The PinK Study - Methodology of the Baseline Survey of a Prospective Cohort Study of Couples Undergoing Fertility Treatment

Der Methodenbericht beschreibt die Basiserhebung der PinK-Studie "Paare in Kinderwunschbehandlung". Ziel der Studie ist ein besseres Verständnis der Situation von Paaren mit unerfülltem Kinderwunsch und umfassende Erkenntnisse über die Wege in die Kinderwunschbehandlung. Der Ansatz der Studie ist interdisziplinär. Sie ist als prospektive Kohortenstudie in einem klinischen Umfeld angelegt. Zielgruppe der Studie sind Paare mit unerfülltem Kinderwunsch, die zwischen Juli 2012 und Mai 2013 ein Kinderwunschzentrum in Rheinland-Pfalz oder in der hessischen Landeshauptstadt aufgesucht haben. Als Erhebungsinstrument kamen schriftliche Fragebögen zum Einsatz, die den Patienten durch das Personal der Kinderwunschzentren übergeben wurden. Der finale Datensatz enthält alle bis Ende Juli 2013 zurückgesendete Fragebögen. Es haben 323 Frauen und 242 Männer an der Befragung teilgenommen, darunter 234 Paare, für die vollständige Informationen zu beiden Partnern vorliegen. Der Datensatz ermöglicht damit neben Geschlechtervergleichen auch Paaranalysen. Die Gesamtrücklaufquote liegt bei 31% mit teilweise erheblichen Unterschieden zwischen den Kliniken - mögliche Ursachen und Folgen werden diskutiert. Die Studienpopulation wird hinsichtlich zentraler soziodemografischer Merkmale beschrieben.This paper describes the realization of the baseline survey of the study ‘PinK- Paare in Kinderwunschbehandlung’ (couples undergoing fertility treatment). The study aims at a broader and better understanding of the situation of couples with an unfulfilled desire to have a child and of pathways leading couples to the fertility clinic. The approach of the study is interdisciplinary. It is designed as a prospective cohort study in a clinical setting. The study population consists of couples with an unfulfilled desire to have a child who presented themselves in a fertility clinic in the German state of Rhineland-Palatinate (RP) or in the capital city of the state of Hesse between July 2012 and May 2013. Self-administered questionnaires were used to gather information from patients at fertility clinics. These were handed out to the patients by the staff at the fertility clinics. Questionnaires returned by the end of July 2013 were included in the data set. The final sample consists of 323 female and 242 male respondents. In 234 couples, both partners participated. The overall response rate is 31%, with considerable variation across the clinics - reasons for and consequences of this are discussed. The final sample is described in terms of the distribution of core socio-demographic variables

The PinK Study - Methodology of the Follow-up Survey of a Cohort Study of Couples Undergoing Fertility Treatment

The paper describes the follow-up survey of the PinK study 'Paare in Kinderwunschbehandlung' (couples undergoing fertility treatment). This interdisciplinary study aims at a broader and better understanding of the situation of couples with an unfulfilled desire to have a child. The focus in the follow-up survey is on the situation of the couples one year after their first visit to a fertility clinic in Rhineland-Palatinate or in the capital of Hesse, Wiesbaden. Approximately one year after the baseline survey, self-administered questionnaires were sent to respondents who had signed a written agreement to remain in the study. The field period lasted from June 2013 to August 2014. The final sample consists of 140 women and 93 men. In 89 couples both partners participated. The longitudinal data set includes 224 respondents. The share of baseline survey participants who also participated in the follow-up is 39.6 %. This report describes the study design and materials for the follow-up as well as the sample and analyses the selectivity of dropouts from the baseline sample

Experimental and theoretical aspects of the formation of radical cations from tripyrrolidinobenzenes and their follow-up reactions

