Changes of Ex Vivo Cervical Epithelial Cells Due to Electroporation with JMY.

The ionic environment within the nucleoplasm might diverge from the conditions found in the cytoplasm, potentially playing a role in the cellular stress response. As a result, it is conceivable that interactions of nuclear actin and actin-binding proteins (ABPs) with apoptosis factors may differ in the nucleoplasm and cytoplasm. The primary intracellular stress response is Ca2+ influx. The junctional mediating and regulating Y protein (JMY) is an actin-binding protein and has the capability to interact with the apoptosis factor p53 in a Ca2+-dependent manner, forming complexes that play a regulatory role in cytoskeletal remodelling and motility. JMY's presence is observed in both the cytoplasm and nucleoplasm. Here, we show that ex vivo ectocervical squamous cells subjected to electroporation with JMY protein exhibited varying morphological alterations. Specifically, the highly differentiated superficial and intermediate cells displayed reduced nuclear size. In inflamed samples, nuclear enlargement and simultaneous cytoplasmic reduction were observable and showed signs of apoptotic processes. In contrast, the less differentiated parabasal and metaplastic cells showed increased cytoplasmic activity and the formation of membrane protrusions. Surprisingly, in severe inflammation, vaginosis or ASC-US (Atypical Squamous Cells of Undetermined Significance), JMY appears to influence only the nuclear and perinuclear irregularities of differentiated cells, and cytoplasmic abnormalities still existed after the electroporation. Our observations can provide an appropriate basis for the exploration of the relationship between cytopathologically relevant morphological changes of epithelial cells and the function of ABPs. This is particularly important since ABPs are considered potential diagnostic and therapeutic biomarkers for both cancers and chronic inflammation.

Female reproductive functions of the neuropeptide PACAP.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide originally isolated as a hypothalamic peptide. It has a widespread distribution in the body and has a diverse spectrum of actions. Among other processes, PACAP has been shown to be involved in reproduction. In this review we summarize findings related to the entire spectrum of female reproduction. PACAP is a regulatory factor in gonadal hormone production, influences follicular development and plays a role in fertilization and embryonic/placental development. Furthermore, PACAP is involved in hormonal changes during and after birth and affects maternal behavior. Although most data come from cell cultures and animal experiments, increasing number of evidence suggests that similar effects of PACAP can be found in humans. Among other instances, PACAP levels show changes in the serum during pregnancy and birth. PACAP is also present in the human follicular and amniotic fluids and in the milk. Levels of PACAP in follicular fluid correlate with the number of retrieved oocytes in hyperstimulated women. Human milk contains very high levels of PACAP compared to plasma levels, with colostrum showing the highest concentration, remaining steady thereafter for the first 7 months of lactation. All these data imply that PACAP has important functions in reproduction both under physiological and pathological conditions.

Cross-sectional study of female pelvic floor dysfunction in a Hungarian population / Noi kismedencei funkciózavarok keresztmetszeti vizsgálata magyarországi populáción.

