Search

Introduction The prevalence of endometriosis among reproductive age women is 7-17%; however, these figures reach 20-50% in patients suffering from infertility. Matrix metalloproteinases (MMPs) activity is thought to be particularly essential in the early phases of endometriosis development. Any changes in the equilibrium between MMPs activity and their tissue inhibitors (TIMPs) could be potentially harmful, promoting endometriosis development. The aim of this study was to investigate whether the MMP-2, MMP-9, TIMP-1 or TGF-B2 expression in eutopic endometrium from women with early endometriosis differ when compared with healthy subjects. The results were referred to the serum progesterone levels. Materials and method Endometrial biopsy was taken from 42 patients (18 in the study group, 22 in thecontrol group) at the time of hysteroscopy for routine histology and for RT-PCR procedures. Comparison of the quantity of gene products was performed with a programme for densitometry and compared to GADPH product, which was a reference value. Results The obtained results did not reveal any statistical difference in endometrial expression of MMP-2, MMp-9, TIMP-1, and TGF-β2 or serum progesterone level between women with endometriosis and without visible signs of this illness. Conclusion Despite the lack of statistical differences, it was observed that both examined metalloproteinases expressed a tendency to higher gene expression in the eutopic endometrium of women with endometriosis. However, both TIMP-1 and TGF-β2 expressions had the same tendency - higher values in endometriosis patients.

Objectives: The aim of the study was to analyze the levels of pro-inflammatory interleukins in cervical secretions of women with PROM, depending on Ureaplasma spp. infection and the time elapsed since the rupture of the membranes, and to correlate their concentration in cervical secretions and in cord blood of the newborns. Material and methods: The study included 30 women with PROM between 24 and 33+6 weeks of gestation. Cervical swabs from women with confirmed rupture of membranes taken at certain intervals and umbilical cord blood of their newborns constituted the study material. Cervical secretions were evaluated microbiologically and by the PCR method. Concentrations of IL-6, IL-19, IL-10 and TNF-α were analyzed by ELISA. Results: Ureaplasma spp. were the most frequently isolated microorganisms in cervical secretions of women with PROM. Secretion of interleukins in the cervix was not influenced by time elapsed since the PROM. Comparison of interleukin levels in cord blood of newborns born to mothers with and without Ureaplasma spp infection revealed significantly higher levels of IL-6 in the case of Ureaplasma spp. A positive correlation between IL-6 and TNF-α levels in cervical secretions and in cord blood of mothers with PROM and Ureaplasma spp. was detected. Conclusions: 1. Cervical culture method appears to be sufficient for detecting Ureaplasma spp. 2. Pro-inflammatory interleukins, especially IL-6, obtained by non-invasive methods can be used to predict fetal inflammatory response.

OBJECTIVES Preterm premature rupture of membranes (PPROM) complicates about 5% of pregnancies. Ureaplasma species is the most common pathogen found in the amniotic fluid in pregnancieneonatal outcome. The aim of the following study was to evaluate the impact of colonization with the Ureaplasma spp. on pregnant women with PPROM, coin fection with different microorganisms, and antimicrobial treatment on neonatal outcome. MATERIAL AND METHODS The study included 30 women with PPROM hospitalized in Division of Reproduction in s complicated by PPROM. It is speculated that it requires a coin fection to produce unfavorable Poznan's K. Marcinkowski University of Medical Sciences. Swabs from cenvical canal were obtained for the identifidation of bacterial and ureaplasma tic infections by culture and POR. RESULTS The presence of any infection during the pregnancy a fter PP ROM was con firmed in 22 patients (Ureaplasma spp. in 12 patients, coin fection in 10 women). The cure rate for Ureaplasma species and other infections was 17% (2/12 patients) and 23% (5/22 patients), respectively There was no correlation between Ureaplasma species infection, coin fection, and cure status with the infection in the newborn. The PPROM to delivery duration also did not affect the newborn infection status. A negative relationship with leukocyte level was detected in patient with newborn infection. CONCLUSIONS The presence of colonization with Ureaplasma species is not attributable to neonatal short-term morbidity The evaluation of maternal biochemical and microbiological data, regardless of the duration of the pregnancy after PPROM or the cure status, does not add any insight into the newborn infection status.

