Neonatal outcome following metformin-treated gestational diabetes mellitus: A population-based cohort study.

INTRODUCTION: Neonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5-min Apgar score, and preterm birth. MATERIAL AND METHODS: This Swedish population-based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019-2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual-level, linkage register-data in multivariable logistic regression models. RESULTS: In the main analysis, MT was associated with a lower risk of neonatal hypoglycemia vs NT (aOR 0.85, 95% CI: 0.74-0.96), vs MIT (0.74 [0.64-0.87]), and vs IT (0.47 [0.40-0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia vs NT (1.14 [0.99-1.30]) and with lower risk vs IT (0.63 [0.53-0.75]). However, supplemental feeding rates were lower for NT vs pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT vs NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5-min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories. CONCLUSIONS: The risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors.

International evidence-based guideline on assessment and management of PCOS-A Nordic perspective.

Polycystic ovary syndrome (PCOS) affects about 12% of women of reproductive age. In 2018, the first evidence-based guideline on assessment and management of PCOS was published, and an updated extended guideline was released in August 2023. These guidelines followed best practice and are endorsed by 39 organizations worldwide, making them the most robust source of evidence to guide clinical practice. In the 2023 guideline, diagnostic criteria have been further refined as polycystic ovary morphology can now be assessed with gynecological ultrasound or elevated anti-Müllerian hormone levels. A healthy lifestyle should be at the focus of care for all women with PCOS; however, with no specific diet or physical exercise recommended. The latest evidence on medical treatments and fertility management are reviewed, including special considerations regarding long-term follow-up of metabolic and psychiatric comorbidities and pregnancy in women with PCOS. Here we summarize the recommendations from a Nordic perspective.

Childbirth experiences in women with polycystic ovary syndrome: A cohort study.

INTRODUCTION: Women with polycystic ovary syndrome (PCOS) have more pregnancy complications like gestational diabetes, hypertension, and preterm labor than other women. Metformin has been used in an attempt to improve pregnancy outcomes. Our study aims to explore childbirth experiences in women with PCOS compared with a reference population. It also explores the potential influence of metformin, obesity, pregnancy complications, and the duration and mode of birth on childbirth experiences. MATERIAL AND METHODS: This study is a cohort study combining data from two randomized trials conducted in Norway, Sweden and Iceland. The PregMet2 study (ClinicalTrials.gov, NCT01587378) investigated the use of metformin vs. placebo in pregnant women with PCOS. The Labour Progression Study (ClinicalTrials.gov, NCT02221427) compared the WHO partograph to Zhang's guidelines for progression of labor and were used as the reference population. A total of 365 women with PCOS and 3604 reference women were included. Both studies used the Childbirth Experience Questionnaire (CEQ). Main outcome measures were total CEQ score and four domain scores. The CEQ scores were compared using Mann-Whitney U test for women in Robson group 1 with PCOS (n = 131) and reference women (n = 3604). CEQ scores were also compared between metformin-treated (n = 180) and placebo-treated (n = 185) women with PCOS, and for different subgroups of women with PCOS. RESULTS: There was no difference in total CEQ score between women with PCOS and reference women-Wilcoxon-Mann-Whitney (WMW)-odds 0.96 (95% confidence interval [CI] 0.78-1.17). We detected no difference in CEQ scores between the metformin- and placebo-treated women with PCOS (WMW-odds 1.13, 95% CI 0.89-1.43). Complications in pregnancy did not affect CEQ (WMW-odds 1, 95% CI 0.76-1.31). Higher body mass index (WMW-odds 0.75, 95% CI 0.58-0.96), longer duration of labor (WMW-odds 0.69, 95% CI 0.49-0.96), and cesarean section (WMW-odds 0.29, 95% CI 0.2-0.42) were associated with lower CEQ scores in women with PCOS. CONCLUSIONS: Women with PCOS experience childbirth similarly to the reference women. Metformin did not influence childbirth experience in women with PCOS, neither did pregnancy complications. Obesity, long duration of labor or cesarean section had a negative impact on childbirth experience.

Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero.

INTRODUCTION: Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre-pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. MATERIAL AND METHODS: Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z-scores. Linear regression models were used to estimate the effect of metformin on offspring z-scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S-testosterone, s-androstenedione, and s-sex-hormone binding globulin from four timepoints in pregnancy were analyzed. RESULTS: Compared with the PCOS-placebo group, newborns in the PCOS-metformin group had larger head circumference (head circumference z-score: mean difference = 0.25, 95% CI = 0.11- 0.40). This effect of metformin on head circumference z-score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS-phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS-placebo group were shorter than in the reference population (birth length z-score: mean = -0.04, 95% CI = -0.05 to -0.03), but head circumference and birthweight were similar. CONCLUSIONS: Larger head circumference was observed at birth in metformin-exposed offspring of mothers with PCOS. PCOS-offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight-to-height ratio at birth.

The impact of obesity surgery on newborn anthropometrics in women with and without polycystic ovary syndrome.

PURPOSE: Obesity surgery and polycystic ovary syndrome (PCOS) are both associated with increased risk of intrauterine growth restriction. We investigated whether offspring of mothers with PCOS who underwent obesity surgery had an increased risk of deviating birth anthropometrics compared to offspring of mothers without PCOS. METHODS: In this observational study, data from two study databases (BAROBS and PregMet2) were supplemented with data from patient's records from secondary and tertiary hospitals. In total, 162 offspring born to mothers with PCOS (n = 48) and without PCOS (n = 114) were included. Forty-nine offspring were born prior to, and 113 after obesity surgery. RESULTS: Mean ± SD birthweight (BW), birth length (BL), and head circumference (HC) before and after surgery for offspring born to mothers with PCOS were 3987 ± 495 g vs 3396 ± 526 g (P = 0.001), 52.2 ± 1.6 cm vs 50.1 ± 2.2 cm (P = 0.010), and 36.3 ± 1.97 cm vs 35.3 ± 1.66 cm (P = 0.183), respectively. In the non-PCOS group BW, BL and HC before and after were 3859 ± 603 g vs 3490 ± 538 g (P = 0.001), 51.3 ± 2.0 cm vs 49.9 ± 2.5 cm (P = 0.013), and 36.4 ± 2.0 cm vs 35.3 ± 1.8 cm (P = 0.016), respectively. Post-surgery, we found no difference in z-score BW, (∆-0.08, P = 0.677), BL (∆0.21, P = 0.184), and HC (∆0.14, P = 0.476) between children of PCOS and non-PCOS mothers. COMCLUSION: Babies born after obesity surgery were smaller and shorter in both the PCOS and non-PCOS group. Post-surgery anthropometrics were similar in babies born to mothers with and without PCOS.

Polycystic ovary syndrome and risk of pre-eclampsia: A national register-based cohort study.

OBJECTIVE: To explore whether the association between polycystic ovary syndrome (PCOS) and pre-eclampsia depends on treated clinical hyperandrogenism and whether PCOS is associated with different subtypes of pre-eclampsia. DESIGN: Nationwide register-based cohort study. SETTING: Sweden. POPULATION: Nulliparous women with PCOS (n = 22 947) and non-PCOS controls (n = 115 272) giving singleton birth at ≥22 gestational weeks during 1997-2015. Treated clinical hyperandrogenism was defined as filled prescriptions of anti-androgenic drugs during 2005-2017 (n = 2301 among PCOS women). METHODS: The risk of pre-eclampsia was estimated with conditional logistic regression, expressed as adjusted odds ratio (OR) with 95% confidence interval (CI). Adjustments were performed individually for confounders and predictors. MAIN OUTCOME MEASURES: Overall pre-eclampsia. Early/late (delivery <34/≥34 weeks) pre-eclampsia. Pre-eclampsia with or without a small-for-gestational-age (SGA) infant. RESULTS: Compared with controls, women with PCOS had a 29% increased risk of pre-eclampsia (predictor adjusted OR 1.29, 95% CI 1.20-1.39), with similar risk estimates for PCOS women with and without treated clinical hyperandrogenism. The association between PCOS and early pre-eclampsia seemed stronger than its association with late pre-eclampsia (predictor adjusted OR 1.64 (95% CI 1.33-2.02) and 1.26 (95% CI 1.17-1.37). Additionally, the association seemed slightly stronger between PCOS and pre-eclampsia in women with an SGA infant than without. CONCLUSIONS: Women with PCOS face an increased risk for pre-eclampsia, especially early pre-eclampsia and pre-eclampsia with an SGA infant. We were unable to determine on the basis of available data, whether hyperandrogenism is associated with pre-eclampsia.

