Increased rates of complications in singleton pregnancies of women previously diagnosed with polycystic ovary syndrome predominantly in the hyperandrogenic phenotype.

OBJECTIVE: To study the presence of several maternal and neonatal complications in a cohort of women with hyperandrogenic as well as normoandrogenic polycystic ovary syndrome (PCOS) and women with PCOS who received different fertility treatments. DESIGN: Prospective multicenter cohort study. SETTING: Hospitals and midwifery practices. PATIENT(S): One hundred and eighty-eight women with PCOS and singleton pregnancies (study group) and 2,889 women with a naturally conceived singleton pregnancy (reference group). INTERVENTION(S): Observational study. MAIN OUTCOME MEASURE(S): Maternal and neonatal pregnancy complications. RESULT(S): Women with PCOS had a statistically significantly increased risk of developing gestational diabetes (adjusted odds ratio [AOR] 4.15; 95% confidence interval [CI], 2.07-8.33) compared with the reference group, and their infants were more often born small for gestational age (AOR 3.76; 95% CI, 1.69-8.35). In a subgroup analysis, maternal complications were statistically significantly more often present in women with hyperandrogenic (defined as a free androgen index >4.5) PCOS (n = 76; 40% of all PCOS women) compared with those with normoandrogenic PCOS (n = 97; 52% of all PCOS women) (45% vs. 24%; P=.003); no statistically significant differences were observed between these groups regarding neonatal complications. CONCLUSION(S): Women with PCOS have an increased risk of maternal and neonatal pregnancy complications, especially women with the hyperandrogenic phenotype. CLINICAL TRIAL REGISTRATION NUMBER: NCT00821379.

Placental characteristics in women with polycystic ovary syndrome.

STUDY QUESTION: Are macroscopic and microscopic placental characteristics in a heterogeneous group of women diagnosed with polycystic ovary syndrome (PCOS) different from those of a low-risk general population? SUMMARY ANSWER: Women with PCOS have significantly different microscopic placental characteristics compared with control women, independently from pregnancy complications. WHAT IS KNOWN ALREADY: Non-obese women with PCOS who conceived spontaneously have a significantly reduced placental volume and weight, with more chronic villitis and intervillositis compared with healthy controls. STUDY DESIGN, SIZE, DURATION: A subset of a large prospective cohort study of pregnant women with PCOS was used. Healthy (low-risk) women who delivered at term after an uncomplicated pregnancy were used as the reference population. The placentas of 73 women with PCOS were analysed and compared with 209 placentas of healthy women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placentas were collected after delivery from women with PCOS who were followed from prior to conception until delivery. The placentas were macroscopically and microscopically analysed and compared with placentas of healthy women with either a spontaneous start of labour who delivered at term or who had an elective Caesarean section. MAIN RESULTS AND THE ROLE OF CHANCE: After adjusting for potential confounders, placentas from women with PCOS showed more chorioamnionitis (P < 0.001), funisitis (P = 0.019), villitis (P = 0.045), thrombosis (P = 0.018), infarction (P = 0.010), villous immaturity (P = 0.009) and nucleated fetal red blood cells (P < 0.001). In a subgroup analysis, among women with and without pregnancy complications within the PCOS group, only the occurrence of thrombosis was increased in pregnancies complicated by pregnancy-induced hypertension or pre-eclampsia (30%, versus 0% in gestational diabetes pregnancies and 13% in uncomplicated pregnancies; P = 0.008). LIMITATIONS, REASONS FOR CAUTION: There might be a small proportion of women with PCOS in the reference group, since this group was not screened for PCOS. As a result, the observed difference may be an underestimation of the true difference. Placentas were stored for up to 72 h at 4°C, this is common practice but some degenerative changes cannot be ruled out absolutely. Also, there is possibility that baseline differences between the groups may in part explain some of the differences in placental pathology. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that, in general, women with PCOS can have placental alterations associated with an increased hypoxic state, which seems not to be caused by the increased incidence of pregnancy complications.

Insulin action in women with polycystic ovary syndrome and its relation to gestational diabetes.

