Improved diagnostic performance for the diagnosis of polycystic ovary syndrome using age-stratified criteria.

OBJECTIVE: To determine optimal criteria for polycystic ovary morphology. DESIGN: Cross-sectional study. SETTING: Multidisciplinary polycystic ovary syndrome (PCOS) clinic at a tertiary academic center. PATIENT(S): Subjects with PCOS were seen between 2006 and 2015 and met PCOS 1992 National Institutes of Health criteria. Controls were from the Ovarian Aging (OVA) study (2006-2011), a longitudinal study including healthy women with regular menstrual cycles. INTERVENTION(S): Clinical data collection. MAIN OUTCOME MEASURE(S): Follicle number per ovary (FNPO) and ovarian volume (OV). RESULT(S): A total of 245 subjects with PCOS and 756 OVA study subjects were included in the FNPO analysis and had a mean (± SD) FNPO of 22.6 ± 12.4 and 10 ± 5.3, respectively. Receiver operating characteristic curves were created for both FNPO and OV and analyzed across age group categories (25 to <30, 30 to <35, and 35 to <40 years). Youden's and minimum distance (d) were used to compare efficacies of FNPO and OV thresholds. The optimal threshold for distinguishing PCOS from OVA controls was FNPO > 13. There was a decreasing trend in FNPO threshold with increasing age group (>15, >14, and >12, respectively). A total of 297 PCOS subjects and 756 OVA study subjects were included in the OV analysis and had a mean maximum OV of 10 ± 5 cm3 and 6.5 ± 5 cm3, respectively. The overall threshold was OV > 6.75 cm3, with a trend toward decreasing OV with increase in age group (>8.5, >7, and >6.25 cm3, respectively). CONCLUSION(S): Our findings reflect that age-stratified thresholds demonstrate superior diagnostic performance, with an improved balance of sensitivity and specificity compared with a single threshold. We propose age-specific thresholds for better diagnostic performance.

Differential rate in decline in ovarian reserve markers in women with polycystic ovary syndrome compared with control subjects: results of a longitudinal study.

OBJECTIVE: To estimate rates of ovarian aging in polycystic ovary syndrome (PCOS) subjects versus a community control population. DESIGN: Longitudinal. SETTING: Tertiary academic center. SUBJECT(S): PCOS subjects diagnosed according to the 2004 Rotterdam criteria were systematically enrolled in a PCOS cohort study. The comparison control subjects were from the Ovarian Aging study, a prospective longitudinal study of ovarian aging in healthy women with regular menstrual cycles. INTERVENTION(S): Clinical data collection over two study visits. MAIN OUTCOME MEASURE(S): Antral follicle count (AFC), ovarian volume (OV), and antimüllerian hormone level (AMH). RESULT(S): PCOS subjects were found to have higher baseline values for all ovarian reserve markers compared with control subjects. Univariate models indicated that, compared with control subjects, PCOS patients experienced significantly faster rates of decline for both AFC and AMH. Change in OV did not differ significantly. To account for potential confounder effects, multiple analysis of covariance models were evaluated for the best fit, considering age, body mass index, and baseline ovarian reserve markers. Adjusted models demonstrated that PCOS patients do not experience a significant difference in AFC decline compared with control subjects, but they do experience a faster rate of decline in AMH (P<.01) and slower rate of decline in OV (P<.01). CONCLUSION(S): Ovarian aging in PCOS is characterized by a more rapid decline in AMH and a slower decline in OV compared with control subjects.

Age-stratified thresholds of anti-Müllerian hormone improve prediction of polycystic ovary syndrome over a population-based threshold.