Gestational weight gain, appetite regulating hormones, and metformin treatment in polycystic ovary syndrome: A longitudinal, placebo-controlled study.

OBJECTIVE: To explore mechanisms that modulate gestational weight gain (GWG) in women with polycystic ovary syndrome (PCOS) and healthy controls. DESIGN: Sub-sample of randomised controlled trials (PCOS) combined with a prospective cohort (controls). SETTING: Eleven Norwegian, Swedish, and Icelandic hospitals. POPULATION: Pregnant women with PCOS treated with metformin (PCOS-M, n = 36) or placebo (PCOS-P, n = 37), and healthy pregnant women (HC, n = 15). METHODS: Serum levels of the appetite regulating hormones leptin, ghrelin, allopregnanolone, and soluble leptin receptor (sOB-R) were determined in the first and third trimesters. MAIN OUTCOME MEASURES: Excessive GWG (eGWG) relative to body mass index according to Institute of Medicine (IOM) guideline. Serum leptin/sOB-R ratio, or free-leptin-index (FLI), as biomarker of leptin sensitivity. Serum ghrelin and allopregnanolone levels. RESULTS: The overall prevalence of eGWG was 44% (38/86). Women with eGWG had higher first and third trimester FLI (P < 0.001), and lower third trimester allopregnanolone levels (P = 0.003) versus women with non-eGWG. The prevalence of eGWG was lower in PCOS-M versus PCOS-P (28% versus 62%, odds ratio = 0.4, 95% CI 0.2-0.8, P = 0.005). FLI decreased during pregnancy in PCOS-M (P = 0.01), but remained unaltered in PCOS-P and HC. Ghrelin and allopregnanolone levels were comparable in PCOS-M, PCOS-P and HC throughout pregnancy. CONCLUSION: Excessive GWG is associated with enhanced leptin resistance, and attenuated physiological increase in serum allopregnanolone levels during pregnancy. Metformin reduces the risk for eGWG and improves leptin sensitivity in pregnant women with PCOS. TWEETABLE ABSTRACT: Metformin counteracts excessive weight gain and leptin resistance in pregnant women with polycystic ovary syndrome.

Ureteric injuries during hysterectomy-A Norwegian retrospective study of occurrence and claims for compensation over an 11-year period.

