[Nocebo, informed consent and doctor-patient communication]. / Nocebo, Aufklärung und Arzt-Patienten-Kommunikation.

Negative previous experiences (conditioning), observational learning and expectations can trigger nocebo effects. They are responsible for a substantial proportion of the side effects of medical treatment, and are induced primarily by risk information for informed consent. This has been demonstrated in studies on patient groups with or without modified medical information. Drug trials in the field of neurology and psychiatry have regularly revealed side effects and drop-out also in placebo groups. The underlying neurobiological mechanisms were experimentally investigated especially for nocebo-induced hyperalgesia, whereby the specifically involved regions of the brain could be identified by functional imaging as well as changes in the dopamine, endorphin and cholecystokinin systems. Nocebo effects are specific, i.e. they are closely related to patient information and can induce or aggravate exactly the symptoms addressed. Nevertheless, informed consent is an essential part of doctor-patient communication; however, information on risks can be markedly less damaging when unnecessary repetitions are avoided, misunderstandings are recognized or resolved and several different options are given. In addition, risks should always be named together with positive aspects, such as the advantages of the appropriate treatment, the prophylactic measures applied or the early detection and treatment of developing side effects. The best protection against harm caused by information on risks is a trustful doctor-patient relationship. Poor knowledge of nocebo effects or lack of countermeasures constitute a serious threat to patients and according to the current state of knowledge could be rated as medical malpractice.

[Placebo and nocebo : How can they be used or avoided?] / Placebo und Nocebo : Wie einsetzen bzw. vermeiden?

The expectations of patients enhance the probability of their occurrence and are thereby the main triggers for inducing placebo and nocebo responses. Strong placebo effects are not only regularly observed in pharmaceutical and non-pharmaceutical sham treatment in placebo controlled studies but also make a considerable contribution to any real treatment. The accompanying words are essential to ensure maximum impact of drugs and other forms of treatment. They should contain positive expressions instead of negations. Such a strengthening of drug therapy by placebo effects is more important than the widespread use of placebos that remains a problem because of the obligation to provide information and effective therapy and because of inherently induced side effects. Any false comments about symptoms or side effects can aggravate or induce them. Nocebo effects are not imagined but real symptoms that can definitely be harmful. They constitute a considerable proportion of the side effects requiring treatment. Awareness and knowledge is needed to prevent or neutralize them. Nocebo effects are avoidable when risk information is always directly combined with positive aspects, such as the expected benefits of the treatment or the prophylactic measures and therapeutic options for side effects. Existing negative expectations are disrupted by providing more alternative options and by leaving negative experiences in the past where they belong. Placebo and nocebo effects are strongly sensitive to the context. They are dependent on the experiences and conceptions of the individual patient, as well as on the physician-patient relationship. The latter can provide the best protection against harm from risk disclosure. In addition, the expectations of patients and their consequences are strongly affected by the expectations of the treating doctor, by fellow patients, the media and society.

Efficacy, acceptability and safety of guided imagery/hypnosis in fibromyalgia - A systematic review and meta-analysis of randomized controlled trials.

This systematic review aimed at evaluating the efficacy, acceptability and safety of guided imagery/hypnosis (GI/H) in fibromyalgia. Cochrane Library, MEDLINE, PsycINFO and SCOPUS were screened through February 2016. Randomized controlled trials (RCTs) comparing GI/H with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health-related quality of life, psychological distress, disability, acceptability and safety at end of therapy and 3-month follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI).Seven RCTs with 387 subjects were included into a comparison of GI/H versus controls. There was a clinically relevant benefit of GI/H compared to controls on ≥50% pain relief [RD 0.18 (95% CI 0.02, 0.35)] and psychological distress [SMD -0.40 (95% CI -0.70, -0.11)] at the end of therapy. Acceptability at the end of treatment for GI/H was not significantly different to the control. Two RCTs with 95 subjects were included in the comparison of hypnosis combined with cognitive behavioural therapy (CBT) versus CBT alone. Combined therapy was superior to CBT alone in reducing psychological distress at the end of therapy [SMD -0.50 (95% CI -0.91, -0.09)]. There were no statistically significant differences between combined therapy and CBT alone in other primary outcomes at the end of treatment and follow-up. No study reported on safety. GI/H hold promise in a multicomponent management of fibromyalgia. SIGNIFICANCE: We provide a systematic review with meta-analysis on guided imagery and hypnosis for fibromyalgia. Current analyses endorse the efficacy and tolerability of guided imagery/hypnosis and of the combination of hypnosis with cognitive-behavioural therapy in reducing key symptoms of fibromyalgia.

