Mol, B.W.J.

Obstetrical outcome valuations by patients, professionals, and laypersons: Differences within and between groups using three valuation methods (Article)

2011-11-12T00:00:00Z

Background: Decision-making can be based on treatment preferences of the patient, the doctor, or by guidelines based on lay people's preferences. We compared valuations assigned by three groups: patients, obstetrical care professionals, and laypersons, for health states involving both mother and (unborn) child. Our aim was to compare the valuations of different groups using different valuation methods and complex obstetric health outcome vignettes that involve both maternal and neonatal outcomes.Methods: Patients (n = 24), professionals (n = 30), and laypersons (n = 27) valued the vignettes using three valuation methods: visual analogue scale (VAS), time trade-off (TTO), and discrete choice experimentation (DCE). Each vignette covered five health attributes: maternal health ante partum, time between diagnosis and delivery, process of delivery, maternal outcome, and neonatal outcome. We used feasibility questionnaires, Generalization theory, test-retest reliability and within-group reliability to compare the valuation patterns between groups and methods. We assessed relative weights from each valuation method to test for consistency across groups.Results: Test-retest reliability was equal across groups, but different across methods: highest for VAS (ICC = 0.61-0.73), intermediate for TTO (ICC = 0.24-0.74) and lowest for DCE (kappa = 0.15-0.37). Within-group reliability was highest in all groups with VAS (ICC = 0.70-0.73), intermediate with DCE (kappa = 0.56-0.76) and lowest with TTO (ICC = 0.20-0.66). Effects of groups were smaller than effects of methods. Differences between groups were largest for severe health states.Conclusion: Based on our results, decision making among laypersons should use TTO or DCE; patients should use VAS or TTO.

Chlamydia trachomatis IgG seropositivity is associated with lower natural conception rates in ovulatory subfertile women without visible tubal pathology (Article)

2011-11-01T00:00:00Z

Background The relation between Chlamydia trachomatis infection and subsequent tubal damage is widely recognized. As such, C. trachomatis antibody (CAT) testing can be used to triage women for immediate tubal testing with hysterosalpingography (HSG) or laparoscopy. However, once invasive tubal testing has ruled out tubal pathology, CAT serology status is ignored, as its clinical significance is currently unknown. This study aimed to determine whether positive CAT serology is associated with lower spontaneous pregnancy rates in women in whom HSG and/or diagnostic laparoscopy showed no visible tubal pathology. Methods We studied ovulatory women in whom HSG or laparoscopy showed patent tubes. Women were tested for C. trachomatis immunoglobulin G (IgG) antibodies with either micro-immunofluorescence (MIF) or an ELISA. CAT serology was positive if the MIF titre was <1:32 or if the ELISA index was >1.1. The proportion of couples pregnant without treatment was estimated at 12 months of follow-up. Time to pregnancy was considered censored at the date of the last contact when the woman was not pregnant or at the start of treatment. The association between CAT positivity and an ongoing pregnancy was evaluated with Cox regression analyses. Results Of the 1882 included women without visible tubal pathology, 338 (18) had a treatment-independent pregnancy within 1 year [estimated cumulative pregnancy rate 31; 95 confidence interval (CI): 2735]. Because of differential censoring after 9 months of follow-up, regression analyses were limited to the first 9 months after tubal testing. Positive C. trachomatis IgG serology was associated with a statistically significant 33 lower probability of an ongoing pregnancy [adjusted fecundity rate ratio 0.66 (95 CI 0.490.89)]. Conclusions Even after HSG or laparoscopy has shown no visible tubal pathology, subfertile women with a positive CAT have lower pregnancy chances than CAT negative women. After external validation, this finding could be incorporated into existing prognostic models.

Preventing preterm birth with progesterone: Costs and effects of screening low risk women with a singleton pregnancy for short cervical length, the Triple P study (Article)

2011-10-24T00:00:00Z

Background: Women with a short cervical length in mid-trimester pregnancy have a higher risk of preterm birth and therefore a higher rate of neonatal mortality and morbidity. Progesterone can potentially decrease the number of preterm births and lower neonatal mortality and morbidity. Previous studies showed good results of progesterone in women with either a history of preterm birth or a short cervix. However, it is unknown whether screening for a short cervix and subsequent treatment in mid trimester pregnancy is effective in low risk women.Methods/Design: We plan a combined screen and treat study among women with a singleton pregnancy without a previous preterm birth. In these women, we will measure cervical length at the standard anomaly scan performed between 18 and 22 weeks. Women with cervical length ≤ 30 mm at two independent measurements will be randomly allocated to receive either vaginal progesterone tablets or placebo between 22 and 34 weeks. The primary outcome of this trial is adverse neonatal condition, defined as a composite outcome of neonatal mortality and severe morbidity. Secondary outcomes are time to delivery, preterm birth rate before 32, 34 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We will assess growth, physical condition and neurodevelopmental outcome of the children at two years of age.Discussion: This study will provide evidence for the usefulness and cost-effectiveness of screening for short cervical length at the 18-22 weeks and subsequent progesterone treatment among low risk women.Trial registration: Netherlands Trial Register (NTR): NTR207.