INTRODUCTION: Ureteric injury is a rare but serious, iatrogenic complication of hysterectomy. The risk depends on indication for surgery, predisposing risk factors, and peroperative conditions. Our aims were to evaluate and learn from compensation claims to The Norwegian System of Patient Injury Compensation (NPE) for ureteric injury occurring during hysterectomies to predict risk factors, time of identification, symptoms, and consequences, and to relate these cases to injuries registered in The Norwegian Patient Registry. MATERIAL AND METHODS: A retrospective study of ureteric injuries occurring during hysterectomies, reported to NPE and the Norwegian Patient Registry from 2009 through 2019. RESULTS: During the study period, 53 096 hysterectomies were registered in The Norwegian Patient Registry, of which ureteric injury was documented in 643 (1.2%). More ureteric injuries were registered in large hospital trusts than in small trusts (1.3% vs. 0.7%, p < 0.05). NPE received 69 claims due to ureteric injury occurring during hysterectomy, comprising 11% of all injuries in the study period. Compensation was approved for 15%. Women who claimed compensation were younger (48.1 ± 8.9 years vs. 55.1 ± 13.6 years, p < 0.01), more likely to have had a benign diagnosis (89.9% vs. 52.1%, p < 0.01), and more likely to have had the ureteric injury recognized after discharge (58.0% vs. 33.0%, p < 0.001) compared with non-complainants. Identification of the ureters during the hysterectomy was documented in 30% of the NPE patient files. Additional information for the NPE cases included the following. The most common symptoms of unidentified injury were pain (77%), fever (12%), urinary leakage (13%), and anuria (8%). Re-operation was necessary in 77% of the cases, and 10% of the women lost one kidney. Long-term consequences after repair, such as loss of a kidney or persistent pain, were seen in 17%. No women died because of the injury. CONCLUSIONS: The incidence of ureteric injury occurring during hysterectomy in Norway was 1.2%; 11% involved a claim for compensation, and 15% of these had their case approved. Most ureteric injuries were not recognized during the hysterectomy. Documentation of peroperative identification of the ureters during hysterectomy was often missing. Vigilance to pain as a postoperative symptom of peroperative unrecognized ureteric injury may result in earlier diagnosis and treatment.

Claims for compensation from women with cervical cancer in Norway-A retrospective, descriptive study of a 12-year period.

INTRODUCTION: In Norway, all patient-reported claims for compensation are evaluated by The Norwegian System of Patient Injury Compensation (NPE). The number of claims from women with cervical cancer is rising, and the approval rate is high. Our aim was to study claims for compensation from women with cervical cancer to identify the type of failures, when, during the time-course of treatment, the medical failures occurred, and the consequences of the failures. MATERIAL AND METHODS: A retrospective, descriptive study of claims for compensation to NPE from cervical cancer patients during a 12-year period, from 2007 through 2018. We used anonymized medical expert statements and summaries of NPE cases. RESULTS: In all, 161 women claimed compensation for alleged medical failure related to cervical cancer. Compensation was approved for 100 (62%) women. Mean age at the time of alleged failure was 37.5 years (SD ±9.9). The main reasons why women sought medical attention were routine cervical screening (56%), or vaginal bleeding or discharge (30%). In approved cases, incorrect evaluation of cytology and histology was the cause of most failures (72%). Mean delay of cervical cancer diagnosis for approved cases was 28 months (SD ±22). Treatment not in accordance with guidelines was the cause of failure in 2% of the cases, and failure during follow up was the cause of failure in 12%. Consequences of the failures were as follows: worsening of cancer prognosis (89%), treatment-induced adverse effects, such as loss of fertility (43%) and/or loss of ovarian function in premenopausal women (50%), and permanent injury after chemo-radiation (27%). Seven women (7%) died, most probably as a consequence of the failure. CONCLUSIONS: The main cause of medical failure in women with cervical cancer was incorrect pathological diagnosis. The main consequences of failures were worsening of cancer prognosis and treatment-induced adverse effects. Increased focus on the quality of pathological examinations, and better routines in all parts of the cervical examinations might improve patient safety for women in risk of cervical cancer.

Cognitive function in metformin exposed children, born to mothers with PCOS - follow-up of an RCT.

