József Bódis

Endometriosis: Harmful survival of an ectopic tissue

Endometriosis results from implantation of endometrial tissue outside the uterine cavity. Endometriosis might remain asymptomatic and discovered accidentally. However, it may cause symptoms, which include chronic pelvic pain, bleeding, infertility, and increases susceptibility to development of adenocarcinoma. The most prevailing hypothesis is that endometriosis results from implantation of endometrial tissue that gains access to peritoneal cavity by retrograde flow during menstruation. The factors contributing to the establishment and persistence of the endometriotic lesions (plaques) most probably include abnormalities of the genital tract, genetic predisposition, hormonal imbalance, altered immune surveillance, inflammatory response and abnormal regulation of the endometrial cells. The mediators that contribute to survival and progression of endometriosis are likely involved in the development of the symptoms of this process. Genomic studies have started to delineate the wide array of mediators involved and the complex genetic background required in the development of endometriosis. This review summarizes our current knowledge regarding the pathogenesis of endometriosis, including progress made with transgenic animals, and a clinical perspective on the diagnosis and management of this common process.

Low-dose aspirin therapy to prevent ovarian hyperstimulation syndrome

OBJECTIVE To evaluate the effect of low-dose aspirin therapy on ovarian hyperstimulation syndrome (OHSS) in an unselected group of patients undergoing in vitro fertilization (IVF). DESIGN Randomized clinical trial. SETTING Division of Reproductive Medicine at the Department of Obstetrics and Gynecology, University of Pécs, Faculty of Medicine, Pécs, Hungary. PATIENT(S) Patients who underwent IVF between 2000 and 2006. INTERVENTION(S) Initiation of 3154 IVF cycles, for which gonadotropin-releasing hormone agonist was used in 2425 cycles; 1503 cycles randomly selected for low-dose aspirin treatment starting from the first day of controlled ovarian hyperstimulation compared with no treatment in the remaining 922 cycles. MAIN OUTCOME MEASURE(S) The incidence of severe or critical OHSS and the rate of clinical pregnancy. RESULT(S) During this time period, 45 cases of severe OHSS were detected. Only two of the OHSS patients had received aspirin previously. CONCLUSION(S) Based on our preliminary results, introduction of low-dose aspirin therapy during ovulation induction for the prevention of OHSS in high-risk patients should be considered.

Male reproductive tract abnormalities: more common after assisted reproduction?

BACKGROUND In this era of increased use of assisted reproduction (AR) techniques, the prevalence rates of hypospadias, cryptorchidism, poor semen quality have been increasing in parallel with a rising incidence of testicular cancer. It is suggested that these problems result from the disruption of gonadal development during fetal life causing the testicular dysgenesis syndrome (TDS). AIM The aim of our study was to evaluate the influence of conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), on the development of male genital tract abnormalities. STUDY DESIGN AND SUBJECTS We analyzed a cohort of 15,206 neonates born from January 1, 1999 through December 31, 2008 at the Department of Obstetrics and Gynecology, Medical School, University of Pécs, including 890 children (5.9%) born after IVF or ICSI. We examined the association between these AR methods and developmental abnormalities of the genital tract (hypospadias, cryptorchidism), after controlling for potential confounding factors, such as prematurity, low birthweight and twinning. RESULTS Preterm birth and low birthweight are risk factors for hypospadias and cryptorchidism (p<0.001), twinning increases the risk of hypospadias (p<0.001). ICSI was revealed as a risk factor for hypospadias in singletons (OR: 3.190, 95%CI: 1.266-8.042) and in normal birthweight (>2500 g) infants (OR: 3.966, 95%CI: 1.193-13.181, respectively). Similar but not nonsignificant trends were seen for cryptorchidism. CONCLUSION IVF and ICSI, by increasing the risks of prematurity, low birthweight, and multiple gestation, are indirect risk factors for developing male genital malformations. In infants with normal birhtweight or from singleton pregnancies, ICSI is a specific risk factor for hypospadias.

