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.

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.

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.

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.

Vascular anastomoses in intrauterine growth in monochorionic twins.

Objectives To evaluate the impact of placental anastomoses on the intrauterine growth of monochorionic (MC) twins. Methods A prospective study was conducted in a group of 53 MC twins. Intrapartally umbilical cords were clamped to identify placental sides corresponding to each twin. The postnatal dye injection technique was administered to evaluate vascular anastomoses, their number and type and visualize placental territory sharing patterns. Data from digital analysis were correlated with obstetrical follow-up. Results Vascular anastomoses were revealed in 88.7% of cases. Arteriovenous (AV) anastomoses occurred in 75.4% and arterioarterial (AA) in 71.1% while venovenous (VV) in 26.4%. In the subgroup of MC twins without placental anastomoses, significantly higher birthweight difference and discordance were revealed when compared to MC twins without anastomoses (382.0 vs. 22 g; P = 0.03 and 49.14% vs. 16.02%; P = 0.03). On the other hand, in subgroups of MC twins with at least one AA anastomosis, twins' birthweights were similar (p = ns) despite significantly higher placental territory sharing discordance (30.44% vs. 15.81%; P = 0.31). Conclusions Vascular anastomoses have a major impact on the intrauterine growth of MC twins. In certain cases, they may cause specific complications; however, in general, they regulate intertwin blood exchange and may compensate unequal placental territory.

The use of atosiban prolongs pregnancy in patients treated with fetoscopic endotracheal occlusion (FETO).

Objective To evaluate the impact of atosiban as a tocolytic agent in patients treated with the fetoscopic endotracheal occlusion (FETO) procedure due to congenital diaphragmatic hernia (CDH). As premature birth after fetoscopy remains a serious concern, an effort to reduce prematurity is required. Methods A total of 43 patients with severe CDH treated with FETO were enrolled in this study. The study group consisted of 22 patients who received atosiban during the FETO procedure and a control group of 21 patients who did not receive atosiban during the FETO procedure. Demographic data, gestational age (GA) at delivery, cervical length and GA at premature rupture of membranes (PROM) were evaluated. Results The GA at delivery was significantly different between the two groups studied. The median GA at delivery was 32.6 and 34.5 weeks in the no-atosiban vs. atosiban groups, respectively (P = 0.013). The median cervical length was 29.9 and 31.2 mm for the no-atosiban and atosiban groups, respectively, and was not statistically significant (P = 0.28). There were no significant correlations between groups for the occurrence of PROM, GA at the time of PROM, duration of the procedures, parity, maternal body mass index (BMI) or age. In the univariate linear regression model, the only factor independently associated with GA at delivery was the use of atosiban during FETO procedures (ß = 0.375; P < 0.013). Conclusion In cases of severe CDH treated with FETO, the use of atosiban as a tocolytic agent during the procedure prolonged pregnancy by 2 weeks. Cervical length, duration of FETO or maternal characteristics were not associated with GA at delivery.

Cervical Measurement and Pessary Application in Relation to Gestational Age at Delivery in Patients Treated with Fetoscopic Endotracheal Occlusion.

OBJECTIVE: To evaluate the impact of cervical length and cervical pessary application in congenital diaphragmatic hernia (CDH) treated by the fetoscopic endotracheal occlusion (FETO) procedure. METHODS: The study group consisted of 80 patients with severe CDH treated by FETO. Cervical length measurement was performed by transvaginal ultrasound in all patients within the 24 h prior to the FETO procedure. The study group (n = 44) had cervical pessaries applied routinely within the 24 h following the FETO procedure, whereas the control group (n = 36) were not offered pessaries and only had cervical length measurement performed. RESULTS: The median cervical length was 31 (range 22-45) mm. The median gestational age at delivery was 34.7 (range 27.8-39.2) weeks. Gestational age at delivery correlated significantly with gestational age at balloon removal (r = 0.768; p < 0.0001) and premature rupture of membranes (r = 0.501; p = 0.003). There was no significant correlation between gestational age at delivery and cervical length before the procedure (r = 0.141; p = 0.26) or pessary application (r = 0.081; p = 0.51). In the multivariate linear regression model, the only factor independently associated with gestational age at delivery was gestational age at fetoscopic balloon removal (ß = 0.713; p < 0.0001). CONCLUSION: In cases of severe CDH treated by the FETO procedure, neither cervical length before the procedure nor cervical pessary application was associated with gestational age at delivery.

