The accuracy of ultrasound scan in diagnosing retained products of conception: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to analyze and summarize the evidence on the accuracy of different ultrasound methods in the diagnosis of retained products of conception. DATA SOURCES: We searched Ovid SP, the Cumulative Register to Nursing & Allied Health Literature, EBSCO, and grey literature including Core, Trip, Networked Digital Library of Theses and Dissertations Global ETD search, BMJ Best Practice, PubMed, GreyLit report website (http://www.greylit.org/), Cochrane Central Register of Controlled Trials, and Google scholar (https://scholar.google.com/). STUDY ELIGIBILITY CRITERIA: We included prospective and retrospective cross-sectional or Cohort studies that evaluated both ultrasound findings (before management of retained products of conception) and histopathologic results of retained products of conception at all gestational ages. METHODS: We used Covidence for data extraction from the studies and quality assessment. The meta-analysis was performed using RevMan 5.4 (forest plot), MetaDTA version 2.01, and Meta-DiSc 2.0 online software. RESULTS: In total, 11 studies were eligible for data extraction and meta-analysis. The total number of study participants from these 11 studies were 1567. Of these, 9 studies were included to test the accuracy of an echogenic mass, 4 studies analyzed the accuracy of endometrial thickness, and 5 studies analyzed the accuracy of color Doppler flow to predict retained products of conception. We found that echogenic mass had the highest sensitivity, specificity, and diagnostic odds ratio for predicting retained products of conception. The sensitivity, specificity, and diagnostic odds ratio were 0.915 (95% confidence interval, 0.844-0.955), 0.843 (95% confidence interval, 0.615-0.947), and 57.787 (95% confidence interval, 15.171-220.112), respectively. The diagnostic threshold for endometrial thickness was set at 10 mm with a sensitivity, specificity, and diagnostic odds ratio of 0.667 (95% confidence interval, 0.072-0.981), 0.866 (95% confidence interval, 0.375-0.986), and 12.927 (95% confidence interval, 0.23-726.582). The sensitivity, specificity, and diagnostic odds ratio of color Doppler flow were 0.850 (95% confidence interval, 0.756-0.913), 0.406 (95% confidence interval, 0.198-0.655), and 3.893 (95% confidence interval, 1.005-15.081). CONCLUSION: Our review concluded that an echogenic mass is the most sensitive and specific predictor of retained products of conception after any pregnancy event. The most important limitation of our review is that the design of the studies included led to significant statistical heterogeneity.

The Relationship between Number of Supernumerary Blastocysts Cryopreserved and Probability of a Live Birth Outcome after Single Fresh Blastocyst Transfer: Analysis of over 10 Thousand Cycles.

The ability to predict the likelihood of a live birth after single fresh embryo transfer is an important part of fertility treatment. While past studies have examined the likelihood of live birth based on the number of oocytes retrieved and cleavage-stage embryos available, the odds of a live birth based on the number of supernumerary blastocysts cryopreserved following a fresh embryo transfer has not been rigorously studied. We performed a retrospective analysis, stratified by age, on patients undergoing their first fresh autologous single day 5 blastocyst transfer to assess relationship between the likelihood of a live birth and number of supernumerary blastocysts cryopreserved. In patients aged <35 years and 35-39 years old, the likelihood of a live birth increased linearly between 1 and 6 supplementary blastocysts and non-linearly if 10 or more blastocysts were cryopreserved. When aged 40 years and above, the likelihood of a live birth increased linearly up to 4 cryopreserved blastocysts and then non-linearly if 10 or more blastocysts were cryopreserved. The present study demonstrated a non-linear relationship between the number of supernumerary blastocysts cryopreserved and the likelihood of a live birth after single blastocyst transfer in the first autologous fresh IVF/ICSI cycle across different age groups.

Data-Driven Medicine in the Diagnosis and Treatment of Infertility.

