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Context.--Detecting copy number variations (CNVs) at certain loci can aid in the diagnosis of histologically ambiguous melanocytic neoplasms. Droplet digital polymerase chain reaction (ddPCR) is a rapid, automated, and inexpensive method for CNV detection in other cancers, but not yet melanoma. Objective.--To evaluate the performance of a 4-gene ddPCR panel that simultaneously tests for ras responsive binding element protein 1 (RREB1) gain; cyclin-dependent kinase inhibitor 2A (CDKN2A) loss; MYC proto-oncogene, bHLH transcription factor (MYC) gain; and MYB protooncogene, transcription factor (MYB) loss in melanocytic neoplasms. Design.--One hundred sixty-four formalin-fixed, paraffin-embedded skin samples were used to develop the assay, of which 65 were used to evaluate its performance. Chromosomal microarray analysis (CMA) data were used as the gold standard. Results.--ddPCR demonstrated high concordance with CMA in detecting RREB1 gain (sensitivity, 86.7%; specificity, 88.9%), CDKN2A loss (sensitivity, 80%; specificity, 100%), MYC gain (sensitivity, 70%; specificity, 100%), and MYB loss (sensitivity, 71.4%; specificity, 100%). When one CNV was required to designate the test as positive, the 4-gene ddPCR panel distinguished nevi from melanomas with a sensitivity of 78.4% and a specificity of 71.4%. For reference, CMA had a sensitivity of 86.2% and a specificity of 78.6%. Our data also revealed interesting relationships with histology, namely (1) a positive correlation between RREB1 ddPCR copy number and degree of tumor progression; (2) a statistically significant correlation between MYC gain and nodular growth; and (3) a statistically significant correlation between MYB loss and a sheetlike pattern of growth. Conclusions.--With further validation, ddPCR may aid both in our understanding of melanomagenesis and in the diagnosis of challenging melanocytic neoplasms. doi: 10.5858/arpa.2024-0027OA, Melanoma is an aggressive malignancy with a high rate of metastasis. It is the most common cause of death from skin cancer. (1,2) Early diagnosis and resection is often associated [...]

The entity commonly referred to as chondrolipoma is a rare and enigmatic breast lesion with unclear histogenesis and a complete lack of molecular characterization. It is uncertain whether it represents a hamartoma, choristoma, or a distinct neoplasm, including possibly a variant of mammary-type myofibroblastoma. We report two additional chondrolipomatous lesions of the breast. The lesions had varying histologic and immunohistochemical features similar to myofibroblastoma, including the loss of retinoblastoma (Rb) protein expression in one lesion. Molecular analysis by chromosomal microarray analysis performed on a second lesion did not demonstrate a loss of 13q14 or 16q typical of myofibroblastoma. Our findings further support the concept that at least a subset of breast lesions that historically have been classified as chondrolipoma are related to myofibroblastoma. However, the lack of myofibroblastoma-specific molecular alterations in one lesion suggests chondrolipomas may also have varying origins. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 46-year-old woman who presented with left retro-orbital headaches and other symptoms. Magnetic resonance imaging (MRI) revealed a 2.7 cm pituitary mass. Intraoperative and histological examinations showed a poorly differentiated neoplasm with high mitotic counts and loss of nuclear SMARCB1/INI1 staining. Chromosomal microarray analysis and next-generation sequencing detected copy neutral loss of heterozygosity (cnLOH) in chromosome 22 and a frameshift deletion in the SMARCB1 gene. The tumor was classified as an adult sellar atypical teratoid/rhabdoid tumor (AT/RT) and was found to be of the MYC subtype. The article emphasizes the rarity of adult sellar AT/RT and the importance of accurate diagnosis through molecular and cytogenetic analysis. [Extracted from the article]