The assessment of retina in pregnant women with myopia.

OBJECTIVES: Myopia is associated with increased frequency of retinal degenerative changes which are the risk factors of intra- and postpartal ophthalmological complications. Aim of this study was to analyze the degenerative lesions detected in opthalmological examination (including peripheral retinal lesions) as a potential risk factors for eyes' status in terms of delivery in myopic women. MATERIAL AND METHODS: 254 pregnant women affected with myopia underwent opthalmological examination as a screening method to examine retina. In case of any degenerative lesions, the qualification for laser photocoagulation treatment was performed. Furthermore, study group was divided into two subgroups due to presence or absence of the retinal lesions and opthalmological outcomes compared. Follow up examination was performed in every patient from the study group between 3 and 6 months after the delivery. RESULTS: Among 508 eyes, retinal lesions were revealed in 69 women (121 eyes) what constituted for 23.8%. In remaining 185 patients results of the opthalmological examination were normal. Average maternal age was higher in group affected with degenerative lesions (p<0.001). Myopia in women with retinal lesions ranged between -0.25 and -12 dioptries (D), while in 43 cases of degenerative lesions qualified for laser photocoagulation this value ranged between -0.5 and -12.0 D (p=ns). Postpartal follow-up examination did not reveal any abnormalities in this group, as well. CONCLUSION: Degenerative retinal lesions are present in one fourth of pregnant women. Both the severity and type of the lesions are not associated with severity of myopia. Among pregnant patients, retinal lesions occur in patients with more advanced maternal age. opthalmological examination remains an important prophylactic modality in retinal disorders, especially in primary retinal detachment due degenerative disorders.

Sudden Fetal Hematologic Changes as a Complication of Amnioreduction in Twin-Twin Transfusion Syndrome.

We present the first case of a monochorionic twin pregnancy in which sudden hematologic changes occurred as a complication of the amnioreduction procedure for twin-twin transfusion syndrome (TTTS). At 33 weeks of gestation, 4 days after the amnioreduction, the recipient developed severe anemia while the donor developed severe polycythemia. Postnatal placental examination revealed several arteriovenous and venoarterial anastomoses, a pale placental mass of the recipient and a congested and plethoric placental mass of the donor. We speculate on the pathophysiologic changes and potential deleterious effects provoked by the decompressive amnioreduction. Decompression of the placenta and anastomoses after the amnioreduction may have led to an acute blood shift from recipient to donor (thus also a reversal of feto-fetal transfusion), resulting in anemia in the recipient and polycythemia in the donor twin. In the past 15 years, 13 TTTS cases with late presentation were treated with amnioreduction. This is the first time we encountered this severe complication, yielding an incidence of 8%. Although the optimal treatment in TTTS with late presentation is not known, perinatologists should be aware that treatment with amnioreduction can lead to sudden hematologic changes.

Contemporary management of prenatally diagnosed spina bifida aperta - an update.

Spina bifida aperta is a relatively common congenital defect that occurs in the general population. Once the disorder has been diagnosed, a discussion, that can be emotionally-charged, ensues about whether to treat it prenatally or to only offer surgery postnatally. Given that there are good arguments for and against both options, it is of paramount importance to gain a good understanding of the major advantages and disadvantages of the various surgical approaches. The aim of our paper is to summarize current knowledge about spina bifida and the potential benefits of prenatal surgery.

Three-dimensional neurosonography - a novel field in fetal medicine.