Anesthesiologic regimen and intraoperative delirium in deep brain stimulation surgery for Parkinson's disease.

BACKGROUND: In many centers the standard anesthesiological care for deep brain stimulation (DBS) surgery in Parkinson's disease patients is an asleep-awake-asleep procedure. However, sedative drugs and anesthetics can compromise ventilation and hemodynamic stability during the operation and some patients develop a delirious mental state after the initial asleep phase. Further, these drugs interfere with the patient's alertness and cooperativeness, the quality of microelectrode recordings, and the recognition of undesired stimulation effects. In this study, we correlated the incidence of intraoperative delirium with the amount of anesthetics used intraoperatively. METHODS: The anesthesiologic approach is based on continuous presence and care, avoidance of negative suggestions, use of positive suggestions, and utilization of the patient's own resources. Clinical data from the operations were analyzed retrospectively, the occurrence of intraoperative delirium was extracted from patients' charts. The last 16 patients undergoing the standard conscious sedation procedure (group I) were compared to the first 22 (group II) psychologically-guided patients. RESULTS: The median amount of propofol decreased from 146 mg (group I) to 0mg (group II), remifentanyl from 0.70 mg to 0.00 mg, respectively (P<0.001 for propofol and remifentanyl). Using the new procedure, 12 of 22 patients (55%) in group II required no anesthetics. Intraoperative delirium was significantly less frequent in group II (P=0.03). CONCLUSIONS: The occurrence of intraoperative delirium correlates with the amount of intraoperative sedative and anesthetic drugs. Sedation and powerful analgesia are not prerequisites for patients' comfort during awake-DBS-surgery.

[Optimization of blood gas analysis in intensive care units : Reduction of preanalytical errors and improvement of workflow]. / Optimierung von Blutgasanalysen auf der Intensivstation : Reduzierung präanalytischer Fehler und Verbesserung der zeitlichen Abläufe.

BACKGROUND: Point of care testing with blood gas analysis (BGA) is an important factor for intensive care medicine. Continuous efforts to optimize workflow, improve safety for the staff and avoid preanalytical mistakes are important and should reflect quality management standards. AIM: In a prospective observational study it was investigated whether the implementation of a new system for BGA using labeled syringes and automated processing of the specimens leads to improvements compared to the previously used procedure. MATERIAL AND METHODS: In a 4-week test period the time until receiving the final results of the BGA with the standard method used in the clinical routine (control group) was compared to the results in a second 4-week test period using the new labeled syringes and automated processing of the specimens (intervention group). In addition, preanalytical mistakes with both systems were checked during routine daily use. Finally, it was investigated whether a delay of 10 min between taking and analyzing the blood samples alters the results of the BGA. RESULTS: Preanalytical errors were frequently observed in the control group where non-deaerated samples were recorded in 87.3 % but in the intervention group almost all samples (98.9 %) were correctly deaerated. Insufficient homogenization due to omission of manual pivoting was seen in 83.2 % in the control group and in 89.9 % in the intervention group; however, in the intervention group the samples were homogenized automatically during the further analytical process. Although a survey among the staff revealed a high acceptance of the new system and a subjective improvement of workflow, a measurable gain in time after conversion to the new procedure could not be seen. The mean time needed for a complete analysis process until receiving the final results was 244 s in the intervention group and 201 s in the control group. A 10-min delay between taking and analyzing the blood samples led to a significant and clinically relevant elevation of the values for partial pressure of oxygen (pO2) in both groups compared to the results when analyzing the samples immediately (118.4 vs. 148.6 mmHg in the control group and 115.3 vs. 123.7 mmHg in the intervention group). When using standard syringes the partial pressure of carbon dioxide (pCO2) was significantly lower (40.5 vs. 38.3 mmHg) whereas no alterations were seen when using the labeled syringes. CONCLUSION: The implementation of a new BGA system with labeled syringes and automated processing of the specimens was possible without any difficulties under daily clinical routine conditions in this 10-bed intensive care unit (ICU). A gain of time could not be measured but a reduction in preanalytical errors using the labeled syringes with automated processing was found. Delayed analysis of blood samples can lead to significant changes in pO2 and pCO2 depending on the type of syringe used.

