Polycystic Ovary Syndrome: Pathophysiology, Phenotype Expression and Clinical Implications

Annemarie Geerdina Maria Geertruida Johanna Mulders was born on the 29th of April 1972 in Waalwijk, The Netherlands. She passed secondary school at the Dr. Mollercollege in Waalwijk. She attended Medical School at the Erasmus University in Rotterdam from 1992 - 1999 from which she graduated cum laude. From December 1999 - August 2000 she worked as a resident at the department of Obstetrics and Gynaecology of the Sint Lucas Andreas Hospital (head: Dr. J.Th.M. van der Schoot) in Amsterdam. From August 2000 -December 2003 she worked as a PhD student at the division of Reproductive Medicine (head: Prof. Dr. B.C.J.M. Fauser) of the department of Obstetrics and Gynaecology of the Erasmus MC in Rotterdam performing the studies described in this thesis. In January 2004 she started her training in Obstetrics and Gynaecology at the Amphia Hospital in BredaPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age women and a major cause of subfertility. Women with PCOS might present with a number of various features and hence PCOS does not seem to be a clear-cut clinical phenomenon. In order to elucidate the background and pathophysiology of all symptoms displayed in PCOS it might be helpful to focus on these specific characteristics and features. In this chapter pathophysiology of ovarian dysfunction is highlighted. Additionally, several characteristic PCOS features used for classification and involved in phenotypical heterogeneity, will be briefly described. Furthermore, the complexity of research regarding the genetic c

Polycystic Ovary Syndrome: Pathophysiology, Phenotype Expression and Clinical Implications

Annemarie Geerdina Maria Geertruida Johanna Mulders was born on the 29th of April 1972 in Waalwijk, The Netherlands. She passed secondary school at the Dr. Mollercollege in Waalwijk. She attended Medical School at the Erasmus University in Rotterdam from 1992 - 1999 from which she graduated cum laude. From December 1999 - August 2000 she worked as a resident at the department of Obstetrics and Gynaecology of the Sint Lucas Andreas Hospital (head: Dr. J.Th.M. van der Schoot) in Amsterdam. From August 2000 -December 2003 she worked as a PhD student at the division of Reproductive Medicine (head: Prof. Dr. B.C.J.M. Fauser) of the department of Obstetrics and Gynaecology of the Erasmus MC in Rotterdam performing the studies described in this thesis. In January 2004 she started her training in Obstetrics and Gynaecology at the Amphia Hospital in BredaPolycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive age women and a major cause of subfertility. Women with PCOS might present with a number of various features and hence PCOS does not seem to be a clear-cut clinical phenomenon. In order to elucidate the background and pathophysiology of all symptoms displayed in PCOS it might be helpful to focus on these specific characteristics and features. In this chapter pathophysiology of ovarian dysfunction is highlighted. Additionally, several characteristic PCOS features used for classification and involved in phenotypical heterogeneity, will be briefly described. Furthermore, the complexity of research regarding the genetic c

Childhood Blood Pressure, Carotid Intima Media Thickness, and Distensibility After In Utero Exposure to Gestational Hypertensive Disorders

BACKGROUND: Offspring exposed to gestational hypertensive disorders have higher blood pressure and increased risk of stroke in later life. Gestational hypertensive disorders might influence vascular development in the offspring, predisposing them to a higher blood pressure and stroke in later life. METHODS AND RESULTS: In a population‐based cohort among 4777 mother–offspring pairs, we examined whether gestational hypertension, preeclampsia, and higher gestational blood pressure across the full blood pressure spectrum were associated with offspring blood pressure, carotid intima media thickness, and distensibility at the age of 10 years. Offspring exposed to gestational hypertension, but not preeclampsia, had higher systolic and diastolic blood pressure (0.17 [95% CI, 0.02–0.31] and 0.23 [95% CI, 0.08–0.38] increases in standard deviation scores, respectively), whereas no associations with intima media thickness and distensibility were present. Higher maternal systolic and diastolic blood pressure in early, mid, and late pregnancy were associated with higher offspring systolic and diastolic blood pressure and lower distensibility (P values <0.05), but not with intima media thickness. The associations were not explained by maternal, birth, or child factors. Paternal systolic and diastolic blood pressure were also associated with these offspring outcomes (P values <0.05), with a comparable strength as maternal–offspring associations. CONCLUSIONS: Gestational hypertension and higher gestational blood pressure, even below the diagnostic threshold for gestational hypertensive disorders, are associated with higher offspring blood pressure and lower carotid distensibility. No associations were found for preeclampsia with offspring vascular outcomes. As maternal–offspring and paternal–offspring associations were comparable, these associations are more likely driven by genetic predisposition and shared lifestyle rather than by a direct intrauterine effect