Infertility, although not a life-threatening condition, affects around 15% of couples trying for a pregnancy. The increasing availability of large datasets from various sources, together with advances in machine learning (ML) and artificial intelligence (AI), are enabling a transformational change in infertility care. However, real-world applications of data-driven medicine in infertility care are still relatively limited. At present, very little can prevent infertility from arising; more work is required to learn about ways to improve natural conception and the detection and diagnosis of infertility, improve assisted reproduction treatments (ART) and ultimately develop useful clinical-decision support systems to assure the successful outcome of either fertility preservation or infertility treatment. In this opinion article, we discuss recent influential work on the application of big data and AI in the prevention, diagnosis and treatment of infertility. We evaluate the challenges of the sector and present an interpretation of the different innovation forces that are driving the emergence of a systems approach to infertility care. Efforts including the integration of multi-omics information, collection of well-curated biological samples in specialised biobanks, and stimulation of the active participation of patients are considered. In the era of Big Data and AI, there is now an exciting opportunity to leverage the progress in genomics and digital technologies and develop more sophisticated approaches to diagnose and treat infertility disorders.

Management of recurrent implantation failure: British Fertility Society policy and practice guideline.

Recurrent implantation failure (RIF) is defined as the absence of a positive pregnancy test after three consecutive transfers of good quality embryos. There remains significant variation in clinical practice in the management of RIF. This British Fertility Society (BFS) Policy and Practice guideline analyses the evidence for investigations and therapies that are employed in RIF and provides recommendations for clinical practice and for further research. Evidence for investigations of sperm and egg quality, uterine and adnexal factors, immunological factors and thrombophilia, endocrine conditions and genetic factors and for associated therapies have been evaluated. This guideline has been devised to assist reproductive medicine specialists and patients in making shared decisions concerning management of RIF. Finally, suggestions for research towards improving understanding and management of RIF have also been provided.

Endometrial Receptivity Testing and Therapy in Assisted Reproductive Treatment.

Assisted reproductive treatment (ART) gave numerous couples the chance to have their biological child. Improvement in laboratory and culture conditions allows for selection of embryos with the best developmental potential, although replacement of these top-quality embryos does not, however, guarantee reproductive success. Endometrial receptivity is essential for pregnancy establishment and may be the limiting factor for the observed pregnancy rates with ART. Multiple modalities have been in use to assess endometrial receptivity, with ultrasound assessment of the endometrial morphology most commonly used due to its noninvasive nature and availability. Utilization of various "omics" increases our understanding of endometrial receptivity and selectivity; however, significantly more work is required to develop clinically relevant and validated tests of endometrial receptivity and treatments which could improve a suboptimal endometrial milieu. Current evidence for and against use of various tests of endometrial receptivity in women undergoing ART is presented in this article.

Suboptimal mid-luteal progesterone concentrations are associated with aberrant endometrial gene expression, potentially resulting in implantation failure.

RESEARCH QUESTION: What is the difference in endometrial transcriptomics between women with normal and with low mid-luteal progesterone during the implantation window? DESIGN: An endometrial biopsy and serum progesterone concentration were taken from participants during the mid-luteal phase (LH+7 to LH+9). A total of 12 participants were recruited and categorized into two groups based on their progesterone concentrations: normal progesterone (>15 ng/ml, n = 6) and low progesterone (<15 ng/ml, n = 6). Global endometrial gene expression between the two groups was compared by microarray techniques. Principal component analysis was used to display the gene's expression pattern. Pathway and gene ontology enrichment analysis were performed to determine the biological mechanism of progesterone on the endometrium. RESULTS: Several key genes related to endometrial receptivity were found to be regulated by progesterone. With regard to gene ontology and pathway analysis, progesterone was shown to be mainly involved in structure morphogenesis predominantly during a process of decidualization, extracellular matrix-receptor interaction and cell adhesion. Distinct differences were observed in the transcriptomic profiles between the two groups, indicating potential impairment of endometrial receptivity in women with suboptimal progesterone concentrations. There was a relatively similar pattern of gene expression between endometrial samples with progesterone concentrations approximately 10 ng/ml and >15 ng/ml. Thus, a progesterone concentration of between 10 and 15 ng/ml appears to be sufficient to induce endometrial receptivity. CONCLUSIONS: Abnormally low progesterone below the threshold of 10-15 ng/ml during the implantation window results in aberrant endometrial gene expression that may affect implantation potential.

Thyroid disorders in subfertility and early pregnancy.