Neurosonography is a promising technique for prenatal diagnosis, combining features of ultrasound imaging with fetal neurology. The brain is a three-dimensional structure, therefore observing brain structure in the three basic planes (sagittal, coronal and axial) is mandatory. The anterior fontanelle and sagittal suture may serve as acoustic ultrasound windows in the transvaginal brain scan, allowing to obtain high-resolution neuroimages of the intracranial structures. Furthermore, three-dimensional (3D) ultrasound combined with the transvaginal brain approach provides detailed and sophisticated neuroimages. Three orthogonal planes of the brain, tomographic ultrasound imaging (TUI) and other off-line approaches (e.g. volume contrast imaging (VCI) or HDlive silhouette imaging) may be obtained from a single 3D dataset. 3D Doppler ultrasound enables visualization of the intracerebral vascularity, allowing to obtain more precise information on cerebral perfusion. Various abnormal brain conditions, including ventriculomegaly, agenesis of the corpus callosum, posterior fossa abnormalities and others, can be well-demonstrated. Due to high rates of the associated anomalies and uncertain prognosis, any suspicion of CNS abnormalities shall imply detailed ultrasonographic evaluation of the fetal anatomy to exclude the associated anomalies. Despite a growing number of neuroimaging modalities, prenatal counselling remains a challenge as prediction of brain functionality and the neurological prognosis often remain uncertain. New investigations on the relations between various migration disorders and gene mutations, as well as recent clinical research on the relations between neuroimaging detection of local migration disorders using sophisticated imaging technologies and the postnatal neurological prognosis will contribute to the development of maternal-fetal medicine as well as pediatric neurology.

Comparison Between Monochorionic and Dichorionic Placentas With Special Attention to Vascular Anastomoses and Placental Share.

Placental vascular anastomoses in twins lead to a shared circulation and may subsequently enable the development of severe complications such as twin-twin transfusion syndrome (TTTS) and twin anemia-polycythemia sequence (TAPS). The presence of vascular anastomoses has frequently and systematically been studied in monochorionic (MC) placentas, but only rarely in dichorionic (DC) placentas. The aim of this study was to compare the prevalence of vascular anastomoses and evaluate the sharing discordance in MC and DC placentas. All consecutive placentas of MC and DC twins delivered at the Leiden University Medical Center (the Netherlands) and Medical University of Warsaw (Poland) from 2012 to 2015 were routinely injected with colored dye and included in the study. We excluded twin pregnancies treated with fetoscopic laser surgery. A total of 258 placentas were analyzed in this study, including 134 MC placentas and 124 DC placentas. Vascular anastomoses were present in 99% (133/134) of MC placentas and 0% of DC placentas (p < .01). Placental share discordance between MC twins was significantly larger compared to DC twins, 19.8 (interquartile range [IQR] 8.1-33.3) and 10.8 (IQR 6.2-19.0), respectively (p < .01). Vascular anastomoses associated complications occurred in 16% (22/134) MC twins. Our findings show that vascular anastomoses are almost ubiquitous in MC placentas, but non-existent in DC placentas. In addition, unequal placental sharing appears to be more common in MC than in DC placentas.

Placental examination with dye injections in post-delivery chorionicity assessment in dichorionic triplet pregnancy.

The incidence of spontaneous triplet pregnancy is approximately 1 in 7000 deliveries. Due to the fact that every presentation of a triplet and higher order pregnancy is associated with high rate of morbidity and preterm delivery, chorionicity and amnionicity remain significant predictive factors which determine specific management throughout the pregnancy. Ultrasound chorionicity assessment in triplet pregnancies is more complex than in twins, and in many cases it remains unknown. We present a case report of a 24-year-old primipara in a spontaneous dichorionic triplet pregnancy, qualified for a cesarean section at 33 weeks of gestation, with subsequent placental examination with dye injections and post-delivery chorionicity assessment.

[Fetal hepatic artery flow assessment in prenatal diagnostics--a review of the literature]. / Ocena przeplywów w tetnicy watrobowej plodu w diagnostyce prenatalnej. Przeglad literatury.

Standards of screening tests for the most frequent fetal chromosomal defects in modern non-invasive prenatal diagnostics provide sensitivity of about 93-96%, with the false positive rate of 2.5%. During the first trimester scan, routinely performed between 11 and 13+6 week of pregnancy the calculation of the risk for chromosomal aberrations is based on maternal age (MA), nuchal translucency (NT), levels of free beta human chorionic gonadotropin (free beta-hCG), pregnancy associated plasma protein A (PAPP-A) in maternal blood, as well as the parameters from extended ultrasound examination like evaluation of the nasal bone (NB), blood flow in ductus venosus (DV), visualization of the tricuspid valve with potential regurgitation (TR) or measurement of the frontomaxillary facial angle (FMFA). The 100% detection rate remains unachievable at present, despite constantly improving guidelines for specialists, quality of imaging, and advancement in ultrasound technology Therefore, several studies have been undertaken to establish the group of 'additional markers' of chromosomal defects which, when combined with basic markers of routine screening tests, might increase the detection rate and approach it to 100%. Results of recent studies imply that evaluation of blood flow in fetal hepatic artery performed during the first trimester scan may become a new additional marker for chromosomal defects.