17α-hydroxyprogesterone caproate for the prevention of adverse neonatal outcome in multiple pregnancies: A randomized controlled trial (Article)

2011-09-01T00:00:00Z

Objective: To estimate whether administration of 17α- hydroxyprogesterone caproate can prevent neonatal morbidity in multiple pregnancies by reducing the preterm birth rate. Methods: We conducted a multicenter, double-blind, placebo-controlled randomized trial in 55 obstetric clinics in the Netherlands. Women with a multiple pregnancy were randomized to weekly injections of either 250 mg 17α-hydroxyprogesterone caproate or placebo, starting between 16 and 20 weeks of gestation and continuing until 36 weeks of gestation. The main outcome measure was adverse neonatal outcome. Secondary outcome measures were gestational age at delivery and delivery before 28, 32, and 37 weeks of gestation. Results: We randomized 671 women. A composite measure of adverse neonatal outcome was present in 110 children (16%) born to mothers in the 17α-hydroxyprogesterone caproate group, and in 80 children (12%) of mothers in the placebo group (relative risk [RR] 1.34; 95% confidence interval [CI] 0.95-1.89). The mean gestational age at delivery was 35.4 weeks for the 17α-hydroxyprogesterone caproate group and 35.7 weeks for the placebo group (P=.32). Treatment with 17α-hydroxyprogesterone caproate did not reduce the delivery rate before 28 weeks (6% in the 17α- hydroxyprogesterone caproate group compared with 5% in the placebo group, RR 1.04; 95% CI 0.56-1.94), 32 weeks (14% compared with 10%, RR 1.37; 95% CI 0.91-2.05), or 37 weeks of gestation (55% compared with 50%, RR 1.11; 95% CI 0.97-1.28). Conclusion: 17α-hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in multiple pregnancies.

Health-related quality of life after induction of labor versus expectant monitoring in gestational hypertension or preeclampsia at term (Article)

2011-08-01T00:00:00Z

Objective. Gestational hypertension (GH) and preeclampsia (PE) are major contributors to maternal and neonatal morbidity and mortality. In GH or PE, labor may be either induced or monitored expectantly. We studied maternal health-related quality of life (HR-QoL) after induction of labor versus expectant monitoring in GH or PE at term. We performed the HR-QoL study alongside a multicenter randomized controlled trial comparing induction of labor to expectant monitoring in women with GH or PE after 36 weeks. Methods. We used written questionnaires, covering background characteristics, condition-specific issues, and validated measures: the Short-Form (SF-36), European Quality of Life (EuroQoL 6D3L), Hospital Anxiety and Depression Scale (HADS), and Symptom Checklist (SCL-90). Measurements were at the following time points: baseline, 6 weeks postpartum, and 6 months postpartum. A multivariate mixed model with repeated measures was defined to assess the effect of the treatments on the physical component score (PCS) and mental component score (MCS) of the SF-36. Analysis was by intention to treat. Results. We analyzed the data of 491 randomized and 220 nonrandomized women. We did not find treatment effect on long-term HR-QoL (PCS: p = 0.09; MCS: p = 0.82). The PCS improved over time (p < 0.001) and was better in nonrandomized patients (p = 0.02). Conclusion. Despite a clinical benefit of induction of labor, long-term HR-QoL is equal after the induction of labor and expectant management in women with GH or PE beyond 36 weeks of gestation.

Perinatal mortality and mode of delivery in monochorionic diamniotic twin pregnancies ≥32 weeks of gestation: A multicentre retrospective cohort study (Article)

2011-08-01T00:00:00Z

Objective To study perinatal mortality rates in a cohort of 465 monochorionic (MC) twins without twin-twin transfusion syndrome (TTS) born at 32 weeks of gestation or later since reported interauterine fetal death (IUFD) rates >32 weeks of gestations in the literature vary, leading to varying recommendations on the optimal timing of delivery, and to investigate the relation between perinatal mortality and mode of delivery. Design Multicentre retrospective cohort study. Setting Ten perinatal referral centres in the Netherlands. Population All MC twin pregnancies without TTTS delivered at ≥32 weeks of gestation between January 2000 and December 2005. Methods The medical records of all MC twin pregnancies without TTTS delivered at the ten perinatal referral centres in the Netherlands between January 2000 and December 2005 were reviewed. Main outcome measures Perinatal mortality in relation to gestational age and mode of delivery at ≥32 weeks of gestation. Results After 32 weeks of gestation, five out of 930 fetuses died in utero and there were six neonatal deaths (6 per 1000 infants). In women who delivered ≥37 weeks, perinatal mortality was 7 per 1000 infants. Trial of labour was attempted in 376 women and was successful in 77%. There were three deaths in deliveries with a trial of labour (8 per 1000 deliveries), of which two were related to mode of delivery. Infants born by caesarean section without labour had an increased risk of neonatal morbidity and respiratory distress syndrome. Conclusions In MC twin pregnancies the incidence of intrauterine fetal death is low ≥32 weeks of gestation. Therefore, planned preterm delivery before 36 weeks does not seem to be justified. The risk of intrapartum death is also low, at least in tertiary centres.

