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Study Question: What are the patient-reported outcomes (PROs) and patient-reported experiences (PREs) in home-based monitoring compared to those in hospital-based monitoring of ovulation for scheduling frozen-thawed embryo transfer (FET)?Summary Answer: Women undergoing either home-based or hospital-based monitoring experience an increase in anxiety/sadness symptoms over time, but women undergoing home-based monitoring felt more empowered during the treatment and classified the monitoring as more discreet compared to hospital-based monitoring.What Is Known Already: FET is at the heart of modern IVF. The two types of FET cycles that are mainly are used are artificial cycle FET, using artificial preparation of the endometrium with exogenous progesterone and oestrogen, and natural cycle FET (NC-FET). During a natural cycle FET, women visit the hospital repeatedly and receive an ovulation trigger to time FET (i.e. modified NC-FET or hospital-based monitoring). The previously published Antarctica randomised controlled trial (NTR 1586) showed that modified NC-FET is more cost-effective compared to artificial cycle FET. From the women's point of view a more natural approach using home-based monitoring of ovulation with LH urine tests to time FET may be desired (true NC-FET or home-based monitoring). Currently, the multicentre Antarctica-2 randomised controlled trial (RCT) is comparing the cost-effectiveness of home-based monitoring of ovulation with that of hospital-based monitoring of ovulation. The Antarctica-2 RCT enables us to study PROs, defined as the view of participating women of their healthcare status, and PREs, defined as the perception of the received care of participating women, in both FET strategies.Study Design, Size, Duration: PROs and PREs were assessed alongside the Antarctica-2 RCT. PROs were assessed using the validated EuroQol-5D-5L questionnaire. Currently, there are no guidelines for assessing PREs in this population. Therefore, members of the Dutch Patient Organisation for Couples with Fertility Problems (FREYA) filled out an online survey and selected the following PREs to assess (i) anxiety about missing ovulation, (ii) perceived level of partner participation, (iii) level of discretion, (iv) feeling of empowerment and (v) satisfaction with treatment.Participants/materials, Setting, Methods: Women participating in the RCT also participated in PRO and PRE assessment. We assessed PROs and PREs at three time points: (i) before randomisation, (ii) at the time of the FET and (iii) at the time of the pregnancy test. A sample size of 200 participants was needed to find a difference of 0.3 with a standard deviation in both groups of 0.7, an alpha of 5%, power of 80% and a drop-out rate of 10%. We performed mixed model analysis for between-group comparison of treatment and time effects.Main Results and Role Of Chance: A total of 260 women were randomised. Of these, 132 women were treated with home-based monitoring and 128 women were treated with hospital-based monitoring. Data before randomisation were available for 232 women (home-based monitoring n = 116, hospital-based monitoring n = 116). For the PROs, we found a significant increase in anxiety/sadness symptoms over time (P < 0.001) in both groups. We found no treatment effect of home-based versus hospital-based monitoring for the PROs (P = 0.8). Concerning the PRES, we found that women felt more empowered during home-based monitoring (P = 0.001) and classified the home-based monitoring as more discreet (P = 0.000) compared to the hospital-based monitoring.Limitations, Reasons For Caution: The results are applicable only to women undergoing NC-FET and not to women undergoing artificial cycle FET.Wider Implications Of the Findings: Apart from clinical outcomes, PROs and PREs are also of importance in clinical decision-making and to support tailoring treatment even more specifically to the wishes of patients. Measurement of PROs and PREs should therefore be incorporated in future clinical research.Study Funding/competing Interest(s): The Antarctica-2 RCT is supported by a grant of the Netherlands Organisation for Health Research and Development (ZonMw 843002807). J.B. receives unconditional educational grants from Merck Serono and Ferring and is a member of the medical advisory board of Ferring. C.L. reports that his department receives unrestricted research grants from Ferring, Merck and Guerbet. E.G. receives personal fees from Titus Health Care outside submitted work. The remaining authors have no conflicts of interest.Trial Registration Number: Trial NL6414 (NTR6590).Trial Register Date: 23 July 2017.Date Of First Patient’s Enrolment: 10 April 2018. [ABSTRACT FROM AUTHOR]

