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Introduction For some patients, undergoing medical treatment for infertility is a cause of major emotional stress which the couple needs to deal with together; it can be said that infertility is a shared stressor. From the literature it is known that a subjectively perceived sense of self-efficacy supports the patient’s ability to cope adaptively with an illness. As the basis for this study, we assumed that high levels of self-efficacy are associated with low psychological risk scores (e.g., for anxiety or depressiveness), both in the patient themselves and in their partner. Accordingly, in infertility patients, targeted support to promote helpful self-efficacy expectations could represent a new counselling strategy that could enable psychologically vulnerable patients to better cope with the treatment procedure and treatment failures of medically assisted reproduction, making these patients less at risk with regard to psychosocial factors. Methods 721 women and men attending five fertility centers in Germany (Heidelberg, Berlin), Austria (Innsbruck), and Switzerland (St. Gallen, Basel) completed the SCREENIVF-R questionnaire to identify psychological risk factors for amplified emotional problems, as well as the ISE scale to measure self-efficacy. Using paired t-tests and the actor–partner interdependence model, we analyzed the data of 320 couples. Results Considering the study participants as couples, women had a higher risk score than men for four out of five risk factors (depressiveness, anxiety, lack of acceptance, helplessness). In all of the risk areas, it was possible to identify a protective effect from self-efficacy on the patient’s own risk factors (actor effect). There was a negative correlation between the men’s self-efficacy level and the women’s feelings of depressiveness and helplessness (partner effect, man → woman). The women’s self-efficacy levels had a positive correlation with acceptance and access to social support in the men (partner effect, woman → man). Conclusion Because infertility is generally something that a couple has to deal with together, future studies should focus on couples as the unit of analysis instead of just analyzing the men and women separately. In addition, couples therapy should be the gold standard in psychotherapy for infertility patients.

Einleitung Etwa 1% aller Männer sind von Azoospermie betroffen; davon suchen bis zu 15% Rat bezüglich einer Infertilitätsbehandlung. Informationen über prädiktive Faktoren für betroffene Paare sind hierbei sehr begrenzt. Patienten, Materialien und Methoden Wir führten eine retrospektive Analyse medizinischer Aufzeichnungen von 118 Zyklen intrazytoplasmatischer Spermieninjektionen nach vorheriger testikulärer Spermienextraktion wegen Azoospermie durch. Die Behandlungen wurden zwischen Januar 2008 und Oktober 2015 vorgenommen. Von 188 Zyklen waren 66 erste Behandlungszyklen; 35 waren zweite Behandlungszyklen, und 17 waren dritte Behandlungszyklen. Eine statistische Signifikanz wurde bei p < 0,05 angenommen. Es wurden prädiktive Faktoren für eine erfolgreiche Schwangerschaft ausgewertet; dazu gehörten männliches/weibliches Alter, männlicher/weiblicher Body-Mass-Index, männlicher/weiblicher Tabakkonsum und histologische Ergebnisse von testikulären Biopsien. Ergebnisse Die Embryonenqualität und die Anzahl der transferrierten Embryonen waren positiv mit einer erfolgreichen Schwangerschaft assoziiert (p = 0,003). Männer, deren Partnerinnen schwanger wurden, hatten einen signifikant niedrigeren Body-Mass-Index verglichen mit Männern, deren Partnerinnen nicht schwanger wurden (p = 0,023). Weder weibliches Gewicht noch Alter noch Tabakkonsum beim Mann oder bei der Frau waren signifikante Faktoren. Bei Männern mit einer tubulären Atrophie ≥ SIGG Grad 4 war die Wahrscheinlichkeit einer Schwangerschaft gering, ungeachtet dem Vorfinden reifer Spermien und der Anzahl durchgeführter Zyklen. Schlussfolgerung Übergewichtigen Patienten sollte zu einer Gewichtsreduktion vor Beginn der Behandlung geraten werden, und die Beratung samt Erfolgsraten sollte Informationen über histologische und positive Biopsieergebnisse enthalten. Introduction Azoospermia affects about 1% of men, of whom up to 15% inquire about infertility treatment. Information about predictive factors for these couples is very limited. Patients, Materials and Methods We performed a retrospective analysis of the clinical records of 118 cycles of intracytoplasmic sperm injection treatment after testicular sperm extraction for male azoospermia carried out between January 2008 and October 2015. Of those, 66 were first, 35 second, and 17 third cycles. Statistical significance was set at p < 0.05. Predictive factors for successful pregnancy were evaluated and included male/female age, male/female body mass index, male/female nicotine use, and histological results of testes biopsies. Results Embryo quality and the number of embryos transferred were positively associated with pregnancy success (p = 0.003). Males whose partners conceived had a significantly lower body mass index than those whose partners did not conceive (p = 0.023). Neither female weight nor age nor smoking status of the male or female were significant factors. In cases with tubular atrophy ≥ SIGG grade 4 the chance of pregnancy was poor, irrespective of the existence of mature sperm and the number of cycles performed. Conclusion Overweight male patients should be advised about weight reduction prior to treatment, and counseling about success rates should include histological and spermpositive biopsy results.