Maternal health-related quality of life after induction of labor or expectant monitoring in pregnancy complicated by intrauterine growth retardation beyond 36 weeks (Article)

2011-04-06T00:00:00Z

Objective: Pregnancies complicated by intrauterine growth retardation (IUGR) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality. Optimal treatment in IUGR at term is highly debated. Results from the multicenter DIGITAT (Disproportionate Intrauterine Growth Intervention Trial At Term) trial show that induction of labor and expectant monitoring result in equal neonatal and maternal outcomes for comparable cesarean section rates. We report the maternal health-related quality of life (HR-QoL) that was measured alongside the trial at several points in time. Methods: Both randomized and non-randomized women were asked to participate in the HR-QoL study. Women were asked to fill out written validated questionnaires, covering background characteristics, condition-specific issues and the Short Form (SF-36), European Quality of Life (EuroQoL 6D3L), Hospital Anxiety and Depression scale (HADS), and Symptom Check List (SCL-90) at baseline, 6 weeks postpartum and 6 months postpartum. We compared the difference scores of all summary measures between the two management strategies by ANOVA. A repeated measures multivariate mixed model was defined to assess the effect of the management strategies on the physical (PCS) and mental (MCS) components of the SF-36. Analysis was by intention to treat. Results: We analyzed data of 361 randomized and 198 non-randomized patients. There were no clinically relevant differences between the treatments at 6 weeks or 6 months postpartum on any summary measures; e.g., on the SF-36 (PCS: P = .09; MCS: P = .48). The PCS and the MCS were below norm values at inclusion. The PCS improved over time but stayed below norm values at 6 months, while the MCS did not improve. Conclusion: In pregnancies complicated by IUGR beyond 36 weeks, induction of labor does not affect the long-term maternal quality of life.

Role of semen analysis in subfertile couples (Article)

2011-03-01T00:00:00Z

Objective: To evaluate the associations between the results of the male partner's semen analysis (classified according to the World Health Organization [WHO] criteria) and fathering a child without any treatment. Design: Prospective multicenter cohort study. Setting: Twenty subfertility centers in The Netherlands. Patient(s): A total of 3,345 consecutive couples presenting for subfertility. Intervention(s): None. Main Outcome Measure(s): Associations between the results of the male partner's semen analysis, classified according to the WHO criteria, and fathering a child without any treatment within a time horizon of 1 year. Subsequently, we redefined semen quality criteria and reevaluated the associations. Result(s): Follow-up data of 3,129 couples (94%) were available, of which 517 (17%) had a healthy pregnancy without treatment. The 1-year pregnancy rate in men with WHO normozoospermia did not differ significantly from that in men with WHO impaired semen (24% vs. 23%). In contrast, we observed lower chances of fathering a child for sperm concentrations <40 Ã 106/mL, total sperm count <200 Ã 106, and sperm morphology <20% normal forms. With a multivariable regression model based on the redefined male semen subfertility criteria we were able to make a finer differentiation between subfertile men, with probabilities of fathering a child ranging from 7% to 41%. Conclusion(s): The current WHO criteria for semen quality do not discriminate between fertile and subfertile men. Our redefined and graded semen criteria have strong predictive value. If interpreted correctly, the fast and inexpensive semen analysis remains the gold standard for defining a man's role in subfertility.

Role of semen analysis in subfertile couples (Article)

2011-03-01T00:00:00Z

Induction versus expectant monitoring for intrauterine growth restriction at term: Randomised equivalence trial (DIGITAT) (Article)

2010-12-21T00:00:00Z

Objective: To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term. Design: Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)). Setting: Eight academic and 44 non-academic hospitals in the Netherlands between November 2004 and November 2008. Participants: Pregnant women who had a singleton pregnancy beyond 36+0 weeks' gestation with suspected intrauterine growth restriction. Interventions: Induction of labour or expectant monitoring. Main outcome measures: The primary outcome was a composite measure of adverse neonatal outcome, defined as death before hospital discharge, five minute Apgar score of less than 7, umbilical artery pH of less than 7.05, or admission to the intensive care unit. Operative delivery (vaginal instrumental delivery or caesarean section) was a secondary outcome. Analysis was by intention to treat, with confidence intervals calculated for the differences in percentages or means. Results: 321 pregnant women were randomly allocated to induction and 329 to expectant monitoring. Induction group infants were delivered 10 days earlier (mean difference -9.9 days, 95% CI -11.3 to -8.6) and weighed 130 g less (mean difference -130 g, 95% CI -188 g to -71 g) than babies in the expectant monitoring group. A total of 17 (5.3%) infants in the induction group experienced the composite adverse neonatal outcome, compared with 20 (61%) in the expectant monitoring group (difference -0.8%, 95% CI -4.3% to 3.2%). Caesarean sections were performed on 45 (14.0%) mothers in the induction group and 45 (13.7%) in the expectant monitoring group (difference 0.3%, 95% CI -5.0% to 5.6%). Conclusions: In women with suspected intrauterine growth restriction at term, we found no important differences in adverse outcomes between induction of labour and expectant monitoring. Patients who are keen on non-intervention can safely choose expectant management with intensive maternal and fetal monitoring; however, it is rational to choose induction to prevent possible neonatal morbidity and stillbirth. Trial registration: International Standard Randomised Controlled Trial number ISRCTN10363217.