[Communication with children: practical hints and tools for the anesthesiology routine]. / Kommunikation mit Kindern: Praktische Strategien und Hilfsmittel für den anästhesiologischen Alltag.

BACKGROUND: Pediatric patients represent a special challenge both for the management of anesthesia and for communication, especially the anxious and screaming child. Children have specific features of fears, cognition, comprehension and skills depending on the stage of development. In addition, behavior and anxiety are strongly shaped by the parents who have to be incorporated. AIM: This article presents the special features of children as well as practical strategies and aids for dealing with children in a perioperative setting. MATERIAL AND METHODS: In children suggestibility and susceptibility to placebo and nocebo effects are increased. This makes them more sensitive to negative factors but can also be utilized for positive, constructive effects. Possibilities are presented which make use of the special characteristics of children. A number of examples from daily clinical routine are given. RESULTS: A child's imagination, creativity and capability for dissociation in particular allow an effective application of indirect suggestion, metaphors, stories, changes in focus of attention, retreat to an inner or imagined safe place, reframing of disturbing noises and events, pacing and leading in small steps and an activation of inner resources. A hand puppet, a pet toy, a little magic trick, introducing a magic friend, acupoint for palpitations with self-affirmation, stick figure drawings, ceiling pictures or holding hands can be quite helpful. All medical devices and interventions can be explained in a way that children can understand and in positive statements without lying or neglecting the need for information. CONCLUSION: Meeting at eye level, talking to the child instead of just about it, a language appropriate for children but not childish, comprehensible information and explanations, return of control and care more than pure technical distance, all play an important role. A serious look into such communication strategies can help the anesthetist to overcome uncertainties that a child can easily sense.

Ovarian stimulation in ART - Unwinding pressing issues.

Conventional controlled ovarian stimulation (cCOS) can cause significant discomfort, including ovarian hyperstimulation syndrome (OHSS). Clearly, management of OHSS and poor responder patients requires new strategies to overcome these problems and facilitate the birth of a healthy child with the fewest stimulation cycles. Several alternative methods have been developed. Non-conventional controlled ovarian stimulation (non-cCOS) is based on low-dose stimulation regimens and is often termed "light", "soft", "mini", "minimal", "mild", "low cost", or "low dose IVF". Non-controlled ovarian stimulation therapies (non-COS) include natural cycle IVF or a mixture between non-controlled and non-cCOS, termed "modified natural IVF" or "antiestrogen/aromatase inhibitor/low dose FSH-cycles", in which cycles are monitored but not controlled. These approaches promise to reduce the physical, emotional, and financial burden of IVF therapy while maintaining acceptable pregnancy rates. Such approaches might reduce the risk of OHSS. However, the overall cost per baby increases due to the higher number of stimulation cycles required, and the inconvenience of ovum pick-up still remains. The primary focus should be to obtain several good quality blastocysts after a single cCOS cycle. Thus, adequate numbers of mature oocytes are mandatory. What is more difficult and expensive for patients: several non-COS/non-cCOS cycles to obtain a baby or a single cCOS cycle with a high probability to obtain more than one child? Classic cCOS using the GnRH agonist long protocol followed by single embryo transfer (SET) at the blastocyst stage and aseptic vitrification of surplus embryos optimizes the IVF outcome. This strategy, combined with outpatient management in the case of OHSS, minimizes inconvenience and risks of OHSS. Accumulation cycles (AC) by repeated COS with subsequent freezing of blastocysts, combined with preimplantation genetic screening (PGS), is a promising new approach for low responders, especially in cases of advanced maternal age (AMA).

