Hysteroscopy for treating subfertility associated with suspected major uterine cavity abnormalities

Background : Observational studies suggest higher pregnancy rates after the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions, which are detectable in 10% to 15% of women seeking treatment for subfertility. Objectives : To assess the effects of the hysteroscopic removal of endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions suspected on ultrasound, hysterosalpingography, diagnostic hysteroscopy or any combination of thesemethods inwomenwith otherwise unexplained subfertility or prior to intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Search methods : We searched theCochraneMenstrualDisorders and Subfertility SpecialisedRegister (8 September 2014), theCochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 9), MEDLINE (1950 to 12 October 2014), EMBASE (inception to 12 October 2014), CINAHL (inception to 11 October 2014) and other electronic sources of trials including trial registers, sources of unpublished literature and reference lists. We handsearched the American Society for Reproductive Medicine (ASRM) conference abstracts and proceedings (from January 2013 to October 2014) and we contacted experts in the field. Selection criteria : Randomised comparisons between operative hysteroscopy versus control in women with otherwise unexplained subfertility or undergoing IUI, IVF or ICSI and suspected major uterine cavity abnormalities diagnosed by ultrasonography, saline infusion/ gel instillation sonography, hysterosalpingography, diagnostic hysteroscopy or any combination of these methods. Primary outcomes were live birth and hysteroscopy complications. Secondary outcomes were pregnancy and miscarriage. Data collection and analysis : Two review authors independently assessed studies for inclusion and risk of bias, and extracted data. We contacted study authors for additional information. Main results : We retrieved 12 randomised trials possibly addressing the research questions. Only two studies (309 women) met the inclusion criteria. Neither reported the primary outcomes of live birth or procedure related complications. In women with otherwise unexplained subfertility and submucous fibroids there was no conclusive evidence of a difference between the intervention group treated with hysteroscopic myomectomy and the control group having regular fertility-oriented intercourse during 12 months for the outcome of clinical pregnancy. A large clinical benefit with hysteroscopic myomectomy cannot be excluded: if 21% of women with fibroids achieve a clinical pregnancy having timed intercourse only, the evidence suggests that 39% of women (95% CI 21% to 58%) will achieve a successful outcome following the hysteroscopic removal of the fibroids (odds ratio (OR) 2.44, 95% confidence interval (CI) 0.97 to 6.17, P = 0.06, 94 women, very low quality evidence). There is no evidence of a difference between the comparison groups for the outcome of miscarriage (OR 0.58, 95% CI 0.12 to 2.85, P = 0.50, 30 clinical pregnancies in 94 women, very low quality evidence). The hysteroscopic removal of polyps prior to IUI can increase the chance of a clinical pregnancy compared to simple diagnostic hysteroscopy and polyp biopsy: if 28% of women achieve a clinical pregnancy with a simple diagnostic hysteroscopy, the evidence suggests that 63% of women (95% CI 50% to 76%) will achieve a clinical pregnancy after the hysteroscopic removal of the endometrial polyps (OR 4.41, 95% CI 2.45 to 7.96, P < 0.00001, 204 women, moderate quality evidence). Authors' conclusions : A large benefit with the hysteroscopic removal of submucous fibroids for improving the chance of clinical pregnancy in women with otherwise unexplained subfertility cannot be excluded. The hysteroscopic removal of endometrial polyps suspected on ultrasound in women prior to IUI may increase the clinical pregnancy rate. More randomised studies are needed to substantiate the effectiveness of the hysteroscopic removal of suspected endometrial polyps, submucous fibroids, uterine septum or intrauterine adhesions in women with unexplained subfertility or prior to IUI, IVF or ICSI

Cost-benefit analysis of abatement measures for nutrient emission from agriculture