Introduction Assisted reproductive technologies are typically perceived by couples as being an emotional burden. The objective of the study “Positive Ausrichtung bei unerfülltem Kinderwunsch” [Positive adjustment in infertility] (PACI) is to examine the efficacy and acceptance of a smartphone-supported psychosocial intervention during infertility treatment. In this investigation, the early drop-out of study subjects from the study is of primary interest. The objective of the investigation was to find predictors for ending a psychological intervention prematurely. Materials and Methods There are data available from an eight-month randomised, controlled study in which 141 patients and their partners participated. Sociodemographic and fertility-related data were collected at the start of the study. The couples received the ScreenIVF questionnaire at two points in time. As part of a post-evaluation, a survey was conducted on the efficacy of the psychological online intervention. To analyse the data, a dyadic data structure was used in order to determine connections within the study subject couples between the selected stress indicators and the drop-out. In addition, a “risk score” as a possible predictor for the drop-out was tested. Results The descriptive observation of the sample indicates in this interim assessment that the study subjects recruited are less stressed patient couples. Actor–partner interdependence models indicate statistically significant connections between the stress indicators of anxiety, little social support and helplessness and an early drop-out. Conclusions The statistically significant effects found in this study with regard to the stress indicators in connection with drop-outs from psychosocial intervention studies indicate that it is advisable to continue to seek measures for people undergoing stressful medical treatments in order to motivate and support them and thus optimally utilise the opportunities of a medical treatment. The number of patients who endure their ART treatment may also increase as a result, which could lead in turn to increased patient satisfaction over the long term (and thus possibly to higher pregnancy rates).

OBJECTIVES Major complications affecting the central nervous system (CNS) present a challenge after allogeneic stem cell transplantation (allo-SCT). METHODS Incidence, risk factors, and outcome were retrospectively analyzed in 888 patients in a monocentric study. RESULTS Cumulative incidence (CI) of major CNS complications at 1 year was 14.8% (95%CI 12.3%-17.2%). Median follow-up is 11 months. CNS complications were documented in 132 patients: in 36 cases, classified metabolic; 26, drug-related neurotoxicity (14 attributed to cyclosporine A, 4 to antilymphocyte globulin); 11, cerebrovascular (ischemic n = 8, bleeding n = 3); 9, infections; 9, psychiatric; and 9, malignant. The cause of CNS symptoms remained unclear for 37 patients (28%). Multivariate analysis demonstrated an association of CNS complication with patient age (P

Summary Goal of this study was to investigate differences in quality of life in men contingent upon various fertility treatment stages, infertility causes and adoption of roles. A quantitative study with n = 115 men in three German fertility centres was devised. Participants completed a standardised, fertility-specific questionnaire devised for men (TLMK), sociodemographic and role items. Men having experienced severe medical conditions, for example cancer, reported significant higher quality of life compared to men with other infertility reasons [F(1,56) = 12.77, P = 0.001]. Furthermore, allocating participants into distinctive groups by means of kind and duration of treatment revealed significant group differences [F(2,111) = 4.94, P = 0.009], with quality of life decreasing with the use of more invasive fertility methods. A higher satisfaction with life was also stated by men adopting many tasks in the treatment process. The high quality of life displayed by men having experienced severe medical conditions contains valuable and far-reaching information about possible resilience factors that need to be researched more in detail. The finding of decreasing quality of life in men with the use of more invasive methods in treatment applies for increased psychosocial services in fertility clinics.