[Anesthesiological management of awake craniotomy : Asleep-awake-asleep technique or without sedation]. / Anästhesiologisches Management zur Wachkraniotomie : Schlaf-Wach-Schlaf-Technik oder ohne Sedierung.

Awake craniotomy is indicated in deep brain stimulation (DBS) for treatment of certain movement disorders, such as in Parkinson disease patients or in the surgery of brain tumors in close vicinity to the language area. The standard procedure is the asleep-awake-asleep technique where general anesthesia or analgosedation is intermittently interrupted for neurological testing. In DBS the intraoperative improvement of symptoms, stereotactic navigation and microelectrode reading guide to the optimal position. In brain tumor resection, reversible functional impairments during electrical stimulation on the brain surface (brain mapping) show the exact individual position of eloquent or motoric areas that should be protected.The anesthesiology procedures used are very variable. It is a balancing act between overdosing of anesthetics with impairment of respiration and alertness and underdosing with pain, strain and stress for the patient. For the asleep-awake-asleep technique high acceptance but also frequent and partly severe complications have been reported. The psychological stress for the patient can be immense. Obviously, a feeling of being left alone and being at someone's mercy is not adequately treated by drugs and performance of the neurological tests is undoubtedly better and more reliable with less pharmacological impairment. Cranial nerve blocks can reduce the amount of anesthetics as they provide analgesia of the scalp more efficiently than local infiltration. With these nerve blocks, a strong therapeutic relationship and a specific communication, sedatives can be avoided and the need for opioids markedly reduced or abolished. The suggestive communication promotes for instance dissociation to an inner safe refuge, as well as reframing of disturbing noises and sensations. Each of the methods applied for awake craniotomy can profit from the principles of this awake-awake-awake technique.

Implications of Blood Type for Ovarian Reserve and Infertility - Impact on Oocyte Yield in IVF Patients.

Introduction: Diminished ovarian reserve (DOR) has been linked to certain subpopulations and distinct gene polymorphisms. It has even been hypothesized that the AB0 blood group system could be linked to ovarian reserve (OR) as reflected by early follicular phase follicle stimulating hormone (FSH) levels. Although estimation of OR is routinely done using levels of anti-Müllerian hormone (AMH), FSH, estradiol or inhibin B, the diagnostic accuracy of these markers is often limited. The aim of this study was to evaluate whether there is any correlation between IVF patients' AB0 blood group system and ART outcome. Methods: In this retrospective observational single-center study we investigated the outcome of 1889 IVF cycles carried out between 2005 and 2012 with regard to blood type and OR in different age groups (21-36 years and 37-43 years). The number of cumulus oocyte complexes (COCs) and metaphase II oocytes obtained after ovarian stimulation, fertilization rate (FR), pregnancy rate (PR) and birth rate (BR) were evaluated with respect to maternal age (21-36 and 37-43 years, respectively). Results: We found no significant differences in the average number of COCs after ovum pick-up in either of the age groups. Moreover, the mean number of MII oocytes and 2PN stages were similar for all blood type groups. As regards IVF outcome measured in terms of PR and BR, no significant differences were observed between the different blood groups. In conclusion, no correlation was found between blood type and female fertility. Discussion: The most precise definition of OR is determining the number of competent oocytes. Based on the finding of our study, the hypothesis that there is a correlation between OR and AB0 blood group system can be dismissed for Caucasian IVF patients.

[Nocebo effects and negative suggestion in anesthesia]. / Noceboeffekte und Negativsuggestionen in der Anästhesie.