Well being of obstetric patients on minimal blood transfusions (WOMB trial) (Article)

2010-12-16T00:00:00Z

Background: Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands.Methods/Design: The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs.The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%).Discussion: This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs.Trial registration: ClinicalTrials.gov NCT00335023, Nederlands Trial Register NTR335.

IMproving participation of patients in clinical trials - Rationale and design of IMPACT (Article)

2010-10-20T00:00:00Z

Background. One of the most commonly reported problems of randomised trials is that recruitment is usually slower than expected. Trials will cost more and take longer, thus delaying the use of the results in clinical practice, and incomplete samples imply decreased statistical power and usefulness of its results. We aim to identify barriers and facilitators for successful patient recruitment at the level of the patient, the doctor and the hospital organization as well as the organization and design of trials over a broad range of studies. Methods/design. We will perform two cohort studies and a case-control study in the Netherlands. The first cohort study will report on a series of multicenter trials performed in a nationwide network of clinical trials in obstetrics and gynaecology. A questionnaire will be sent to all clinicians recruiting for these trials to identify determinants - aggregated at centre level - for the recruitment rate. In a case control-study nested in this cohort we will interview patients who refused or consented participation to identify factors associated with patients' consent or refusal. In a second cohort study, we will study trials that were prospectively registered in the Netherlands Trial Register. Using a questionnaire survey we will assess whether issues on hospital organization, trial organization, planning and trial design were associated with successful recruitment, i.e. 80% of the predefined number of patients recruited within the planned time. Discussion. This study will provide insight in barriers and facilitators for successful patient recruitment in trials. The results will be used to provide recommendations and a checklist for individual trialists to identify potential pitfalls for recruitment and judge the feasibility prior to the start of the study. Identified barriers and motivators coupled to evidence-based interventions can improve recruitment of patients in clinical trials.

Time to pregnancy after a previous miscarriage in subfertile couples (Article)

2010-07-01T00:00:00Z

Objective: To assess the time to spontaneous ongoing pregnancy after a previous miscarriage in subfertile couples. Design: A prospective cohort study. Setting: The study was conducted in 38 fertility centers in the Netherlands. Patient(s): Subfertile couples who miscarried after completing their basic fertility work-up. Intervention(s): Expectant management after a miscarriage. Main Outcome Measure(s): Spontaneous ongoing pregnancy. Result(s): We included 5,663 subfertile couples, of which 1,098 (19%) conceived spontaneously. Among these 1,098 couples, 199 (18%) miscarried and these couples were included in the present study. Follow-up was completed for 171 couples, of which 95 conceived again within 24 months of follow-up. Of these 95 pregnancies, 86 (91%) were ongoing. The cumulative spontaneous ongoing pregnancy rate (PR) after 24 months was 70% (95% confidence interval [CI] 59%-81%). Conclusion(s): Subfertile couples, who experience a treatment-independent pregnancy resulting in a miscarriage, have very good prospects of a spontaneous ongoing pregnancy in the near future. This information is useful in counseling couples who had a miscarriage after a previous period of subfertility.

Consecutive or non-consecutive recurrent miscarriage: Is there any difference in carrier status? (Article)

2010-06-01T00:00:00Z

Background Carrier status of a structural balanced chromosome abnormality is associated with recurrent miscarriage. There is, at present, no evidence of the impact of the sequence of preceding pregnancies on the probability of carrier status. The aim of our study was therefore to examine whether the history of consecutive versus non-consecutive miscarriages in couples with two or more miscarriages has any impact on the probability of carrying a chromosome abnormality. Methods A nested case-control study was performed in six centres for clinical genetics in the Netherlands. Couples referred for chromosome analysis after two or more miscarriages were included: 279 couples with a carrier of a structural chromosomal abnormality and 428 non-carrier couples who served as controls. Univariable and multivariable logistic regression analyses, corrected for known risk factors for carrier status, were performed. The main outcome measure was the probability of carrier status. Result STwo hundred and fifty-six of 279 (92%) carrier couples and 381 of 428 (89) non-carrier couples had experienced consecutive miscarriages (P = 0.21). A history of two or three consecutive miscarriages did not alter the probability of carrier status when compared with two [odds ratio (OR) 0.90, 95% confidence interval (CI) 0.48-1.7] or three (OR 0.71, 95 CI 0.39-1.3) non-consecutive miscarriages. Conclusions The sequence of preceding pregnancies is not a risk factor for carrier status. Therefore, couples with miscarriages interspersed with healthy child(ren) should be managed the same as couples with consecutive miscarriages regarding chromosome diagnosis.

Neonatal outcome following elective cesarean section beyond 37 weeks of gestation: a 7-year retrospective analysis of a national registry (Article)

2010-03-01T00:00:00Z

Objective: We sought to evaluate number and timing of elective cesarean sections at term and to assess perinatal outcome associated with this timing. Study Design: We conducted a recent retrospective cohort study including all elective cesarean sections of singleton pregnancies at term (n = 20,973) with neonatal follow-up. Primary outcome was defined as a composite of neonatal mortality and morbidity. Results: More than half of the neonates were born at <39 weeks of gestation, and they were at significantly higher risk for the composite primary outcome than neonates born thereafter. The absolute risks were 20.6% and 12.5% for birth at <38 and 39 weeks, respectively, as compared to 9.5% for neonates born ≥39 weeks. The corresponding adjusted odds ratios (95% confidence interval) were 2.4 (2.1-2.8) and 1.4 (1.2-1.5), respectively. Conclusion: More than 50% of the elective cesarean sections are applied at <39 weeks, thus jeopardizing neonatal outcome.