Objective: To develop and test a nonidentifying prospective data collection system for cross-border reproductive care (CBRC) in Canada and the United States (U.S.).Design: Survey and cross-sectional study.Setting: Fertility clinics.Patient(s): Women traveling to and from Canada and the U.S. for reproductive care.Intervention(s): None.Main Outcome Measure(s): Patients' home country, reason for crossing borders, and type of care received.Result(s): Of 32 Canadian and 440 U.S. clinics contacted, seven and 46, respectively, responded to the initial questionnaire. Three out of seven Canadian and 44 out of 46 U.S. clinics reported providing CBRC. Seventy five percent agreed that nonidentifying data on country of origin and reason for travel should be collected. However, only one of seven Canadian and none of 46 U.S. clinics that expressed initial interest actually collected data, despite multiple communications.Conclusion(s): Although CBRC is a major component of assisted reproductive technology in North America (3%-10% of IVF cycles are provided to out-of-country patients in Canada and the U.S.), clinicians are not motivated to collect the simplest of data regarding CBRC patients. Despite this, reliable data are needed to help better understand the reasons for and impact of CBRC. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness of education provided by health care professionals during and after IVF treatment in preparing couples for surplus embryo disposition decisions.Design: Cross-sectional survey.Setting: University-affiliated fertility center.Patient(s): Couples with embryos cryopreserved for more than 2 years.Intervention(s): Self-administered questionnaire.Main Outcome Measure(s): A Likert scale was used to rate the response to questions about patients' preparedness to make decisions regarding their surplus embryos.Result(s): The survey response rate was 70% (131 of 187). Education provided by health care professionals before initiating treatment met the needs of the majority of participants (n = 86). After treatment, the education received was not adequate to assist couples in making embryo disposition decisions. Of the 127 respondents who provided feedback on their intention for their cryopreserved embryos, 37% (n = 47) had no intention of using cryopreserved embryos for their own reproduction, 24% (n = 30) intended to use embryos for procreation, and the remaining 39% (n = 50) remained undecided regarding their future use of their embryos. Participants with more than 3 years of infertility (n = 49) were most likely to feel conflicted about the decision after treatment.Conclusion(s): The education received after treatment was considered inadequate. Couples with a long duration of infertility and those conflicted about final embryo disposition may be appropriate targets for further intervention. More written information and/or counseling services after treatment may help patients make informed and timely decisions regarding their surplus embryos. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management. Outcomes: These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes. Evidence: Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words “ovarian hyperstimulation syndrome” and “gonadotropins,” and guidelines created by other professional societies were reviewed. Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). [Copyright &y& Elsevier]

Objective: To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management.Outcomes: These guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes.Evidence: Medline, Embase, and the Cochrane database were searched for relevant articles, using the key words "ovarian hyperstimulation syndrome" and "gonadotropins," and guidelines created by other professional societies were reviewed.Values: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are central to the understanding of treatment effectiveness and diagnostic test utility. If they are to be relied upon in clinical practice, data from trials should have three main attributes: validity (be free from bias); clinical relevance (be based on patients similar to your own, reporting outcomes that matter to them); and importance (demonstrate effect sizes that are large enough to justify the costs and risks entailed). With these principles in mind, this brief article reviews key questions to pose while deciding whether new evidence from RCTs should influence subfertility patient care. [ABSTRACT FROM AUTHOR]

Improvements in oocyte culture technique, sperm preparation, oocyte retrieval method and ovarian stimulation regimens have produced higher pregnancy rates with in-vitro fertilization (IVF) treatment. However, because ovarian stimulation is expensive and not without risk, there is increasing interest in the option of using natural cycles for IVF. This study was performed to document the experience and outcome in 240 natural cycles. Cancellation occurred in 28 cycles (12%), and LH surge was observed in 56 (23%), leaving 156 (65%) cycles which progressed to oocyte retrieval. No oocytes were retrieved in 26 cycles. Among the successful oocyte retrievals, the majority yielded one oocyte. There was no evidence of fertilization in 26 cases, and triploid fertilization was observed in 12 cases. Embryos suitable for transfer were available in 92 cycles in which 11 (12%) clinical pregnancies were confirmed. Despite the high failure rate at each step in the process, natural cycles are more cost-effective than stimulated cycles which incur an incremental cost per live birth of $48 000. Natural cycles offer a low-cost alternative that may be more accessible to patients. [ABSTRACT FROM PUBLISHER]