Anesthetists have an impact on patients and healing processes not only through drugs, interventions and therapy but also significantly by their words and personality. A substantial part of observed side effects is caused by nocebo effects and negative suggestion, i.e. by the doctor and the medical surroundings. Every symptom of an illness, side effect or complication can also be induced by the wrong way of talking about it. Patients perceive medical situations, such as an emergency, anesthesia or intensive care as extreme or even as life-threatening. This can induce a natural trance, an altered state of consciousness characterized by increased suggestibility. Suggestions affect mental functions, such as anxiety and pain as well as physical functions. Strong figurative words, ambiguity, misunderstandings, incidental conversations, medical jargon and risk information are prone to generate negative suggestion. Not the informed consent per se but the way it is presented should be under scrutiny. Knowledge about nocebo effects and negative suggestion can help recognize and avoid these more easily. These negative factors depend on the context, i.e. they are strongly influenced by the individual background history and anxieties of the patient and also by the physician-patient relationship. The best protection against harm from informed consent and negative suggestion is a supportive therapeutic relationship.

[Sperm mitochondrial function in men with normozoospermia and asthenozoospermia]. / Funkce mitochondrií ve spermii u muzu s normozoospermií a astenozoospermií

OBJECTIVE: One of causes of male infertility is reduced sperm motility. It turns out that the reduced efficiency of the mitochondrial respiratory activity may play a role in the development of this disorder. The aim of our study was to comprehensively determine mitochondrial respiratory activity of sperm with normal and reduced motility. DESIGN: Prospective study. SETTING: Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague; Department of Physiology, Faculty of Medicine in Pilsen, Charles University in Prague; Institute of Reproductive Medicine and Endocrinology, IVF Centers Prof. Zech, Plzen. METHODS: Ejaculates of 14 men were obtained from IVF Center Prof. Zech, Pilsen. According to the World Health Organization classification, samples were divided into normozoospermatic (n = 7) and asthenozoospermatic(n = 7) groups. Respiratory activity of sperm was measured on two-chamber oxygraph Oroboros. RESULTS: In asthenozoospermatic samples, significantly reduced activity of complex I (p = 0.007) and increased respiration after application of ATP-synthase inhibitor oligomycin (showing increased uncoupled oxidation and phosphorylation, p = 0.046) were found. Inhibition of complex I by rotenone showed that complex I contribution to the total capacity of oxidative phosphorylation of healthy sperm was relatively lower than it is typical for somatic cells. CONCLUSION: In our study, we measured mitochondrial respiratory activity of human sperm, permeabilized by digitonin, by high-resolution oxygraphy, which allows the determination of oxygen consumption from the smallest possible number of germ cells. The study results confirm reduced activity of complex I in asthenozoospermatics and suggest that increased leakage of protons from the mitochondrial matrix, which leads to reduced efficiency of phosphorylating process, could participate in the reduced sperm motility. Better characterization of male germ cells, either completely healthy or with affected motility, will help us to understand better the physiological process of fertilization and also to choose the most viable sperm for infertility treatment by methods of assisted reproduction.

[Effect of overweight on the outcome of assisted reproductive technology in infertile women]. / Vliv nadváhy na úspesnost technik asistované reprodukce u neplodných zen.

OBJECTIVE: Obesity and overweight negatively affect the ability of women to conceive naturally, contributes to the increased incidence of obstetric complications during pregnancy and affect the outcome of assisted reproduction techniques (ART). The aim of our study was to compare the results of treatment of infertilityin a group of infertile women undergoing ART, depending on the values of BMI and changes in levels of selected hormones and markers of oxidative stress in follicular fluid. DESIGN: Retrospective comparative study. SETTING: Faculty of Medicine in Pilsen, Charles University in Prague; Institute of Reproductive Medicine and Endocrinology, IVF Centers - Prof. Zech, Plzen. METHODS: The studied group consisted of 44 women (mean age of 31.9 years, SD = 4.35) treated for infertility at the Institute of Reproductive Medicine and Endocrinology - IVF Centers Prof. Zech. Women were divided into 2 groups according to BMI (37 women had normal BMI, 7 women were overweight). Prolactin, free T3 and T4 hormone, homocysteine, malondialdehyde, glutathione peroxidase, total antioxidant capacity and total protein were analyzed in the follicular fluid both groups. Only blood free samples were studied after pooling of all FF samples of each patient. RESULTS: We observed significantly lower levels of glutathion peroxidase in the group of overweight women(p = 0.0044). The pregnancy success rate with women with normal BMI and overweight women did not differ significantly from each other (p = 0.4430). CONCLUSION: Our study did not confirm the negative effect of obesity on the results of treatment of infertility, specifical-ly pregnancy rate in a group of infertile women undergoing treatment with assisted reproduction techniques.