Diagnostic Strategies for Postmenopausal Bleeding (Article)

2010-01-01T00:00:00Z

Postmenopausal bleeding (PMB) is a common clinical problem. Patients with PMB have 10%-15% chance of having endometrial carcinoma and therefore the diagnostic workup is aimed at excluding malignancy. Patient characteristics can alter the probability of having endometrial carcinoma in patients with PMB; in certain groups of patients the incidence has been reported to be as high as 29%. Transvaginal sonography (TVS) is used as a first step in the diagnostic workup, but different authors have come to different conclusions assessing the accuracy of TVS for excluding endometrial carcinoma. Diagnostic procedures obtaining material for histological assessment (e.g., dilatation and curettage, hysteroscopy, and endometrial biopsy) can be more accurate but are also more invasive. The best diagnostic strategy for diagnosing endometrial carcinoma in patients with PMB still remains controversial. Future research should be focussed on achieving a higher accuracy of different diagnostic strategies.

Pessaries in multiple pregnancy as a prevention of preterm birth: The ProTwin trial (Article)

2009-09-17T00:00:00Z

Background: Multiple pregnancies are at high risk for preterm birth, and therefore an important cause of infant mortality and morbidity. A pessary is a simple and potentially effective measure for the prevention of preterm birth. Small studies have indicated its effectiveness, but large studies with sufficient power on the subject are lacking. Despite this lack of evidence, the treatment is at present applied by some gynaecologists in The Netherlands. Methods/Design: We aim to investigate the hypothesis that prophylactic use of a cervical pessary will be effective in the prevention of preterm delivery and the neonatal mortality and morbidity resulting from preterm delivery in multiple pregnancy. We will evaluate the costs and effects of this intervention. At study entry, cervical length will be measured. Eligible women will be randomly allocated to receive either a cervical pessary or no intervention. The cervical pessary will be placed in situ at 16 to 20 weeks, and will stay in situ up to 36 weeks gestation or until delivery, whatever comes first. Discussion: The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 7.2% without to 3.9% with a cervical pessary, using a two-sided test with an alpha of 0.05 and a power of 0.80. Trial registration: This trial will provide evidence on whether a cervical pessary will decrease the incidence of early preterm birth and its concomitant bad neonatal outcome in multiple pregnancies. Current Controlled Trials: NTR 1858.

Assessment of perinatal outcome after sustained tocolysis in early labour (APOSTEL-II trial) (Article)

2009-09-09T00:00:00Z

Background: Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours. Methods/Design: The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0and 32+2weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first. Discussion: Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, β 0.2 at alpha 0.05). Trial Registration: This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks. Clinical trial registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3rd2008.

Cost-effectiveness of fibronectin testing in a triage in women with threatened preterm labor: Alleviation of pregnancy outcome by suspending tocolysis in early labor (APOSTEL-I trial) (Article)

2009-09-01T00:00:00Z

Background: At present, women with threatened preterm labor before 32 weeks of gestation are, after transfer to a perinatal center, treated with tocolytics and corticosteroids. Many of these women are treated unnecessarily. Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor. We will assess whether triage of these women with fibronectin testing, cervical length or their combination is cost-effective. Methods/Design: We will investigate a prospective cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes. All women will be tested for fibronectin and cervical length. Women with a cervical length <10 mm and women with a cervical length between 10-30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol. Women with a cervical length between 10-30 mm in combination with a negative fibronectin test will be randomised between treatment with nifedipine (intervention) and placebo (control) for 48 hours. Women with a cervical length > 30 mm will be managed according to local protocol. Corticosteroids may be given to all women at the discretion of the attending physician. Primary outcome measure will be delivery within 7 days. Secondary outcome measures will be neonatal morbidity and mortality, complications of tocolytics, costs and health related quality of life. The analysis will be according to the intention to treat principle. We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5%. Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5% (one sided test, β 0.2, α 0.05). Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin. Discussion: This study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor. Trial registration: Nederlands Trial Register (NTR) number 1857, http://www.trialregister.nl.

Prediction models in reproductive medicine: A critical appraisal (Article)

2009-08-27T00:00:00Z

Background: Prediction models have been developed in reproductive medicine to help assess the chances of a treatment-(in)dependent pregnancy. Careful evaluation is needed before these models can be implemented in clinical practice. Methods: We systematically searched the literature for papers reporting prediction models in reproductive medicine for three strategies: expectant management, intrauterine insemination (IUI) or in vitro fertilization (IVF). We evaluated which phases of development these models had passed, distinguishing between (i) model derivation, (ii) internal and/or external validation, and (iii) impact analysis. We summarized their performance at external validation in terms of discrimination and calibration. Results: We identified 36 papers reporting on 29 prediction models. There were 9 models for the prediction of treatment-independent pregnancy, 3 for the prediction of pregnancy after IUI and 17 for the prediction of pregnancy after IVF. All of the models had completed the phase of model derivation. For six models, the validity of the model was assessed only in the population in which it was developed (internal validation). For eight models, the validity was assessed in populations other than the one in which the model was developed (external validation), and only three of these showed good performance. One model had reached the phase of impact analysis. Conclusions: Currently, there are three models with good predictive performance. These models can be used reliably as a guide for making decisions about fertility treatment, in patients similar to the development population. The effects of using these models in patient care have to be further investigated.