Összefoglaló. Bevezetés és célkituzés: A noi kismedencei funkciózavarok változatos tünetekkel jelentkezhetnek, és jelentosen befolyásolják az érintettek életminoségét. Vizsgálatunk célja volt felmérni a medencefenék-diszfunkciós tüneteket és azok hatását az egyén életminoségére. Módszer: Vizsgálatunkba 203 not vontunk be. Az adatgyujtést két kérdoív, egy általunk összeállított és az Australian Pelvic Floor Questionnaire segítségével végeztük. Az adatok statisztikai elemzéséhez SPSS 20.0 rendszert használtunk. Spearman-korrelációt, khi-négyzet-próbát, Mann-Whitney-féle U-tesztet, Kruskal-Wallis-próbát és többváltozós lineáris regressziót alkalmaztunk. A szignifikanciaszintet p≤0,05 határnál állapítottuk meg. Eredmények: A hólyagdiszfunkciók gyakorisága (56,2%) szignifikáns kapcsolatot mutatott az életkor növekedésével (p<0,001), az obesitassal (p<0,001), a szülésszámmal és -móddal (p<0,001; p<0,001), az episiotomiával (p<0,001) és a prolapsusmutétekkel (p = 0,010). A süllyedéses kismedencei kórképek gyakorisága (27,1%) szignifikáns kapcsolatot mutatott az életkor növekedésével (p = 0,002), a szülésszámmal és -móddal (p<0,001; p<0,001) és a korábbi episiotomiával (p<0,001). Az analis incontinentia gyakorisága (58,9%) a magasabb testtömegindexszel (p = 0,029) volt szignifikáns kapcsolatban. Szexuális diszfunkciót (53,2%) allergia és tüdobetegségek (p = 0,048) jelenlétével kapcsolatban találtunk. A többes diszfunkció elofordulási gyakorisága az életkor növekedésével (p<0,001), az obesitassal (p = 0,043), a korábbi hysterectomiával (p = 0,046) és prolapsusmutétekkel (p<0,001) mutatott szignifikáns kapcsolatot. Minden diszfunkció esetén kimutatható volt az életminoség-romlás (hólyagfunkciók: p<0,001; bél- és székletürítési funkciók: p<0,001, hüvelyfali süllyedés: p<0,001, szexuális funkciók: p<0,001). Következtetés: Az általunk vizsgált noi populációban nagy arányban találtunk kismedencei funkciózavarokat, melyek kedvezotlen hatással voltak az érintettek életminoségére. Orv Hetil. 2021; 162(43): 1724-1731. INTRODUCTION AND OBJECTIVE: Pelvic floor dysfunction (PFD) can cause several complaints in women and has an adverse effect on the quality of life (Qol). The aim of our study was to evaluate the prevalence of pelvic floor dysfunction and its effect on Qol. METHOD: 203 women were included. We used two questionnaires, a self-constructed and the Australian Pelvic Floor Questionnaire. Statistical analysis was performed by SPSS 20.0. Spearman's correlation, chi-square, Mann-Whitney U, Kruskal-Wallis tests and multivariate linear regression were used. Statistical significance was set at p≤0.05. RESULTS: There was a significant association between the prevalence of urinary incontinence (56.2%) and age (p<0.001), obesity (p<0.001), number and mode of deliveries (p<0.001; p<0.001), episiotomy (p<0.001) and pelvic organ prolapse (POP) surgery (p = 0.010); between the occurrence of POP (27.1%) and age (p = 0.002), the number and mode of deliveries (p<0.001; p<0.001) and episiotomy (p<0.001); between the prevalence of anal incontinence (58.9%) and obesity (p = 0.029); between sexual dysfunction (SD) (53.2%) and respiratory disease and allergy (p = 0.048). Multiple PFD was significantly associated with age (p<0.001), obesity (p = 0.043), hysterectomy (p = 0.046) and POP surgery (p = 0.010). There was a significant difference between women having more severe PFD than milder complaints regarding Qol (bladder p<0.001; bowel p<0.001; SD p<0.001 and POP p<0.001). CONCLUSION: Pelvic floor dysfunction was common in our study population and had a great adverse effect on Qol. Orv Hetil. 2021; 162(43): 1724-1731.

Multicausal analysis on psychosocial and lifestyle factors among patients undergoing assisted reproductive therapy - with special regard to self-reported and objective measures of pre-treatment habitual physical activity.