Study Question: What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?.Summary Answer: Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child.What Is Known Already: IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF.Study Design, Size, Duration: We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization.Participants/materials, Setting, Methods: We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates.Main Results and the Role Of Chance: There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were €7187 for IVF-SET, €8206 for IVF-MNC and €5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences €2117; 95% CI: €1544-€2657 and €3136, 95% CI: €2519-€3754, respectively).The ICER for IVF-SET compared with IUI-COH was €43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs.Limitations, Reasons For Caution: We only report on direct health care costs. The present analysis is limited to 12 months.Wider Implications Of the Findings: Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice.Study Funding/competing Interests: The study was supported by a grant from ZonMw, the Netherlands Organization for Health Research and Development, (120620027) and a grant from Zorgverzekeraars Nederland, the Netherlands' association of health care insurers (09-003).Trial Registration Number: Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939. [ABSTRACT FROM AUTHOR]

Background: Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called 'scratching', has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle.Method: Multicenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure.Discussion: Multiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle.Trial Registration: NTR 5342 , registered July 31st, 2015.Protocol Version: Version 4.10, January 4th, 2017. [ABSTRACT FROM AUTHOR]

Purpose: There is growing recognition that transformation of healthcare systems towards health and well-being systems requires a continuous learning process. This explorative study aims to gain insight into the experiences with and investment in these learning processes within regional partnerships for health and in what they need to enhance their learning capacity to use the learning for transformation., Design/methodology/approach: 17 interviews were held with programme managers, data scientists, trusted advisors and a citizen representative, all involved in the learning process on a regional level in ten Dutch regional partnerships. The interviews were inductively and thematically analysed, focusing on the experiences and perceptions underlying the learning processes., Findings: Regional partnerships invest in learning processes by organizing interactions between different groups of stakeholders and by reflecting on specific themes or on a region-wide level. Difficulty was found in region-wide reflection and in enhancing the learning capacity within the partnerships. Further enhancing the learning capacity required: (1) Investment in (the use of) expertise for translating learning outcomes into concrete action; (2) Leadership for change, underpinned by a shared sense of urgency to learn for transformation and (3) A facilitative environment for change which is both based on facilitative system structures and a basis of trust and commitment to learn and adapt., Originality/value: The study highlighted the difficulty of learning on a region-wide level and the struggle to apply this learning for transformation. It provides insights into how learning processes and learning capacity can be further improved., (© Natascha van Vooren, Esther de Weger, Josefien de Bruin and Caroline Baan.)

In this paper we apply a gravity framework to user-generated data of a large online housing market platform. We show that gravity describes the patterns of inflow and outflow of hits (mouse clicks, etc.) from one municipality to another, where the municipality of the user defines the origin and the municipality of the property that is viewed defines the destination. By distinguishing serious searchers from recreational searchers we demonstrate that the gravity framework describes geographic search patterns of both types of users. The results indicate that recreational search is centered more around the user's location than serious search. However, this finding is driven entirely by differences in border effects as there is no difference in the distance effect. By demonstrating that geographic search patterns of both serious and recreational searchers are explained by their physical locations, we present clear evidence that physical location is an important determinant of economic behavior in the virtual realm too., Competing Interests: The authors have declared that no competing interests exist.

