery the collected data does not reflect the full spectrum of the Polish reproductive medicine.

[Legal aspects of selling medical products by gynecologists]. / Aspekty prawne sprzedazy produktów leczniczych przez lekarza ginekologa.

Sales and distribution of medical products and drugs in Poland remains under strict regulations, especially legal regulation contained in the Medical and Dental Practitioners Act, that banned sales of medical products by doctors. It needs to be emphasized that currently doctors are allowed to sell drugs and medical products only in rigorously specified situations. Knowledge of current legal regulations concerning sales of medical products by gynecologists allows to conform with the law and to distribute drugs and medical products under special and predefined conditions.

Free fatty acid binding protein-4 and retinol binding protein-4 in polycystic ovary syndrome: response to simvastatin and metformin therapies.

Free fatty acid binding protein-4 (FABP4) and retinol binding protein-4 (RBP4) contribute to metabolic syndrome. We investigated serum FABP4 and RBP4 responses to insulin sensitizing and lipid lowering therapies in polycystic ovary syndrome (PCOS). Sixty-two healthy, untreated women with PCOS (age 25.1 ± 3.6 years, BMI: 24.0 ± 4.7 kg/m(2)) were randomized to metformin (n = 24), simvastatin (n = 20) or metformin plus simvastatin (n = 18) for 3 months. Anthropometric measures, fasting blood tests and oral glucose tolerance tests (OGTT) were obtained at the baseline and the end. At the baseline serum FABP4 correlated with obesity (BMI: r = 0.63, p < 0.001), insulin resistance (fasting insulin: r = 0.44, p = 0.0002; QUICKI: r = -0.30, p = 0.02; OGTT-insulin sensitivity index: r = -0.27, p = 0.04), dyslipidemia (HDL: r = -0.26, p = 0.03) and hyperandrogenemia (free-testosterone: r = 0.23, p = 0.03; SHBG: r = -0.28, p = 0.03); while RBP4 correlated with total-cholesterol (r = 0.33, p = 0.009). Multiple regression analysis indicated that t best predictors of serum FABP4 and RBP4 were BMI (ß = 1.02, p = 0.0003) and total cholesterol (ß = 2326, p = 0.01), respectively. Simvastatin, alone or with metformin did not affect serum FABP4 or RBP4. Serum FABP4 related to the obesity, insulin resistance and inflammation while RBP4 related to lipids. Insulin sensitizing and lipid lowering therapies did not affect FABP4 or RBP4 levels in PCOS.

[The CHOICE study (Contraceptive Health Research Of Informed Choice Experience)--an educational research program for Polish women planning combined hormonal contraceptives use]. / CHOICE (Contraceptive Health Research of Informed Choice Experience)--edukacyjny program badawczy dla kobiet planujacych stosowanie zlozonej antykoncepcji hormonalnej w Polsce.

OBJECTIVES: The aim of the study was to develop an optimal educational model for contraceptive counseling, to analyze conditions influencing choice of hormonal contraception, to study patients' opinions on present, planned and proposed contraceptive methods and to link these data with socioeconomic and demographic conditions. MATERIALS AND METHODS: One thousand eight hundred fifty women (mean age 26.8 +/- 5.9 yrs) willing to use hormonal contraception were presented with essential information on combined hormonal contraception and asked to fill the anonymous questionnaire investigating factors influencing contraceptive choice and patients' opinion on alternative forms of birth regulation. The study was conducted in selected 185 centers in Poland and was a part of a larger survey (CHOICE) conducted on 11 216 women in Europe and Israel. RESULTS: Majority of the studied women were in stable relationship (85,5%), had higher or incomplete higher education (54.8%) and permanent job (54%). The purpose of the visit was to start/change contraception (64.2%), a routine gynecologic check-up (36.7%) or the need for a prescription for the continued contraceptive medication (18.7%). The most commonly used contraceptive methods were oral contraceptive pills (OCP 38.7%) and condom (24.9%). Majority of women highly valued contraceptive counseling and more than 90% were eager to get familiarized with information leaflets. Before the counseling majority of subjects stated that were convinced to use OCP (52.7%; major advantages named: easy to use, favorable bleeding profile, amelioration of menstrual discomfort, comfortable, discrete) and contraceptive patch (22%; major advantages named: applied once a week, comfortable, simple, low risk for noncompliance, favorable bleeding profile). After the counseling there was an increase in proportion of women interested in contraceptive hormonal ring (by 19%; major advantages named: applied once a month, comfortable, very low risk for noncompliance, high efficacy and positive recommendation from a physician). In 58 women no hormonal contraception was recommended, predominantly due to medical contraindications. CONCLUSIONS: Appropriate patient counseling on all forms of combined hormonal contraception, with special attention paid to benefits and safety issues, suited to women's expectations and education is fundamental for the selection of an optimal birth control method.

Effects of simvastatin and metformin on polycystic ovary syndrome after six months of treatment.

CONTEXT: A randomized trial on women with polycystic ovary syndrome (PCOS) compared simvastatin, metformin, and a combination of these drugs. OBJECTIVE: The aim of the study was to evaluate long-term effects of simvastatin and metformin on PCOS. DESIGN: Women with PCOS (n = 139) were randomized to simvastatin (S), metformin (M), or simvastatin plus metformin (SM) groups. Evaluations were performed at baseline and at 3 and 6 months. SETTING: The study was conducted at a university medical center. PRIMARY OUTCOME: We measured the change of serum total testosterone. RESULTS: Ninety-seven subjects completed the study. Total testosterone decreased significantly and comparably in all groups: by 25.6, 25.6, and 20.1% in the S, M, and SM groups, respectively. Both simvastatin and metformin improved menstrual cyclicity and decreased hirsutism, acne, ovarian volume, body mass index, C-reactive protein, and soluble vascular cell adhesion molecule-1. Dehydroepiandrosterone sulfate declined significantly only in the S group. Total cholesterol and low-density lipoprotein cholesterol significantly declined only in the S and SM groups. Ongoing reduction of ovarian volume, decreased hirsutism, acne and testosterone were observed between 0 and 3 months as well as between 3 and 6 months. Improvement of lipid profile, C-reactive protein, and soluble vascular cell adhesion molecule-1 occurred only during the first 3 months of treatment, with little change thereafter. Treatments were well tolerated, and no significant adverse effects were encountered. CONCLUSIONS: Long-term treatment with simvastatin was superior to metformin. Improvement of ovarian hyperandrogenism continued throughout the duration of the study.