BACKGROUND: National, regional and global trends in prevalence of infertility indicate its public health importance, however it effects various life dimensions of individuals and couples as well. Lifestyle habits may counteract with these factors. The aim of the study was the multicausal analysis of psychosocial and lifestyle factors undergoing assisted reproductive therapy (ART) with special regard to pre-treatment habitual physical activity (PA). METHODS: In a cross-sectional, observational cohort study on ART patients (N = 60, age 34.6 ± 5.2 years, BMI 24.2 ± 4.9 kg/m2) with follow up on outcome measures a detailed description was given on PA patterns (ActriGraph GT3X, GPAQ-H) and on general and infertility related distress (BDI-13, FPI). RESULTS: Respondents reported normal mood state (BDI-13) but moderately high infertility-related distress (FPI) in Social- and very high distress in Sexual Concern. It was revealed that time spent with recreational PA (RPA) could counteract with infertility-related distress (Social Concern R = -0.378, p = 0.013; Relationship Concern R = -0.365, p = 0.019). In the presence of clinical pregnancy GPAQ-H RPA MET was significantly higher (p = 0.048), in the non-pregnant group cumulative values and work-related PA were higher. Correlations could be found between RPA time and the number of oocytes (R = 0.315, p = 0.045), matured oocytes (R = 0.339, p = 0.030) and embryos (R = 0.294, p = 0.062) by women who reached at least 150 min RPA (GPAQ-H). Multivariate linear regression revealed that the number of oocytes was positively influenced by the GPAQ-H recreation MET (R2 = 0.367; F = 10.994, p = 0.004; B = 0.005, p = 0.004, B Constant = 4.604). Regarding the number of embryos (R2 = 0.757, F = 17.692, p < 0.001, B Constant = 1.342) positive relationship was found with GPAQ-H RPA MET (B = 0.004, p < 0.001) and negative with BMI (B = -0.167, p = 0.038). It was disclosed (R2 = 0.958, F = 408.479, p < 0.001) that higher Very Vigorous Activity (ActiGraph) was accompanied with higher hCG (B = 63.703, p ≤ 0.001). However, time spent with moderate PA (GPAQ-H) (B = 0.002, SE = 0.001, Wald = 3.944, p = 0.047, OR = 1.002) was significantly associated with live births. CONCLUSIONS: Amount of PA alone did not have a positive effect on outcome of ART. Type and intensity seemed to be more significant. Existing differences in response to infertility due to recreational PA suggest the importance of the development of a specific intervention. The robust overestimation of PA in self-reports highlights the need to improve physical literacy of women undergoing ART.

Investigations of follicular fluid biomarkers in patients undergoing / A tüszofolyadék biomarkereinek vizsgálata in vitro fertilizációs kezelésben részesült betegekben.

