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1.  Treating suspected uterine cavity abnormalities by hysteroscopy to improve reproductive outcome in women with unexplained infertility or prior to IUI, IVF, or ICSI 
Gynecological Surgery  2013;10(3):165-167.
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.
PMCID: PMC3718997  PMID: 23894233
Hysteroscopy; Subfertility; Uterine cavity abnormalities; Randomized controlled trial
2.  The European Society of Human Reproduction and Embryology guideline for the diagnosis and treatment of endometriosis: an electronic guideline implementability appraisal 
Clinical guidelines are intended to improve healthcare. However, even if guidelines are excellent, their implementation is not assured. In subfertility care, the European Society of Human Reproduction and Embryology (ESHRE) guidelines have been inventoried, and their methodological quality has been assessed. To improve the impact of the ESHRE guidelines and to improve European subfertility care, it is important to optimise the implementability of guidelines. We therefore investigated the implementation barriers of the ESHRE guideline with the best methodological quality and evaluated the used instrument for usability and feasibility.
We reviewed the ESHRE guideline for the diagnosis and treatment of endometriosis to assess its implementability. We used an electronic version of the guideline implementability appraisal (eGLIA) instrument. This eGLIA tool consists of 31 questions grouped into 10 dimensions. Seven items address the guideline as a whole, and 24 items assess the individual recommendations in the guideline. The eGLIA instrument identifies factors that influence the implementability of the guideline recommendations. These factors can be divided into facilitators that promote implementation and barriers that oppose implementation. A panel of 10 experts from three European countries appraised all 36 recommendations of the guideline. They discussed discrepancies in a teleconference and completed a questionnaire to evaluate the ease of use and overall utility of the eGLIA instrument.
Two of the 36 guideline recommendations were straightforward to implement. Five recommendations were considered simply statements because they contained no actions. The remaining 29 recommendations were implementable with some adjustments. We found facilitators of the guideline implementability in the quality of decidability, presentation and formatting, apparent validity, and novelty or innovation of the recommendations. Vaguely defined actions, lack of facilities, immeasurable outcomes, and inflexibility within the recommendations formed barriers to implementation. The eGLIA instrument was generally useful and easy to use. However, assessment with the eGLIA instrument is very time-consuming.
The ESHRE guideline for the diagnosis and treatment of endometriosis could be improved to facilitate its implementation in daily practice. The eGLIA instrument is a helpful tool for identifying obstacles to implementation of a guideline. However, we recommend a concise version of this instrument.
PMCID: PMC3034686  PMID: 21247418
3.  Early embryo development in a sequential versus single medium: a randomized study 
The success of in vitro fertilization techniques is defined by multiple factors including embryo culture conditions, related to the composition of the culture medium. In view of the lack of solid scientific data and in view of the current general belief that sequential media are superior to single media, the aim of this randomized study was to compare the embryo quality in two types of culture media.
In this study, the embryo quality on day 3 was measured as primary outcome. In total, 147 patients younger than 36 years treated with IVF/ICSI during the first or second cycle were included in this study. Embryos were randomly cultured in a sequential (group A) or a single medium (group B) to compare the embryo quality on day 1, day 2 and day 3. The embryo quality was compared in both groups using a Chi-square test with a significance level of 0.05.
At day 1, the percentage of embryos with a cytoplasmic halo was higher in group B (46%) than in group A (32%). At day 2, number of blastomeres, degree of fragmentation and the percentage of unequally sized blastomeres were higher in group B than in group A. At day 3, a higher percentage of embryos had a higher number of blastomeres and unequally sized blastomeres in group B. The number of good quality embryos (GQE) was comparable in both groups. The embryo utilization rate was higher in group B (56%) compared to group A (49%).
Although, no significant difference in the number of GQE was found in both media, the utilization rate was significantly higher when the embryos were cultured in the single medium compared to the sequential medium. The results of this study have a possible positive effect on the cumulative cryo-augmented pregnancy rate.
Trial registration number
PMCID: PMC2907384  PMID: 20609226
4.  Intra- and inter-observer analysis in the morphological assessment of early-stage embryos 
The aim of this study was to determine the intra- and inter-observer variability in the evaluation of embryo quality. Multilevel images of embryos on day 1, day 2 and day 3, were analysed using different morphological parameters.
Multilevel images of embryos on day 1, day 2 and day 3, were analysed using a standard scoring system. The kappa coefficient was calculated to measure intra- and inter-observer variability before and after training sessions.
Good to excellent intra-observer agreement was present for most parameters exceptions being scoring the position of pronuclei and the presence of a cytoplasmic halo on day 1, multinucleation on day 2 and the size of fragments on day 3. Inter-observer agreement was only good to excellent for the number of blastomeres on day 2 and day 3 and the orientation of the cleavage axes on day 2. Training sessions had a positive impact on inter-observer agreement.
In conclusion, assessment of morphological characteristics of early stage embryos using multilevel images was marked by a high intra-observer and a moderate inter-observer agreement. Training sessions were useful to increase inter-observer agreement.