Disorders of thyroid function are common in pregnancy and have implications for foetal and maternal health. Thyroid autoimmunity, as evidenced by the presence of elevated levels of anti-thyroid antibodies (anti-TPO and anti-Tg antibodies) is associated with an increased risk of miscarriage, though the mechanism remains poorly understood. There has been considerable focus on the implications and optimal management of pregnant women with thyroid disease, especially those undergoing assisted reproduction. Pregnancy results in significant changes in thyroid physiology and these need to be understood by clinicians involved in the care of pregnant women. Guidelines for the use of thyroxine and target thyroid function tests have been produced by international bodies but it is recognised that these predominantly reflect expert opinion rather than established evidence-based practice. Importantly a number of key clinical trials have been performed to aid understanding, particularly of the consequences of hypothyroidism for mother and baby, and the effectiveness of thyroid hormone use in autoimmune and subclinical hypothyroidism. This review summarises the current knowledge base and guidance for practice relating to thyroid disorders in pregnancy and subfertility.

Endometrial scratching for infertile women undergoing a first embryo transfer: a systematic review and meta-analysis of published and unpublished data from randomized controlled trials.

OBJECTIVE: To investigate endometrial scratch injury (ESI) as an intervention to improve IVF outcome in women undergoing a first ET. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women undergoing a first fresh/frozen embryo transfer. INTERVENTION(S): We included published and unpublished data from randomized controlled trials in which the intervention group received ESI and controls received placebo or no intervention. Pooled results were expressed as relative risk (RR) with 95% confidence interval (CI). The review protocol was registered in PROSPERO to start the data extraction (CRD42018087786). MAIN OUTCOME MEASURE(S): Ongoing pregnancy/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), miscarriage rate (MR), and ectopic pregnancy rate (EPR). RESULT(S): Seven studies were included (1,354 participants). We found a nonsignificant difference between groups in terms of OPR/LBR, CPR, MR, MPR, and EPR. Subgroup analysis found that ESI on the day of oocyte retrieval (achieved by a Novak curette) reduced OPR/LBR (RR 0.31, 95% CI 0.14-0.69) and CPR (RR 0.36, 95% CI 0.18-0.71), whereas ESI during the cycle preceding ET (performed through soft devices) had no effect on OPR/LBR and CPR. No difference in the impact of ESI was observed between fresh and frozen embryo transfer. CONCLUSION(S): Current evidence does not support performing ESI with the purpose of improving the success of a first ET attempt.

Efficacy of Dehydroepiandrosterone (DHEA) to overcome the effect of ovarian ageing (DITTO): A proof of principle double blinded randomized placebo controlled trial.

OBJECTIVE: To evaluate the effect of DHEA supplementation on In-Vitro Fertilisation (IVF) outcome as assessed by ovarian response, oocyte developmental competence and live birth rates in women predicted to have poor ovarian reserve (OR). The feasibility of conducting a large trial is also assessed by evaluating the recruitment rates and compliance of the recruited participants with DHEA/placebo intake and follow-up rates. STUDY DESIGN: A single centre, double blinded, placebo controlled, randomized trial was performed over two years with 60 women undergoing in-vitro fertilisation (IVF). Subjects were randomized, based on a computer-generated pseudo-random code to receive either DHEA or placebo with both capsules having similar colour, size and appearance. 60 women with poor OR based on antral follicle count or anti-Mullerian hormone thresholds undergoing IVF were recruited. They were randomised to receive DHEA 75mg/day or placebo for at-least 12 weeks before starting ovarian stimulation. They had long protocol using hMG 300 IU/day. Data analysed by "intention to treat". Ovarian response, live birth rates and molecular markers of oocyte quality were compared between the study and control groups. RESULTS: The recruitment rate was 39% (60/154). A total of 52 participants (27 versus 25 in the study and placebo groups) were included in the final analysis after excluding eight. While the mean (standard deviation) DHEA levels were similar at recruitment (9.4 (5) versus 7.5 (2.4) ng/ml; P=0.1), the DHEA levels at pre-stimulation were higher in the study group than in the controls (16.3 (5.8) versus 11.1 (4.5) ng/ml; P<0.01). The number (median, range) of oocytes retrieved (4, 0-18 versus 4, 0-15 respectively; P=0.54) and live birth rates (7/27, 26% versus 8/25, 32% respectively; RR (95% CI): 0.74 (0.22-2.48) and mRNA expression of developmental biomarkers in granulosa and cumulus cells were similar between the groups. CONCLUSION: Pre-treatment DHEA supplementation, albeit statistical power in this study is low, did not improve the response to controlled ovarian hyperstimulation or oocyte quality or live birth rates during IVF treatment with long protocol in women predicted to have poor OR.