Study Question: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle?, Summary Answer: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%., What Is Known Already: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes., Study Design, Size, Duration: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate., Participants/materials, Setting, Methods: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%)., Main Results and the Role of Chance: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI)., Limitations, Reasons for Caution: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%., Wider Implications of the Findings: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials., Study Funding/competing Interest(s): This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work., Trial Registration Number: Registered in the Netherlands Trial Register (NL5193/NTR 5342)., Trial Registration Date: 31 July 2015., Date of First Patient’s Enrolment: 26 January 2016., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR)., Methods: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests., Results: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively)., Conclusion: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: In the Netherlands, couples with unexplained infertility and a good prognosis to conceive spontaneously (i.e. Hunault > 30%) are advised to perform timed intercourse for at least another 6 months. If couples fail to conceive within this period, they will usually start assisted reproductive technology (ART). However, treatment of unexplained infertility by ART is empirical and can involve significant burdens. Intentional endometrial injury, also called 'endometrial scratching', has been proposed to positively affect the chance of embryo implantation in patients undergoing in vitro fertilization (IVF). It might also be beneficial for couples with unexplained infertility as defective endometrial receptivity may play a role in these women. The primary aim of this study is to determine whether endometrial scratching increases live birth rates in women with unexplained infertility., Method: A multicentre randomized controlled trial will be conducted in Dutch academic and non-academic hospitals starting from November 2017. A total of 792 women with unexplained infertility and a good prognosis for spontaneous conception < 12 months (Hunault > 30%) will be included, of whom half will undergo endometrial scratching in the luteal phase of the natural cycle. The women in the control group will not undergo endometrial scratching. According to Dutch guidelines, both groups will subsequently perform timed intercourse for at least 6 months. The primary endpoint is cumulative live birth rate. Secondary endpoints are clinical and ongoing pregnancy rate; miscarriage rate; biochemical pregnancy loss; multiple pregnancy rate; time to pregnancy; progression to intrauterine insemination (IUI) or IVF; pregnancy complications; complications of endometrial scratching; costs and endometrial tissue parameters associated with reproductive success or failure. The follow-up duration is 12 months., Discussion: Several small studies show a possible beneficial effect of endometrial scratching in women with unexplained infertility trying to conceive naturally or through IUI. However, the quality of this evidence is very low, making it unclear whether these women will truly benefit from this procedure. The SCRaTCH-OFO trial aims to investigate the effect of endometrial scratching on live birth rate in women with unexplained infertility and a good prognosis for spontaneous conception < 12 months., Trial Registration: NTR6687 , registered August 31st, 2017., Protocol Version: Version 2.6, November 14th, 2018.

Introduction: Future doctors must be trained in giving appropriate care to terminal patients. In several countries, medical curricula have been reviewed for the attention devoted to end-of-life care (ELC). In the Netherlands, no formal review had been performed. Therefore, the aim of this study was to provide an overview of the Dutch medical curricula regarding ELC., Methods: We formed a checklist based on international standards consisting of five domains of ELC education that are considered essential. Firstly, we studied the Dutch national blueprint on medical education. Secondly, using a questionnaire based on the checklist we studied the curricula of the eight medical faculties. A questionnaire was sent to all Dutch medical faculties to study the compulsory courses of the curricula. To assess the elective courses, we consulted the study guides., Results: The national blueprint included four of the five domains of ELC. None of the eight medical faculties taught all domains specifically on ELC; they were taught within other courses. Most attention was given to the domains on psychological, sociological, cultural and spiritual aspects; communication and conversational techniques; and juridical and ethical aspects. One faculty taught an elective course that included all essential aspects of the international standards., Discussion: Our study shows that ELC is currently insufficiently mentioned in the national blueprint and that none of the faculties fully integrated ELC as a part of their compulsory medical curricula. To improve ELC education, we recommend the Dutch Federation of University Medical Centres to add the five ELC domains to the national blueprint and we recommend the medical faculties to review their curricula and offer a separate and compulsory course on ELC to prepare their students for their future medical practice.