BACKGROUND: Metformin is widely used in pregnancy to treat gestational diabetes mellitus and polycystic ovary syndrome (PCOS). Association between PCOS and developmental delay in offspring, and larger head circumference of metformin-exposed newborns has been reported. The objective of this study was to explore whether metformin exposure in utero had any effect on offspring cognitive function. METHOD: The current study is a follow-up of two randomized, placebo-controlled studies which were conducted at 11 public hospitals in Norway In the baseline studies (conducted in 2000-2003, and 2005-2009), participants were randomized to metformin 1700 and 2000 mg/d or placebo from first trimester to delivery. There was no intervention in the current study. We invited parents of 292 children to give permission for their children to participate; 93 children were included (mean age 7.7 years). The follow-up study was conducted in 2014-2016. The Wechsler Preschool and Primary Scale of Intelligence version III and the Wechsler Intelligence Scale for Children version IV were applied for cognitive assessment. Androstenedione and testosterone were measured in maternal blood samples at four time-points in pregnancy. RESULTS: We found no difference in mean, full scale IQ in metformin (100.0 (SD 13.2)) vs. placebo-exposed (100.9 (SD 10.1)) children. There was an association between metformin exposure in utero and borderline intellectual function of children (full scale IQ between 70 and 85). Free testosterone index in gestational week 19, and androstenedione in gestational week 36 correlated positively to full scale IQ. CONCLUSIONS: We found no evidence of long-term effect of metformin on average child cognitive function. The increase of borderline intellectual functioning in metformin-exposed children must be interpreted with caution due to small sample size. TRIAL REGISTRATION: The baseline study was registered on 12 September 2005 at the US National Institute of Health (ClinicalTrials.gov) # NCT00159536.

Serum cytokine patterns in first half of pregnancy.

INTRODUCTION: Human pregnancy is a state of elevated maternal systemic inflammation, and pregnancy complications are often associated with a dysfunctional immune response. The network of cytokines reflects this complex immune activity, and broad serum cytokine profiling provides a new tool to understand the changes in immune status during pregnancy. OBJECTIVE: This study aimed to determine how maternal serum cytokine patterns change during the first half of pregnancy. METHODS: Maternal peripheral serum samples collected at a mean gestation of 10, 13, 18 and 24 weeks were included from a prospective clinical study of healthy women (n = 110) in first half of normal pregnancy. The serum samples were analysed for 27 different cytokines using multiplex magnetic bead-based immunoassays, and high sensitivity C-reactive protein (CRP) was analysed by ELISA. Serum cytokine and CRP patterns were explored with linear mixed effects models (LMM) and multilevel partial least squares discriminant analysis (PLS-DA). RESULTS: Serum cytokine profiling provided partial overview of the maternal immune status and corresponding reference values for serum cytokine levels during the first half of pregnancy. Several cytokines decreased in concentration from first to second trimester. Cytokine pattern analysis revealed that chemokines provided the most sensitive measurement of variation with gestational age in normal pregnancies. The nine inflammatory cytokines showed the highest intra-group correlation during pregnancy, while CRP levels did not correlate with changes in the inflammatory cytokines. CONCLUSION: Chemokines showed the greatest gestational variation and inflammatory cytokines showed a strong intra-group correlation during the first half of pregnancy.

Approved claims for compensation from gynecological patients in Norway-What characterizes the cases? A 14-year nationwide study.

INTRODUCTION: The Norwegian System of Patient Injury Compensation (NPE) evaluates all patient-reported claims in Norway. Our aim was to study the cases from gynecological patients approved by NPE in order to identify the main reasons for the injuries, the consequences of the treatment failure for the women, and the time course when the treatment failure occurred. MATERIAL AND METHODS: A retrospective, descriptive study of approved gynecological compensation claims during a 14-year period, based on patient files from NPE. RESULTS: In all, 1454 women claimed compensation for injury related to gynecological treatment in Norway from 2000 to 2013. Compensation was approved for 438 (30.1%) women. Eleven women declined participation in the study and 16 cases were excluded, leaving 411 cases for further analyses. Consent to participate was given by 211 (51.3%) women, who gave full access to all their NPE files. Anonymized resumes and expert statements were used for the 138 (33.6%) women who did not respond and the 62 (15.1%) women who were deceased. Guidelines or good clinical practice were not followed in 40.5% of the cases. The most common reasons for injury were surgical complications (67.6%), delayed (22.4%) and incorrect (17.0%) diagnoses, and failure of communication (11.7%). The main consequences of injuries were need for extensive treatment (64.2%), permanent injury (55.2%) and impaired physical ability (41.9%). Worsening of cancer prognosis occurred in 58 women (14.1%) and death due to treatment failure in 29 (7.1%) women. Most failures occurred during the treatment period (75.2%). CONCLUSIONS: We found that the main reason for injuries in gynecological patients was non-adherence to guidelines or good clinical practice. Surgery-related injuries were most common. Increased focus on adherence to guidelines and surgical skills might improve patient safety for gynecological patients in Norway.