In intensive animal husbandry areas surface water N and P concentrations often remain too high. The Water Framework Directive calls for additional nutrient emission abatement measures. Therefore, costs and benefits for possible agricultural measures in Flanders were first analysed in terms of soil balance surplus. Finally, abatement measures for agriculture, households and industry were set off against each other and ranked according to their cost-efficiency by the Environmental Costing Model. Increased dairy cattle efficiency, winter cover crops and increased pig feed efficiency turn out very cost efficient. Other agricultural measures are less cost efficient than for instance collective treatment for households and industry.nitrogen and phosphorus abatement, surface water, cost efficiency, Environmental Economics and Policy, Livestock Production/Industries,

Treating suspected uterine cavity abnormalities by hysteroscopy to improve reproductive outcome in women with unexplained infertility or prior to IUI, IVF, or ICSI

Endometrial polyps, submucous fibroids, uterine septa, and intrauterine adhesions can be found by ultrasound (US), HSG, hysteroscopy, or any combined in 10–15 % of infertile women. Observational studies suggest a better reproductive outcome when these anomalies are removed by operative hysteroscopy. The current Cochrane review assesses the effectiveness of hysteroscopy for treating these suspected anomalies in women with otherwise unexplained infertility or prior to intrauterine insemination, in vitro fertilization, or intracytoplasmic sperm injection

Anti-adhesion therapy following operative hysteroscopy for treatment of female subfertility

Background : Observational evidence suggests a potential benefit with several anti-adhesion therapies in women undergoing operative hysteroscopy (e.g. insertion of an intrauterine device or balloon, hormonal treatment, barrier gels or human amniotic membrane grafting) for decreasing intrauterine adhesions (IUAs). Objectives : To assess the effectiveness of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy, following operative hysteroscopy for treatment of female subfertility. Search methods : We searched the following databases from inception to June 2017: the Cochrane Gynaecology and Fertility Group Specialised Register; the Cochrane Central Register of Studies (CRSO); MEDLINE; Embase; CINAHL and other electronic sources of trials, including trial registers, sources of unpublished literature and reference lists. We handsearched the Journal of Minimally Invasive Gynecology, and we contacted experts in the field. We also searched reference lists of appropriate papers. Selection criteria : Randomised controlled trials (RCTs) of anti-adhesion therapies versus placebo, no treatment or any other anti-adhesion therapy following operative hysteroscopy in subfertilewomen. The primary outcomewas live birth. Secondary outcomeswere clinical pregnancy, miscarriage and IUAs present at second-look hysteroscopy, along with mean adhesion scores and severity of IUAs. Data collection and analysis : Two review authors independently selected studies, assessed risk of bias, extracted data and evaluated quality of evidence using the GRADE method. Main results : The overall quality of the evidence was low to very low. The main limitations were serious risk of bias related to blinding of participants and personnel, indirectness and imprecision. We identified 16 RCTs comparing a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with graft versus device without graft (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) and device combined with gel versus device (one study; 120 women). The total number of participants was 1273, but data on 1133 women were available for analysis. Only two of 16 studies included 100% infertile women; in all other studies, the proportion was variable or unknown. No study reported live birth, but some (five studies) reported outcomes that were used as surrogate outcomes for live birth (term delivery or ongoing pregnancy). Anti-adhesion therapy versus placebo or no treatment following operative hysteroscopy. There was insufficient evidence to determine whether therewas a difference between the use of a device or hormonal treatment compared to no treatment or placebo with respect to term delivery or ongoing pregnancy rates (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.42 to 2.12; 107 women; 2 studies; I-2 = 0%; very-low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without hormonal treatment or hormonal treatment or barrier gels compared with no treatment or placebo (OR 0.35, 95% CI 0.21 to 0.60; 560 women; 8 studies; I y = 0%; low-quality evidence). The number needed to treat for an additional beneficial outcome (NNTB) was 9 (95% CI 5 to 17). Comparisons of different anti-adhesion therapies following operative hysteroscopy : It was unclear whether there was a difference between the use of a device combined with graft versus device only for the outcome of ongoing pregnancy (OR 1.48, 95% CI 0.57 to 3.83; 180 women; 3 studies; I-2 = 0%; low-quality evidence). There were fewer IUAs at second-look hysteroscopy using a device with or without graft/gel or gel combined with hormonal treatment and antibiotics compared with using a device only or hormonal treatment combined with antibiotics, but the findings of this meta-analysis were affected by evidence quality (OR 0.55, 95% CI 0.36 to 0.83; 451 women; 5 studies; I-2 = 0%; low-quality evidence). Authors' conclusions : Implications for clinical practice : The quality of the evidence ranged from very low to low. The effectiveness of anti-adhesion treatment for improving key reproductive outcomes or for decreasing IUAs following operative hysteroscopy in subfertile women remains uncertain. Implications for research : More research is needed to assess the comparative safety and (cost-) effectiveness of different anti-adhesion treatments compared to no treatment or other interventions for improving key reproductive outcomes in subfertile women

