BACKGROUND Polycystic ovary syndrome (PCOS) is associated with metabolic abnormalities. It is debated whether all women with PCOS should be screened for metabolic abnormalities as these may vary with ...PCOS phenotype, age and ethnicity. The aims of this study were to assess the prevalence of metabolic abnormalities in Dutch anovulatory PCOS women and to define criteria for metabolic screening. METHODS Anovulatory patients, diagnosed with PCOS according to the Rotterdam consensus criteria, underwent metabolic screening. Through stepwise multivariate analysis patient characteristics associated with metabolic syndrome (MetS) and insulin resistance (IR) were evaluated for their use as selection parameters for metabolic screening. RESULTS Overall, prevalence of MetS and IR was 15.9% (n = 25) and 14% (n = 22), respectively, in 157 PCOS women (age 29.0 ± 4.8 years, BMI 26.1 ± 6.7 kg/m2). Anovulatory hyperandrogenic women (with or without polycystic ovaries) had more often MetS and IR (with, 20.8 and 19.8%; without, 100 and 40%, respectively) than non-hyperandrogenic PCOS women (0 and 1.8%; P < 0.001). Waist circumference >83.5 cm along with increased free androgen index (FAI) had the most powerful association with the presence of MetS and IR (area under the receiver operating characteristic curve 0.912) and offered a reduction in the necessity of screening for metabolic derailments of about 50%. CONCLUSIONS The hyperandrogenic PCOS phenotypes are highly linked to the presence of MetS and IR in Dutch PCOS women. Waist circumference combined with FAI was identified as an efficient combination test to select those PCOS women who should be screened for the presence of MetS and/or IR.
Couples affected by idiopathic subfertility or male subfertility have an estimated spontaneous conception rate of about 2% per cycle. Although various infertility treatments are available, ...counselling of a couple in their choice of treatment is difficult because of the lack of consistent data from good-quality comparative studies. We compared the results of treatment with intrauterine insemination (IUI) with those of in-vitro fertilisation (IVF), and did a cost-effectiveness analysis.
In a prospective, randomised, parallel trial, 258 couples with idiopathic subfertility or male subfertility were treated for a maximum of six cycles of either IUI in the spontaneous cycle (IUI alone), IUI after mild ovarian hyperstimulation, or IVF. The primary endpoint was a pregnancy resulting in at least one livebirth after treatment. Cost-effectiveness based on real costs was studied by Markov chain analysis.
86 couples were assigned IUI alone, 85 IUI plus ovarian hyperstimulation, and 87 IVF. Ten couples dropped out before treatment began. Although the pregnancy rate per cycle was higher in the IVF group than in the IUI groups (12·2%
vs 7·4% and 8·7%, respectively; p=0·09), the cumulative pregnancy rate for IVF was not significantly better than that for IUI. Couples in the IVF group were more likely than those in the IUI groups to give up treatment before their maximum of six attempts (37 42% drop-outs
vs 13 15% and 14 16%, respectively; p < 0·01). The woman's age was the only factor that influenced a couple's chance of success. IUI was a more cost-effective treatment than IVF (costs per pregnancy resulting in at least one livebirth 8423–10 661 Dutch guilders US$4511–5710 for IUI
vs 27 409 Dutch guilders US$14 679 for IVF).
Couples with idiopathic or male subfertility should be counselled that IUI offers the same likelihood of successful pregnancy as IVF, and is a more cost-effective approach. IUI in the spontaneous cycle carries fewer health risks than does IUI after mild hormonal stimulation and is therefore the first-choice treatment.
BACKGROUND: The high iatrogenic multiple pregnancy rate associated with intrauterine insemination (IUI) in hyperstimulated cycles is becoming less acceptable. Therefore we investigated data from an ...earlier prospective trial with regard to the specific question of whether the application of mild hyperstimulation in IUI cycles could be an alternative strategy for obtaining acceptable pregnancy rates while preventing a high multiple pregnancy rate, compared with natural cycles for IUI. METHODS: Pregnancy outcome of 310 natural and 334 mildly hyperstimulated cycles for IUI in 171 couples with unexplained or mild male factor subfertility was analysed on a patient level with random coefficient models. RESULTS: Pregnancy rates were similar: 35 and 39.8% per couple in the natural and mildly hyperstimulated cycles respectively (P = 0.60). Multiple pregnancies, all twin pregnancies, were conceived significantly more frequently in the mild hyperstimulation group (27% of the pregnancies) than in the natural cycle group (4% of the pregnancies) (P = 0.01). All multiple pregnancies in the hyperstimulation group were conceived in multifollicular cycles. Multifollicular development was strongly associated with the application of mild hyperstimulation only (odds ratio 21.14, 95% confidence interval 8.15–54.79). CONCLUSION: The application of a mild hyperstimulation protocol as an alternative to a standard hyperstimulation protocol for IUI does not result in higher pregnancy rates than IUI in the natural cycle, while at the same time multiple pregnancies cannot be avoided. Therefore, there is no place for the use of gonadotrophins in IUI treatment.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a complex disorder with variable prevalence and clinical presentation in different populations, which may be mediated by geographical and ethnic ...background.