Background: Manual workers in the public sector have previously been found to be at risk of mental sickness absence (SA). As the impact of mental illness differs across economic sectors, this study investigated mental SA in the industrial sector, differentiating between office and production workers., Methods: Ten-year observational cohort study including 14 369 (8164 production and 6205 office) workers with a total of 101 118 person years. SA data were retrieved from an occupational health register. Mental SA episodes were medically certified as emotional disturbances [10th version of the International Classification of Diseases (ICD-10 R45)] or mental and behavioural disorders (ICD-10 F00-F99). The first mental SA episode since baseline was called index mental SA. Recurrences were defined as any mental SA episode occurring >28 days after recovery from index mental SA., Results: The incidence of mental SA was higher in production workers than in office workers, but office workers needed longer time to recover from mental SA. Mental SA recurred as frequently in production workers as in office workers. The median time to recurrence was 15.9 months and tangibly shorter in office workers (14.9 months) than in production workers (16.7 months). Production and office workers aged >55 years were at increased risk of recurrent mental SA within 12 months of recovery from index mental SA., Conclusions: The incidence of mental SA was higher in production workers than in office workers, whereas recurrence rates did not differ between them. Occupational health providers should pay special attention to older workers as they are at increased risk of recurrent mental SA., (© The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Objectives: To investigate the Maslach Burnout Inventory-General Survey (MBI-GS) and the Utrecht Work Engagement Scale (UWES) for their ability to identify non-sicklisted employees at increased risk of long-term sickness absence (LTSA)., Methods: One-year prospective cohort study including 4,921 employees participating in occupational health surveys in the period 2008-2010. The MBI-GS and UWES were part of the health survey questionnaire and LTSA in the year following the health survey was retrieved from an occupational health register. Associations of baseline MBI-GS and UWES scores with LTSA during 1-year follow-up were stratified by the cause (mental, musculoskeletal, and other somatic illness) of LTSA. Discrimination was assessed by the area (AUC) under the receiver operating characteristic curve and considered practically useful for AUC ≥0.75., Results: During 1-year follow-up, 103 employees (2%) had LTSA due to mental (N = 43), musculoskeletal (N = 31), or other somatic (N = 29) illness. MBI-GS scores were positively and UWES scores negatively associated with mental LTSA, but not musculoskeletal or other somatic LTSA. Discrimination between employees at high and low risk of mental LTSA was moderate: AUC = 0.68 for the MBI-GS and AUC = 0.70 for the UWES. Discrimination did not improve when the MBI-GS and UWES were used simultaneously., Conclusion: The MBI-GS and UWES predicted future mental LTSA in non-sicklisted employees, but discrimination was not practically useful for identifying employees at high risk of LTSA. However, both instruments could be used to select employees for further assessment of mental LTSA risk.

Objectives: To compare the effectiveness of in vitro fertilisation with single embryo transfer or in vitro fertilisation in a modified natural cycle with that of intrauterine insemination with controlled ovarian hyperstimulation in terms of a healthy child., Design: Multicentre, open label, three arm, parallel group, randomised controlled non-inferiority trial., Setting: 17 centres in the Netherlands., Participants: Couples seeking fertility treatment after at least 12 months of unprotected intercourse, with the female partner aged between 18 and 38 years, an unfavourable prognosis for natural conception, and a diagnosis of unexplained or mild male subfertility., Interventions: Three cycles of in vitro fertilisation with single embryo transfer (plus subsequent cryocycles), six cycles of in vitro fertilisation in a modified natural cycle, or six cycles of intrauterine insemination with ovarian hyperstimulation within 12 months after randomisation., Main Outcome Measures: The primary outcome was birth of a healthy child resulting from a singleton pregnancy conceived within 12 months after randomisation. Secondary outcomes were live birth, clinical pregnancy, ongoing pregnancy, multiple pregnancy, time to pregnancy, complications of pregnancy, and neonatal morbidity and mortality, Results: 602 couples were randomly assigned between January 2009 and February 2012; 201 were allocated to in vitro fertilisation with single embryo transfer, 194 to in vitro fertilisation in a modified natural cycle, and 207 to intrauterine insemination with controlled ovarian hyperstimulation. Birth of a healthy child occurred in 104 (52%) couples in the in vitro fertilisation with single embryo transfer group, 83 (43%) in the in vitro fertilisation in a modified natural cycle group, and 97 (47%) in the intrauterine insemination with controlled ovarian hyperstimulation group. This corresponds to a risk, relative to intrauterine insemination with ovarian hyperstimulation, of 1.10 (95% confidence interval 0.91 to 1.34) for in vitro fertilisation with single embryo transfer and 0.91 (0.73 to 1.14) for in vitro fertilisation in a modified natural cycle. These 95% confidence intervals do not extend below the predefined threshold of 0.69 for inferiority. Multiple pregnancy rates per ongoing pregnancy were 6% (7/121) after in vitro fertilisation with single embryo transfer, 5% (5/102) after in vitro fertilisation in a modified natural cycle, and 7% (8/119) after intrauterine insemination with ovarian hyperstimulation (one sided P=0.52 for in vitro fertilisation with single embryo transfer compared with intrauterine insemination with ovarian hyperstimulation; one sided P=0.33 for in vitro fertilisation in a modified natural cycle compared with intrauterine insemination with controlled ovarian hyperstimulation)., Conclusions: In vitro fertilisation with single embryo transfer and in vitro fertilisation in a modified natural cycle were non-inferior to intrauterine insemination with controlled ovarian hyperstimulation in terms of the birth of a healthy child and showed comparable, low multiple pregnancy rates.Trial registration Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939., (© Bensdorp et al 2015.)