The goal of this study was to explore the experience and perception of men during the diagnosis of infertility and subsequent treatment, and the impact on role concepts, control beliefs, and quality of life on these processes. Furthermore, it aimed to derive improvements in how men should be counselled. A qualitative study was conducted. It consisted of 13 semi-structured individual interviews with men undergoing or about to start fertility treatment at Heidelberg University Hospital. Data were analyzed using a grounded theory approach. Men emphasized the rare opportunities for being involved in treatment, lack of control and the ambivalence of social support. Furthermore, their experiences differed enormously regarding the cause of infertility and the period for which they were preoccupied with the topic. Dealing with involuntary childlessness is challenging for all men. Nevertheless, participants revealed major differences in dealing with fertility treatment in relation to role concepts, control beliefs, social support and the cause of infertility. The significance of diverse causes of infertility and the need for men to adopt certain roles ought to be more valued and a holistic approach improving quality of life enhanced.

STUDY QUESTION Does intrauterine application of diluted seminal plasma (SP) at the time of ovum pick-up improve the pregnancy rate by ≥14% in IVF treatment? SUMMARY ANSWER Intrauterine instillation of diluted SP at the time of ovum pick-up is unlikely to increase the pregnancy rate by ≥14% in IVF. WHAT IS KNOWN ALREADY SP modulates endometrial function, and sexual intercourse around the time of embryo transfer has been suggested to increase the likelihood of pregnancy. A previous randomized double-blind pilot study demonstrated a strong trend towards increased pregnancy rates following the intracervical application of undiluted SP. As this study was not conclusive and as the finding could have been confounded by sexual intercourse, the intrauterine application of diluted SP was investigated in the present trial. STUDY DESIGN, SIZE, DURATION A single-centre, prospective, double-blind, placebo-controlled, randomized, superiority trial on women undergoing IVF was conducted from April 2007 until February 2012 at the University Department of Gynaecological Endocrinology and Reproductive Medicine, Heidelberg, Germany. PARTICIPANTS/MATERIALS, SETTING, METHODS The study was powered to detect an 14% increase in the clinical pregnancy rate and two sequential tests were planned using the Pocock spending function. At the first interim analysis, 279 women had been randomly assigned to intrauterine diluted SP (20% SP in saline from the patients' partner) (n = 138) or placebo (n = 141) at the time of ovum pick-up. MAIN RESULTS AND THE ROLE OF CHANCE The clinical pregnancy rate per randomized patient was 37/138 (26.8%) in the SP group and 41/141 (29.1%) in the placebo group (difference: -2.3%, 95% confidence interval of the difference: -12.7 to +8.2%; P = 0.69). The live birth rate per randomized patient was 28/138 (20.3%) in the SP group and 33/141 (23.4%) in the placebo group (difference: -3.1%, 95% confidence interval of the difference: -12.7 to +6.6%; P = 0.56). It was decided to terminate the trial due to futility at the first interim analysis, at a conditional power of 62%. LIMITATIONS, REASONS FOR CAUTION The confidence interval of the difference remains wide, thus clinically relevant differences cannot reliably be excluded based on this single study. WIDER IMPLICATIONS OF THE FINDINGS The results of this study cast doubt on the validity of the concept that SP increases endometrial receptivity and thus implantation in humans. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by the department's own research facilities. TRIAL REGISTRATION NUMBER DRKS00004615.