OBJECTIVE: Due to its consistent elevation in polycystic ovary syndrome (PCOS) and correlation with polycystic ovarian morphology (PCOM), anti-Mullerian hormone (AMH) has been proposed as a marker of the syndrome. However, prior studies reporting thresholds of AMH for a PCOS diagnosis have been limited by small sample size, inappropriate controls, and heterogeneous AMH assays. We sought to evaluate the suitability of a standardized AMH assay as a biomarker of PCOS. DESIGN: Cross-sectional study at academic medical centres across the United States. PATIENTS: Women with PCOS were diagnosed by Rotterdam criteria and included 282 subjects from the multisite PPCOS II trial and 109 patients from a tertiary academic centre's multidisciplinary PCOS clinic. Controls included 245 participants in the ovarian ageing (OVA) study, a community-based cohort of ovulatory women not seeking treatment for fertility. MEASUREMENTS: Determination of AMH by a central laboratory. Receiver-operating characteristic (ROC) analyses were used to investigate the accuracy of AMH thresholds for prediction of PCOS diagnosis with stratification by age. RESULTS: The optimal threshold of AMH to distinguish PCOS from controls was 55.36 pmol/L (sensitivity: 0.82, specificity: 0.78, J: 0.60). When examining the population by age groups, the optimal AMH threshold decreased with increasing age. CONCLUSIONS: AMH is an effective biomarker of PCOS. Age-stratified thresholds more accurately predicted PCOS than an overall population-based threshold.

Raising threshold for diagnosis of polycystic ovary syndrome excludes population of patients with metabolic risk.

OBJECTIVE: To characterize the population of patients excluded from a diagnosis of polycystic ovary syndrome (PCOS) when follicle number criteria are increased to 25 per ovary as suggested by the Androgen Excess and Polycystic Ovary Syndrome Society's recent task force. DESIGN: Cross-sectional study. SETTING: Tertiary academic center. PATIENT(S): A total of 259 women with PCOS according to Rotterdam criteria who were systematically examined from 2007 to 2015, with 1,100 ovulatory women participating in the Ovarian Aging (OVA) Study as controls. INTERVENTION(S): Anthropometric measurements, serum testing, ultrasonic imaging, and comprehensive dermatologic exams. MAIN OUTCOME MEASURE(S): Body mass index (BMI), waist to hip ratio (WHR), serum cholesterol, fasting glucose and insulin, follicle count per ovary, biochemical hyperandrogenemia, and hirsutism. RESULT(S): Forty-seven of 259 women meeting the Rotterdam criteria (18.1%) were excluded from a diagnosis of PCOS when the follicle number criteria was increased to 25. These women had clinical evidence of hyperandrogenism (68.1%) and biochemical hyperandrogenemia (44.7%), although fewer reported oligoanovulation (26.8%). The excluded women had elevated total cholesterol, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR) when compared with controls despite controlling for age and BMI. CONCLUSION(S): The women excluded from the PCOS diagnosis by raising the threshold of follicle number per ovary to ≥25 continue to show evidence of metabolic risk.

Institutional review of primary non-hodgkin lymphoma of the female genital tract: a 33-year experience.

OBJECTIVE: The aim of this is to provide an updated review of the literature and to report our institutional experience with this rare gynecologic malignancy. METHODS: The medical records of patients with diagnosis of non-Hodgkin lymphoma of the female genital tract from 1980 to 2013 at the Yale-New Haven Hospital were reviewed retrospectively. Histological classification and staging were determined by the World Health Organization and Ann Arbor systems, respectively. Kaplan-Meier was used to calculate the survival. RESULTS: There were 36 patients with diagnosis of non-Hodgkin lymphoma of the female genital tract and followed for a median of 61 months (0-361 months). The median age of diagnosis was 44 years (19-87 years), and 76% (n = 28) were classified as stage IV.Of these, 4 patients were asymptomatic on presentation, and 13 were identified incidentally during surgery/radiography (n = 9), on prenatal ultrasound (n = 1), and on Papanicolaou test (n = 3). The location of the disease included the ovary (n = 6), uterine corpus and cervix (n= 9), vagina (n = 1), a pelvic mass (n = 7), isolated pelvic/para-aortic lymph nodes (n = 3), and/or multiple sites (n = 9). There were 6 cases that were concomitant with other gynecologic malignancies.Diffuse large B-cell lymphoma (n= 18) was the most common histologic type. A total of 28 patients underwent surgery. Combination chemotherapy was used in 34 patients, with concomitant radiation therapy in 7 and stem cell transplantation in 3. A total of 5 patients had recurrent disease.The overall median survival from the diagnosis of lymphoma was 70 months (0.3-361 months) with a 91% 1-year survival, 86% 5-year survival, and a 79% 10-year survival. CONCLUSIONS: Our report is the largest published single-institution experience of this disease. It demonstrates a more favorable prognosis and proposes that with early diagnosis and appropriate therapy, radical gynecologic surgery can be avoided.