A brief update on the evidence supporting the treatment of infertility in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is complex with reproductive, metabolic and psychological features. Infertility is a prevalent presenting feature of PCOS with approximately 75% of these women suffering infertility due to anovulation, making PCOS by far the most common cause of anovulatory infertility. Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. AIMS: This review paper aims to provide a brief update on the best available and most current research evidence supporting the treatment of PCOS which informed the recommendations in the assessment and treatment of infertility section of the international evidence-based guideline on PCOS 2018. MATERIALS AND METHODS: International evidence-based guideline development engaged professional societies and consumer organisations with multidisciplinary experts and women with PCOS directly involved at all stages. RESULTS: Lifestyle change alone is considered the first-line treatment for the management of infertile anovulatory PCOS women who are overweight or obese. Letrozole should now be considered first-line pharmacological treatment for ovulation induction to improve fertility outcomes. Clomiphene citrate alone and metformin alone could also be used as first-line pharmacological therapy, although both are less effective than letrozole and metformin is less effective than clomiphene citrate in obese women. Gonadotrophins or laparoscopic ovarian surgery are usually second-line ovulation induction therapies. In the absence of an absolute indication for in vitro fertilisation (IVF) / intracytoplasmic sperm injection, women with PCOS and anovulatory infertility could be offered IVF as third-line therapy where first- or second-line ovulation induction therapies have failed. CONCLUSION: This review provides the best available evidence informing recommendations (along with clinical expertise and consumer preference) which provide clinicians with clear advice on best practice for the management of infertile women with PCOS.

Polycystic ovary syndrome and adverse pregnancy outcomes: Current state of knowledge, challenges and potential implications for practice.

Although there is a growing body of literature reporting that pregnancies in women with polycystic ovary syndrome (PCOS) are associated with greater complications than those without PCOS, methodological differences across studies make these results difficult to consolidate. This narrative review outlines potential mechanisms involved in adverse pregnancy outcomes in PCOS and the nature of the complications. It covers limitations of current evidence and future research directions. Future research should include prospective studies with phenotypic stratification of PCOS and matching or consideration of specific PCOS manifestations and risk factors specific to each pregnancy complication. This review also emphasizes the importance of following a healthy lifestyle for women with PCOS and of individualized care according to overall risk factors for pregnancy complications.

Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome: a regional cross-sectional study.