This longitudinal multicentre cohort study aimed to identify the role of the conception mode in infertile couples with an early pregnancy loss (EPL). All couples referred to the fertility clinic for the first time in the period 2002-2006 because of infertility were followed up to their first clinical pregnancy (n=1809). EPL was the outcome of 286 (15.8%) pregnancies. EPL rates for the different conception modes were as follows: spontaneous 14.5% (125/864), ovulation induction 15.8% (42/266), intrauterine insemination 25.0% (5/20), intrauterine insemination combined with ovarian stimulation 18.2% (37/203), IVF 16.3% (31/190), intracytoplasmic sperm injection (ICSI) 14.9% (30/202) and frozen embryo transfer (FET) 26.2% (16/61). After adjusting for female age, male age, hospital, obstetric history, female smoking habit, male alcohol use, menstrual cycle type and infertility diagnosis, the EPL rate after FET was significantly increased (odds ratio 2.2, 95% CI 1.14-4.19) compared with spontaneous conception. Embryo quality was comparable in fresh and frozen embryos. Other fertility treatments showed no increased miscarriage rate. Therefore, it is concluded that even after adjustment for confounding factors conception through FET remained an independent risk factor for EPL. Other modes of conception were not related with EPL., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Unexplained infertility is one of the most common diagnoses in fertility care. The aim of this study was to evaluate the outcome of current fertility management in unexplained infertility., Methods: In an observational, longitudinal, multicentre cohort study, 437 couples were diagnosed with unexplained infertility and were available for analysis. They were treated according to their prognosis using standing national treatment protocols: (i) expectant management-IUI-IVF (main treatment route), (ii) IUI-IVF and (iii) directly IVF. Primary outcome measures were: ongoing pregnancy rate, patient flow over the strategies, numbers of protocol violation and drop out rates. A secondary outcome measure was the prediction of ongoing pregnancy and mode of conception., Results: Of all couples 81.5% (356/437) achieved an ongoing pregnancy and 73.9% (263/356) of the pregnancies were conceived spontaneously. There were 408 couples (93.4%) in strategy-1, 21 (5.0%) in strategy-2 and 8 (1.8%) in strategy-3. In total, 33 (7.6%) couples entered the wrong strategy. There were 104 couples (23.8%) who discontinued fertility treatment prematurely: 26 on doctor's advice (with 4 still becoming pregnant) and 78 on their own initiative (with 33 still achieving a pregnancy). Predictors for overall pregnancy chance and mode of conception were duration of infertility, female age and obstetrical history., Conclusions: Overall success rate in couples with unexplained infertility is high. Most pregnancies are conceived spontaneously. We recommend that if the pregnancy prognosis is good, expectant management should be suggested. The prognosis criteria for treatment with IUI or IVF needs to be investigated in randomized controlled trials.

Objective: To determine whether an investigation of microsatellite instability (MSI) in patients with colorectal carcinoma that have been selected by the pathologist could increase the number of detected families with hereditary non-polyposis colorectal carcinoma (HNPCC)., Design: Prospective inventory., Method: Pathologists selected patients with a newly diagnosed colorectal carcinoma for MSI analysis of their tumour tissue if they met one of the following four criteria: (a) colorectal carcinoma diagnosed below 50 years of age; (b) a second colorectal carcinoma; (c) a combination of colorectal carcinoma and another HNPCC-related cancer; (d) colorectal adenoma with high-grade dysplasia diagnosed below 40 years of age. Patients with a positive MSI-test were referred to a clinical geneticist. The new strategy was introduced and explored in 5 hospitals for a period of to months., Results: The new strategy was adopted and implemented successfully by pathologists and surgeons and accepted with satisfaction by the patients. Of the 55 patients included, 10 had a positive MSI-test. In 8/10 patients, DNA-mutation analysis was started by the clinical geneticist and 3 germline mutations in the MSH2-gene were detected. In 2 of 3 families with a pathogenic mutation, the family history alone did not fulfil the clinical criteria for HNPCC., Conclusion: Selection by the pathologist for MSI investigation was feasible in daily practice and identified more HNPCC patients than selection based on family history alone.