Összefoglaló. A szerzok ismertetik vizsgálataik eredményeit, melyeket a közelmúltban az in vitro fertilizációs kezelésben részesülo betegeikben a tüszofolyadék biomarkereinek analízisével értek el. A vizsgálatok célja annak feltárása volt, hogy az in vitro fertilizációs eljárás során a petesejtek aspirációjakor nyert tüszofolyadék-biomarkerek lokális/ovarialis vagy szisztémás eredetuek, és milyen összefüggést mutatnak az in vitro fertilizáció eredményességét jelzo paraméterekkel. Megerosítettük, hogy az autokrin/parakrin szerotoninrendszer már a fejlodés legkorábbi idoszakában is muködoképes, és mind az anyai szérum, mind a tüszofolyadék szerotoninszintje szignifikáns pozitív összefüggést mutatott az érett petesejtek számával és a klinikai terhességgel (ß = 0,447, p = 0,015, illetve ß = 0,443, p = 0,016). Az agyi eredetu neurotrofikus faktor (BDNF) esetében ilyen kapcsolat nem volt igazolható, de a tüszofolyadék BDNF- és szerotoninszintjei közötti pozitív korreláció (r = 0,377, p = 0,040) azt mutatja, hogy a két neurohormon 'feed-forward' (elorecsatoló ) szabályozása ovarialis szinten is muködik. A hypothalamicus kisspeptin esetében csupán a posztstimulációs anyai szérumhormonszint befolyásolta az érett petesejtek számát (ß = 0,398, p = 0,029). A triptofán-kinurenin-szerotonin rendszer elemzése azt mutatta, hogy kedvezobb in vitro fertilizációs kimenetel várható, ha a szerotonin-kinurenin egyensúly a szerotonin javára tolódik el. Az oxidatívstressz-markerek közül vizsgálták a DNS-károsodás biomarkerét, a 8-hidroxi-2'-deoxiguanozin és a totális antioxidáns-kapacitás szérum- és tüszofolyadékszintjeit, és megállapították, hogy mindkét marker kedvezotlenül befolyásolja az életképes embriók számát (r = 0,302, p = 0,027 és r = 0,268, p = 0,039). A protektív hatású szirtuinok - nikotinamid-adenin-dinukleotid-függo hiszton-deacetiláz fehérjék - közül a vizsgált szirtuin-1 és szirtuin-6 a szérumszintektol függetlenül kimutatható a tüszofolyadékban. Szignifikáns pozitív korreláció van a tüszofolyadék-szirtuin-6 és az érettpetesejt-szám (F = 6,609, p = 0,016), valamint a szérum-szirtuin-1 (F = 10,008, p = 0,005) és a szérum-szirtuin-6 (F = 5,268, p = 0,031) és a klinikai terhesség gyakorisága között. Eredményeink alapján megállapítható, hogy a tüszofolyadék biomarkereinek vizsgálata javíthatja az in vitro fertilizáció kimenetelének megítélését. Orv Hetil. 2021; 162(14): 523-529. Summary. This article outlines the result of recent studies on several follicular fluid biomarkers in patients undergoing in vitro fertilization. The aim of these studies was to investigate whether 1) the follicular fluid biomarkers in question are produced locally by the ovaries or they originate from the circulating plasma, 2) and to establish their association with parameters of in vitro fertilization outcome. It was confirmed that the autocrine/paracrine serotonin system is functional already at the earliest stage of development and both maternal serum and follicular fluid serotonin levels were positively related to the number of mature oocytes (ß = 0.447, p = 0.015 and ß = 0.443, p = 0.016, respectively) and clinical pregnancy (ß = 1.028, p = 0.047). Such associations for brain-derived neurotrophic factor (BDNF) could not be found, but BDNF and serotonin in the follicular fluid were closely related (r = 0.377, p<0.040) suggesting that the feed-forward regulation of these neurohormones is activated at ovarian level. The hypothalamic kisspeptin in the post-stimulation maternal serum also increased the number of mature oocytes (ß = 0.398, p = 0.029). Analysis of the tryptophan-kynurenine-serotonin system showed a more favourable in vitro fertilization outcome when the serotonin-kynurenine balance was shifted and serotonin predominated over kynurenine. The oxidative stress markers, 8-hydroxy-2'-deoxyguanosine, an indicator of DNA damage and the total antioxidant capacity in follicular fluid and maternal serum had negative impact on the number of viable embryos (r = 0.302, p = 0.027 and r = 0.268, p = 0.039), respectively. The protective sirtuins - the nicotinamide adenine dinucleotide-dependent histone deacetylase proteins - could be detected in follicular fluid irrespective of their maternal serum levels. Significant positive relationship was demonstrated between follicular fluid sirtuin 6 and mature oocytes (F = 6.609, p = 0.016) as well as between serum sirtuin 1 (F = 10.008, p = 0.005) and serum sirtuin 6 (F = 5.268, p = 0.031) and the rate of clinical pregnancy, respectively. On the basis of these results, it can be concluded that measuring several follicular fluid biomarkers may improve the prediction of the outcome of in vitro fertilization. Orv Hetil. 2021; 162(14): 523-529.

Investigation of pituitary adenylate cyclase activating polypeptide (PACAP) in human amniotic fluid samples.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide acting as a hormone, a neuromodulator, a neurotransmitter, a trophic factor and is involved in a variety of developmental and regenerative processes. PACAP is present in several human tissues and biological fluids. In many pathological conditions, changes in PACAP levels have been described to reflect disease progression, therefore PACAP has diagnostic value as a potential biomarker. Since PACAP has been shown to play an important role in reproductive physiology and development, it was of interest to examine whether this neuropeptide occurs in the human amniotic fluid. Amniotic fluid samples were collected between the 15-19th weeks of gestation from volunteering pregnant women undergoing amniocentesis as a prenatal diagnostic tool due to maternal age. Pathological cases were excluded after prenatal karyotype analysis. PACAP-like immunoreactivity was measured by radioimmunoassay and could be detected in all samples. The present study provides evidence for the presence of PACAP in human amniotic fluid, but determination of the exact physiological or pathological significance awaits further investigation.