Possible role of natural killer and natural killer T-like cells in implantation failure after IVF

During implantation, maternal immunoactivation and tolerance are not only limited to the decidua but are also observed in the periphery, predominantly affecting the innate immune system. Since unexplained female infertility, as well as recurrent spontaneous abortion and implantation failure, are thought to be associated with pathological maternal immunotolerance mechanisms, this study focused on immune profile analysis of IVF candidates. Previous studies on peripheral natural killer (NK) cell characteristics of IVF patients have been limited to the comparison of blood samples taken prior to the IVF procedure. This study performed a follow-up study and compared patients data obtained on the day of oocyte collection with the data 1 week after embryo transfer. The aim was to investigate phenotypic (subpopulations, CD69, T-cell immunoglobulin mucin 3 and NK-activating receptor expression) and functional (perforin and CD107a expression) changes in the peripheral NK and NK T (NKT)-like cell populations. During this short period of time around the IVF procedure, women with failed IVF reflected unfavourable Th1-oriented changes of NK and NKT-like cells. In comparison the follow-up data for women with successful conception remained principally constant. The observed peripheral changes during early pregnancy in the same individual may also have importance in successful embryo implantation.

The occurrence of acute myocardial infarction in relation to weather conditions

The spatial and temporal changes of weather factors depend on geographical location, seasons and the time of the day. Our study examines the relationships of meteorological factors and the incidence of acute myocardial infarction (AMI). A retrospective analysis of patients diagnosed with AMI between 2000 and 2004 in Hungary (n = 81,956 patients) was carried out. Data were collected by the National Health Insurance Fund Administration (OEP) and the National Meteorology Service (OMSZ). A peak period of the occurrence of AMI was found during spring, while minimum number of events were recorded during summer. Significant difference was observed between the number of events each season (F = 34.741; p < 0.001; N = 81,956). A medium level negative correlation was found between the monthly average temperature and the occurrence of AMI (r = -0.404) during the period examined. A positive correlation was shown between front movements and the number of events per season (r = 0.053). Average barometric pressure changes, the number of front movements and the number of AMI events also showed a nearly similar seasonal deviation. Our findings show that certain meteorological factors may be related to the onset of AMI, however other factors also play an important role.

The effect of catecholamines, acetylcholine and histamine on progesterone release by human granulosa cells in a granulosa cell superfusion system

There are experimental data demonstrating the presence and actions of various neurotransmitters in the ovary, thus supporting the view that they might play a role in intraovarian regulatory mechanisms, although their exact function in the regulation of ovarian hormone secretion is unclear. The objective of the present study was to investigate the direct action of catecholamines, acetylcholine and histamine on progesterone secretion of human granulosa cells in a superfused cell system. Human granulosa cells were isolated from preovulatory follicular fluid using a Percoll gradient centrifugation method. Approximately 2 × 106 cells were mixed with Sephadex G-10 and were transferred into two chambers of the superfusion apparatus. The system was perfused with a culture medium and test materials were added to the system at a dose of 100 pmol/ml. The progesterone concentration of samples was measured using an 125I radioimmunoassay. Administration of epinephrine (adrenaline), norepinephrine (noradrenaline), dopamine and histamine had no effect on progesterone release. However, acetylcholine produced a significant progesterone release, which could be blocked by atropine. The observed effect of acetylcholine on progesterone release of superfused human granulosa cells may reflect a physiological role of acetylcholine in the regulation of granulosa cell function during the menstrual cycle.

Silent chorioamnionitis and associated pregnancy outcomes: a review of clinical data gathered over a 16-year period

Abstract Objective: To assess neonatal outcomes and associated findings in pregnant women identified after delivery as having had underlying subclinical chorioamnionitis by either histology or bacterial culture. Methods: In 16 years, 8974 clinical, histological, and bacterial culture data were obtained retrospectively. Results: Placental histology was analyzed in 4237 pregnancies (2785 term and 1452 preterm) and 4737 amniotic cavity cultures were obtained during 5446 cesarean deliveries (3268 term and 1469 preterm). Histological results and bacterial cultures were both available in 1270 of the preterm deliveries. Histology revealed inflammation, suggestive of infection, in 13.6% of placentas. Subclinical acute chorioamnionic inflammation was confirmed in 142 out of 2785 term pregnancies (5.1%) and in 436 out of 1452 preterm pregnancies (30.0%, P<0.001). Bacteriological culture of the intrauterine cavity was obtained from the lower uterine segment of the uterus during cesarean section. A positive culture was found in 19.9% of all cases (941/4737), this proportion was significantly higher in preterm deliveries (343/1273, 26.9%) than in term (17.3%, P<0.001). The lower the birth-weight or gestational age, the higher the frequency of silent infections in the uterine cavity. Conclusions: Our study findings support the association between intra-amniotic infections and preterm delivery.