Reference values for placental growth factor (PlGF) concentration and uterine artery doppler pulsatility index (PI) at 11-13(+6) weeks of gestation in the Polish population.

OBJECTIVES: The aim of the study was to determine placental growth factor (PIGF) concentration and uterine artery (UtA) Doppler pulsatility index (PI) at 11-13(+6) weeks of gestation in the Polish population. MATERIAL AND METHODS: A prospective study was performed in pregnant women who underwent routine ultrasound scan at 11-13(+6) weeks of gestation. All participants completed a questionnaire about their medical history demographics and current pregnancy. Mean arterial pressure (MAP) was calculated. Gestational age was confirmed by CRL and mean UtA PI was calculated. Blood samples were taken to measure beta HCG, PAPP-A and P/GF concentrations. RESULTS: Out of the 577 analyzed participants, 60 (10.4%) were found to have abnormal placentation disorders (20 -hypertensive disorders and 40-IUGR). The patients were subdivided into two groups, depending on pregnancy outcome: unaffected (n = 517) and affected (n = 60). The study did not confirm the anticipated correlation between maternal BMI and PIGF, but the concentration of PIGF was significantly increased in smokers. UtA PI values were not statistically significantly different depending on maternal age, BMI, method of conception, smoking or parity The study confirms that both, UtA PI and PIGF concentrations are CRL-dependent. Median MoM values for PIGF and UtA PI were obtained for each set of CRL measurements. Median PIGF MoM was decreased in pregnancies complicated by hypertensive disorders and IUGR as compared to the unaffected group. CONCLUSIONS: The established reference ranges for UtA PI and PIGF at 11-13(+6) weeks of gestation may be of clinical value in predicting placenta-associated diseases in early stages of pregnancy in the Polish population.

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.

Clinical consequences of maternal serum PAPP-A and free beta hCG levels above 2.0 multiple of median in the first trimester screening.

INTRODUCTION: Extreme levels of either PAPP-A or free ß-hCG may be a serious clinical concern. A multicentre study was carried out to determine the frequency and clinical consequences of high (minimum 2,0 MoM) maternal (PAPP)-A and free beta hCG. METHODS: A total number of 8591 patients with singleton pregnancies between 11 + 0-13 + 6 weeks of gestation were enrolled. A total number of 612 cases with first trimester serum level of PAPP-A corresponding to ≥ 2,0 MoM and/or free ß-hCG to ≥ 2,0 MoM were included in the statistical analysis. All serum samples were analysed with Roche (Cobas) or Kryptor (Brahms) devices. A retrospective analysis of perinatal outcomes was conducted. RESULTS: Values of PAPP-A ≥ 2,0 MoM and free ß-hCG < 2.0 MoM were detected in 48,5% of patients (n = 297), free ß-hCG ≥ 2,0 MoM and PAPP-A concentration < 2,0 MoM in 38,1% of patients (n = 233) and both PAPP-A and free ß-hCG ≥ 2,0 multiple of median in 13,4% of patients (n = 82). The highest PAPP-A and free ß-hCG concentrations were 19,2 MoM and 16,3 MoM respectively. Patients with both PAPP-A and free ß-hCG above 2,0 MoM had a slightly higher (but statistically not significant) prevalence of history of low birthweight (8,3%). DISCUSSION: Pregnancy outcomes in women with normal ultrasound findings and high PAPP-A /free ß-hCG concentration are good. Higher prevalence of pregnancy complications was not detected in either extremely high PAPP-A and free ß-hCG concentration groups. In cases of normal ultrasound and isolated high (even extreme) biochemical markers levels the counselling should be comforting.