An intrauterine genomic classifier reliably delineates the location of nonviable pregnancies.

OBJECTIVE: To compare the intrauterine gene expression signatures of women with surgically confirmed ectopic pregnancy (ECT) and those of women with miscarriage to inform the development of a genomic classifier for the reliable delineation of pregnancy location in women with clinically nonviable pregnancies of unknown location (NV-PULs). DESIGN: Discovery-based prospective cohort study. SETTING: Academic medical center. PATIENT(S): Women with clinically nonviable early pregnancy to include abnormal intrauterine pregnancy (AIUP), ECT, or NV-PUL. INTERVENTION(S): Endometrial (EM) pipelle sampling of the uterus was conducted at the time of scheduled surgery for clinically nonviable early pregnancy (dilation and curettage, manual vacuum aspiration, or laparoscopy). All pregnancy locations were surgically and/or histologically confirmed as intrauterine or ectopic. MAIN OUTCOME MEASURE(S): Gene expression profiles as determined by array hybridization, quantitative real-time polymerase chain reaction, and nCounter technology. RESULT(S): Intrauterine samples were obtained by EM pipelle from 27 women undergoing surgery for a clinically nonviable early pregnancy. Comparison of array-based global gene expression signatures from women with histologically confirmed ECT versus AIUP revealed 61 differentially expressed genes from which the 5 most informative were included in the pregnancy location classifier. All 5 genes (C20orf85, LRRC46, RSPH4A, WDR49, and ZBBX) were cilia-associated and showed increased expression in pipelle samples from women with ECT relative to expression in samples from women with AIUP. The 5-gene classifier demonstrated an average area under the receiver operator characteristic curve of 0.97 for the detection of ECT. In an external test set composed of publicly available EM pipelle-based gene expression data from a study with similar ECT and AIUP cohorts (n = 19), the classifier revealed an average area under the receiver operator characteristic curve of 0.84. CONCLUSION(S): Consistently increased expression of cilia-associated genes in the uterine cavity of women with ECT provides a reliable molecular signal for the delineation of pregnancy location in women with clinically assessed NV-PUL. A classifier consisting of the 5 most informative cilia-associated genes demonstrated 91% (42/46) accuracy in predicting the pregnancy location.

Polycystic Ovarian Syndrome and Fertility.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that has been associated with impaired fertility. This chapter reviews the underlying pathophysiology of PCOS and the associated fertility barriers of the condition. Psychologic concerns, hypothalamic-pituitary, ovarian, and mitochondria dysfunction, obesity, and the role of vitamin D in PCOS are considered with respect to fertility. Lastly, pregnancy risk factors associated with PCOS are also reviewed.

Clinical Presentation and Diagnosis of Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy with many clinical manifestations. The effects on women's lives start at puberty and can last throughout her lifetime. Women frequently experience anovulatory menstrual cycles, infertility, hirsutism, obesity and increased risk of diabetes mellitus, hypertension, lipid abnormalities, and metabolic syndrome. PCOS is a heterogenous disorder, and a diagnosis of exclusion. In general, women afflicted will have menstrual irregularities, ultrasound findings of abnormal ovarian size and morphology, and clinical or laboratory evidence of hyperandrogenism. This chapter reviews the current understanding of PCOS, associated metabolic abnormalities, and diagnosis in reproductive-aged women, as well as adolescents.

Polycystic Ovary Syndrome and Medical Conditions.

Polycystic ovary syndrome is a common endocrinopathy that has been associated with many medical conditions across nearly every specialty. This chapter reviews the current understanding of polycystic ovary syndrome and associated medical conditions.

Postdeployment Fertility Challenges and Treatment in the Modern Era.

Current war-fighting environments have shifted dramatically over the past decade, and with this change, new types of injuries are afflicting American soldiers. Operative Enduring Freedom and Operation Iraqi Freedom have noted an increased use of sophisticated improvised explosive devices by adversaries. Injuries not frequently seen in previous conflict are dismounted complex blast injuries, which involve multiple proximal amputations, pelvic fractures, and extensive perineal wounds. Thus, an unforeseen consequence of the decreased mortality rate after these complex blast injuries is a new wave of U.S. service members facing the challenges of recovering from the catastrophic amputations and genitourinary injuries. New applications of sperm retrieval methods may be used in these specific populations, as they recover and wish to purse family-building goals. Spinal cord injuries, traumatic brain injuries, and considerations unique to the female soldier are explored in this review of urologic care in wounded veterans.

Appraising Medical Literature: The Effect of a Structured Journal Club Curriculum Using The Lancet Handbook of Essential Concepts in Clinical Research on Resident Self-Assessment and Knowledge in Milestone-Based Competencies.

BACKGROUND: Training in literature appraisal and statistical interpretation is one of the residency training requirements outlined by the Accreditation Council for Graduate Medical Education. Frequently, a journal club format is used to teach this competency although this teaching modality is not standardized or well studied in regard to its efficacy. METHODS: This study sought to determine the effect of a structured journal club curriculum that incorporated The Lancet Handbook of Essential Concepts in Clinical Research on objective and self-assessed knowledge pertaining to study design and interpretation. The study was a retrospective observational study evaluating the effect of a structured journal club curriculum using the Lancet text with pre- and postimplementation assessment using a resident self-assessment survey. The study examined a monthly journal club curriculum that covered 1 topic/chapter from the assigned text, paired with a contemporary article to highlight the chapter topic. Resident self-assessed and objective knowledge was evaluated and compared using a survey taken before and after the curriculum change. The study was completed during 1 academic year at Madigan Army Medical Center in Tacoma, Washington, an academic military medical training and tertiary care center. Study surveys were distributed to all 17 obstetrics and gynecology residents throughout the 4 residency training years. Of the 17 potential participants, 13 (76%) participated in the precurriculum assessment and 14 (82%) participated after its completion. FINDINGS: There was no significant improvement in resident self-assessed knowledge following curriculum implementation. There was a trend toward improved objective knowledge pertaining to study design and interpretation after curriculum completion, but this was not statistically significant. DISCUSSION: There is a lack of standardized and well-studied methods to teach residents how to evaluate and appraise medical literature and research. The Lancet Handbook of Essential Concepts in Clinical Research may be a useful tool to teach some of these tenets in the residency training environment, but this limited study did not prove this assertion. IMPACT: Three is a dearth of proven and well-studied means to teach the tenets of study design, statistical interpretation, and critical literature appraisal to trainees with any consistency or validity. This study demonstrated a trend toward better objective knowledge related to study design, interpretation, and understanding after a change in our training curriculum that implemented The Lancet Handbook of Essential Concepts in Clinical Research into the monthly journal club curriculum. Resident self-rated knowledge and proficiency in their abilities to understand research and study design were not significantly changed with the curriculum. RECOMMENDATIONS: Better evidence is needed to guide future educational curricula directed toward teaching the competency of medical literature review and appraisal.