Synthesis and biological evaluation of novel quinoline-piperidine scaffolds as antiplasmodium agents

The parasitic disease malaria places almost half of the world's population at risk of infection and is responsible for more than 400,000 deaths each year. The first-line treatment, artemisinin combination therapies (ACT) regimen, is under threat due to emerging resistance of Plasmodium falciparum strains in e.g. the Mekong delta. Therefore, the development of new antimalarial agents is crucial in order to circumvent the growing resistance. Chloroquine, the long-established antimalarial drug, still serves as model compound for the design of new quinoline analogues, resulting in numerous new active derivatives against chloroquine-resistant P. falciparum strains over the past twenty years. In this work, a set of functionalized quinoline analogues, decorated with a modified piperidine-containing side chain, was synthesized. Both amino- and (aminomethyl)quinolines were prepared, resulting in a total of 18 novel quinoline-piperidine conjugates representing four different chemical series. Evaluation of their in vitro antiplasmodium activity against a CQ-sensitive (NF54) and a CQ-resistant (K1) strain of P. falciparum unveiled highly potent activities in the nanomolar range against both strains for five 4-aminoquinoline derivatives. Moreover, no cytotoxicity was observed for all active compounds at the maximum concentration tested. These five new aminoquinoline hit structures are therefore of considerable value for antimalarial research and have the potency to be transformed into novel antimalarial agents upon further hit-to-lead optimization studies

Economic evaluation of Medically Assisted Reproduction: An educational overview of methods and applications for healthcare professionals

Economic evaluations of the value-for-money of Medically Assisted Reproduction (MAR) interventions are increasingly important due to growing pressure on healthcare budgets. Although such evaluations are commonplace in the published literature, the number/methodological complexity of different evaluations available, and the challenges specific to MAR interventions, can complicate the interpretation of such analyses for fertility treatments. This article aims to serve as an educational resource and provide context on the design/interpretation of economic analyses for MAR interventions. Several areas are relevant for first-line providers and decision makers: scope of analysis, comparator used, perspective/time horizon considered, outcomes used to measure success, and how results from cost-effectiveness studies can be summarised and used in clinical practice. We aim to help clinicians better understand the strengths/weaknesses of economic analyses, to enable the best use of the evidence in practice, so resources available for MAR interventions can provide maximum value to patients and society