Implantation depends on two factors — embryo and endometrium. The period of maximal endometrial receptivity is a poorly understood phenomenon. We decided to look at three possible markers of implantation: pinopodes, leukemia inhibitory factor, and matrix metalloproteinase 2 and their correlations. We included in the study 23 idiopathic infertility patients and 21 patients with recurrent spontaneous abortions of unknown etiology. Twenty one fertile patients were also recruited. A biopsy was used for endometrial dating according to the Noyes and Hertig criteria, and assessed for the presence of pinopodes via a scanning electron microscope. Endometria were examined in Real Time-Polymerase Chain Reaction cycles for the mRNA expression of leukemia inhibitory factor (LIF) and matrix metalloproteinase 2 (MMP2). No difference was found in the stage of pinopodes development, nor in the coverage of endometrial surface between the studied groups. The expression level for LIF mRNA was lower in control patients compared to idiopathic infertility and recurrent miscarriage patients. No difference was detected in the expression of MMP2 between all studied groups. No correlation was found between pinopodes development stage and LIF and MMP2 expressions in endometrium. Of the studied factors, LIF and pinopodes show the most promise as potential markers of endometrial receptivity. However, the results achieved suggest that these markers are independent of each other. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 615–621)

Problem To determine the value of leukemia inhibitory factor (LIF) assessment for predicting the reproductive outcome. Method of study Two phase study. Phase I: assessment of LIF in uterine flushing. Phase II: 1,5 years after examining the last patient, a questionnaire was sent to all participants of the phase I. Phase I: Uterine flushing and endometrial samples were collected during implantation window from infertile patients with stage I/II endometriosis (n = 14), patients with idiopathic infertility (n = 27), luteal phase deficiency (n = 13), and fertile control (n = 21). LIF was assessed in uterine flushings in all patients by ELISA. In endometrium, semiquantitative RT-PCR was performed for LIF mRNA expression. Phase II: questionnaire has been sent to all infertile women taking part in the first phase of the experiment, regarding their reproductive outcome. Results 65.4% patients who had returned the questionnaire did get pregnant. LIF concentration at a cut-off point of 2.31 pg/ml had a 95.7% sensitivity and 81.8% specificity in predicting the reproductive outcome. Conclusion This prospective study for the first time in literature indicates that the LIF assessment can be used as a predictor of reproductive success.

Objective To assess the total antioxidant potential of women with endometriosis-associated infertility, women with idiopathic infertility, and fertile controls. Design Retrospective study. Setting University medical hospital. Patient(s) Sixty-five women admitted for diagnostic laparoscopy. Main outcomes measure(s) Peritoneal fluid samples were analyzed for superoxide dismutase activity and total antioxidant status on spectrophotometry, glutathione peroxidase activity on enzyme-linked immunosorbent assay, and lipid peroxides levels on colorimetry. Result(s) Mean activity of superoxide dismutase, glutathione peroxidase, and total antioxidant status was lowest and lipid peroxide level was highest among infertile patients with endometriosis. Women with idiopathic infertility, in contrast, had the highest superoxide dismutase, glutathione peroxidase, and total antioxidant status activity and the lowest lipid peroxide level. Conclusion(s) High antioxidant potential is not a contributing factor in women with idiopathic infertility. Low total antioxidant status and low activity of antioxidant enzymes in the peritoneal fluid of infertile women with endometriosis probably do not influence fertility in these women, but these factors may play a role in the development of the disease.

Infertility remains a challenge to modern medicine. Despite extensive diagnostic and therapeutic procedures, the achievement of pregnancy remains an elusive goal in some patients. The endometrium is one of the key factors in embryo implantation. Older methods of describing endometrial receptivity like histology or ultrasound, did not bring noticeable improvement in pregnancy rates. New technologies, including genomics, proteomics, lipidomics, and secretomics promise to improve the detection of the implantation window in the endometrium and result in better counseling of patients with infertility.