STUDY QUESTION: How does insulin action change during pregnancy in women with polycystic ovary syndrome (PCOS) who develop gestational diabetes (GDM) compared with women with PCOS who do not? SUMMARY ANSWER: Women with PCOS who develop GDM already show disturbed insulin action early in pregnancy. WHAT IS KNOWN ALREADY: Pregnant women with PCOS are at increased risk of developing GDM compared with women without PCOS. STUDY DESIGN, SIZE, DURATION: This study represents a post hoc analysis of a subgroup of pregnant women with PCOS participating in a multicentre prospective cohort study. A total of 72 women were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with PCOS and a wish to conceive were included before conception and followed during pregnancy. Insulin, glucose, homeostasis model assessment of insulin resistance (HOMA-IR), sex hormone-binding globulin (SHBG) and testosterone were analysed at three different time points in women who developed GDM and women who did not. MAIN RESULTS AND THE ROLE OF CHANCE: Seventy-two pregnant women with PCOS were included of which 22 (31%) women developed GDM. Both insulin levels and HOMA-IR were significantly higher at each sampling point in women with PCOS who developed GDM. SHBG levels were significantly lower before conception and in the second trimester compared with women who did not develop GDM. Testosterone concentrations were significantly lower before conception in women who developed GDM. After adjusting for BMI, waist circumference and waist/hip ratio, the differences in insulin, HOMA-IR, SHBG and testosterone levels remained largely the same. LIMITATIONS, REASONS FOR CAUTION: Selection bias cannot be excluded since only women from one centre with a complete blood sampling set were included in this study. WIDER IMPLICATIONS OF THE FINDINGS: The knowledge that women with PCOS who develop GDM already have a disturbed insulin action early in pregnancy is likely to be useful in considering the pathophysiology processes underlying this disorder in this specific group of women. STUDY FUNDING/COMPETING INTERESTS: This study was funded by the Child Health research programme of the University Medical Centre Utrecht. M.A.d.W., A.J.G., S.M.V.-V., A.F. and M.P.H.K. have no conflicts of interest to disclose. M.J.C.E. has received grant support from the following companies (in alphabetic order): Illumina and MSD. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Ferring, Ova-Science, PregLem SA, Roche and Watson Laboratories. The authors declare complete independence from funders. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov, number NCT00821379.

Fasting glucose measurement as a potential first step screening for glucose metabolism abnormalities in women with anovulatory polycystic ovary syndrome.

STUDY QUESTION: Is routine screening by oral glucose tolerance test (OGTT) needed for all women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Screening for glucose metabolism abnormalities of PCOS patients by an OGTT could potentially be limited to patients who present with a fasting glucose concentration between 6.1 and 7.0 mmol/l only. WHAT IS KNOWN ALREADY: Women with PCOS are at increased risk of developing diabetes. This study proposes a stepwise screening strategy for (pre)diabetes for PCOS patients based on risk stratification by fasting plasma glucose. STUDY DESIGN, SIZE, DURATION: A cross-sectional study of 226 women diagnosed with anovulatory PCOS. PARTICIPANTS AND SETTING: A consecutive series of 226 patients, diagnosed with PCOS at the University Medical Centre Utrecht, the Netherlands, were screened for glucose metabolism abnormalities by OGTT (75 g glucose load). MAIN RESULTS AND ROLE OF CHANCE: The majority of the 226 women (mean age: 29.6 ± 4.3 years; BMI: 27.3 ± 6.7 kg/m(2); 81% Caucasian) presented with a normal OGTT (169 women (75%)). Of the 57 (25%) women presenting with mild to moderate glucose abnormalities, 53 (93%) could be identified by fasting glucose concentrations only. Diabetes was diagnosed in a total of eight women (3.5%). In six women, the diagnosis was based on fasting glucose >7.0 mmol/l. The other two cases of diabetes initially presented with fasting glucose between 6.1 and 7.0 mmol/l and were diagnosed by OGTT assessment. No women diagnosed with diabetes presented with fasting glucose levels below 6.1 mmol/l. We therefore conclude that all diabetes patients could potentially be found by initial fasting glucose assessment followed by OGTT only in patients with fasting glucose between 6.1 and 7.0 mmol/l. LIMITATIONS, REASONS FOR CAUTION: Before general implementation can be advised, this screening algorithm should be validated in a prospective study of a similar or greater number of PCOS women. WIDER IMPLICATIONS OF THE FINDINGS: Our study comprised of a mostly Caucasian (81%) population, therefore generalization to other ethnic populations should be done with caution. STUDY FUNDING/COMPETING INTEREST(S): No external finance was involved in this study. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order); Andromed, Ardana, Ferring, Genovum, Merck Serono, MSD, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono and Wyeth. A.J.G. has received fees from Abbott, Bayer Schering and IBSA. T.W.H. has received fees from Merck, Sharpe & Dohme, GlaxoSmithKline, NovoNordisk and Eli Lilly. The authors declare complete independence from funders. CLINICAL TRIAL REGISTRATION NUMBER: NCT00821379.

Emotional distress is a common risk in women with polycystic ovary syndrome: a systematic review and meta-analysis of 28 studies.

