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Premature ovarian insufficiency is a complex condition with a heterogenous aetiology, and is defined as loss of ovarian function before the age of 40. Early diagnosis and initiation of hormone replacement therapy is essential to alleviate symptoms and prevent later complications as a result of premature oestrogen deficiency. In this clinical review article we present an update on the diagnostics and treatment of the condition.

BACKGROUND The rising prevalence of gestational diabetes mellitus (GDM) calls for the use of innovative methods to inform and empower these pregnant women. An information chatbot, Dina, was developed for women with GDM and is Norway’s first health chatbot, integrated into the national digital health platform. OBJECTIVE The aim of this study is to investigate what kind of information users seek in a health chatbot providing support on GDM. Furthermore, we sought to explore when and how the chatbot is used by time of day and the number of questions in each dialogue and to categorize the questions the chatbot was unable to answer (fallback). The overall goal is to explore quantitative user data in the chatbot’s log, thereby contributing to further development of the chatbot. METHODS An observational study was designed. We used quantitative anonymous data (dialogues) from the chatbot’s log and platform during an 8-week period in 2018 and a 12-week period in 2019 and 2020. Dialogues between the user and the chatbot were the unit of analysis. Questions from the users were categorized by theme. The time of day the dialogue occurred and the number of questions in each dialogue were registered, and questions resulting in a fallback message were identified. Results are presented using descriptive statistics. RESULTS We identified 610 dialogues with a total of 2838 questions during the 20 weeks of data collection. Questions regarding blood glucose, GDM, diet, and physical activity represented 58.81% (1669/2838) of all questions. In total, 58.0% (354/610) of dialogues occurred during daytime (8 AM to 3:59 PM), Monday through Friday. Most dialogues were short, containing 1-3 questions (340/610, 55.7%), and there was a decrease in dialogues containing 4-6 questions in the second period (P=.013). The chatbot was able to answer 88.51% (2512/2838) of all posed questions. The mean number of dialogues per week was 36 in the first period and 26.83 in the second period. CONCLUSIONS Frequently asked questions seem to mirror the cornerstones of GDM treatment and may indicate that the chatbot is used to quickly access information already provided for them by the health care service but providing a low-threshold way to access that information. Our results underline the need to actively promote and integrate the chatbot into antenatal care as well as the importance of continuous content improvement in order to provide relevant information.

INTRODUCTION Despite adequate glycemic control, the risks of fetal macrosomia and perinatal complications are increased in diabetic pregnancies. Adjustments of the umbilical venous distribution, including increased ductus venosus shunting, can be important fetal compensatory mechanisms, but the impact of pregestational diabetes on umbilical venous and ductus venosus flow is not known. MATERIAL AND METHODS In this prospective study, 49 women with pregestational diabetes mellitus underwent monthly ultrasound examinations from gestational week 20 to 36. The blood velocity and the mean diameters of the umbilical vein and ductus venosus were used for calculating blood flow volumes. The development of the umbilical venous flow, ductus venosus flow and ductus venosus shunt fraction (% of umbilical venous blood shunted through the ductus venosus) was compared with a reference population, and the effect of HbA1c on the ductus venosus flow was assessed. RESULTS The umbilical venous flow was larger in pregnancies with pregestational diabetes mellitus than in low-risk pregnancies (p

Circadian rhythmicity is fundamental to human physiology, and is present even during fetal life in normal pregnancies. The impact of maternal endocrine disease on the fetal circadian rhythm is not well understood. The present study aimed to determine the fetal circadian rhythm in pregnancies complicated by pregestational diabetes mellitus (PGDM), compare it with a low-risk reference population, and identify the effects of maternal glycemic control and morning cortisol concentrations. Long-term fetal electrocardiogram recordings were made in 40 women with PGDM at 28 and 36 weeks of gestation. Two recordings were made in 18 of the women (45.0%) and one recording was made in 22 (55.0%). The mean fetal heart rate (fHR) and the fHR variation (root mean square of squared differences) were extracted in 1-min epochs, and circadian rhythmicity was detected by cosinor analysis. The study cohort was divided based on HbA1c levels and morning cortisol concentrations. Statistically, significant circadian rhythms in the fHR and the fHR variation were found in 45 (100%) and 44 (95.7%) of the 45 acceptable PGDM recordings, respectively. The rhythms were similar to those of the reference population. However, there was no statistically significant population-mean rhythm in the fHR among PGDM pregnancies at 36 weeks, indicating an increased interindividual variation. The group with higher HbA1c levels (6.0%) had no significant population-mean fHR rhythm at 28 or 36 weeks, and no significant fHR-variation rhythm at 36 weeks. Similarly, the group with a lower morning cortisol concentration (≤8.8 µg/dl) had no significant population-mean fHR-variation rhythm at 28 and 36 weeks. These findings indicate that individual fetal rhythmicity is present in pregnancies complicated by PGDM. However, suboptimal maternal glycemic control and a lower maternal morning cortisol concentration are associated with a less-well-synchronized circadian system of the fetus.

Background Pregestational diabetes is associated with fetal macrosomia, and umbilical perfusion of the fetal liver has a role in regulating fetal growth. We therefore hypothesized that pregestational diabetes alters fetal liver blood flow depending on degree of glycemic control. Methods In a prospective study, 49 women with pregestational diabetes underwent monthly ultrasound examinations during 24-36 gestational weeks. Blood flow was determined in the umbilical vein, ductus venosus and portal vein, and blood velocity was measured in the left portal vein, the latter reflecting the watershed between splanchnic and umbilical flow. The measurements were compared with reference values by z-score statistics, and the effect of HbA 1c assessed. Results The umbilical venous flow to the liver (z-score 0.36, p = 0.002), total venous liver flow (z-score 0.51, p1C . Conclusions In spite of increased umbilical blood distribution to the fetal liver, graded according to glycemic control, the total venous liver flow did not match third trimester fetal growth in pregnancies with pregestational diabetes, thus contributing towards increased perinatal risks and possibly altered liver function with long-term metabolic consequences.