How to Reduce the Potential Harmful Effects of Light on Blastocyst Development during IVF.

PURPOSE: Earlier findings revealed the damaging effect of visible light on zygotes and gametes. The aim of our study is to eliminate or significantly reduce the potentially harmful effects of light exposure during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and to investigate the effect of light protection on embryo development and implantation. MATERIALS AND METHODS: To protect sperm cells, oocytes, and embryos from the potential harmful effects of light exposure during laboratory procedures, we created a dark environment for the cells and applied red filters on laboratory lamps and UV or infrared filters in the microscopes in order to eliminate white light exposure of the cells throughout all work stages. RESULTS: The fertilization rate was significantly (p = 0.011) higher in light-protected ICSI cycles. Blastocyst development rates (blastocyst/embryo) were significantly (p < 0.001) higher in light-protected embryos than in those manipulated in conventional light conditions both in IVF (20.9% difference) and ICSI (38.6% difference). Numbers of clinical pregnancies/transfers of ICSI fertilized day 5 blastocysts were also significantly (p = 0.040) higher in light-protected conditions. CONCLUSIONS: These data show that light protection has a positive effect on fertilization rate and increases the blastocyst development as well as the number of clinical pregnancies/transfers. Implementation of this light protection method in IVF centers may improve the success rate while maintaining maximal embryo safety.

Different Expression Pattern of TIM-3 and Galectin-9 Molecules by Peripheral and Peritoneal Lymphocytes in Women with and without Endometriosis.

Endometriosis is a gynecological condition that is associated with chronic pelvic inflammation, pain, and infertility. Although substantial evidence supports that immunological alterations contribute to its pathogenesis and we previously posed a pivotal role of Galectin-9 (Gal-9) in this disorder, the involvement of the TIM-3/Gal-9 pathway in the development of endometriosis-associated immunological abnormalities is not yet known. In the present study, multicolor flow cytometry was used to compare the immunophenotype and cell surface expression of TIM-3 and Gal-9 molecules on peripheral blood (PB) and peritoneal fluid (PF) lymphocytes of women with and without endometriosis. We found an altered distribution of different lymphocyte subpopulations, a markedly decreased TIM-3 labeling on all T and NK subsets and a significantly increased Gal-9 positivity on peripheral CD4+ T and Treg cells of the affected cohort. Furthermore, a significantly increased TIM-3 expression on CD4+T-cells and elevated Gal-9 labeling on all T and NK subsets was also revealed in the PF of the examined patients. In conclusion, our results suggest a persistent activation and disturbed TIM-3/Gal-9-dependent regulatory function in endometriosis, which may be involved in the impaired immune surveillance mechanisms, promotes the survival of ectopic lesions, and aids the evolution of reproductive failures in endometriosis.

Comparative analysis of abdominal fluid cytokine levels in ovarian hyperstimulation syndrome (OHSS).