Deregulation of the endometrial stromal cell secretome precedes embryo implantation failure.

STUDY QUESTION: Is implantation failure following ART associated with a perturbed decidual response in endometrial stromal cells (EnSCs)? SUMMARY ANSWER: Dynamic changes in the secretome of decidualizing EnSCs underpin the transition of a hostile to a supportive endometrial microenvironment for embryo implantation; perturbation in this transitional pathway prior to ART is associated with implantation failure. WHAT IS KNOWN ALREADY: Implantation is the rate-limiting step in ART, although the contribution of an aberrant endometrial microenvironment in IVF failure remains ill defined. STUDY DESIGN, SIZE, DURATION: In vitro characterization of the temporal changes in the decidual response of primary EnSCs isolated prior to a successful or failed ART cycle. An analysis of embryo responses to secreted cues from undifferentiated and decidualizing EnSCs was performed. The primary clinical outcome of the study was a positive urinary pregnancy test 14 days after embryo transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS: Primary EnSCs were isolated from endometrial biopsies obtained prior to IVF treatment and cryopreserved. EnSCs from 10 pregnant and 10 non-pregnant patients were then thawed, expanded in culture, subjected to clonogenic assays, and decidualized for either 2 or 8 days. Transcript levels of decidual marker gene [prolactin (PRL), insulin-like growth factor binding protein 1 (IGFBP1) and 11ß-hydroxysteroid dehydrogenase (HSD11B1)] were analysed using real-time quantitative PCR and temporal secretome changes of 45 cytokines, chemokines and growth factors were measured by multiplex suspension bead immunoassay. The impact of the EnSC secretome on human blastocyst development was scored morphologically; and embryo secretions in response to EnSC cues analyzed by multiplex suspension bead immunoassay. MAIN RESULTS AND THE ROLE OF CHANCE: Clonogenicity and induction of decidual marker genes were comparable between EnSC cultures from pregnant and non-pregnant group groups (P > 0.05). Analysis of 23 secreted factors revealed that successful implantation was associated with co-ordinated secretome changes in decidualizing EnSCs, which were most pronounced on Day 2 of differentiation: 17 differentially secreted proteins on Day 2 of decidualization relative to undifferentiated (Day 0) EnSCs (P < 0.05); 11 differentially secreted proteins on Day 8 relative to Day 2 (P < 0.05); and eight differentially secreted proteins on Day 8 relative to Day 0 (P < 0.05). By contrast, failed implantation was associated with a disordered secretome response. Blastocyst development was compromised when cultured for 24 h in medium conditioned by undifferentiated EnSCs when compared to decidualizing EnSCs. Analysis of the embryo microdroplets revealed that human blastocysts mount a secretory cytokine response to soluble decidual factors produced during the early (Day 2) but not late phase (Day 8) of differentiation. The embryo responses to secreted factors from decidualizing EnSCs were comparable between the pregnant and non-pregnant group (P > 0.05). LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Although this study uses primary EnSCs and human embryos, caution is warranted when extrapolating the results to the in vivo situation because of the correlative nature of the study and limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Our finding raises the prospect that endometrial analysis prior to ART could minimize the risk of treatment failure. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by funds from the Biomedical Research Unit in Reproductive Health, a joint initiative of the University Hospitals Coventry & Warwickshire NHS Trust and Warwick Medical School, the University of Nottingham and Nurture Fertility, and the National Medical Research Council, Singapore (NMRC/BNIG14NOV023), the "Instituut voor Innovatie door Wetenschap en Technologie" (IWT, Flanders, Belgium), the "Fonds voor Wetenschappelijk Onderzoek" (FWO, Flanders, Belgium) and the "Wetenschappelijk Fonds Willy Gepts" (WFWG, UZ Brussel). The authors have declared that no conflict of interest exists.

Endometrial spatio-temporal image correlation (STIC) and prediction of outcome following assisted reproductive treatment.