[Placement of a central venous catheter in cases of persistent left superior vena cava]. / Anlage eines zentralen Venenkatheters bei persistierender V. cava superior sinistra.

This article presents a case report on the placement of a central venous catheter (CVC) in a patient with an unknown persistent left superior vena cava (PLSVC). Normally, PLSVCs remain asymptomatic but can be associated with disastrous consequences for the patient during placement of a CVC particularly due to vascular perforation and pulmonary injury. A PLSCV is particularly common in association with congenital heart defects; however, otherwise healthy patients can also be affected. As the presence of a PLSCV is normally unknown special attention must be paid in every patient during placement of a CVC.

The time aspect in storing vitrified blastocysts: its impact on survival rate, implantation potential and babies born.

STUDY QUESTION: Does the storage time of vitrified human blastocysts negatively impact their survival, the implantation potential of embryos or the malformation rate of babies born? SUMMARY ANSWER: There was no evidence that storage times of up to 6 years after vitrification (VIT) had a negative impact on blastocyst survival, the implantation potential of embryos or the malformation rate of babies born. WHAT IS KNOWN ALREADY: Although several thousand children have been born after blastocyst VIT, many aspects of this technique remain to be elucidated. New applications, such as fertility preservation, lead to long storage times of vitrified gametes or embryos but it remains to be determined if these vitrified embryos are stable over time. STUDY DESIGN, SIZE, DURATION: A retrospective study including 603 transfers was conducted between January 2009 and April 2012. Blastocysts were vitrified using a closed system. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent the transfer of aseptically vitrified/warmed blastocysts in a cryo-cycle. A total of 1077 blastocysts were transferred. Survival rates (SRs), implantation potential, birth rates and characteristics of the children born were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: We found that the storage of vitrified blastocysts in aseptic conditions neither impaired blastocyst viability (SR after warming during the first year of storage was 83.0% compared with 83.1% after 5-6 years of storage: NS) nor decreased pregnancy rates (clinical pregnancy rate after 1 year of storage was 40.0 versus 38.5% after 6 years: NS). In addition, no increase in the malformation rate over time was observed. LIMITATIONS, REASONS FOR CAUTION: Our study only included the transfer of blastocysts which had been vitrified aseptically (i.e. using a closed system). Therefore, our results might not be applicable to 'open' VIT systems. The long-term follow-up of children born will be necessary to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that vitrified human blastocysts can be stored for long periods of time without significant negative consequences for the offspring. Therefore, the method should be of benefit to those patients who need to consider taking measures for fertility preservation. STUDY FUNDING/COMPETING INTEREST(S): No external funding was sought for this study and the authors have no conflict of interest to declare.

[Anesthesiological aspects of deep brain stimulation : special features of implementation and dealing with brain pacemaker carriers]. / Anästhesiologische Aspekte der tiefen Hirnstimulation : Besonderheiten bei der Anlage und im Umgang mit Hirnschrittmacherträgern.

Deep brain stimulation (DBS) provides a very effective treatment for a number of neurological diseases including Parkinson's disease, movement disorders and epilepsy. In DBS microelectrodes are positioned in defined cerebral target areas and connected to a pacemaker. It is most often performed as an awake craniotomy with intraoperative testing. Various anesthesiological regimes are used to protect the patient from surgical stress on the one hand and to achieve ideal test conditions on the other. They include local anesthesia or scalp blocks, intermittent general anesthesia or analgosedation with or without airway protection; however, anesthetic agents interfere with hemodynamic stability and ventilation, with vigilance and cooperation and in addition with the symptoms and microelectrode recording. Guidance and communication have a pivotal impact on patient needs for pharmacological interventions. With increasing numbers of DBS procedures, anesthesiologists are more often faced with patients carrying brain pacemakers. For anesthesia the characteristics of the disease as well as the respective long-term medication have to be considered. In addition, the rules for handling patients with pacemakers need to be followed to avoid both dysfunction of the generator and tissue damage due to overheating of the electrodes.