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a rare, yet severe, iatrogenic complication of ovulation induction therapy during assisted reproductive procedures. Our group previously detected atypical cells in the ascitic fluid of OHSS patients, although no malignancy developed during follow up. Here, the aim was to perform a comparative analysis of the cytokines present in the abdominal fluid of patients affected by OHSS versus patients with advanced ovarian cancer, a benign adnexal mass, or ovarian endometriosis. METHODS: This prospective, non-randomized study was conducted at the Clinical Center of the University of Pecs Department of Obstetrics and Gynecology/Reproductive Center between October 2016 and March 2018. Abdominal fluid samples were obtained from 76 patients and subjected to Luminex analysis. The samples were collected from patients with OHSS (OHSS; n = 16), advanced ovarian cancer (OC; n = 22), a benign adnexal mass (BAM; n = 21), or ovarian endometriosis (EM; n = 17). Data were subjected to the non-parametric Kruskal-Wallis test and Spearman's rank correlation coefficient to identify statistical differences between the four study groups. RESULTS: Leukocytosis and hemoconcentration were detected in the peripheral blood of OHSS patients. Abdominal fluid analysis further revealed significantly higher levels of interleukin (IL)-6, IL-8, IL-10, and transforming growth factor (TGF)-ß in both the OHSS and OC groups compared to the BAM and EM groups. The highest concentration of vascular endothelial growth factor (VEGF) was detected in the OC group, while a significantly lower level was detected in the OHSS group. Moreover, VEGF levels in OC and OHSS groups were significantly elevated compared to the levels in the BAM and EM groups. CONCLUSIONS: Vasoactive and hematogenic cytokines were present at higher levels in both the OHSS and OC abdominal fluid samples compared to the fluid samples obtained from the peritoneal cavity of the BAM patients. It is possible that these cytokines play an important role in the formation of ascites.

[Preoperative systemic treatment of locally and locoregionally advanced high-risk endometrial cancer]. / Lokálisan és lokoregionálisan elorehaladott, magas kockázatú endometriumtumorok mutét elotti szisztémás elokezelése.

Introduction: Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The best survival rates are expected after surgical removal, thus the aim of a complex treatment is to achieve resecability in locally and locoregionally advanced disease. Aim: The primary purpose of this study was to evaluate if the neoadjuvant systemic treatment leads to better overall survival compared to irradiation solely. Method: From January 2015 to December 2018, we enrolled 28 patients diagnosed with irresecable, locally and locoregionally advanced high-risk endometrial carcinoma. Patients were treated by neoadjuvant paclitaxel-carboplatin, then radical hysterectomy, bilateral oophorectomy and lymphadenectomy were performed. Results: After administration of 6 cycles of carboplatin-paclitaxel, the control MR test showed tumor shrinkage in all patients. Complete resection was achieved in the case of every patient. Tumor residuum in lymph nodes was verified in 4 cases by pathological evaluation. The 2-year survival and the 2-year progression-free survival rates were 65,1% and 66,1%, respectively. The median overall survival was 16,5 months. Conclusion: Neoadjuvant treatment can be an effective approach in providing the conditions for complete tumor resection, which may result in survival advantage. Despite multimodal treatment, prognosis is poor. Orv Hetil. 2020; 161(11): 425-433.

The Surgical Benefit of Hysterolaparoscopy in Endometriosis-Related Infertility: A Single Centre Retrospective Study with a Minimum 2-Year Follow-Up.

AIM: This study examined the fertility performance of women after combined hysterolaparoscopic surgical management of endometriosis. Design: This study is a hospital-based retrospective review. MATERIALS AND METHODS: Data collected from the records of all patients presented with endometriosis-related infertility using a checklist designed for the purpose. Result: A total of 81.3% (370/455) of women who have had the desire to have children became pregnant during the study period after the surgery. Of those who became pregnant, all three-hundred-forty-seven patients were followed to the end of their pregnancies. A successful live birth occurred in 94.2% (327/347) of individuals, and pregnancy loss occurred in 5.8% (20/347). The mean patient age was 34.1 ± 4.1 years, and the average duration of infertility was 3.4 ± 3.3 years. Pregnancy occurred spontaneously in 39.5% (146/370) of patients, after artificial insemination (AIH) in 3.8% (14/370) of women, and after in vitro fertilization-embryo transfer (IVF-ET) in 56.8% (210/370) of cases. Patients aged ≤ 35 years had a higher chance of conception post-surgery-84% versus 77%, respectively (p = 0.039). Based on the modes of pregnancy, the timely introduction of an assisted reproductive technique (ART) demonstrated a significant effect on fertility performance postsurgery. Comparatively, this effect was 91.3% vs. 74.1% among the ≤35- and >35-year-old age groups, respectively. There was no significant difference in reproductive performance based on stages of endometriosis, nor in the other parameters evaluated. Conclusion: Our data are consistent with previous clinical studies regarding the management options of endometriosis-related infertility. Overall, the combined hysterolaparoscopy treatment is a very effective and reliable procedure, and is even more effective when combined with ART. It enhances women's wellbeing and quality of life, and significantly improves reproductive performance.