Background: Distinguishing hereditary non-polyposis colorectal cancer (HNPCC) from non-hereditary colorectal cancer (CRC) can increase the life expectancy of HNPCC patients and their close relatives., Aim: To determine the effectiveness, efficiency, and feasibility of a new strategy for the detection of HNPCC, using simple criteria for microsatellite instability (MSI) analysis of newly detected tumours that can be applied by pathologists. Criteria for MSI analysis are: (1) CRC before age 50 years; (2) second CRC; (3) CRC and HNPCC associated cancer; or (4) adenoma before age 40 years., Methods: The efficacy and cost effectiveness of the new strategy was evaluated against current practice. Decision analytic models were constructed to estimate the number of extra HNPCC mutation carriers and the costs of this strategy. The incremental costs and gain in life expectancy for a HNPCC mutation carrier were evaluated by Markov modelling. Feasibility was explored in five hospitals., Results: Using the new strategy, 2.2 times more HNPCC patients can be identified among a CRC population compared with current practice. This new strategy was found to be cost effective with an expected cost effectiveness ratio of 3801 per life year gained. When including the group of siblings and children, the cost effectiveness ratio became 2184 per life year gained. Sensitivity analysis showed these findings to be robust., Conclusions: MSI testing in a selection of newly diagnosed CRC patients was shown to be cost effective and a feasible method to identify patients at risk for HNPCC who are not recognised by family history.

In 3 patients, 2 men aged 46 and 51 years and a woman aged 54 years, with colorectal cancer there was insufficient information on the basis of the family history to diagnose 'hereditary non-polyposis colorectal cancer' (HNPCC). Further investigation showed microsatellite instability in the tumour material, an indicator for a mutation in DNA-'mismatch repair' (MMR-) genes. Immunohistochemical study of lymphocytes showed an absence of the gene products MSH2 and MSH6. Study of the MMR genes revealed a pathogenic germ-line mutation in MSH2. All three patients were satisfied with genetic testing of the MMR-genes as this gave their children and their family members the opportunity to clarify genetic status. HNPCC is a clinical diagnosis, based on family history. As family history taking is often incomplete, the diagnosis is regularly not considered. The following individual criteria can help to recognize a patient at risk for HNPCC: (a) colorectal cancer diagnosed below 50 years of age, (b) second colorectal cancer, (c) a combination of colorectal and endometrial cancer.

All pigs passing along the slaughter-line in the slaughter-house of the Livestock and Meat Board of the Christian Farmers' Association of the Province of North Brabant are examined for the presence of lesions of the lung and liver. The proportions of animals without any severe lesions of the lungs and livers and the proportions of those with affected lungs, affected livers, condemned livers and pleurisy are reported every three months. Under the Animal Health Service of the Province of North Brabant, investigations were carried out on 251 farms with less than 10 per cent and 251 farm with more than 25 per cent of the animals with severe lesions of the lungs to study the effect of conditions of management on the incidence of diseases of the lung and liver. Among others, this produced the following results:--The average proportions of affected livers and those of the proportions of cases of pleurisy were higher, whereas the daily growth rate of each pig and the carcass quality were lower.--Slaughtered pigs with lesions of the lung and/or liver showed a significantly smaller daily growth rate during the fattening period. In pigs with pleurisy, retardation of growth was also observed on the breeding farm.--The proportion of affected lungs and livers is significantly affected by a number of factors on the farm. Among others, the following factors were found to be of importance: adopting the all in--all out system, removals, the origin of the piglets, the number of pigs in each compartment of the pig house and the construction of the piggery (width of pig house and slatted floor). Taking these factors into account, a "transverse housing system" is recommended.

The proportion of pigs which died during and shortly after transport was estimated in 1976, like it was in 1968 and 1972. The monthly inquiry included forty-four per cent (approximately 5.2 million animals) of the total number of pigs slaughtered in the Netherlands in 1976. Mortality during and after transport showed a decrease ever since 1968 and was reduced to 0.30 per cent by 1976. The main causes of losses during transport and methods suggested to reduce these losses to a further extent are briefly referred to. The findings will be discussed in greater detail in a following report.