What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate

Preimplantation genetic screening is being scrutinized, as recent randomized clinical trials failed to observe the expected significant increase in live birth rates following fluorescence in situ hybridization (FISH)-based screening. Although these randomized clinical trials are criticized on their design, skills or premature stop, it is generally believed that well-designed and well-executed randomized clinical trials would resolve the debate about the potential benefit of preimplantation genetic screening. Since FISH can analyze only a limited number of chromosomal loci, some of the embryos transferred might be diagnosed as ‘normal’ but in fact be aneuploid for one or more chromosomes not tested. Hence, genome-wide array comparative genome hybridization screening enabling aneuploidy detection of all chromosomes was thought to be a first step toward a better design. We recently showed array screening indeed enables accurate determination of the copy number state of all chromosomes in a single cell. Surprisingly, however, this genome-wide array screening revealed a much higher frequency and complexity of chromosomal aberrations in early embryos than anticipated, with imbalances in a staggering 90% of all embryos. The mitotic error rate in cleavage stage embryos was proven to be higher than the meiotic aneuploidy rate and as a consequence, the genome of a single blastomere is not representative for the genome of the other cells of the embryo. Hence, potentially viable embryos will be discarded upon screening a single blastomere. This observation provides a biological basis for the failure of the randomized clinical trials to increase baby-take-home rates using FISH on cleavage stage embroys

The ENDOCARE questionnaire (ECQ): a valid and reliable instrument to measure the patient-centeredness of endometriosis care in Europe

BACKGROUND: Endometriosis is prevalent and women need high-quality care, which should be patient-centered. This study aimed to develop a valid and reliable patient-centeredness questionnaire, based on a defined concept of patient-centered endometriosis care (PCEC). METHODS: A literature review, focus groups (FGs) with patients and an expert panel defined PCEC with 10 dimensions. The ENDOCARE questionnaire (ECQ) was developed. FGs resulted in 43 specific statements covering the 10 dimensions of PCEC, for which the ECQ measured 'importance' and 'performance'. Medical and demographic questions and an open question were added. The Dutch ECQ questionnaire was piloted and reciprocally translated into English and Italian. Patients with endometriosis from Belgium, The Netherlands, Italy and the UK were invited to complete the ECQ online. Item analysis, inter-item analysis and confirmatory and exploratory factor analyses (EFA) and reliability analysis were performed. The theory-driven dimensions were adapted. RESULTS: The ECQ was completed by 541 patients. Based on item analysis, five statements were deleted. Factor analysis was performed on 322 questionnaires (only from respondents with a partner). Insights from the data-driven EFA suggested adaptations of the theory-driven dimensions. The reliability statistics of 9/10 adapted theory-driven dimensions were satisfactory and the root mean square error of approximation was good. CONCLUSIONS: This study resulted in a valid and reliable instrument to measure PCEC. For data presentation, the adapted theory-driven dimensions of PCEC are preferred over the data-driven factors. The ECQ may serve to benchmark patient-centeredness, conduct cross-cultural European research and set targets for improvement

Coalition unionism : exploring how and when coalitions contribute to union renewal in Sydney, Toronto and Chicago

Item does not contain fulltextWe have previously identified eight novel autoantibody targets in the cerebrospinal fluid of multiple sclerosis (MS) patients, including sperm-associated Ag 16 (SPAG16). In the current study, we further investigated the autoantibody response against SPAG16-a protein with unknown function in the CNS-and its expression in MS pathology. Using isoelectric focusing, we detected SPAG16-specific oligoclonal bands in the cerebrospinal fluid of 5 of 23 MS patients (22%). Analysis of the anti-SPAG16 Ab reactivity in the plasma of a total of 531 donors using ELISA demonstrated significantly elevated anti-SPAG16 Ab levels (p = 0.002) in 32 of 153 MS patients (21%) compared with all other control groups with 95% specificity for the disease. To investigate the pathologic relevance of anti-SPAG16 Abs in vivo, anti-SPAG16 Abs were injected in mice with experimental autoimmune encephalomyelitis, resulting in a significant disease exacerbation. Finally, we demonstrated a consistent upregulation of SPAG16 in MS brain and experimental autoimmune encephalomyelitis spinal cord lesions, more specifically in reactive astrocytes. We conclude that SPAG16 is a novel autoantibody target in a subgroup of MS patients and in combination with other diagnostic criteria, elevated levels of anti-SPAG16 Abs could be used as a biomarker for diagnosis. Furthermore, the pathologic relevance of anti-SPAG16 Abs was shown in vivo