BACKGROUND For a number of reasons, the results of previous meta-analyses may not fully reflect the mental health status of the average woman suffering from polycystic ovary syndrome (PCOS), or the causes of this distress. Our objective was to examine emotional distress and its associated features in women with PCOS. METHODS A comprehensive meta-analysis of comparative studies reporting measures of depression, anxiety or emotional-subscales of quality of life (emoQoL) was performed. PubMed, Embase, PsychInfo and the Cochrane trial register databases were searched up to November 2011 (see Supplementary Data for PUBMED search string). Unpublished data obtained through contact with authors were also included. The standardized mean difference (SMD) of distress scores was calculated. Subgroup analyses and meta-regression analysis of methodological and PCOS-related features were performed. RESULTS Twenty-eight studies (2384 patients and 2705 control women) were included. Higher emotional distress was consistently found for women with PCOS compared with control populations [main outcomes: depression: 26 studies, SMD 0.60 (95% confidence interval (CI) 0.47-0.73), anxiety: 17 studies, SMD of 0.49 (95% CI 0.36-0.63), emoQoL: 8 studies, SMD -0.66 (95% CI -0.92 to -0.41)]. However, heterogeneity was present (I(2) 52-76%). Methodological and clinical aspects only partly explained effect size variation. CONCLUSIONS Women with PCOS exhibit significantly more emotional distress compared with women without PCOS. However, distress scores mostly remain within the normal range. The cause of emotional distress could only partly be explained by methodological or clinical features. Clinicians should be aware of the emotional aspects of PCOS, discuss these with patients and refer for appropriate support where necessary and in accordance with patient preference.

High singleton live birth rate confirmed after ovulation induction in women with anovulatory polycystic ovary syndrome: validation of a prediction model for clinical practice.

OBJECTIVE: To evaluate the cumulative singleton live birth rate after classic ovulation induction in women with anovulatory polycystic ovary syndrome and to validate a previously developed prediction model. DESIGN: Prospective follow-up study. SETTING: Tertiary infertility unit. PATIENT(S): Validation cohort of 108 treatment-naïve anovulatory PCOS patients. INTERVENTION(S): Conventional ovulation induction, applying clomiphene citrate as first-line treatment, followed by exogenous gonadotropins as second-line intervention. MAIN OUTCOME MEASURE(S): Singleton live birth prediction. Model calibration and discrimination were assessed for the initial model (variables included age, duration of infertility, and insulin/glucose ratio) and a second model in which the insulin/glucose ratio was replaced by body mass index. RESULT(S): The cumulative singleton live birth rate after 12 and 24 months was 60% and 78%, respectively. Overall, the observed rates were higher than predicted: hazard ratio 1.21 (95% confidence interval [CI] 0.89, 1.64), first model and 1.25 (95% CI 1.20, 1.30), second model. However, the predictive capacity of the model variables was reliable, with calibration slopes of 0.79 (95% CI -0.04, 1.63) and 1.06 (95% CI 0.95, 1.18), respectively. CONCLUSION(S): The present study confirms the previously reported good treatment prognosis for women with PCOS undergoing classic ovulation induction. Women with a poor prognosis, for whom alternative treatment options may be considered, can best be identified by a prediction model including age, duration of infertility, and body mass index. CLINICAL TRIAL REGISTRATION NUMBER: NCT00821379.

Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk.

OBJECTIVE: Primary prevention of cardiovascular disease (CVD) in women is a major healthcare issue. Detection of premenopausal women with increased risk of CVD could enhance prevention strategies and reduce first event-related morbidity and mortality. In this study, we argue that an unfavorable metabolic constitution in women may present itself early in life as a reproductive complication, such as polycystic ovary syndrome (PCOS) and preeclampsia. We evaluated the cardiovascular risk of women with a history of early-onset preeclampsia and women with PCOS and assessed their need for implementation of early risk factor-reduction strategies. METHODS: We performed a standardized evaluation of 240 women with a history of early-onset preeclampsia and 456 women diagnosed with PCOS for established major CVD risk factors. Metabolic syndrome characteristics were analyzed per body mass index category. RESULTS: Mean age was 30.6 and 29.0 years for women with preeclampsia and PCOS, respectively. High percentages of metabolic syndrome were found in both groups (preeclampsia group, 14.6%; and PCOS group, 18.4%), with an incidence of greater than 50% in both groups of women if body mass index was greater than 30 kg/m. Overall, more than 90% of the women qualified for either lifestyle or medical intervention according to the American Heart Association guideline for CVD prevention in women. CONCLUSIONS: Women with PCOS and early-onset preeclampsia already show an unfavorable cardiovascular risk profile with high need for lifestyle or medical intervention at a young age. We therefore recommend an active role of the gynecologist in routine screening and follow-up of women with reproductive conditions linked to future cardiovascular risk.