https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)66736-0.pdf

Congenital adrenal hyperplasia

Obesity, particularly the abdominal phenotype, is associated with several reproductive disturbances. Whereas mechanisms by which obesity affect fertility are complex and still not completely understood, an important role appears to be played by the presence of a condition of functional hyperandrogenism and hyperinsulinaemia, which accompanies the insulin-resistant state. In women with the polycystic ovary syndrome, abdominal obesity may be co-responsible for the development of hyperandrogenism and associated chronic anovulation, through mechanisms primarily involving the insulin-mediated overstimulation of ovarian steroidogenesis and decreased sex hormone-binding globulin blood concentrations. By these mechanisms, obesity may also favour resistance to clomiphene and gonadotrophin-induced ovulation and reduce outcomes of IVF/ICSI procedures. Due to the beneficial effects of weight loss, lifestyle intervention programmes should represent the first-line approach in the treatment of infertile obese women. Insulin-sensitizing agents may add further benefits, particularly if administered in combination with hypocaloric dieting. Therefore, individualized pharmacological support aimed at favouring weight loss and improving insulin resistance should be widely extended in clinical practice in obese infertile patients. This may be beneficial even during pregnancy, thereby permitting favourable physiological delivery and healthy babies.

Obesity and reproductive disorders in women

SeminarCongenital adrenal hyperplasia

Goal: We hypothesized that COVID-19 subjects, especially including asymptomatics, could be accurately discriminated only from a forced-cough cell phone recording using Artificial Intelligence. To train our MIT Open Voice model we built a data collection pipeline of COVID-19 cough recordings through our website (opensigma.mit.edu) between April and May 2020 and created the largest audio COVID-19 cough balanced dataset reported to date with 5,320 subjects. Methods: We developed an AI speech processing framework that leverages acoustic biomarker feature extractors to pre-screen for COVID-19 from cough recordings, and provide a personalized patient saliency map to longitudinally monitor patients in real-time, non-invasively, and at essentially zero variable cost. Cough recordings are transformed with Mel Frequency Cepstral Coefficient and inputted into a Convolutional Neural Network (CNN) based architecture made up of one Poisson biomarker layer and 3 pre-trained ResNet50's in parallel, outputting a binary pre-screening diagnostic. Our CNN-based models have been trained on 4256 subjects and tested on the remaining 1064 subjects of our dataset. Transfer learning was used to learn biomarker features on larger datasets, previously successfully tested in our Lab on Alzheimer's, which significantly improves the COVID-19 discrimination accuracy of our architecture. Results: When validated with subjects diagnosed using an official test, the model achieves COVID-19 sensitivity of 98.5% with a specificity of 94.2% (AUC: 0.97). For asymptomatic subjects it achieves sensitivity of 100% with a specificity of 83.2% . Conclusions: AI techniques can produce a free, non-invasive, real-time, any-time, instantly distributable, large-scale COVID-19 asymptomatic screening tool to augment current approaches in containing the spread of COVID-19. Practical use cases could be for daily screening of students, workers, and public as schools, jobs, and transport reopen, or for pool testing to quickly alert of outbreaks in groups. General speech biomarkers may exist that cover several disease categories, as we demonstrated using the same ones for COVID-19 and Alzheimer's.

/pdf/covid-19-artificial-intelligence-diagnosis-using-only-cough-4487y32et6.pdf

COVID-19 Artificial Intelligence Diagnosis Using Only Cough Recordings

Women with oligomenorrhea and polycystic ovaries show a high incidence of ovulation failure perhaps linked to insulin resistance and related metabolic features. A number of reports show that the biguanide metformin improves ovarian function. However, in these trials the quality of evidence supporting ovulation is suboptimal, and few studies have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 94 patients randomized, 2 withdrew before treatment commenced, 47 received placebo, and 45 received metformin (850 mg, twice a day). The numbers discontinuing the study prematurely were higher in the treatment group (n = 15) than the placebo group (n = 5; P 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded after 14-wk metformin or placebo therapy. There was an inverse relationship between body mass and treatment efficacy. We show in a large randomized placebo-controlled trial that metformin treatment improves ovulation frequency in women with abnormal ovarian function and polycystic ovaries significantly but to a modest degree, and protracted treatment improves cardiovascular risk factors. These data support a beneficial effect of metformin in improving ovarian function in women with oligomenorrhea and polycystic ovaries.

/pdf/ovarian-function-and-metabolic-factors-in-women-with-3poox60rj8.pdf

Ovarian Function and Metabolic Factors in Women with Oligomenorrhea Treated with Metformin in a Randomized Double Blind Placebo-Controlled Trial

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and a population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. The present review discusses the current literature on these modalities, including nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory-based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers, and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.

Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays.

Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome.

It has recently been proposed that hyperinsulinaemic insulin resistance and increased ovarian cytochrome P-450c17alpha activity, two features of the polycystic ovary syndrome (PCOS), are pathogenetically linked. The aim of the present study was to test the hypothesis of the linkage between hyperinsulinaemia and supranormal activity of cytochrome P-450c17alpha using the human chorionic gonadotrophin (HCG) challenge, which is a more direct ovarian stimulus than gonadotrophin-releasing hormone (GnRH) in detecting modifications in ovarian steroidogenesis. Eleven women with insulin resistance-related PCOS were studied. HCG (10 000 IU) was given i.m., and blood samples were obtained 0, 8, 12, 16 and 24 h thereafter. Next day, metformin was given at a dose of 500 mg three times a day for 30-32 days, at which time the pretreatment study was repeated. Two women ovulated after metformin treatment. The administration of metformin was associated with a decrease in area under the curve for insulin during a 2h, 75g oral glucose tolerance test, in plasma free testosterone concentrations and an increase in plasma sex hormone binding globulin concentration. The plasma 17-hydroxyprogesterone response to HCG was significantly lower after metformin treatment. The present study gives a direct demonstration that metformin leads to a reduction in stimulated ovarian cytochrome P-450c17alpha activity in women with polycystic ovary syndrome.

Metformin treatment reduces ovarian cytochrome P-450c17α response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome

Erratum: Metformin treatment reduces ovarian cytochrome P-450c17α response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome (Hum. Reprod. (2000) 15 (21-23))

Tiziana Paglia

Papers

Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays.

Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome.

Metformin treatment reduces ovarian cytochrome P-450c17α response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome

Erratum: Metformin treatment reduces ovarian cytochrome P-450c17α response to human chorionic gonadotrophin in women with insulin resistance-related polycystic ovary syndrome (Hum. Reprod. (2000) 15 (21-23))