Histological chorioamnionitis is associated with cerebral palsy in preterm neonates.

OBJECTIVE To determine the interaction between histological chorioamnionitis and unexplained neonatal cerebral palsy among low birth weight infants. STUDY DESIGN We studied 141 preterm infants below 1500 g delivered between 2000 and 2010. Clinical data, neonatal neuroimaging, laboratory results, the histopathological features of the placenta and gastric smear within the first hour of delivery, were evaluated. RESULTS Cerebral palsy was detected in 11 out of 141 preterm newborns (7.8%). The incidence of silent histological chorioamnionitis was 33.6% (43 of 128 cases). Chorioamniontis was significantly associated with the risk of unexplained cerebral palsy (p=0.024). There were also significant correlations between maternal genital infections and chorioamnionitis (p=0.005), and between maternal infections and a positive smear of neonatal gastric aspirates (p=0.000). The rate of cesarean section was 67.4% (95 out of 141 deliveries), and elective cesarean section was performed in 68 cases. CONCLUSION Intrauterine exposure to maternal infection was associated with a marked increase in the risk of cerebral palsy in preterm infants.

Permanent stress may be the trigger of an acute myocardial infarction on the first work-day of the week

Numerous studies have reported the weekly variation of an acute myocardial infarction. The Monday peek has been connected with higher rate of physical and mental, work-related stress. We wished to study the weekly variation of an acute myocardial infarction (AMI) in the group of workers and pensioners, and to find out whether National Holidays on the first day of the week could influence the weekly rhythm of an acute myocardial infarction. We carried out the retrospective analysis of patients admitted to Hungarian hospitals with the diagnose of an AMI (n=90,187) between 2002 and 2007. According to the morbidity data of an AMI, the weekly peek was detected on the first work-day of the week, showing a gradually decreasing tendency until the end of the week. Morbidity rates on Mondays being National Holidays were similar to the number of events on Saturdays and Sundays (Z=-24,431; p<0.001). There was a significant difference between the number of events on work-days and weekends (Z=-27,321; p<0.001). No marked difference was found between workers under the age of 65 and pensioners above the age of 65, or between the two sexes. The results of our study reveal that the occurrence of an AMI shows characteristic changes throughout the days of the week, and the first work-days of the week may be related to higher incidence of an acute myocardial infarction.

Involvement of Galectin-9/TIM-3 Pathway in the Systemic Inflammatory Response in Early-Onset Preeclampsia

Background Preeclampsia is a common obstetrical disease affecting 3-5% of pregnancies and representing one of the leading causes of both maternal and fetal mortality. Maternal symptoms occur as an excessive systemic inflammatory reaction in response to the placental factors released by the oxidatively stressed and functional impaired placenta. The T-cell immunoglobulin domain and mucin domain (TIM) family is a relatively newly described group of molecules with a conserved structure and important immunological functions. Identification of Galectin-9 as a ligand for TIM-3 has established the Galectin-9/TIM-3 pathway as an important regulator of Th1 immunity and tolerance induction. Methods The aim of our study was to investigate the expression and function of Galectin-9 and TIM-3 molecules by peripheral blood mononuclear cells and the possible role of Galectin-9/TIM-3 pathway in the immunoregulation of healthy pregnancy and early-onset preeclampsia. We determined TIM-3 and Gal-9 expression and cytotoxicicty of peripheral lymphocytes of early-onset preeclamptic women and healthy pregnant woman using flow cytometry. Results Investigating peripheral lymphocytes of women with early-onset preeclampsia, our results showed a decreased TIM-3 expression by T cells, cytotoxic T cells, NK cells and CD56dim NK cells compared to healthy pregnant women. Interestingly, we found a notably increased frequency of Galectin-9 positive cells in each investigated lymphocyte population in the case of early-onset preeclamptic patients. We further demonstrated increased cytotoxic activity by cytotoxic T and CD56dim NK cells in women with early-onset preeclampsia. Our findings showed that the strongest cellular cytotoxic response of lymphocytes occurred in the TIM-3 positive subpopulations of different lymphocytes subsets in early-onset preeclampsia. Conclusion These data suggest that Gal-9/TIM-3 pathway could play an important role in the immune regulation during pregnancy and the altered Galectin-9 and TIM-3 expression could result an enhanced systemic inflammatory response including the activation of Th1 lymphocytes in preeclampsia.