PMCID: PMC2761923  PMID: 19788739
5.  Potential involvement of the immune system in the development of endometriosis 
This article presents an overview of immunological factors and their role in the development of endometriosis, with emphasis on inflammatory cytokines, growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women who have retrograde menstruation develop endometriosis. The development of endometriosis is hypothesised to be a complex process, which may be facilitated by several factors, including the quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies upregulated during development of endometriosis may be useful in the development of a non-surgical diagnostic tool. Although endometriosis can be treated using hormonal suppression, there is need for non-hormonal drugs, which can inhibit the development of endometriosis and alleviate pain or infertility without inhibition of ovulation. New molecules that modulate immune function in endometriosis should be the targets for future research.
PMCID: PMC305339  PMID: 14651748
6.  Priorities for Endometriosis Research 
Reproductive Sciences  2009;16(4):335-346.
Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis.
PMCID: PMC3682634  PMID: 19196878
Endometriosis; research directions; international workshop; consensus report
7.  Intra- and interobserver analysis in the morphological assessment of early stage embryos during an IVF procedure: a multicentre study 
Quality control programs are necessary to maintain good clinical practice. Embryo grading has been described as one of the external quality assurance schemes. Although the evaluation of embryos is based on the assessment of morphological characteristics, considerable intra- and inter-observer variability has been described. In this multicentre study, the variability in the embryo evaluation has been evaluated using morphological characteristics on day 1, day 2 and day 3 of embryo development.
Five embryologists of four different IVF centers participated in this study. Multilevel images of embryos were presented on a website at different time points to evaluate intra-and inter-observer agreement in the assessment of embryo morphology. The embryos were evaluated on day 1, day 2 and day 3 of their development and each embryologist had to decide if the embryo had to be transferred, cryopreserved or discarded.
Both intra-observer agreement and inter-observer agreement were good to excellent for the position of the pronuclei on day 1, the number of blastomeres on day 2 and day 3 and the clinical decision (transfer, cryopreservation, discard). For all other characteristics (size of pronuclei, presence of cytoplasomic halo, degree of fragmentation and size of blastomeres) the intra- and inter-observer agreement was moderate to very poor.
Mono- or multicentre quality control on embryo scoring by morphological assessment can easily be performed through the design of a simple website. In the future the website design can be adapted to generate statistical feedback upon scoring and can even include a training module.
PMCID: PMC3181205  PMID: 21920032
8.  A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis 
Endometriosis is associated with chronic subclinical inflammation. C-reactive protein (CRP), a marker of inflammation, could serve as a biomarker of endometriosis. We tested the hypothesis that a high sensitivity CRP assay (hsCRP) is more accurate than a classical CRP assay in the detection of subclinical inflammation in plasma of women with endometriosis.
CRP levels were measured by hsCRP and classical CRP assays in plasma of 204 women with endometriosis and 91 women without endometriosis. Both assays were compared with respect to their value for the diagnosis of endometriosis.
The number of plasma samples with detectable CRP was significantly higher (100%) using the hsCRP assay when compared to the classical CRP assay (42.7%) (p < 0.0001). Significantly increased CRP plasma levels were found in women with endometriosis when compared with controls when the hsCRP assay was used in samples obtained during the luteal phase (p = 0.008). The highest discriminative ability for the diagnosis of endometriosis was also obtained using the hsCRP assay during the luteal phase, especially for moderate -severe endometriosis. At a cut-off level of hsCRP > 0.71 mg/L, moderate-severe stages were diagnosed with 80.7% sensitivity and 63.9% specificity during the luteal phase. Using a similar cut-off value for CRP analyzed by the classical method, moderate-severe endometriosis was diagnosed with lower sensitivity (67.7%, p = 0.06) and comparable specificity (63.9%).
The hsCRP assay was superior to the classical CRP assay for the detection of low CRP levels and for revealing subclinical inflammation in plasma of women with endometriosis.
PMCID: PMC3169460  PMID: 21827658
10.  TRIzol treatment of secretory phase endometrium allows combined proteomic and mRNA microarray analysis of the same sample in women with and without endometriosis 
According to mRNA microarray, proteomics and other studies, biological abnormalities of eutopic endometrium (EM) are involved in the pathogenesis of endometriosis, but the relationship between mRNA and protein expression in EM is not clear. We tested for the first time the hypothesis that EM TRIzol extraction allows proteomic Surface Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry (SELDI-TOF MS) analysis and that these proteomic data can be related to mRNA (microarray) data obtained from the same EM sample from women with and without endometriosis.
Proteomic analysis was performed using SELDI-TOF-MS of TRIzol-extracted EM obtained during secretory phase from patients without endometriosis (n = 6), patients with minimal-mild (n = 5) and with moderate-severe endometriosis (n = 5), classified according to the system of the American Society of Reproductive Medicine. Proteomic data were compared to mRNA microarray data obtained from the same EM samples.
In our SELDI-TOF MS study 32 peaks were differentially expressed in endometrium of all women with endometriosis (stages I-IV) compared with all controls during the secretory phase. Comparison of proteomic results with those from microarray revealed no corresponding genes/proteins.
TRIzol treatment of secretory phase EM allows combined proteomic and mRNA microarray analysis of the same sample, but comparison between proteomic and microarray data was not evident, probably due to post-translational modifications.
PMCID: PMC2987945  PMID: 20964823

Results 1-10 (10)