Serum and follicular fluid levels of serotonin, kisspeptin, and brain-derived neurotrophic factor in patients undergoing in vitro fertilization: an observational study : Neurohormones in patients receiving IVF.

OBJECTIVE: This study aimed to examine the effect of interactions between serotonin (5-HT), brain-derived neurotrophic factor (BDNF), and kisspeptin on the reproductive potential in women receiving in vitro fertilization (IVF). METHODS: Paired serum and follicular fluid (FF) samples were obtained from 30 consecutive patients receiving IVF. Primary and secondary outcome measures were the rate of chemical/clinical pregnancy and the number of mature oocytes and embryos, respectively. Serum and FF 5-HT, BDNF, kisspeptin, and platelet-activating factor (PAF) levels were measured by enzyme-linked immunosorbent assay. RESULTS: In response to ovarian hyperstimulation, serum 5-HT and kisspeptin levels significantly increased, whereas serum BDNF and PAF levels remained unchanged. These factors were detected in FF, but they were unrelated to serum levels. FF 5-HT and BDNF levels were positively correlated. Serum kisspeptin levels were negatively correlated with FF BDNF and serum and FF PAF levels. Women who were pregnant had significantly lower FF BDNF levels compared with women who were not pregnant (21.96±12.75 vs 47.63±52.90 µg/mL). Multivariate stepwise linear regression and logistic regression analyses showed that only 5-HT and kisspeptin improved IVF outcome. CONCLUSIONS: This study indicates a role of serotoninergic mechanisms in success of IVF, but the contribution of interacting neuropeptides requires additional investigation.

Follicular fluid progesterone concentration is associated with fertilization outcome after IVF: a systematic review and meta-analysis.

Follicular fluid is a key biochemical environment for oocyte development. The potential effect of follicular progesterone level on successful fertilization is a subject of debate, and so the aim of this study was to provide a summary of the currently available evidence on the association between follicular fluid progesterone level and fertilization outcome. To do so, a systematic review and a meta-analysis were performed, with the literature searches being conducted in three databases (PubMed, Embase and the Cochrane Library) to identify all relevant studies published up to 19 August 2017. Data were available from 13 studies (four intracytoplasmic sperm injection [ICSI] and nine conventional IVF) and 1009 individually aspirated follicular fluid samples were included in the analysis. The progesterone levels in follicular fluid were significantly higher in normal fertilization than in failed fertilization, both in conventional IVF (33% difference, P < 0.001) and ICSI (34% difference, P = 0.004). Although these data show that fertilized oocytes are derived from follicles with higher levels of progesterone, the results must be interpreted with caution, because of various progesterone measurement methods and different treatment protocols and it is too early to state that follicular fluid progesterone level could be considered as a marker for oocyte quality.

Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis.

Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major nociceptive integrators. They are also present on the rat endometrium in an oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian endometriosis patients, but there is no information about TRPA1 and their pathophysiological significances. In this study, patients undergoing laparoscopic surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep infiltrating endometriosis ( n = 15), uterine fibroid-induced moderate dysmenorrhoea ( n = 7) and tubal infertility with no pain ( n = 6). TRPA1 and TRPV1 mRNA and protein expressions were determined by quantitative polymerase chain reaction and semi-quantitative immunohistochemistry from the endometrium samples taken by curettage. Results were correlated with the clinical characteristics including pain intensity. TRPA1 and TRPV1 receptors were expressed in the healthy human endometrium at mRNA and protein levels. Sparse, scattered cytoplasmic TRPA1 and TRPV1 immunopositivities were found in the stroma and epithelial layers. We detected upregulated mRNA levels in deep infiltrating endometriosis lesions, and TRPV1 gene expression was also elevated in autocontrol endometrium of deep infiltrating endometriosis patients. Histological scoring revealed significant TRPA1 and TRPV1 difference between deep infiltrating endometriosis stroma and epithelium, and in deep infiltrating endometriosis epithelium compared to control samples. Besides, we measured elevated stromal TRPV1 immunopositivity in deep infiltrating endometriosis. Stromal TRPA1 and TRPV1 immunoreactivities strongly correlated with dysmenorrhoea severity, as well TRPV1 expression on ectopic epithelial cells and macrophages with dyspareunia. Epithelial TRPA1 and stromal TRPV1 immunopositivity also positively correlated with dyschezia severity. We provide the first evidence for the presence of non-neuronal TRPA1 receptor in the healthy human endometrium and confirm the expression of TRPV1 channels. Their upregulations in rectosigmoid deep infiltrating endometriosis lesions and correlations with pain intensity suggest potential roles in pathophysiological mechanisms of the disease.

Environmental enrichment decreases asphyxia-induced neurobehavioral developmental delay in neonatal rats.

Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.

Role of PACAP in Female Fertility and Reproduction at Gonadal Level - Recent Advances.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a pleiotropic neuropeptide, first isolated from hypothalamic extracts, but later shown in peripheral organs, such as endocrine glands, gastrointestinal system, cardiovascular system, and reproductive organs. PACAP plays a role in fertility and reproduction. Numerous studies report on the gonadal regulatory effects of PACAP at hypothalamo-hypophyseal levels. However, the local effects of PACAP at gonadal levels are also important. The present review summarizes the effects of PACAP in the ovary. PACAP and its receptors are present in the ovary, and PACAP plays a role in germ cell migration, meiotic division, follicular development, and atresia. The autocrine-paracrine hormonal effects seem to play a regulatory role in ovulation, luteinization, and follicular atrophy. Altogether, PACAP belongs to the ovarian regulatory peptides.

Assessment of postoperative postvoid residual bladder volume using three-dimensional ultrasound volumetry.

The aim of our prospective study was to assess the concordance between postvoid residual volumes (PVR) of the urinary bladder obtained by two different three-dimensional (3-D) ultrasound (US) volumetric methods (VOCAL and XI VOCAL) and with measurement by the catheter in postoperative patients who have undergone radical hysterectomy. The 3-D sonographic volume-determination of PVR with both methods correlated significantly with the actual amount of PVR by the catheter. The accuracy of both 3-D US volumetric methods was significantly higher under 300 mL of PVR. Bland-Altman plots were generated to examine limits of agreement. Both noninvasive 3-D sonographic methods are appropriate for the correct volume-determination of PVR following radical hysterectomy. Thus, we may avoid routine, albeit often unnecessary, catheterization to measure postoperative residual bladder volumes and subsequently the incidence of lower urinary tract infection may be reduced and better postoperative comfort for patients may be permitted.

The time of sunrise and the number of hours with daylight may influence the diurnal rhythm of acute heart attack mortality.

We investigated whether the time of sunrise and the number of daylight hours have an effect on the seasonality, or the daily rhythm of heart attack mortality. We analyzed retrospectively data of patients admitted to hospitals with the diagnosis of heart attack (n=32,329) and patients who deceased of a heart attack (n=5142) between January 1, 2004 and December 31, 2005 in Hungary. Heart attack mortality was highest during winter, while lowest number of events was recorded during summer . The daily peak of diurnality was between 6:00 am and 12:00 pm (33.77%). A positive correlation was found between the time of sunrise, time of sunset and the mortality caused by myocardial infarction (p<0,01). In the analysis of the number of daylight hours and the heart attack mortality we found a negative correlation (r=-0.105, p<0.05). No significant difference was found between sexes and different age-groups in heart attack mortality. Our data suggest, that the occurrence and the mortality of heart attack may be related to the time of sunrise and the number of daylight hours.

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.