BACKGROUND: Polycystic ovary syndrome is a heterogeneous disorder and its presentation varies with race and ethnicity. Reproductive-age women with polycystic ovary syndrome are at increased risk of metabolic syndrome; however, it is not clear if prevalence of metabolic syndrome and clustering of its components differs based on race and ethnicity. Moreover, the majority of these women do not undergo routine screening for metabolic syndrome. OBJECTIVE: We sought to compare the prevalence of metabolic syndrome and clustering of its components in women with polycystic ovary syndrome in the United States with women in India, Brazil, Finland, and Norway. STUDY DESIGN: This is a cross-sectional study performed in 1089 women with polycystic ovary syndrome from 1999 through 2016 in 5 outpatient clinics in the United States, India, Brazil, Finland, and Norway. Polycystic ovary syndrome was defined by the Rotterdam criteria. Main outcome measures were: metabolic syndrome prevalence, blood pressure, body mass index, fasting high-density lipoprotein cholesterol, fasting triglycerides, and fasting glucose. Data from all sites were reevaluated for appropriate application of diagnostic criteria for polycystic ovary syndrome, identification of polycystic ovary syndrome phenotype, and complete metabolic workup. The US White women with polycystic ovary syndrome were used as the referent group. Logistic regression models were used to evaluate associations between race and metabolic syndrome prevalence and its components and to adjust for potential confounders, including age and body mass index. RESULTS: The median age of the entire cohort was 28 years. Women from India had the highest mean Ferriman-Gallwey score for clinical hyperandrogenism (15.6 ± 6.5, P < .001). The age-adjusted odds ratio for metabolic syndrome was highest in US Black women at 4.52 (95% confidence interval, 2.46-8.35) compared with US White women. When adjusted for age and body mass index, the prevalence was similar in the 2 groups. Significantly more Black women met body mass index and blood pressure criteria (P < .001), and fewer met fasting triglycerides criteria (P < .05). The age- and body mass index-adjusted prevalence of metabolic syndrome was highest in Indian women (odds ratio, 6.53; 95% confidence interval, 3.47-12.30) with abnormalities in glucose and fasting high-density lipoprotein cholesterol criterion and in Norwegian women (odds ratio, 2.16; 95% confidence interval, 1.17-3.98) with abnormalities in blood pressure, glucose, and fasting high-density lipoprotein cholesterol criterion. The Brazilian and Finnish cohorts had similar prevalence of metabolic syndrome and its components compared to US White women. CONCLUSION: Despite a unifying diagnosis of polycystic ovary syndrome, there are significant differences in the prevalence of metabolic syndrome and clustering of its components based on race and ethnicity, which may reflect contributions from both racial and environmental factors. Our findings indicate the prevalence of metabolic syndrome components varies in women with polycystic ovary syndrome, such that compared to White women from the United States, Black US women had the highest prevalence, whereas women from India and Norway had a higher prevalence of metabolic syndrome independent of obesity. The differences in clustering of components of metabolic syndrome based on ethnicity highlight the need to routinely perform complete metabolic screening to identify specific targets for cardiovascular risk reduction strategies in these reproductive-age women.

Uterine artery Doppler measurements during first and second trimesters of normal pregnancy.

INTRODUCTION: The aim of this study was to construct a reference curve based on longitudinal Doppler blood flow measurements of the uterine artery during the first and second trimesters of normal pregnancy. MATERIAL AND METHODS: Healthy pregnant women (n = 124) between 18 and 38 years of age were included. The uterine artery pulsatility index (UtAPI) was measured with transvaginal ultrasound in the first trimester (gestational weeks 8-10 and 11-13) and with transabdominal ultrasound in the second trimester (gestational weeks 18 and 24). Individual longitudinal curves were constructed and a reference curve was created. RESULTS: A centile curve with the normal distribution of the UtAPI during the first and second trimesters was constructed. We found that 90% of the women alternated between quartiles during the four examinations between gestational weeks 8 and 24, but 75% remained within the higher or lower range. CONCLUSIONS: A UtAPI reference curve was constructed for the first and second trimesters of pregnancy. Although the mean UtAPI values may vary from one examination to the next, most mean UtAPI values remain within the higher or lower range, i.e. above or below the 50th centile.

Should we individualize lipid profiling in women with polycystic ovary syndrome?