Objective To answer the question as to whether the markers of thrombophilia in pregnant women, whose pregnancies ended in success, are reflected in the level of inflammation in the blood of the umbilical cord of the newborn. Materials and methods Umbilical cord blood and placenta after childbirth were secured from 16 patients with inherited (n = 7), acquired (n = 9) thrombophilia, and control group (n = 20). The concentrations of cytokines IL1β, IL10, TNFα, C5a anaphylatoxin, and granzyme A were assessed. decay accelerating factor (DAF) and membrane cofactor protein (MCP) levels were determined in the placentas, and the incidence of thrombotic changes was evaluated. Results Higher levels of anaphylatoxin C5a (P = 0.041), TNFα (P = 0.016), and IL1β (P = 0.037) were observed in the study group compared to the control group. In the study group, C5a levels correlated with the levels of TNFα (P = 0.018) and IL1β (P = 0.012). Higher levels of DAF and MCP proteins in study group were found in the control group (P

Objectives: The object of our study was to assess the efficacy, measured as achievement of pregnancy, of artificial insemination with husband sperm in couples that fulfilled the WHO criteria for infertility. Material and methods: We have identified 120 patients that were diagnosed with infertility, defined as at least one year of unprotected intercourse without achieving pregnancy. After 2 year follow up the study group comprised 96 women and their partners. All couples had normal outcome of all standard infertility test, except for some with decline in sperm parameters that allowed the husband sperm to be used for fertilization in the IUI procedure according to the 2010 WHO guidelines. After IUI procedure patients were followed either by contact with their physicians, mail questionnaire, or by identification of their national ID number in computerized database of our hospital. Results: A total of 32 patients got pregnant (33%). Of those that achieved pregnancy during the two year follow up period, fifteen (46.9%) had done so as a result of AIH, another 15 as a result of spontaneous conception, and two as a result of IVF (6.2%). The mean number of AIH procedures in a group of women that did achieve pregnancy was 3,56 (median 3.0), and was statistically higher than the number of AIH in those patients who have failed to achieve pregnancy (mean 2.54; median 2.0; p=0.009). Conclucions: Our study seems to support the new criteria for assessment of sperm parameters. Judging the sperm according to the new, lessened criteria, did produce comparable pregnancy rates as with historical cohortsbased on old criteria.

Although it was suggested that heparanase (HPSE) may affect implantation and pregnancy, so far there have been no wide-ranging studies on the expression of and possible disturbances in the interactions between HPSE, heparan sulfate (HS) and related growth factors, such as heparin-binding EGF-like growth factor (HB-EGF). The aim of this study was to evaluate whether the expression profile of both HPSE and HB-EGF can be associated with impaired reproduction in the endometrial implantation window, in the non-conception cycle. The study group consisted of 32 women with two or more unexplained, consecutive miscarriages, and 61 idiopathic infertility patients, while the control comprised of 22 women with normal reproductive potential. We compared the expression of HB-EGF and HPSE at the transcript (qPCR) and protein (Western Blot) levels in eutopic endometrium. Also assessed were correlations between both factors in the studied groups. In women with consecutive miscarriages we observed lower HPSE relative transcript (p = 0.003) and lower protein (p = 0.002) level compared with the control group. Level of the HB-EGF protein was decreased (p = 0.017). HPSE mRNA level was higher in idiopathic infertility (p = 0.003) compared with women with miscarriages. We found statistically significant correlations in both transcript and protein levels in all groups (p < 0.05). Our results allow the assumption of the existence of a process by which, in normal human endometrium, HB-EGF expression coincides with the synthesis of HPSE. As a result, the HB-EGF molecule can bind to the HS on the cell surface, enhancing its affinity to the receptor. Then, the release of growth factors associated with HS oligomers occurs that is catalyzed by HPSE. We suggest that one of the causes of unexplained miscarriages may result from the impaired expression of HPSE and HB-EGF.

Introduction: Claudin-4 (CLDN4) is a transmembrane protein, responsible for cellular contact and organization. A different expression of claudin 4 in the endometrium, depending on the menstrual cycle and with peak at the aim of the ‘implantation window’, has been observed. CLDN4 is believed to play an important role in embryo implantation. The aim: The aim of the study was to compare the mRNA CLDN4 expression levels in two subgroups of infertile women (idiopathic infertility or minimal endometriosis) and compare them to fertile controls. Method: The study included 36 women with idiopathic infertility and 24 with minimal endometriosis. The control group comprised 26 women. Eutopic endometrium samples were collected with a Pipelle device during the implantation window. Firstly, mRNA was extracted from the endometrium and reverse transcribed into cDNA. Real time PCR was used for the assessment of relative expression levels. Results: The observed transcription level of CLDN4 did not differ statistically between the studied groups, but was significantly higher when compared to controls. Conclusions: Exceedingly high levels of CLDN4 might negatively influence fertility rates.