METHODS
We performed a comparison of phenotypic characteristics between 547 Chinese and 427 Dutch women with PCOS and oligo/amenorrhoea attending University Reproductive Centers in China and the Netherlands.
RESULTS
Chinese women presenting with a clinical diagnosis of PCOS were observed to have a higher incidence of hyperandrogenism (HA) (P < 0.001) and amenorrhoea (P < 0.001) compared with Dutch women, but no difference was observed in the incidence of polycystic ovaries (PCOs). Using population-specific cut-off values, Chinese women with PCOS demonstrated a higher incidence of increased BMI (P < 0.001), waist circumference (WC) (P < 0.001) and waist–hip ratio (P < 0.001) than Dutch women. In both groups, HA was associated with increased age, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and serum LH while PCOs correlated with BMI, WC, HOMA-IR, fasting insulin and elevated total testosterone. Associations specific for ethnic background were found between LH and HA, and between both BMI and HOMA-IR, and PCOs.
CONCLUSIONS
Reproductive and metabolic characteristics differed between the two ethnic groups. Chinese women were found to present more frequently with a phenotype associated with increased risk of metabolic complications later in life, compared with Dutch Caucasian women. Ethnicity seems to determine part of the specific phenotypical presentation of PCOS.
BACKGROUND Low plasma sex hormone-binding globulin (SHBG) concentrations during pregnancy have been associated with the risk of developing gestational diabetes mellitus (GDM). Women presenting with ...polycystic ovary syndrome (PCOS) often exhibit low plasma SHBG concentration and are at increased risk of developing GDM. In this study, we investigate whether SHBG levels before conception are predictive of GDM in women with PCOS. METHODS A total of 50 women with PCOS were enrolled and followed up during pregnancy. Initial endocrine, metabolic and physical features were assessed according to a standardized preconception screening program. At 24–26 weeks of gestational age a 100-g glucose tolerance test was performed to screen for GDM. RESULTS Of the 50 women, 21 (42%) were diagnosed with GDM by a 100-g glucose tolerance test. Waist circumference, BMI, blood pressure, plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and SHBG levels before conception were significantly different between women who did and did not develop GDM. Stepwise logistic regression analysis showed that SHBG was the most significant predictive parameter for GDM (odds ratio 0.92; 95% confidence interval 0.87–0.97), without significant contribution of waist circumference and HOMA-IR. Receiver operator characteristic (ROC) analysis indicated that plasma SHBG (area under the curve 0.86) had the highest predictive value for subsequent development of GDM, however, the limited group size did not allow for calculation of a threshold value of SHBG. CONCLUSIONS In women with PCOS, preconception SHBG levels are strongly associated with subsequent development of GDM. Regression and ROC analysis show that preconception SHBG levels may be a better predictor for GDM in PCOS women compared with waist circumference or HOMA-IR. Clinical trial registration number: NCT00821379
STUDY QUESTION
Can we develop an adequate preconception prediction model to identify those women with polycystic ovary syndrome (PCOS) who have an increased risk of developing gestational diabetes ...mellitus (GDM) during subsequent pregnancy?
STUDY ANSWER
The risk of developing GDM in women with PCOS can be adequately predicted prior to conception by a prediction model.
WHAT IS KNOWN ALREADY
Women with PCOS are at increased risk of pregnancy complications, especially GDM. GDM has serious short-term and long-term effects on mother and baby.