Tripyrrolidinobenzene radical cations(1*+), obtained from the corresponding arenes by oxidation with silver nitrate, are specially stabilized and thus allow specific reaction pathways of arene radical cations to be investigated separately and individually. Radical cations 1*+ ,for instance, generated under exclusion of oxygen, undergo dimerization to 2, or they abstract hydrogen from the solvent to form 3. In a pure oxygen atmosphere, the O2 reaction products 6 and 7 are formed, respectively, either exclusively or together with 2 and 3. Kinetic measurements give the following order of reactivity for these individual processes: reaction with O2 > dimerization. > H-abstraction from solvent. The changes in the product spectrum upon modification of the reaction conditions are in accord with the kinetic results. The dimeric u complexes 2 show surprisingly facile dissociation into two radical cations, two (1*+)with a much higher dissociation rate for the alkyl derivatives 2b-d than for 2a. Dissociation is enhanced substantially by light or in the presence of π donors. Individual product formation, rate of reactions of the radical cations 1*+, and photochemical cleavage of the dimeric σ complexes 2 can be rationalized, by qualitative and quantitative MO considerations, in terms of their relative frontier orbital energies

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Who is the gate keeper for treatment in a fertility clinic in Germany? -baseline results of a prospective cohort study (PinK study)-

Abstract Background It is estimated that 5-15% of all couples in industrialised nations are infertile. A perceived unfulfilled desire for a child or self-identification as infertile can lead to psychological strain and social isolation. About 53.000 women underwent assisted reproduction treatments in Germany in 2014. Little is known about the first medical consultation and patient needs prior to the first visit in a fertility clinic in Germany. The baseline survey of the prospective cohort study on couples undergoing fertility treatment in Germany (PinK Study) provides first results on this topic for Germany. Methods The baseline survey was conducted between 2012 and 2013. Self-administered questionnaires were handed out to patients of six fertility clinics at the beginning of treatment by clinic staff. At a participation rate of 31.0%, we were able to analyse data on 323 women and 242 men. Results 92.6% of the women had their initial medical consultation on their unfulfilled desire for a child with a gynaecologist. After the urologist (44.2%), the general practitioner (12.0%) was the second most approached initial contact person for men. 36.4% of all men had no medical consultation on the unfulfilled desire for a child before visiting a fertility clinic. 46.9% of the respondents expressed the wish that the conversation about infertility should be initiated by a physician. Prior to their first visit to a fertility clinic, 11.2% of the men and 24.8% of the women were informed by a physician that infertility treatment can cause emotional strain. Conclusion While almost all women consult a gynaecologist prior to the first visit in a fertility centre, one out of three men do not consult any physician at that stage. For the remaining group of men, urologists and general practitioners are the most important contact persons. Gender-specific health care needs are evident. In order to close the health care gap for men in Germany, more opportunities for discreet access to consultation should be offered. Due to its low threshold and family-oriented approach, general practice could make an important contribution to this effect

Epigenetic heterogeneity of developmentally important genes in human sperm: Implications for assisted reproduction outcome

<div><p>The molecular basis of male infertility is poorly understood, the majority of cases remaining unsolved. The association of aberrant sperm DNA methylation patterns and compromised semen parameters suggests that disturbances in male germline epigenetic reprogramming contribute to this problem. So far there are only few data on the epigenetic heterogeneity of sperm within a given sample and how to select the best sperm for successful infertility treatment. Limiting dilution bisulfite sequencing of small pools of sperm from fertile donors did not reveal significant differences in the occurrence of abnormal methylation imprints between sperm with and without morphological abnormalities. Intracytoplasmic morphologically selected sperm injection was not associated with an improved epigenetic quality, compared to standard intracytoplasmatic sperm injection. Deep bisulfite sequencing (DBS) of 2 imprinted and 2 pluripotency genes in sperm from men attending a fertility center showed that in both samples with normozoospermia and oligoasthenoteratozoospermia (OAT) the vast majority of sperm alleles was normally (de)methylated and the percentage of epimutations (allele methylation errors) was generally low (<1%). However, DBS allowed one to identify and quantify these rare epimutations with high accuracy. Sperm samples not leading to a pregnancy, in particular in the OAT group, had significantly more epimutations in the paternally methylated <i>GTL2</i> gene than samples leading to a live birth. All 13 normozoospermic and 13 OAT samples leading to a child had <1% <i>GTL2</i> epimutations, whereas one (7%) of 14 normozoospermic and 7 (50%) of 14 OAT samples without pregnancy displayed 1–14% <i>GTL2</i> epimutations.</p></div