Associations of dietary glycemic index and load during pregnancy with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders

PURPOSE: The aim of this study was to examine the associations of dietary glycemic index and load with gestational blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. METHODS: In a population-based cohort among 3378 pregnant Dutch women, dietary glycemic index and load were assessed from food frequency questionnaires at median 13.4 (95% range 9.9–22.9) weeks gestation. Blood pressure was measured in early-, mid- and late-pregnancy. Placental hemodynamic parameters were measured in mid- and late-pregnancy by ultrasound. Data on gestational hypertensive disorders was acquired from medical records. RESULTS: Mean dietary glycemic index (SD) was 58 (3) and mean dietary glycemic load (SD) was 155 (47). Dietary glycemic index was not associated with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. Higher dietary glycemic load SDS was associated with a higher diastolic blood pressure in early-pregnancy, remaining after adjustment for socio-demographic and lifestyle factors ((0.98 (95% CI 0.35–1.61) mmHg per SDS increase in glycemic load). No other associations of glycemic load with blood pressure or placental hemodynamic parameters and the risk of gestational hypertensive disorders were present. No significant associations of dietary glycemic index and load quartiles with longitudinal blood pressure patterns from early to late-pregnancy were present. CONCLUSION: Within this low-risk pregnant population, we did not find consistent associations of dietary glycemic index and load with blood pressure, placental hemodynamic parameters and the risk of gestational hypertensive disorders. Further studies need to assess whether the effects on gestational hemodynamic adaptations are more pronounced among high-risk women with an impaired glucose metabolism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00394-021-02670-5

Patient predictors for outcome of gonadotrophin ovulation induction in women with normogonadotrophic anovulatory infertility: a meta-analysis

A systematic review was conducted to determine whether initial screening characteristics of wo

High singleton live birth rate following classical ovulation induction in normogonadotrophic anovulatory infertility (WHO 2)

BACKGROUND: Medical induction of ovulation using clomiphene citrate (CC) as first line and exogenous gonadotrophins as second line forms the classical treatment algorithm in normogonadotrophic anovulatory infertility. Because the chances of success following classical ovulation induction are not well established, a shift in first-line therapy can be observed towards alternative treatment. The study aim was to: (i) reliably assess the probability of singleton live birth following classical induction of ovulation; and (ii) construct a prediction model, based on individual patient characteristics assessed upon standardized initial screening, to help identify patients with poor chances of success. METHODS: A total of 240 consecutive women visiting a specialist academic fertility unit with a history of infertility, oligomenorrhoea or amenorrhoea, and normal FSH and estradiol serum concentrations (WHO group 2) was prospectively followed. The women had not been previously treated with ovulation-inducing agents. All patients commenced with CC. Patients who did not ovulate within three treatment cycles of incremental daily doses up to 150 mg for 5 consecutive days or ovulatory CC patients who did not conceive within six cycles, subsequently underwent gonadotrophin induction of ovulation applying a step-down dose regimen. The main outcome measure was pregnancy resulting in singleton live birth. Cox regression was used to construct a multivariable prediction model. RESULTS: Overall, there were 134 pregnancies ending in a singleton live birth (56% of women). The cumulative pregnancy rate after 12 and 24 months of follow-up was 50% and 71% respectively. Polycystic ovary syndrome (PCOS) patients (49%), clearly non-PCOS patients (13%) and the in-between group did not differ in prognosis (P = 0.9). The multivariable Cox regression model contained the woman's age, the insulin:glucose ratio and duration of infertility. With a cut-off value of 30% for low chance, the model predicted probabilities at 12 months lower than this cut-off for 25 out of 240 patients (10.4%). CONCLUSIONS: Classical ovulation induction produces very good results in normogonadotrophic anovulatory infertility. Alternative treatment options may not be indicated as first-line therapy in these patients, except for subgroups with poor prognosis. These women can be identified by older age, longer duration of infertility and higher insulin:glucose ratio