STUDY DESIGN, SIZE, DURATION
This study is a part of a multicentre prospective cohort study, which was conducted between April 2008 and April 2012. A total of 326 women with PCOS were included.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women with PCOS and a wish to conceive were included prior to conception and followed until 6 weeks after delivery. Maternal, neonatal and birth complications were reported. A multivariate model was developed to predict the most common pregnancy complication, GDM, by using univariate and multivariate logistic regression of preconception patient characteristics. The area under the curve (AUC) of the receiver-operating characteristic was used to test the performance of the model.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 189 women (58%) achieved an ongoing pregnancy (8% multiples) and delivered a live-born neonate. One or two maternal complications occurred in 62 (33%) pregnant women, mainly GDM (n = 41; 22%) and pregnancy-induced hypertension (n = 14; 7%). In children, one or two complications were observed in 49 (26%) of 206 children born, e.g. premature delivery (n = 23; 12%) and small for gestational age (n = 15; 8%). The preconception prediction model for GDM performed well (AUC 0.87, 95% CI 0.81–0.93). First-degree relatives with type 2 diabetes mellitus, serum levels of fasting glucose, fasting insulin, androstenedione and sex hormone-binding globulin before conception were identified as predictors.
LIMITATIONS, REASONS FOR CAUTIONS
The prediction model has not yet been externally validated in another group of patients. Also, there were missing data for some of the determinants, which were accounted for by multiple imputation.
WIDER IMPLICATIONS OF THE FINDINGS
Women with PCOS who achieve a pregnancy have an increased risk of GDM. The prediction model can be used to identify women particularly at risk for GDM who should be monitored closely to enable preventative measures that may reduce the risk of developing GDM and its adverse consequences.
STUDY FUNDING/COMPETING INTEREST(S)
No external funding was used for the study. M.A.W., S.M.V.V., A.J.G., A.F. and M.P.H.K. have nothing to disclose. C.B.L has received fees and grant support from the following companies (in alphabetic order): Auxogen, European Society of Human Reproduction and Embryology and MSD. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Gennovum, Merck-Serono, MSD, Organon, Schering Plough, Sharp & Dome and Serono. M.J.C. 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.
TRIAL REGISTRATION NUMBER
NCT00821379 Clinicaltrials.gov.
STUDY QUESTION
Are fragile X mental retardation gene 1 (FMR1) CGG repeats in the normal and intermediate range (up to 55 repeats) associated with primary ovarian insufficiency (POI) in a large ...case–control study?
SUMMARY ANSWER
No association was found between CGG repeats of intermediate size and POI compared with controls.
WHAT IS KNOWN ALREADY
CGG repeats in the FMR1 gene in the premutation range (55–200 repeats) have consistenly associated with POI. Intermediate range CGG repeats have been considered for a potential association with POI.
STUDY DESIGN, SIZE
A case–control study in 375 well-phenotyped Dutch women diagnosed with POI and 3368 controls with natural menopause ≥40 years of age.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The FMR1 CGG repeat number was determined by PCR amplification in women diagnosed with POI and women with a known age at natural menopause ≥40 years. The prevalence of intermediate sized CGG repeats (45–54 repeats) was compared between POI cases and controls using Fisher's exact test. Differences in mean CGG repeat lengths on allele 1 and allele 2 between POI cases and controls were tested using analysis of variance.
MAIN RESULTS AND THE ROLE OF CHANCE
The frequency of intermediate sized CGG repeats on the allele with the longest triple repeat number was not statistically significantly different between POI cases and controls (2.7 and 3.8%, respectively, odds ratio 0.72, 95% confidence interval: 0.38–1.39, P = 0.38). In women with POI, linear regression analysis for age at POI diagnosis and CGG repeat size also failed to show any association (β = −0.018, P = 0.74).
LIMITATIONS, REASONS FOR CAUTION
FMR1 CGG repeat lengths in POI cases and controls were genotyped in two different laboratories. The distributions of CGG repeats may vary among the different ethnic populations in our study. Also, in our study women with primary amenorrhea (N = 17) were included in the POI group.
WIDER IMPLICATIONS OF THE FINDINGS
We found no association between intermediate sized CGG repeats and POI compared with controls. Therefore, a role for FMR1 CGG repeat sizes up to 55 repeats in the ovarian ageing process may be questioned. Moreover, there seems limited value in the evaluation of normal- and intermediate FMR1 repeat size in the diagnostic work-up of women affected by POI, or for prognostic purposes in women at risk of developing POI.
