A value-based healthcare approach: Health-related quality of life and psychosocial functioning in women with Turner syndrome.

OBJECTIVE: As part of the value-based healthcare programme in our hospital, a set of patient-reported outcome measures was developed together with patients and implemented in the dedicated Turner Syndrome (TS) outpatient clinic. This study aims to investigate different aspects of health-related quality of life (HR-QoL) and psychosocial functioning in women with TS in order to establish new possible targets for therapy. DESIGN/PARTICIPANTS: A comprehensive set of questionnaires (EQ-5D, PSS-10, CIS-20, Ferti-QoL, FSFI) was developed and used to capture different aspects of HR-QoL and psychosocial functioning in a large cohort of adult women with Turner syndrome. All consecutive women, ≥18 years, who visited the outpatient clinic of our tertiary centre were eligible for inclusion. RESULTS: Of the eligible 201 women who were invited to participate, 177 women (age 34 ± 12 years, mean ± SD) completed at least one of the validated questionnaires (88%). Women with TS reported a lower health-related quality of life (EQ-5D: 0.857 vs 0.892, P = .003), perceived more stress (PSS-10:14.7 vs 13.3; P = .012) and experienced increased fatigue (CIS-20: P < .001) compared to the general Dutch population. A relationship between noncardiac comorbidities (eg diabetes, orthopaedic complaints) and HR-QoL was found (R = .508). CONCLUSIONS: We showed that TS women suffer from impaired HR-QoL, more perceived stress and increased fatigue compared to healthy controls. A relationship between noncardiac comorbidities and HR-QoL was found. Especially perceived stress and increased fatigue can be considered targets for improvement of HR-QoL in TS women.

Long-Term Cortisol Exposure and Associations With Height and Comorbidities in Turner Syndrome.

CONTEXT: Turner syndrome (TS) usually manifests in traits as short stature and premature ovarian failure. Many patients also have an increased risk of cardiometabolic disorders and psychological distress, which are features that overlap with those of a prolonged state of hypercortisolism. OBJECTIVE: To investigate whether TS is associated with increased long-term cortisol concentrations as measured in scalp hair and whether these are linked to cardiometabolic and psychological parameters. DESIGN: Prospective observational case-control study. SETTING: Academic outpatient TS expertise center. PARTICIPANTS: Fifty-five patients with TS (53% 45,X karyotype), and 110 age-matched female community control subjects from the general population-based Lifelines cohort study. MAIN OUTCOME MEASURES: Hair cortisol concentrations (HCC), anthropometrics, biochemical parameters, and psychological questionnaires for perceived stress (Perceived Stress Scale-14), fatigue (Checklist Individual Strength-20), and health-related quality of life (RAND-36). RESULTS: Compared with control subjects, patients with TS had higher HCC [geometric mean, 3.51 pg/mg (95% CI, 2.64 to 4.65) vs 2.39 pg/mg (2.13 to 2.68); P = 0.003] and a worse cardiometabolic profile in terms of fasting glucose, and triglycerides. HCC was only associated with total cholesterol levels (standardized ß = 0.294; P = 0.047) and was not associated with the psychological outcomes. A higher HCC was inversely associated with height only in patients with TS (standardized ß = -0.307; P = 0.023). CONCLUSION: Patients with TS are chronically exposed to higher cortisol levels, which is associated with short stature and increased total cholesterol levels, and potentially contributes to the known elevated cardiovascular disease risk.

Wish to conceive and concerns to develop cardiovascular complications during pregnancy in patients with Turner syndrome.

INTRODUCTION: Turner syndrome (TS) is associated with subfertility and infertility. Nevertheless, an increasing number of women become pregnant through oocyte donation. The wish to conceive may be negatively influenced by the fear of cardiovascular complications. The aim was to investigate the wish to conceive and the concerns about cardiovascular complications during pregnancy in women with TS. METHODS: The patient association for TS invited all members of ≥18 years old (n = 344) to complete a specifically developed, disease-specific questionnaire, including questions about fertility, wish to conceive, attempts and concerns. Results were compared with previously published results of this questionnaire in women with congenital heart disease. RESULTS: The questionnaire was completed by 89 women (median age 30.1 years, Q1-Q3 = 22.9-39.4). Of them, 51% had 45, X0-monosomy and 38% had ≥1 cardiac abnormality. Seventeen women (19%) had attempted to become pregnant and 12 of them succeeded to become pregnant. Women who had not undertaken attempts to conceive (81%), considered themselves mainly too young or had no partner. Of the total sample, 58% were concerned about the influence of pregnancy on their cardiovascular status. This was higher (75%) in the sample of women with TS and cardiac abnormalities, than in women with congenital heart disease from a previously published cohort (21%), (p < .001). There were no differences in concerns about pregnancy complications between women with TS who respectively had or had not attempted to become pregnant. DISCUSSION: Women with TS, especially those with cardiac abnormalities, show serious concerns about the risks pregnancy may have. Patients should be timely counseled and specifically asked about their concerns. Psychosocial care should be provided when necessary.

Hysteroscopy before in-vitro fertilisation (inSIGHT): a multicentre, randomised controlled trial.