OBJECTIVE: The aim of this study was to correlate manual and spherical endometrial spatio-temporal image correlation (STIC) vascularity indices with assisted reproductive treatment (ART) outcomes. STUDY DESIGN: STIC ultrasound assessments of the endometrium were carried out at three time-points in 127 women in a prospective observational study. RESULTS: Biochemical pregnancy rate was 69% (88/127), with a biochemical and clinical pregnancy loss of 17%. Endometrial STIC vascularity indices in the assessed time-points did not differ between subjects who achieved a clinical pregnancy and those who did not (P>0.05). For first trimester miscarriage, minimal manual vascularization index (VI) at oocyte collection (cut-off value ≥0.7; sensitivity 80.0% and specificity 68.1%) demonstrated the highest area under the curve (AUC) of 0.8. CONCLUSION: In summary, STIC modality is not a useful tool to predict ART outcome, however manual STIC analysis of endometrial vascularity seems to be more accurate in predicting first trimester pregnancy loss.

4-D Assessment of Endometrial Vascularity Using Spatiotemporal Image Correlation: A Study Comparing Spherical Sampling and Whole-Tissue Analysis.

Our aim in the study described here was to assess the feasibility of spatiotemporal image correlation power Doppler quantification of the endometrium with two techniques: spherical samples and whole tissue. We scanned 51 women in the midluteal phase of the menstrual cycle: STIC assessment of the whole endometrium was not possible in 10% of cases, whereas spherical analysis was possible in all. The time taken for data set analysis was much longer for the whole endometrium compared with spherical analysis (1478.9 ± 291 s vs. 266.8 ± 39.3 s, p < 0.05). Intra-class correlation coefficients for the vascularization flow index (VFI) were similar for both methods. Volumetric vascularity indices were higher when spherical sampling was conducted. Significant cycle-to-cycle variability in the vascularity indices was present, with coefficients of variation exceeding 20% for both techniques. We found that STIC power Doppler quantification of the whole endometrium is possible in the majority of cases, however, it is time consuming and limited by significant cycle-to-cycle variability.

Surgical intervention versus expectant management for endometrial polyps in subfertile women.

BACKGROUND: Endometrial polyps, which are benign growths of the endometrium, may be a factor in female subfertility. Possible mechanisms include physical interference with gamete transport, alteration of the endometrial milieu and unresponsiveness to the cyclical global endometrial changes. As such polyps remain mostly asymptomatic, their diagnosis is often incidental during routine investigations prior to embarking on assisted reproductive treatment. Transvaginal sonography, hysterosalpingography and saline infusion sonography are the diagnostic tools most commonly employed. However, hysteroscopy remains the gold standard for diagnosis, as well as for treatment. Due to the possible effect of endometrial polyps on fertility, their removal prior to any subfertility treatment is widely practiced. OBJECTIVES: To determine the effectiveness and safety of removal of endometrial polyps in subfertile women. SEARCH METHODS: Electronic databases were searched, including the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL and trial registers. The reference lists of identified articles were checked. The last search was performed on 30 July 2014. SELECTION CRITERIA: Only randomised controlled trials, reporting pregnancy or live birth rates and complication rates as primary or secondary outcomes, in which polyps were removed surgically prior to treatment of subfertility were eligible for inclusion. The diagnosis of endometrial polyps was required to be made by transvaginal ultrasound, hysterosalpingography, saline infusion, sono-hysterography or hysteroscopy. Any surgical technique of polyp removal was acceptable, with no intervention in the control groups. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles, abstracts and full articles to assess their suitability for inclusion in this review. Quality assessment was attempted independently by two authors with discrepancies being settled by consensus or consultation with a third review author.No data extraction was performed due to the absence of useable data in the one eligible study. If there had been data to include, two review authors would have independently extracted the data from the studies using a data extraction form designed and pilot tested by the authors. Any disagreements would have been resolved by discussion or by a third review author. MAIN RESULTS: Only one randomised controlled trial of endometrial polypectomy was identified for inclusion. However, a single set of data could not be extracted from this study due to internal inconsistencies of the results reported. Attempts to contact the authors to resolve the issue were unsuccessful, by phone, post and e-mail. AUTHORS' CONCLUSIONS: Removal of endometrial polyps in subfertile women is commonly being performed in many countries with an aim to improve the reproductive outcome. We did not identify any analysable randomised trials which would allow us to reach any sound scientific conclusions on the efficacy of endometrial polypectomy in subfertile women. Well designed, methodologically sound, randomised controlled trials are urgently needed.

What exactly do we mean by 'recurrent implantation failure'? A systematic review and opinion.