STUDY FUNDING/COMPETING INTEREST(S)
The Prospect-EPIC study was funded by ‘Europe Against Cancer’ Program of the European Commission (SANCO); the Dutch Ministry of Health; the Dutch Cancer Society; ZonMW the Netherlands Organization for Health Research and Development; World Cancer Research Fund (WCRF) and the Dutch Heart Association.
Objective In this study the first results are presented of a new endovascular technique using covered stents to reconstruct the aortic bifurcation in patients with aortoiliac occlusive disease. With ...the “Covered Endovascular Reconstruction of the Aortic Bifurcation” (CERAB) technique, the anatomy and physiology of the aortic bifurcation is mimicked. Material and methods Between 2009 and March 2014, 103 patients (51 male, 52 female) suffering from obstructive lesions at the level of the aortic bifurcation were treated with CERAB in two clinics. The median age was 61 years (range 36–85 years). Lesion morphology was evaluated by CT angiography. Six TASC-II B lesions, nine TASC-II C lesions, and 88 TASC-II D lesions were treated. Follow up was a median 12 months (range 0–49 months) and consisted of clinical examination, ankle brachial indices, and duplex ultrasound examination. Results Technical success was obtained in 98 procedures (95.1%). In five cases lesions could not be recanalized. Primary patency was 87.3% at 1 year and 82.3% at 2 years, while secondary patency was 95.0% at 1 year and 95.0% at 2 years. Mean ankle brachial indices improved significantly from 0.64 ± 0.21 before to 0.91 ± 014, after the procedure ( p < .001). The overall 30 day complication rate was 23.3%, including 22 minor complications and two major complications (1.9%). There was no 30 day mortality. Median hospital stay was 2 days (range 1–16 days). Conclusions The CERAB technique appears to be a safe and feasible alternative to open surgical reconstruction of the aortic bifurcation in complex occlusive disease. Comparative studies with the current gold standards are indicated.
Müllerian (paramesonephric) duct anomalies (MDAs) are associated with several coexisting congenital abnormalities, including renal abnormalities. Although congenital renal abnormalities may remain ...asymptomatic, the consequences should not be underestimated. In both the literature and clinical practice, it remains necessary to improve awareness of the co-occurrence of different congenital renal abnormalities in women with MDAs. To gain further insight into this co-occurrence and to estimate whether guidelines for women with MDAs should be optimized, this study was performed.
A descriptive retrospective analysis.
University Medical Centre Utrecht in the Netherlands.
Women with MDAs diagnosed or treated between 1980 and 2015.
None.
The prevalence of the co-occurrence of congenital renal abnormalities in women with MDAs.
Renal status was recorded in 186 of 255 women (72.9%), and the other women (27.1%) did not have a retrievable renal status. Congenital renal abnormalities were present in 90 of 186 women (48.4%) and were observed most frequently in women having a duplex uterus with obstructed hemivagina. The most common renal abnormality was unilateral renal agenesis, which was observed in 58 of 90 women (64.4%).
MDAs are highly associated with different congenital renal abnormalities, and these results emphasize that women with MDAs should be routinely screened for their co-occurrence. However, these results also highlight that there remains a lack of awareness of this association. Whether all women with congenital renal abnormalities should be routinely screened for MDAs requires further investigation.
BACKGROUND: With the occasional reports of unexpectedly poor ovarian response to controlled ovarian hyperstimulation (COH) for IVF in young normally cyclic women in mind, we studied age-related ...ovarian response to COH in a group of women who underwent standard IVF. METHODS: Ovarian response to COH was defined as the number of follicles ≥14 mm on the day of hCG administration. Ovarian response to COH was analysed by multiple regression analysis with woman's age and basal FSH concentration as explanatory variables in a prospective cohort of patients with idiopathic and mild male factor subfertility (n=85), and additionally in a large retrospective cohort of women with unexplained, mild male and tubal subfertility (n=1155), with age as explanatory variable. RESULTS: Ovarian response to COH was associated significantly with age (P<0.001) and basal FSH concentration (P=0.002). However, in women with idiopathic or mild male subfertility, in both cohorts the relationship took the form of an inverted U-shape with both older and—surprisingly—young women having a reduced ovarian response (P<0.001). Maximum ovarian response was around the age of 28 years. In women with tubal infertility, there was only a linear decline of ovarian response with age. CONCLUSION: It is hypothesized that diminished ovarian response to COH in IVF is the very first sign of ovarian ageing in young women diagnosed with idiopathic and mild male subfertility.
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