BACKGROUND: Hysteroscopy is often done in infertile women starting in-vitro fertilisation (IVF) to improve their chance of having a baby. However, no data are available from randomised controlled trials to support this practice. We aimed to assess whether routine hysteroscopy before the first IVF treatment cycle increases the rate of livebirths. METHODS: We did a pragmatic, multicentre, randomised controlled trial in seven university hospitals and 15 large general hospitals in the Netherlands. Women with a normal transvaginal ultrasound of the uterine cavity and no previous hysteroscopy who were scheduled for their first IVF treatment were randomly assigned (1:1) to either hysteroscopy with treatment of detected intracavitary abnormalities before starting IVF (hysteroscopy group) or immediate start of the IVF treatment (immediate IVF group). Randomisation was done with web-based concealed allocation and was stratified by centre with variable block sizes. Participants, doctors, and outcome assessors were not masked to the assigned group. The primary outcome was ongoing pregnancy (detection of a fetal heartbeat at >12 weeks of gestation) within 18 months of randomisation and resulting in livebirth. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01242852. FINDINGS: Between May 25, 2011, and Aug 27, 2013, we randomly assigned 750 women to receive either hysteroscopy (n=373) or immediate IVF (n=377). 209 (57%) of 369 women eligible for assessment in the hysteroscopy group and 200 (54%) of 373 in the immediate IVF group had a livebirth from a pregnancy during the trial period (relative risk 1·06, 95% CI 0·93-1·20; p=0·41). One (<1%) woman in the hysteroscopy group developed endometritis after hysteroscopy. INTERPRETATION: Routine hysteroscopy does not improve livebirth rates in infertile women with a normal transvaginal ultrasound of the uterine cavity scheduled for a first IVF treatment. Women with a normal transvaginal ultrasound should not be offered routine hysteroscopy. FUNDING: The Dutch Organisation for Health Research and Development (ZonMW).

A comparison of perinatal outcomes in singletons and multiples born after in vitro fertilization or intracytoplasmic sperm injection stratified for neonatal risk criteria.

OBJECTIVE: To compare perinatal singleton and multiple outcomes in a large Dutch in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) population and within risk subgroups. Newborns were assigned to a risk category based on gestational age, birthweight, Apgar score and congenital malformation. DESIGN: Register-based retrospective cohort study. SETTING: Netherlands Perinatal Registry data. SAMPLE: A total of 3041 singletons and 1788 multiple children born from IVF/ICSI in 2003-2005. METHODS: Student's t-test or Mann-Whitney U-test was used to analyze continuous data, chi-squared analyses were used for categorical data. Multivariate logistic and linear regression analysis was performed to analyze whether the risk stratification criteria were associated with neonatal hospital admission and length of stay. MAIN OUTCOME MEASURES: Start of labor, mode of delivery, gestational age, birthweight, 5-min Apgar score, congenital malformation, neonatal hospital admission, neonatal intensive care unit admission and mortality. RESULTS: IVF/ICSI-conceived multiples had considerably poorer outcomes than singletons in terms of cesarean section rate, preterm birth, birthweight, being small-for-gestational-age, Apgar score, neonatal hospital admission, neonatal intensive care unit admission and neonatal mortality. As opposed to the results found in the total study population and the low-risk and moderate-risk populations, high-risk multiples showed better outcomes than high-risk singletons regarding cesarean section rate, birthweight and Apgar score. All risk stratification variables were associated with being hospitalized after birth. Length of stay was associated with all risk stratification criteria except Apgar score. CONCLUSIONS: Perinatal outcomes in IVF/ICSI-conceived multiples are considerably poorer than in singletons. This finding mainly pertains to low-risk children. High-risk multiples had significantly better perinatal outcomes than high-risk singletons.

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study.

BACKGROUND: Pregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective. METHODS/DESIGN: A multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness. DISCUSSION: This is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies.

Clinical management of ovarian small-cell carcinoma of the hypercalcemic type: a proposal for conservative surgery in an advanced stage of disease.

Ovarian small-cell carcinoma of the hypercalcemic type is a rare and highly malignant tumor. In two thirds of the patients, the tumor is associated with asymptomatic paraneoplastic hypercalcemia. The diagnosis may be impeded; the tumor must be distinguished from other tumors with similar features.This tumor occurs predominantly in young women and is merely lethal. The 1-year survival is solely 50%, with an overall 5-year survival rate of approximately 10%. It is believed that the empirical treatment characterized by combination of radical surgery, chemotherapy, and radiotherapy results in the most favorable outcome in terms of survival. However, the outcome remains extremely poor despite this aggressive approach.Alternatively, these poor survival rates may justify a less aggressive fertility sparing approach without compromising the outcome. Such an approach is illustrated by a case report involving a patient with ovarian small-cell carcinoma of the hypercalcemic type, FIGO stage IIIC. A fertility-sparing approach was used, consisting of conservative surgery followed by induction chemotherapy, interval debulking surgery, and local radiotherapy. During follow-up of 60 months, there was no evidence of disease and the normal menstrual cycle resumed.In addition to this case report, histopathological features, different therapeutic modalities, and outcome of ovarian small-cell carcinoma of the hypercalcemic type is reviewed. This report suggests that a fertility-sparing approach may be just as feasible as the generally applied aggressive approach.