Cystic fibrosis and fertility.

PURPOSE OF REVIEW: As the life expectancy of cystic fibrosis (CF) patients continues to increase, and more patients become adults with a chronic disease, researching the impact of the disorder on male and female infertility has become increasingly important. Studies suggest that the prevalence of CF mutations may be higher than previously thought and that many mutations are yet to be identified. RECENT FINDINGS: Assisted reproductive technologies can help both infertile male and female patients with CF in achieving successful parenthood. In addition, for women more health characteristics including baseline pulmonary function have been evaluated as predictors of health and pregnancy outcomes. SUMMARY: Mutations in the CF Transmembrane Conductance Regulator (CFTR) gene affect both male and female fertility; however, not all CFTR mutations appear to cause infertility. Although most men with CF have significant anatomical abnormalities of the reproductive tract causing infertility, most women with CF have anatomically normal reproductive tracts and up to half may be able to conceive spontaneously. Less is known about how CF affects female fertility or the treatment options available.

Tracking maternal mortality declines in Mongolia between 1992 and 2007: the importance of collaboration.

OBJECTIVE: To describe the declining trend in maternal mortality observed in Mongolia from 1992 to 2007 and its acceleration after 2001 following implementation of the Maternal Mortality Reduction Strategy by the Ministry of Health and other partners. METHODS: We performed a descriptive analysis of maternal mortality data collected through Mongolia's vital registration system and provided by the Mongolian Ministry of Health. The observed declining mortality trend was analysed for statistical significance using simple linear regression. We present the maternal mortality ratios from 1992 to 2007 by year and review the basic components of Mongolia's Maternal Mortality Reduction Strategy for 2001-2004 and 2005-2010. FINDINGS: Mongolia achieved a statistically significant annual decrease in its maternal mortality ratio of almost 10 deaths per 100 000 live births over the period 1992-2007. From 2001 to 2007, the maternal mortality ratio in Mongolia decreased approximately 47%, from 169 to 89.6 deaths per 100 000 live births. CONCLUSION: Disparities in maternal mortality represent one of the major persisting health inequities between low- and high-resource countries. Nonetheless, important reductions in low-resource settings are possible through collaborative strategies based on a horizontal approach and the coordinated involvement of key partners, including health ministries, national and international agencies and donors, health-care professionals, the media, nongovernmental organizations and the general public.

A prospective observational study of human factors, adverse events, and patient outcomes in surgery for pediatric cardiac disease.

OBJECTIVE: To explore the impact of human factors on intraoperative adverse events and compensation mechanisms in pediatric cardiac surgery. METHODS: Prospective observations of pediatric cardiac surgical procedures were conducted. Patient complexity scores were calculated and outcomes recorded. The process of care was divided into epochs. Events were extracted and coded into compensated or uncompensated major and minor adverse events. Linear regression and analysis of variance were used to analyze the relationships between epochs, complexity, adverse events, and outcome. Patient-specific and procedure-specific variables were tested in a forward stepwise logistic regression as predictors of cases with 1 or more major adverse events. RESULTS: One hundred two patients undergoing pediatric cardiac surgery were observed. An average of 1.2 (range 0-6) major adverse events occurred per case. The most common type of major adverse event was cardiovascular, and most occurred during the surgery/postbypass epoch. Cognitive compensation was the most common compensation mechanism for major adverse events. An average of 15.3 minor adverse events occurred per case. Minor adverse events occurred frequently during the surgery/bypass epoch and related to communication and coordination failures. Higher case complexity, longer surgery duration, and higher number of major adverse events per patient correlated with death compared with other outcome groups (P < .01). Case complexity (P < .01) and surgery duration (P < .05) were both significant predictors of major adverse events. CONCLUSIONS: Pediatric cardiac surgery is an ideal model to study the coordinated efforts of team members in a complex organizational structure. Adverse events occurred routinely during pediatric cardiac surgery and were mostly compensated. Case complexity was a significant predictor of major adverse events. The number of major adverse events per patient correlated with clinical outcomes.