There is no doubt that lifestyle factors can be detrimental to fertility. The aim of the present pilot study was to identify initial prevalence rates for behaviour-related fertility disorders in a clinical sample of couples wanting a child. Between February 2010 and August 2010, all patients coming for the first time to Heidelberg University’s Women’s Hospital for consultation on involuntary childlessness were asked to fill out a questionnaire designed by the authors of this article. The questionnaire was based on a review of the relevant literature, with special reference to the latest research findings on behaviour detrimental to fertility. Of the 156 couples addressed, 110 women and 100 men took part in the study. For behaviour-related infertility, 9 % of the women and 3 % of the men in our sample were classified on the basis of BMI

Objective To evaluate whether intravaginal application of seminal plasma at the time of follicle aspiration in IVF or intracytoplasmic sperm injection treatment cycles has the potential to increase pregnancy rate. To calculate the number of patients needed to achieve significance in a multicenter trial. Design Double-blind, placebo-controlled randomized pilot study. Setting University department of gynecological endocrinology and reproductive medicine. Patient(s) One hundred sixty-eight patients undergoing IVF or intracytoplasmic sperm injection treatment. Intervention(s) Cryopreserved seminal plasma from the patient's partner or sodium chloride (placebo) was injected into the cervix and the posterior fornix of the vagina just after follicle aspiration. Main Outcome Measure(s) Clinical-pregnancy rate. Result(s) One hundred sixty-eight patients agreed to participate in the study. Participation was limited to one treatment cycle. Thirty-one patients (18%) were excluded from the study, mainly as a result of canceled embryo transfers. Seventy patients received placebo, and 67 received seminal plasma. The clinical-pregnancy rate was 25.7% (18/70) in the placebo group. The clinical-pregnancy rate in the seminal plasma group reached 37.3% (25/67), corresponding to a relative increase of 45%. Conclusion(s) Even though significance was not reached in this pilot study, the data suggest that seminal plasma has the potential to improve pregnancy rate. It is estimated that around 450 patients need to be recruited to reach significance in a multicenter study.

Background Only a few studies have reported cross-cultural comparisons regarding psychosocial consequences of infertility. Differences between societies with different cultural backgrounds were revealed and seemed to be based on the importance of pronatalism. Our aim was to measure cross-cultural differences in fertility specific quality of life of infertile couples in Germany, Hungary and Jordan who attend a fertility center in a cross-sectional study. Methods A cross-sectional study was conducted in one fertility clinic in Germany, in five fertility clinics in Hungary and in one fertility clinic in Jordan. Overall 750 couples (252 couples in Jordan, 246 couples in Germany and 252 couples in Hungary) attending the first medical infertility consultation were asked to fill out our questionnaire set. Fertility specific quality of life (FertiQoL) and sociodemographic differences were measured between couples from three countries. Results Jordanian couples had the shortest relationship (5.8 ± 4.3 yrs.), though they reported the longest duration of child wish (4.2 ± 3.6 yrs.) and fertility treatments (3.0 ± 3.3 yrs.). The proportion of high education was considerably higher in Jordanian women and men (60 % and 66 %, respectively) compared to the other two samples. First, marked cross-country differences were obtained on Emotional, Mind/Body and Relational subscales of the FertiQoL, indicating that Jordanian couples reported poorer fertility-related quality of life than Germans and Hungarians (p