Lower intracellular concentration of cryoprotectants after vitrification than after slow freezing despite exposure to higher concentration of cryoprotectant solutions.

STUDY QUESTION: What is the intracellular concentration of cryoprotectant (ICCP) in mouse zygotes during vitrification (VIT) and slow-freezing (SLF) cryopreservation procedures? SUMMARY ANSWER: Contrary to common beliefs, it was observed that the ICCP in vitrified zygotes is lower than after SLF, although the solutions used in VIT contain higher concentrations of cryoprotectants (CPs). WHAT IS KNOWN ALREADY: To reduce the likelihood of intracellular ice crystal formation, which has detrimental effects on cell organelles and membranes, VIT was introduced as an alternative to SLF to cryopreserve embryos and gametes. Combined with high cooling and warming rates, the use of high concentrations of CPs favours an intracellular environment that supports and maintains the transition from a liquid to a solid glass-like state devoid of crystals. Although the up-to-date publications are reassuring in terms of obstetric and perinatal outcomes after VIT, a fear about exposing gametes and embryos to high amounts of CPs that exceed 3-4-fold those found in SLF was central to a debate initiated by advocates of SLF procedures. STUDY DESIGN, SIZE, DURATION: Two experimental set-ups were applied. The objective of a first study was to determine the ICCP at the end of the exposure steps to the CP solutions with our VIT protocol (n = 31). The goal of the second investigation was to compare the ICCP between VIT (n = 30) and SLF (n = 30). All experiments were performed in triplicates using mouse zygotes. The study took place at the GIGA-Research Institute of the University of Liège. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cell volume is modified by changes in extracellular osmolarity. Hence, we estimated the final ICCP after the incubation steps in the VIT solutions by exposing the cells to sucrose (SUC) solutions with defined molarities. The ICCP was calculated from the SUC concentration that produced no change in cell volume, i.e. when intra- and extracellular osmolarities were equivalent. Cell volume was monitored by microscopic cinematography. ICCP was compared between SLF and VIT based on the principle that a high ICCP lowers the probability of (re)crystallization during warming but increases the probability of over-swelling of the cell due to fast inflow of water. The survival rates of mouse zygotes after SLF or VIT were compared using either (i) various warming rates or (ii) various concentrations of SUC in the warming dilution medium. MAIN RESULTS AND THE ROLE OF CHANCE: The ICCP in mouse zygotes during the VIT procedure prior to plunging them in liquid nitrogen was ∼2.14 M, i.e. one-third of the concentration in the VIT solution. After SLF, the warming rate did not affect the zygote survival rate. In contrast, only 3/30 vitrified zygotes survived when warmed slowly but as many as 30/30 zygotes survived when warming was fast (>20 000°C/min). Vitrified zygotes showed significantly higher survival rates than slow-frozen zygotes when they were placed directly in the culture medium or in solutions containing low concentrations of SUC (P < 0.01). These two experiments demonstrate a lower ICCP after VIT than after SLF. LIMITATIONS, REASONS FOR CAUTION: The results should not be directly extrapolated to other stages of development or to other species due to possible differences in membrane permeability to water and CPs. WIDER IMPLICATIONS OF THE FINDINGS: The low ICCP we observed after VIT removes the concern about high ICCP after VIT, at least in murine zygotes and helps to explain the observed efficiency and lack of toxicity of VIT. STUDY FUNDING / COMPETING INTEREST(S): The study was funded by the FNRS (National Funds for Scientific Research). The authors declare that they have no competing interests.