Estrogen is a potent vasodilator through activation of endothelial nitric oxide synthase (eNOS). Arginine and its homologue homoarginine are substrates for NOS, while asymmetric dimethylarginine (ADMA) is a NOS inhibitor. Healthy, never-pregnant women aged 18 to 40 years (n = 158) were categorized according to use of hormonal contraception into non-users (n = 76), users of estrogen contraceptives (EC-users, n = 58) and users of progestins-only contraceptives (PC-users, n = 24). Plasma homoarginine, arginine, ADMA and SDMA concentrations were assayed using a LC-MS/MS method. Compared to non-users, EC users had higher plasma homoarginine (median (interquartile range) 1.63 (1.24, 2.04) vs. 2.39 (2.05, 2.85) µmol/L, p

Objective. To describe patient characteristics according to different diagnostic criteria in early pregnancy, in women with polycystic ovary syndrome (PCOS). Design. Descriptive, cross-sectional study of 257 women with PCOS in the first trimester of pregnancy. Setting. Data from a multicenter trial at the time of inclusion. Population. 257 PCOS women with singleton pregnancies. Methods. Investigator-administrated questionnaires were filled out. Clinical examination was performed by the investigators. Fasting blood samples were collected. Main outcome measures. Biometric data, androgens, glucose and insulin levels. Results. Women who met the National Institutes of Health (NIH) criteria for PCOS had higher body mass index (BMI), testosterone, dehydroepiandrostenedione, free testosterone index (FTI) and insulin levels compared with those who only met the Rotterdam consensus criteria. Adjusted for age and BMI, only testosterone and FTI were higher in those who met the NIH criteria. BMI was a strong, independent predictor of both systolic and diastolic blood pressure in early PCOS pregnancy, while both FTI and fasting insulin were independent predictors of systolic blood pressure. Twenty-two (9%) of the participants had gestational diabetes mellitus in the first trimester of pregnancy. Conclusions. In the first trimester, PCOS women diagnosed according to NIH criteria were more metabolically and endocrinologically abnormal compared with those who only met the Rotterdam consensus criteria. BMI and FTI were independent predictive factors for blood pressure. There was a high prevalence of gestational diabetes mellitus in early PCOS pregnancies.

Context: Metformin is widely prescribed to pregnant women with polycystic ovary syndrome (PCOS) in an attempt to reduce pregnancy complications. Metformin is not approved for this indication, and evidence for this practice is lacking. Objectives: Our objective was to test the hypothesis that metformin, from first trimester to delivery, reduces pregnancy complications in women with PCOS. Design and Setting: We conducted a randomized, placebo-controlled, double-blind, multicenter study at 11 secondary care centers. Participants: The participants were 257 women with PCOS, in the first trimester of pregnancy, aged 18–42 yr. Intervention: We randomly assigned 274 singleton pregnancies (in 257 women) to receive metformin or placebo, from first trimester to delivery. Main Outcome Measures: The prevalence of preeclampsia, gestational diabetes mellitus, preterm delivery, and a composite of these three outcomes is reported. Results: Preeclampsia prevalence was 7.4% in the metformin group and 3.7% in the placebo group (3.7%; 95% CI, −1.7–9.2) (P = 0.18). Preterm delivery prevalence was 3.7% in the metformin group and 8.2% in the placebo group (−4.4%; 95%, CI, −10.1–1.2) (P = 0.12). Gestational diabetes mellitus prevalence was 17.6% in the metformin group and 16.9% in the placebo group (0.8%; 95% CI, −8.6–10.2) (P = 0.87). The composite primary endpoint prevalence was 25.9 and 24.4%, respectively (1.5%; 95% CI, −8.9–11.3) (P = 0.78). Women in the metformin group gained less weight during pregnancy compared with those in the placebo group. There was no difference in fetal birth weight between the groups. Conclusions: Metformin treatment from first trimester to delivery did not reduce pregnancy complications in PCOS.

To describe patient characteristics according to different diagnostic criteria in early pregnancy, in women with polycystic ovary syndrome (PCOS).Descriptive, cross-sectional study of 257 women with PCOS in the first trimester of pregnancy.Data from a multicenter trial at the time of inclusion.257 PCOS women with singleton pregnancies.Investigator-administrated questionnaires were filled out. Clinical examination was performed by the investigators. Fasting blood samples were collected.Biometric data, androgens, glucose and insulin levels.Women who met the National Institutes of Health (NIH) criteria for PCOS had higher body mass index (BMI), testosterone, dehydroepiandrostenedione, free testosterone index (FTI) and insulin levels compared with those who only met the Rotterdam consensus criteria. Adjusted for age and BMI, only testosterone and FTI were higher in those who met the NIH criteria. BMI was a strong, independent predictor of both systolic and diastolic blood pressure in early PCOS pregnancy, while both FTI and fasting insulin were independent predictors of systolic blood pressure. Twenty-two (9%) of the participants had gestational diabetes mellitus in the first trimester of pregnancy.In the first trimester, PCOS women diagnosed according to NIH criteria were more metabolically and endocrinologically abnormal compared with those who only met the Rotterdam consensus criteria. BMI and FTI were independent predictive factors for blood pressure. There was a high prevalence of gestational diabetes mellitus in early PCOS pregnancies.