STUDY QUESTION: Is it necessary to monitor lipid profiles in all young women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Lipid profiling is required when women with PCOS develop type 2 diabetes (T2D) or hypertension, but rarely changes clinical care before the age of 35 years. WHAT IS KNOWN ALREADY: PCOS consensus statements and guidelines recommend that women with PCOS should be screened for dyslipidaemia every second year or annually. STUDY DESIGN, SIZE, DURATION: Women from Denmark, Norway, Finland and Sweden, who had participated in research projects or clinical trials or in whom lipid profiles had been determined routinely as part of clinical care since 2000 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: One thousand three hundred and twenty-seven women with PCOS (Rotterdam criteria) were included. Based on individual cardiovascular risk score and lipid levels, treatment level was guided by the European Society of Cardiology and the European Atherosclerosis Society Task Force for the management of dyslipidaemias. Change in clinical care was defined as need to (i) immediately start statin treatment or (ii) consider statin treatment if life-style intervention fails. MAIN RESULTS AND THE ROLE OF CHANCE: All in all, 74 (5.6%) women with PCOS should immediately start statin treatment, and statin treatment should be considered in 33 women (2.5%). Among women with T2D, 27/28 (96.4%) should initiate statin treatment and the corresponding number for women with hypertension was 42/57 (73.7%). In PCOS women who had not yet developed T2D or hypertension, lipid profiling only changed clinical care in 28 (2.3%). This number was further reduced to 12 (1.2%) in women below the age of 35 years, and to zero in normal-weight women below the age of 35 years. LIMITATIONS, REASONS FOR CAUTION: Findings can only be generalized to countries with low cardiovascular mortality rates. WIDER IMPLICATIONS OF THE FINDINGS: Lipid profiling is required when women with PCOS develop T2D or hypertension. However, lipid profiling rarely changes the clinical care of low risk PCOS patients before the age of 35, especially in the normal-weight women. STUDY FUNDING/COMPETING INTERESTS: The Academy of Finland, Sigrid Juselius Foundation and the Nordic Federation of Obstetrics and Gynecology. There are no conflicts of interest to be declared.

Changes in induction methods have not influenced cesarean section rates among women with induced labor.

INTRODUCTION: Induction of labor has become more common in most countries during the last decade. We have compared methods and routines of labor induction as practiced in Norway in 2003 and 2013, and surveyed practices with regard to induction of labor without a medical indication in 2013. MATERIAL AND METHODS: A telephone interview with all delivery units in Norway was conducted in 2003. Data on preferred induction methods, use of prostaglandin, dosages, dose intervals and routes of administration were collected. In 2013, the same questionnaire was used, with additional questions on induction of labor without a medical indication. Data on overall cesarean section and induction rates were obtained from the Medical Birth Registry of Norway. RESULTS: From 2003 to 2013 the induction rate increased by 62% and the cesarean section rate by 6%. The cesarean section rate in women with induced labor remained stable at 17.1 and 17.4%, respectively. In 2003, 31 of 43 hospitals used dinoprostone for cervical ripening and induction. In 2013, 34 of 39 hospitals used misoprostol. A cervical balloon was used in three of 43 hospitals in 2003 compared with 31 of 39 in 2013. All but one hospital induced labor without a strict medical indication in 2013. CONCLUSION: The preferred methods for induction of labor changed within a decade to the use of misoprostol and cervical balloon. Induction of labor without strict medical indications is widely practiced. The changed induction methods have not influenced the cesarean section rates in women with induced labors.

Obesity, polycystic ovary syndrome and breastfeeding: an observational study.

INTRODUCTION: Polycystic ovary syndrome (PCOS) affects 9-21% of reproductive-age women. The relations between PCOS, body mass index (BMI) and breastfeeding are unclear. Our aim was to examine breastfeeding in women with and without PCOS and the relation with BMI. MATERIAL AND METHODS: This is a cross-sectional study set in the general community. Participants are women, aged 31-36 years, from the Australian Longitudinal Study on Women's Health (ALSWH), a large community-based study. Data was analyzed from the first child of respondents to Survey five (2009) reporting at least one live born child. Logistic regression analysis was used to examine factors associated with breastfeeding. The main outcome measures studied were breastfeeding initiation and duration and the main explanatory variables included self-reported PCOS and BMI. RESULTS: Of the 4898 women, 6.5% reported PCOS (95% confidence interval 5.8-7.2%). Median duration of breastfeeding was lower in women reporting PCOS (6 months, range 2-10 months) than in women not reporting PCOS (7 months, range 3-12 months) (p = 0.001). On multivariable regression analysis, there was no association between PCOS and breastfeeding outcomes. However, being overweight or obese was associated with not initiating breastfeeding and with breastfeeding for less than 6 months, after adjusting for confounders. CONCLUSIONS: High BMI is negatively associated with breastfeeding, whereas PCOS status per se does not appear to be related to breastfeeding initiation and duration, after adjusting for BMI.