Adverse drug reactions to tocolytic treatment for preterm labour: Prospective cohort study (Article)

2009-01-01T00:00:00Z

Objective To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations. Design Prospective cohort study. Setting 28 hospitals in the Netherlands and Belgium. Participants 1920 consecutive women treated with tocolytics for threatened preterm labour. Main outcome measures Maternal adverse events (those suspected of being causally related to treatment were considered adverse drug reactions) leading to cessation of treatment. Results An independent panel evaluated the recorded adverse events, without knowledge of the type of tocolytic used. Of the 1920 women treated with tocolytics, 1327 received a single course of treatment (69.1%), 282 sequential courses (14.7%), and 311 combined courses (16.2%). Adverse drug reactions were categorised as serious or mild in 14 cases each. The overall incidence of serious adverse drug reaction was 0.7%. Compared with atosiban, the relative risk of an adverse drug reaction for single treatment with a (3 adrenoceptor agonist was 22.0 (95% confidence interval 3.6 to 138.0) and for single treatment with a calcium antagonist was 12 (1.9 to 69). Multiple drugtocolysis led to five serious adverse drug reactions (1.6%). Multiple gestation, preterm rupture of membranes, and comorbidity were not independent risk factors for adverse drug reactions. Conclusions The use of (3 adrenoceptor agonists or multiple tocolytics for preventing preterm birth is associated with a high incidence of serious adverse drug reactions. Indometacin and atosiban were the only drugs not associated with serious adverse drug reactions. A direct comparison of the effectiveness of nifedipine and atosiban in postponing preterm delivery is needed.

Predictive value of pregnancy history in subfertile couples: results from a nationwide cohort study in the Netherlands (Article)

2008-09-01T00:00:00Z

Objective: To assess whether pregnancy history can predict the occurrence of a spontaneous ongoing pregnancy in subfertile couples. Design: Prospective cohort study. Setting: Thirty fertility centers in the Netherlands. Patient(s): Subfertile, ovulatory women with at least one patent tube and male partners without severely impaired semen quality. Intervention(s): Fertility work-up, including a detailed pregnancy history. Main Outcome Measure(s): Spontaneous ongoing pregnancy. Result(s): We included 4445 couples, of whom 793 (18%) had a spontaneous ongoing pregnancy within 1 year of follow-up. Previous live birth and miscarriage in current partnership were both associated with higher fecundity as compared with primary infertility (hazard rate ratios for spontaneous pregnancy [HR] 1.4; 95% CI, 1.2-1.7 and 1.3; 95% CI, 1.0-1.5, respectively). Pregnancies in a woman's previous partnerships did not affect the fecundity of the couple. A pregnancy in a previous partnership of the male partner was associated with lower fecundity (HR 0.76; 95% CI, 0.58-0.99). A previous pregnancy after fertility treatment also was associated with lower fecundity (HR 0.52; 95% CI, 0.30-0.90). Conclusion(s): Accurate prediction of the future fertility of a couple requires an exact assessment of the fertility history of both partners.

Obesity affects spontaneous pregnancy chances in subfertile, ovulatory women (Article)

2008-02-01T00:00:00Z

BACKGROUND: Obesity is increasing rapidly among women all over the world. Obesity is a known risk factor for subfertility due to anovulation, but it is unknown whether obesity also affects spontaneous pregnancy chances in subfertile, ovulatory women. METHODS: We evaluated whether obesity affected the chance of a spontaneous pregnancy in a prospectively assembled cohort of 3029 consecutive subfertile couples. Women had to be ovulatory and had to have at least one patent tube, whereas men had to have a normal semen analysis. Time to spontaneous ongoing pregnancy within 12 months was the primary endpoint. RESULTS: The probability of a spontaneous pregnancy declined linearly with a body mass index (BMI) over 29 kg/m2. Corrected for possible related factors, women with a high BMI had a 4% lower pregnancy rate per kg/m2increase [hazard ratio: 0.96 (95% CI 0.91-0.99)]. CONCLUSIONS: These results indicate that obesity is associated with lower pregnancy rates in subfertile ovulatory women.