Introduction: As gender role attitudes and the evaluation of parenthood and childlessness have subtle variations in each society, cross-country studies focusing on infertility are needed to draw a complex picture in the psychosocial context of infertility. This study investigates similarities and differences between German and Hungarian infertile couples regarding infertility specific quality of life and personal gender role attitudes. Methods: A cross-sectional study was conducted with data of 540 participants (270 couples) attending the first fertility consultation in one fertility clinic in Germany and in five fertility clinics in Hungary. Data were collected between February 2012 and March 2013. Two psychological questionnaires were applied: The FertiQoL to measure infertility specific quality of life and the PAQ to measure gender role attitudes like “instrumental” acting (as a traditional “masculine” attitude) and “expressive” communicating (as a traditional “femine” attitude) and their combinations “combined” attitude (as both “instrumental” and “expressive”) and “neutral” attitude (neither “instrumental” nor “expressive”). Results: German couples seeking assisted reproduction treatment are older aged and have longer lasting relationships than Hungarian couples. Hungarian couples scored higher on all quality of life scales than did German couples. In the Hungarian group, “combined” attitudes (use of both “expressive” and “instrumental” attitudes) is associated with higher levels of quality of life compared with other gender role attitudes. In the German group, individuals with “combined” attitudes seem to show better quality of life than those in “expressive” and “neutral” clusters. Conclusions: The strategy of using combined “expressive” and “instrumental” attitudes proved to act as a buffer against infertility-related stress for both members of the couple in two European countries and can therefore be recommended as helpful in counselling the infertile couple.

Objective To study the possible transmission, to the next generation, of epigenetic defects associated with in vitro maturation (IVM) of human oocytes. Design Case–control study using epigenetic data. Setting Two collaborating university departments. Patient(s) Eleven IVM newborns and 19 controls, conceived by conventional assisted reproduction. Intervention(s) Chorionic villus and cord-blood sampling. Main Outcome Measure(s) Using bisulfite pyrosequencing, we have measured average methylation levels of 6 imprinted ( LIT1 , MEG , MEST , NESPas , PEG3 , and SNRPN ), 5 tumor-suppressor ( APC , ATM , BRCA1 , RAD51C , and TP53 ), 2 pluripotency ( NANOG and OCT4 ), and 2 metabolic ( LEP and NR3C1 ) genes, as well as 2 repetitive elements (ALU and LINE1) in 2 tissues of IVM and control neonates. Using deep bisulfite sequencing, we have determined methylation patterns of many individual DNA molecules to detect rare RAD51C epimutations (allele methylation errors). Result(s) No statistically significant impact was found of IVM on chorionic villus and cord-blood DNA methylation at the studied developmentally important genes and interspersed repeats. The RAD51C epimutation rate was low (0.5% ± 0.1%) in all analyzed samples. Conclusion(s) IVM-induced epigenetic changes in offspring, if any, are relatively small in magnitude and/or infrequent.

Introduction: Infertile couples often report quality-of-life impairments, especially in terms of sexuality, self-esteem and partnership quality. So far, there have been no systematic studies of the sex lives and behaviour of infertile women and men before and after the emergence of their mutual desire for a child. Materials and Methods: From February 2010 to August 2010 all couples starting treatment either at Heidelberg Universityʼs Womenʼs Hospital or at the Fertility Center Berlin were asked to fill out the Self-Esteem and Relationship Questionnaire (SEAR). A total of n = 158 women and n = 153 men participated in the study. Results: Decreasing tendencies were observable for both partners in the domains Sexual Relationship Satisfaction and Confidence and in the subscales Self-Esteem and Overall Relationship Satisfaction. There were especially clear indications of a loss of spontaneous sexuality during the experience of infertility. We were also able to establish that infertility has a negative impact on womenʼs self-esteem. Discussion: The results of this study indicate that SEAR can be used as a feasible instrument for identifying infertile women and men whose infertility has a negative effect on their relationship quality and/or sex lives.

Glatiramer acetate (GA), represents an established treatment of relapsing/remitting multiple sclerosis (MS). The mechanisms responsible for the effect of GA are not fully understood. We generated GA-, myelin basic protein (MBP)- and purified protein derivative (PPD)-specific T cell lines from three MS patients and one healthy donor. The GA-specific lines were CD3+, CD4+, CD8- and produced tumor-necrosis-factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-10 (IL-10) after stimulation with GA in the presence of irradiated peripheral blood mononuclear cells. MBP-specific T cell lines showed an identical phenotype and secreted TNF-alpha, IFN-gamma, IL-4, IL-10, but not IL-6. Co-culture experiments demonstrated, that GA-specific T cell lines have the capability to suppress the proliferation of MBP-specific T cell lines.