Molecular diagnosis of polycystic ovary syndrome in obese and non-obese women by targeted plasma miRNA profiling.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is diagnosed based on the clinical signs, but its presentation is heterogeneous and potentially confounded by concurrent conditions, such as obesity and insulin resistance. miRNA have recently emerged as putative pathophysiological and diagnostic factors in PCOS. However, no reliable miRNA-based method for molecular diagnosis of PCOS has been reported. The aim of this study was to develop a tool for accurate diagnosis of PCOS by targeted miRNA profiling of plasma samples, defined on the basis of unbiased biomarker-finding analyses and biostatistical tools. METHODS: A case-control PCOS cohort was cross-sectionally studied, including 170 women classified into four groups: non-PCOS/lean, non-PCOS/obese, PCOS/lean, and PCOS/obese women. High-throughput miRNA analyses were performed in plasma, using NanoString technology and a 800 human miRNA panel, followed by targeted quantitative real-timePCR validation. Statistics were applied to define optimal normalization methods, identify deregulated biomarker miRNAs, and build classification algorithms, considering PCOS and obesity as major categories. RESULTS: The geometric mean of circulating hsa-miR-103a-3p, hsa-miR-125a-5p, and hsa-miR-1976, selected among 125 unchanged miRNAs, was defined as optimal reference for internal normalization (named mR3-method). Ten miRNAs were identified and validated after mR3-normalization as differentially expressed across the groups. Multinomial least absolute shrinkage and selection operator regression and decision-tree models were built to reliably discriminate PCOS vs non-PCOS, either in obese or non-obese women, using subsets of these miRNAs as performers. CONCLUSIONS: We define herein a robust method for molecular classification of PCOS based on unbiased identification of miRNA biomarkers and decision-tree protocols. This method allows not only reliable diagnosis of non-obese women with PCOS but also discrimination between PCOS and obesity. CAPSULE: We define a novel protocol, based on plasma miRNA profiling, for molecular diagnosis of PCOS. This tool not only allows proper discrimination of the condition in non-obese women but also permits distinction between PCOS and obesity, which often display overlapping clinical presentations.

Satisfaction and tolerance with office hysteroscopic tubal sterilization.

OBJECTIVE: To evaluate women's satisfaction and tolerance of hysteroscopic sterilization. DESIGN: Prospective analysis of case series. SETTING: Gynecology department in a teaching hospital. PATIENT(S): A total of 1,630 women who underwent hysteroscopic sterilization by placement of Essure microinserts (Conceptus, Inc., Mountain View, CA) from January 2003 to June 2006. INTERVENTION(S): Transvaginal ultrasound examination, pelvic x-ray examination, and hysterosalpingography 3 months after sterilization with Essure microinserts. Satisfaction was assessed by a visual analog scale. Adverse effects and tolerance also were recorded. MAIN OUTCOME MEASURE(S): Transvaginal ultrasound and pelvic x-ray confirmation of correct localization of microinserts and patient's satisfaction and tolerance after a 3-month follow-up. RESULT(S): The rate of successful insertion was 99%. Most of women returned to their daily activities on the same day of insertion, and 86.5% considered the procedure painless or scarcely painful. All the patients were highly satisfied after hysteroscopic sterilization: 91% of subjects by visual analog scale (on a 0 to 10 scale) rated the method at 10 (high satisfaction degree), and none of the subjects rated it under 8. For patients, the most valuable aspects of the procedure were absence of surgery room (52.7%), method's quickness and comfort (19.9%), and permanent sterilization (18.2%). More than 97% of the patients said that they would recommend the procedure to others. CONCLUSION(S): This study provides evidence that Essure microinserts can be placed in a usual gynecologic consultation room in standard conditions without any type of anesthesia or sedation and are associated with great overall patient satisfaction. Women also have high tolerance for the procedure and describe minor postoperative pain.