What is the recurrence rate of postmenopausal bleeding in women who have a thin endometrium during a first episode of postmenopausal bleeding? (Article)

2008-01-07T00:00:00Z

Objective. To determine the incidence and significance of recurrent postmenopausal bleeding among women diagnosed with an endometrial thickness ≤4 mm after a first episode of postmenopausal bleeding. Methods. Consecutive patients not using hormone replacement therapy (HRT) presenting with a first episode of postmenopausal bleeding and an endometrial thickness ≤4 mm at transvaginal ultrasonography (TVU) were managed expectantly. In case of recurrent bleeding, the patient was evaluated according to the hospital's local policy with TVU, office endometrial sampling, hysteroscopy or dilatation and curettage (D&C) or a combination of these tests. We evaluated the incidence of recurrent bleeding, potential risk factors for recurrent bleeding, and the diagnosis made after recurrent bleeding. Results. A total of 607 patients were registered with a first episode of postmenopausal bleeding, of whom 249 had an endometrial thickness ≤4 mm. Follow-up took place with a median of 174 weeks (range: 4-250 weeks). During follow-up, 25 of the 249 patients (10%; 95% CI: 6.6-14%) had recurrent bleeding. Median time until recurrence of bleeding was 49 weeks (range: 9-186 weeks). Two patients with recurrent bleeding turned out to have an endometrial carcinoma (8%; 95% CI: 2.2-25%), and 1 patient had a malignant melanoma. Time since menopause, age, body mass index, hypertension, diabetes and anticoagulants were not predictive for recurrent bleeding. Conclusion. The recurrence rate after a first episode of postmenopausal bleeding managed expectantly is low and cannot be predicted by patient characteristics. Patients with recurrent bleeding should be re-evaluated, as they bear a considerable risk of carcinoma.

Which factors play a role in clinical decision-making in external cephalic version? (Article)

2008-01-07T00:00:00Z

Objective. To assess the clinical factors that influence the estimates of clinicians of the success of an external cephalic version (ECV), and the subsequent management decisions made by clinicians. Design. We constructed 16 fictional vignettes of women with a term fetus in breech position eligible for ECV. Setting. Secondary and tertiary clinics in The Netherlands. Population. Thirty-seven gynaecologists, residents and midwifes. Methods. Sixteen case summaries concerning a hypothetical patient eligible for ECV. Potential prognostic factors that varied between the cases were parity, maternal body mass index, engagement of the fetus, amniotic fluid, fetal growth, fetal presentation and placental localisation. For each case presentation, the clinicians were asked for their inclination to perform an ECV, and whether or not they would use tocolysis. Results. The estimated probabilities of success varied between 20 and 60%. The number of clinicians that would attempt an ECV varied per case between 32 and 97%. Amniotic fluid and engagement contributed 80% of the variation in the decision to perform ECV. In the case of oligohydramnios or an engaged breech, the clinicians tended not to perform an ECV. Conclusion. Amniotic fluid and engagement seem to be the main factors in the clinical decision-making of clinicians in ECV. This decision-making is probably experience based. Systematic knowledge of clinical prognosticators and subsequent assessment of their prognostic capacity is needed.

Immunoglobulin G antisperm antibodies and prediction of spontaneous pregnancy (Article)

2008-01-01T00:00:00Z

Objective: To investigate the predictive capacity of immunoglobulin G ASA (direct MAR test) for spontaneous ongoing pregnancy in subfertile couples. Design: Prospective cohort study. Setting: Nine fertility centers in The Netherlands. Patient(s): Consecutive ovulatory subfertile couples. Intervention(s): A basic fertility workup, including a mixed agglutination reaction test for IgG (MAR test) at first semen analysis. Main Outcome Measure(s): Spontaneous conception resulting in ongoing pregnancy. Result(s): We included 1,794 couples, of which 283 (16%) had a spontaneous ongoing pregnancy within 1 year. When a threshold 50% was used for an abnormal test result, the MAR test was positive in 3% of the couples. In the univariable analysis, a positive MAR test ≥50% reduced, albeit not statistically significant, the probability of spontaneous pregnancy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.34 to 1.7). In the multivariable analysis, a positive MAR test ≥50% had no contribution in the prediction of spontaneous pregnancy (HR 0.99, 95% CI 0.40 to 2.4). Conclusion(s): This large cohort study shows that the MAR test is not able to predict spontaneous pregnancy chances. Its routine use in the basic fertility workup for identification of couples with low spontaneous pregnancy chances is not justified.

Effectiveness of intrauterine insemination in subfertile couples with an isolated cervical factor: a randomized clinical trial (Article)

2007-12-01T00:00:00Z

After randomization of subfertile couples with an isolated cervical factor to intrauterine insemination for 6 months or expectant management for 6 months, 26 women (51%) vs. 16 women (33%) conceived, respectively. Of these pregnancies, 22 (43%) vs. 13 (27%) were ongoing (relative risk, 1.6; 95% confidence interval, 0.91 to 2.8). There was one multiple pregnancy in the group that was allocated to intrauterine insemination. This trial suggests a beneficial effect of IUI in couples with an isolated cervical factor.