Human endometrium, deciuda and placenta have been shown to express factors that inhibit the complement activation cascade - decay-accelerating factor (DAF), membrane cofactor protein (MCP) and the C3 complement component. In the following study we have analyzed the transcripts levels for DAF, MCP and heparin-binding epidermal growth factor-like growth factor (HB-EGF), the C3 complement component and receptor for vascular endothelial growth factor (VEGFR1) as markers of endometrial unbalance between factors activating the complement system in women with consecutive miscarriages. Study enrolled 30 women with at least two consecutive miscarriages, and 19 healthly women, that comprised the control group. RNA was isolated from endometrial samples. Transcripts levels of DAF and MCP was higher in women with consecutive miscarriages compared to controls, 0.78 vs 5.08 (p

Proprotein convertase 6 (PC6) is known to be the key enzyme involved in the transformation of many hormones, cytokines and their receptors into their active forms. Experimental in vitro studies have also proven that lack of PC6 in the endometrium prevents decidualisation. Therefore in our study we have aimed at determining whether infertility in some patients might be attributable to decreased expression of PC6.With the use of RealTime PCR we have studied the expression level of PC6 in receptive phase endometria from 36 idiopathic infertile patients, 26 infertile patients with minimal grade endometriosis and compared those results with fertile, age-matched controls. The endometria were collected 7-9 days after ovulation.There were no statistically significant differences regarding the expression of PC6 in endometria from patients with idiopathic infertility, infertile patients with endometriosis and controls.Since there is no detectable difference in PC6 expression, the decreased expression of PC6 is unlikely to cause infertility.

During the putative "implantation window", a period of maximal endometrial receptivity that spans 7-9 days after ovulation, a series of changes on the structural and molecular level occur that render the endometrium susceptible to implantation for the human embryo. Many members of the TGFbetas are expressed by human endometrium at different stages of menstrual cycle. Also studies regarding the MMP2 gene expression and activity of MMP2 in the implantation window have shown a higher expression and activity of MMP2 in women with impaired fertility. We have examined by RT-PCR the expression of TGFbeta2 and MMP2, MMP9 and TIMP1 in 28 patients with idiopathic infertility, 16 patients with unexplained recurrent miscarriage and 16 control women were enrolled in this study. Seven to nine days after ovulation endometrial biopsy by Pipelle or hysteroscopy was performed to assess the expression of TGFbeta2 , MMP2, MMP9 and TIMP1. We found that in endometria from women with idiopathic infertility TGFbeta2 expression was 2.8 fold higher than in endometria from control group and 2.1 fold higher in endometrial samples from women with unexplained recurrent miscarriage compared to the control group. The MMP2, MMP9 and TIMP1 expression in endometrial samples revealed no significant differences between the study groups and control group. There was a statistically significant negative correlation between TGFbeta2 and MMP9 expression in endometria from women in control group. The present investigations suggest that dysregulated TGFbeta2, MMP2, MMP9 and TIMP1 expression are associated with infertility and early pregnancy loss. However the exact mechanism of how overexpression of endometrial TGFbetaand MMPs interferes with implantation may be more complex.

Problem Assessment of concentration of the metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinases 1 (TIMP1), urokinase plasminogen activator (uPA) and its receptor (uPAR) and leukaemia inhibitory factor (LIF) in the uterine fluid in women with idiopathic infertility and unknown cause for recurrent miscarriage. Method of study Uterine fluid obtained from patients with idiopathic infertility (n = 13), patients with unknown cause of recurrent miscarriages (n = 16) and healthy fertile women (n = 14). The assessment of MMP9, TIMP1, uPA, uPAR and LIF were performed with enzyme-linked immunosorbent assay. Results Statistically lower expression of MMP9 and TIMP1 in uterine fluid during implantation window in women with infertility and recurrent miscarriage of unknown cause. Conclusion Changed turnover of the extracellular matrix might be a cause of improper endometrial transition and in effect cause faulty implantation.