Population screening for gestational hypertensive disorders using maternal, fetal and placental characteristics

Objective: To determine screening performance of maternal, fetal and placental characteristics for selecting pregnancies at risk of gestational hypertension and preeclampsia in a low-risk multi-ethnic population. Method: In a prospective population-based cohort among 7124 pregnant women, we collected maternal characteristics including body mass index, ethnicity, parity, smoking and blood pressure in early-pregnancy. Fetal characteristics included second and third trimester estimated fetal weight and sex determined by ultrasound. Placental characteristics included first and second trimester placental growth factor concentrations and second and third trimester uterine artery resistance indices. Results: Maternal characteristics provided the best screening result for gestational hypertension (area-under-the-curve [AUC] 0.79 [95% Confidence interval {CI} 0.76-0.81]) with 40% sensitivity at 90% specificity. For preeclampsia, the maternal characteristics model led to a screening performance of AUC 0.74 (95% CI 0.70-0.78) with 33% sensitivity at 90% specificity. Addition of second and third trimester placental ultrasound characteristics only improved screening performance for preeclampsia (AUC 0.78 [95% CI 0.75-0.82], with 48% sensitivity at 90% specificity). Conclusion: Routinely measured maternal characteristics, known at the start of pregnancy, can be used in screening for pregnancies at risk of gestational hypertension or preeclampsia within a low-risk multi-ethnic population. Addition of combined second and third trimester placental ultrasound characteristics only improved screening for preeclampsia

Innovative approach for first-trimester fetal organ volume measurements using a Virtual Reality system:The Generation R <i>Next</i> Study

INTRODUCTION: To investigate the reproducibility of first‐trimester fetal organ volume measurements using three‐dimensional (3D) ultrasound and a Virtual Reality system. METHODS: Within a population‐based prospective cohort study, 3D ultrasound datasets of 25 first‐trimester fetuses were collected by three sonographers. We used the V‐scope application to perform Virtual Reality volume assessments of the fetal heart, lungs, and kidneys. All measurements were performed by two independent researchers. RESULTS: Intraobserver analyses for volume measurements of the fetal heart, lungs, and kidneys showed intraclass correlation coefficients ≥0.86, mean differences ≤8.3%, and coefficients of variation ≤22.8%. Interobserver analyses showed sufficient agreement for right lung volume measurements, but consistent measurement differences between observers for left lung, heart, and kidney volume measurements (p‐values <0.05). CONCLUSION: We observed sufficient intraobserver reproducibility, but overall suboptimal interobserver reproducibility for first‐trimester fetal heart, lung, and kidney volume measurements using an innovative Virtual Reality approach. In the current stage, these measurements might be promising for the use in research settings. The reproducibility of the measurements might be further improved by novel post‐processing algorithms

Second and third trimester fetal ultrasound population screening for risks of preterm birth and small-size and large-size for gestational age at birth: a population-based prospective cohort study

BACKGROUND: Preterm birth, small size for gestational age (SGA) and large size for gestational age (LGA) at birth are major risk factors for neonatal and long-term morbidity and mortality. It is unclear which periods of pregnancy are optimal for ultrasound screening to identify fetuses at risk of preterm birth, SGA or LGA at birth. We aimed to examine whether single or combined second and third trimes