Aspects of Therapy for Cervical Cancer in Germany 2012 - Results from a Survey of German Gynaecological Hospitals.

Introduction: In spite of the existence of guidelines and international recommendations, many aspects in the diagnosis, therapy and follow-up of patients with cervical cancer are not based on validated data. A broad spectrum of different opinions and procedures concerning the therapy for patients with cervical cancer is under controversial discussion by the responsible gynaecologists in German hospitals. Methods: The present study is intended to picture the current treatment situation for cervical cancer in Germany. For this purpose a specially developed questionnaire with questions divided into 19 subsections was sent to all 688 gynaecological hospitals in Germany. Results: The response rate to the questionnaire was 34 %. 91 % of the hospitals treated between 0 and 25 patients with cervical cancer per year. 7.5 % treated between 26 and 50 and 1.4 % of the hospitals more than 50 patients per year. The bimanual examination was the most frequently used staging method (98 %); PET-CT was the least used staging method (2.3 %). Interestingly 48 % of the hospitals used surgical staging. The great majority of the hospitals (71 %) used abdominal radical hysterectomy (Wertheim-Meigs operation) to treat their patients. TMMR via laparotomy was used by 13 %. 16 % of the hospitals performed laparoscopic or robot-assisted radical hysterectomies. The sentinel concept was hardly used even in the early stages. It must be emphasised that in 74 % of the hospitals radical hysterectomies were performed even in cases with positive pelvic lymph nodes and in 43 % also in cases with positive paraaortic lymph nodes. The therapy of choice for FIGO IIB cancers is primary radiochemotherapy (RCTX) in 21 % of the hospitals; operative staging followed by radiochemotherapy in 24 % and treatment by radical hysterectomy followed by adjuvant RCTX was employed in this situation by 46 % of the hospitals. In 15-97 % of the hospitals for node-negative and in sano resected patients in stage pT1B1/1B2 after radical hysterectomy, an adjuvant RCTX is recommended when further risk factors exist (LVSI, tumour > 4 cm, age < 40 years, adenocarcinoma, S3). Conclusion: A broad spectrum of differing staging and therapy concepts is in use for patients with cervical cancer in Germany. A standardisation of therapy is needed. An update of national guidelines could help to achieve more transparency and a standardisation of treatment for patients with cervical cancer.

[Comparison of prolactin, free T3 and free T4 levels in the follicular fluid of infertile women and healthy fertile oocyte donors]. / Srovnání hladin prolaktinu, fT3 a fT4 ve folikulární tekutine zen s poruchou plodnosti a zdravých plodných dárkyn oocytu

OBJECTIVE: Follicular fluid (FF) provides an important microenvironment for the development of oocytes. The biochemical composition of the FF plays critical role in the oocyte competence. The aim of our study was to compare the levels of selected hormones in FF of infertile women and healthy fertile oocyte donors. DESIGN: Retrospective comparative study. SETTING: Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague; Department of Gynecology and Obstetrics, Charles University and University Hospital in Pilsen; Institute of Reproductive Medicine and Endocrinology, IVF Centers Prof. Zech, Plzen. METHODS: Levels of prolactin, free T3 and free T4 hormones in the FF of 146 women were analyzed. We have analysed FF of 74 infertile patients (mean age 31 years, SD = 4.65) and 72 healthy fertile oocyte donors (mean age 26 years, SD = 4.44). Only blood free samples were studied after pooling of all FF samples each patient. Levels of hormones were determined using ECLIA method (Electro-Chemi-Luminiscent Immunoassay) on the Cobas e411. RESULTS: RESULTS showed statistically significantly higher levels of prolactin (p=0.0006) and free T4 hormone (p=0.0246) in FF of infertile women in comparison to the group of healthy fertile oocyte donors. CONCLUSION: Our study confirms the presence of prolactin and thyroid hormones in FF and it can be suggested that they play a key role in the regulation of reproductive processes. The study of FF from donors and their detailed comparison with infertile patients with various gynaecological causes of infertility has great value for better understanding of regulatory mechanisms of fertility.