Recurrent implantation failure (RIF) is an iatrogenic condition, being the result of repetitive unsuccessful cycles of IVF or intracytoplasmic sperm injection (ICSI) treatment. The aim of this review was to assess the definitions of RIF used in literature as well as suggest a uniform definition of this condition. A systematic search of MEDLINE, Embase and Cochrane Library was conducted. The most commonly stated definitions described RIF as 'three or more failed treatment cycles' or 'two or more failed cycles'. Other identified definitions were based solely on the number of embryos transferred in previous cycles or combined the number of previously failed cycles with the number of transferred embryos. Several other definitions were also identified. This review highlights the lack of uniformity of the definition of RIF. Based on the available literature and the expert opinion of the authors, RIF should be defined as the absence of implantation after two consecutive cycles of IVF, ICSI or frozen embryo replacement cycles where the cumulative number of transferred embryos was no less than four for cleavage-stage embryos and no less than two for blastocysts, with all embryos being of good quality and of appropriate developmental stage.

Do dopamine agonists prevent or reduce the severity of ovarian hyperstimulation syndrome in women undergoing assisted reproduction? A systematic review and meta-analysis.

Controlled ovarian stimulation is an integral part of assisted reproduction treatment. This can result in ovarian hyperstimulation syndrome (OHSS), which is associated with significant morbidity and potentially mortality. Recent approaches to ovarian stimulation have led to a reduction in the prevalence of OHSS but it still occurs. Dopamine agonists (DAs) have been used with some success during the ovarian stimulation phase when there are early signs of OHSS but there is no consensus on when to start and stop treatment or on the dose and specific agonist to use. EMBRASE, MEDLINE and Cochrane were searched using the following terms: ovarian hyperstimulation syndrome, controlled ovarian hyperstimulation, DAs, cabergoline, quinagolide, bromocriptide, pergolide, talipexole, ropinirole and pranipexole. The search yielded 20 publications. In total 1646 woman were included and 914 received a DA. In the treated group 86 (9.41%) developed OHSS, compared with 157 (21.45%) in the non-treated group. Nine studies were suitable for meta-analysis. This showed a benefit to the use of DAs (RR 0.51 [0.33, 0.78], Chi² = 16.07). The use of DAs appears to be effective for the prevention of OHSS. DAs are useful but less effective for the treatment of OHSS. No conclusions can be made regarding the most effective drug, the optimal dose or the most appropriate drug regimen.

Influence of gain adjustment on 3-dimensional power Doppler indices and on spatiotemporal image correlation volumetric pulsatility indices using a flow phantom.

Spatiotemporal image correlation can be used to acquire 3-dimensional power Doppler information across a single cardiac cycle. Assessment and comparison of the systolic and diastolic components of the data sets allow measurement of the recently introduced "volumetric pulsatility index" (vPI) through algorithms comparable with those used in 2-dimensional Doppler waveform analysis. The vPI could potentially overcome the dependency on certain machine settings, such as power, color gain, pulse repetition frequency, and attenuation, since these factors would affect the power Doppler signal equally throughout the cardiac cycle. The objective of this study was to compare the effect of color gain on the vascularization index (VI), vascularization-flow index (VFI), and vPI using an in vitro flow phantom model. We separated gains into 3 bands: -8 to -1 (no noise), -1 to +5 (low noise), and +5 to +8 (obvious noise). The vPI was determined from the 3-dimensional VI or VFI using the formula vPI = (maximum - minimum)/mean. Using no-noise gains, we observed that although the VI and VFI increased linearly with gain, the vPI was substantially less dependent on this adjustment. The VI and VFI continued to increase linearly with gain, whereas the vPI decreased slightly using low-noise gains. When gain was increased above the lower limit of obvious noise (+5), the VI and VFI increased noticeably, and there were marked reductions in both vPI values. We conclude that the vPI is less affected by changes in color gain than the VI and VFI at no-noise gains.

Primary amyloidosis presenting as cholestatic jaundice.

This case report describes a rare but fatal presentation of amyloidosis. Multiple organs and systems can be affected by the condition. Cholestatic jaundice is a infrequent manifestation of amyloidosis. An 80-year-old patient died within a month after onset of jaundice as a result of irreversible damage caused by deposition of amyloid. The relatively short period of time did not allow a tissue sample to be obtained from the patient and the final diagnosis was made postmortem.