Background Exact aetiology of infertility in stage I/II endometriosis patients is not known. Interleukin 11 (IL-11) and leukaemia-inhibitory factor (LIF) are factors associated with implantation window in human eutopic endometrium. We decided to test whether there is an altered secretion of these factors, which could explain receptivity defect in patients with minimal endometriosis. Methods Uterine flushing and endometrial samples were collected 7-9 days after ovulation (implantation window) from infertile patients with stage I/II endometriosis (n = 14) and fertile, endometriosis-free controls (n = 21). IL-11 and LIF were assessed in uterine flushings in eutopic endometria in all patients by enzyme-linked immunosorbent assay (ELISA). In eutopic endometrium, semiquantitative RT-PCR was performed for LIF and IL-11 mRNA expressions. Results No statistically significant differences were found in uterine flushing in women with and without endometriosis with regard to IL-11 levels (0.0 pg/ml versus 0.0 pg/ml) and LIF (25.53 pg/ml versus 36.26 pg/ml). These results were confirmed by the results of RT-PCR, where there were also no differences between studied groups. Conclusions There is no receptivity defect with regard to LIF and IL-11 secretions by eutopic endometrium in infertile women with endometriosis.

Problem To evaluate the possible correlation between interleukin-1beta (IL-1β) and integrin expression. Method of study Endometrium and uterine fluid from 77 infertile women and 24 fertile, healthy control were studied with immunohistochemistry and enzyme-linked immunosorbent assay for the presence of IL-1β and integrin alphaVbeta3 and alpha4beta1 expression. Results Highest expression of alphaVbeta3 was found in epithelium and glands in endometria from fertile women. There was no positive correlation between IL-1β and integrin expression pattern. Conclusion This study confirms the importance of alphaVbeta3 as molecular marker of receptive phase. Also supports the views that synchrony in development of endometrium is necessary for successful nidation. There was however, contrary to results of previous in vitro studies, no positive correlation between IL-1β and endometrial integrin patter expression.

Glycodelin A (GdA) is viewed as a uterine endometrium receptivity marker. The expression of GdA in the endometrium is mirrored in uterine fluid and in the serum. Thanks to its immunosuppressive properties GdA might regulate mechanisms of fertilization, implantation and further development of the embryo.The authors assessed the GdA concentration during implantation window of nonconceptional cycles in women with impaired reproduction.Fluid from uterine cavity, serum and endometrial samples were obtained from 116 women, among them 43 have had 2 or more miscarriages, while 52 were infertile. Control constituted 21 fertile women. In uterine fluid and serum the GdA concentration was assessed with ELISA Bioserv Diagnostic kits, and progesterone with electrochemiluminescence. Endometria obtained during hysteroscopy were evaluated in terms of conformity with the cycle dating.Statistically lower (p0,0001) compared to control GdA concentration in uterine fluid was found in infertile women. The lowest GdA values were obtained in women with idiopathic infertility and infertile women with endometriosis. GdA level of women with 2 or more miscarriages was no statistically significant different compared to control. The lowest concentration of GdA in this group of patients was found in women with luteal phase deficiency. The GdA concentration in the serum was three times lower compared to values noted in uterine fluid, and there was no difference between studied groups.Based on our research we might conclude that GdA has a more important role during implantation than in further development of the embryo.

The only possibility to diagnose peritoneal endometriosis is laparoscopy or laparotomy with tissue sampling for histology. Women with impalpable endometriosis not visible on ultrasound suffering from infertility or teenagers with pelvic pain, where endometriosis may also be expected, would greatly benefit from an inoperative diagnostic method. A sure and comfortable method of assessing the effectiveness of endometriosis treatment does not exist. The aim of the study was description of the alpha 3 beta 1, alpha 4 beta 1 integrins and beta 1 chain expression in endometrial biopsies in women suffering from endometriosis.Laparoscopy and hysteroscopy was performed in 32 patients because of infertility (n = 23) and/or pelvic pain (n = 11). For histochemical stainings of endometrial biopsy primary and secondary mouse antibodies to human integrins alpha 3 beta 1, alpha 4 beta 1 and beta 1 chain were used (DAKO).In 17 women peritoneal endometriosis was diagnosed by biopsy at the time of laparoscopy. An alpha 3 beta 1 integrin was more common in the glandular epithelium of women with endometriosis and beta 1 subunit was less frequently observed in the stroma of the endometriosis group than in women without endometriosis. The differences were statistically significant.The selected integrins do not yet allow finding a pattern characteristic for endometriosis.