The adverse effect of raised luteinizing hormone (LH) concentrations on reproductive outcome suggests that exogenous LH administration for ovarian stimulation may not be desirable. The aim of this study was to compare the clinical pregnancy rates between follicle stimulating hormone (FSH) and human menopausal gonadotrophin (HMG) used in in-vitro fertilization (IVF) cycles. A total of 232 infertile patients, with a mean duration of infertility of 67.1 +/- 32.9 months, were selected for IVF (female age < 38 years, FSH < 15 IU/l, and total motile sperm count > 5 x 10(6)). A short (flare-up) protocol with daily leuprolide acetate was followed randomly from day 3 with FSH (n = 115) or human menopausal gonadotrophin (HMG; n = 117), at an initial dose of two ampoules per day. A maximum of three embryos was transferred, and the luteal phase was supported with four doses of HCG (2500 IU). No differences were observed between the two groups in any of the cycle response variables except fertilization rates per oocyte and per patient, both of which were significantly higher with FSH. Clinical pregnancy rates per cycle initiated, per oocyte retrieval and per embryo transfer were 19.1, 21.0 and 22.7% respectively for FSH, and 12.0, 12.8 and 15.4% respectively for HMG. Whilst these differences were not statistically significant, the results of this interim analysis suggest that HMG may be associated with a lower clinical pregnancy rate than FSH. [ABSTRACT FROM AUTHOR]

Helping couples to choose appropriate therapy for their unexplained subfertility demands a review of evidence for treatment benefit and harm, in the context of both patients' and clinicians' experience and perspective. Ovulation induction (OI) with clomiphene (CC) or gonadotrophin (FSH) and intrauterine insemination (IUI) are often chosen before resorting to IVF. The appropriateness of starting with these low and intermediate intensity treatments is supported by evidence that CC/IUI increases cycle fecundity two- to three-fold, and FSH/IUI, three- to five-fold over the baseline chance of pregnancy in this patient group. While both OI/IUI and IVF have adverse effects which deserve vigorous attention, particularly multiple pregnancy and ovarian hyperstimulation syndrome (OHSS), the balance between benefits and costs often favours OI/IUI. The cost per live birth and potential for OHSS appears lower with OI/IUI, and the proportion of multiple pregnancies similar to that seen with IVF. For these as well as physical and spiritual reasons, OI/IUI is often a natural starting point for couples, especially when female age and duration of subfertility are favourable. [ABSTRACT FROM AUTHOR]

The mechanisms by which the Wingless (Wg) morphogen modulates the activity of the transcriptional activator Armadillo (Arm) to elicit precise, concentration-dependent cellular responses remain uncertain. Arm is targeted for proteolysis by the Axin/Adenomatous polyposis coli (Apc1 and Apc2)/Zeste-white 3 destruction complex, and Wg-dependent inactivation of destruction complex activity is crucial to trigger Arm signaling. In the prevailing model for Wg transduction, only Axin levels limit destruction complex activity, whereas Apc is present in vast excess. To test this model, we reduced Apc activity to different degrees, and analyzed the effects on three concentration-dependent responses to Arm signaling that specify distinct retinal photoreceptor fates. We find that both Apc1 and Apc2 negatively regulate Arm activity in photoreceptors, but that the relative contribution of Apc1 is much greater than that of Apc2. Unexpectedly, a less than twofold reduction in total Apc activity, achieved by loss of Apc2, decreases the effective threshold at which Wg elicits a cellular response, thereby resulting in ectopic responses that are spatially restricted to regions with low Wg concentration. We conclude that Apc activity is not present in vast excess, but instead is near the minimal level required for accurate graded responses to the Wg morphogen. [ABSTRACT FROM AUTHOR]