Inadequate office endometrial sample requires further evaluation in women with postmenopausal bleeding and abnormal ultrasound results (Article)

2007-11-01T00:00:00Z

Objective: To determine whether further histologic assessment can be omitted after office sampling produced a nondiagnostic specimen. Methods: Data were retrieved from a prospective cohort study of 913 women presenting with postmenopausal bleeding. This study was limited to women with an endometrial thickness either 5 mm or greater or that could not be measured, and in whom an endometrial biopsy performed in the office yielded nondiagnostic results. Results: Endometrial thickness was nonreassuring or unknown in 516 women, of whom 403 (78.1%) underwent office endometrial sampling. In 66 women the amount of tissue obtained was not sufficient for pathologic characterization. Further investigation revealed an endometrial malignancy in 3 of these 66 women and atypical hyperplasia in 1. Conclusion: In women with postmenopausal bleeding and a nonreassuring transvaginal ultrasound evaluation, a nondiagnostic office endometrial sample does not rule out endometrial cancer and further endometrial sampling is advisable.

Identifying subfertile ovulatory women for timely tubal patency testing: A clinical decision rule based on medical history (Article)

2007-10-01T00:00:00Z

Background: The aim of tubal testing is to identify women with bilateral tubal pathology in a timely manner, so they can be treated with IVF or tubal surgery. At present, it is unclear for which women early tubal testing is indicated, and in whom it can be deferred. Methods: Data on 3716 women who underwent tubal patency testing as a part of their routine fertility workup were used to relate elements in their medical history to the presence of tubal pathology. With multivariable logistic regression, we constructed two diagnostic models. One in which tubal disease was defined as occlusion and/or severe adhesions of at least one tube, whereas in a second model, tubal disease was defined as the presence of bilateral abnormalities. Results: Both models discriminated moderately well between women with and women without tubal disease with an area under the receiver-operating characteristic curve (AUC) of 0.65 (95% CI: 0.63-0.68) for any tubal pathology and 0.68 (95% CI: 0.65-0.71) for bilateral tubal pathology, respectively. However, the models could make an almost perfect distinction between women with a high and a low probability of tubal pathology. A decision rule in the form of a simple diagnostic score chart was developed for application of the models in clinical practice. Conclusions: In conclusion, the present study provides two easy to use decision rules that can accurately express a woman's probability of (severe) tubal pathology at the couple's first consultation. They could be used to select women for tubal testing more efficiently.

The relation between age, time since menopause, and endometrial cancer in women with postmenopausal bleeding (Article)

2007-09-01T00:00:00Z

The objective is to assess among women with postmenopausal bleeding the relationship of age and time since menopause on one hand and the presence of endometrial cancer and atypical hyperplasia on the other hand. In a multicenter prospective cohort study, 614 women presenting with postmenopausal bleeding were included. Women underwent transvaginal sonography and, in cases where the endometrial thickness was >4 mm, endometrial sampling. Splines were used to assess the association between each of the continuous variables and (pre)malignancy of the endometrium. Subsequently, univariate and multivariate analysis were performed. The average age for women without (pre)malignancy was 61.7 years (SD 9.8). As malignant and premalignant cases were found to have similar age, these subgroups were merged in the analyses. Age was an independent predictor of (pre)malignancy. In women younger than 55 years, the odds ratio was 1.9 (95% CI: 1.1-3.3) for each year under 55 years of age and 1.03 (95% CI: 1.00-1.06) for each year over 55 years of age. The risk of (pre)malignancy of the endometrium was 4.9% in women less than 3 years postmenopausal versus 19.7% in women more than 20 years postmenopausal. However, in a multivariate analysis only age contributed to the prediction of risk. This study demonstrates that, in postmenopausal women with vaginal bleeding, the risk of (pre)malignancy of the endometrium is low in women under 50 years of age, increases considerably until 55 years of age, and rises only modestly with further advancing age. Future studies should explore whether these findings can be incorporated in the diagnostic work-up of women with postmenopausal bleeding.

Reply: Pregnancy is predictable: A large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples [2] (Article)

2007-08-01T00:00:00Z

Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT (Article)

2007-07-10T00:00:00Z

Background: Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term. Methods/design: The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm. Discussion: This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term.

Induction of labour versus expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks (the PPROMEXIL-trial) (Article)

2007-07-06T00:00:00Z

Background: Preterm prelabour rupture of the membranes (PPROM) is an important clinical problem and a dilemma for the gynaecologist. On the one hand, awaiting spontaneous labour increases the probability of infectious disease for both mother and child, whereas on the other hand induction of labour leads to preterm birth with an increase in neonatal morbidity (e.g., respiratory distress syndrome (RDS)) and a possible rise in the number of instrumental deliveries. Methods/Design: We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management. Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34+0 weeks until 37+0 weeks will be included in a multicentre prospective randomised controlled trial. We will compare early delivery with expectant monitoring. The primary outcome of this study is neonatal sepsis. Secondary outcome measures are maternal morbidity (chorioamnionitis, puerperal sepsis) and neonatal disease, instrumental delivery rate, maternal quality of life, maternal preferences and costs. We anticipate that a reduction of neonatal infection from 7.5% to 2.5% after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity. Under these assumptions, we aim to randomly allocate 520 women to two groups of 260 women each. Analysis will be by intention to treat. Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management. Long term outcomes will be evaluated using modelling. Discussion: This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis.

When outcome is a balance: Methods to measure combined utility for the choice between induction of labour and expectant management in mild risk pregnancy at term (Article)

2007-07-04T00:00:00Z

Background: When the primary and secondary outcomes of clinical studies yield ambiguous or conflicting recommendations, preference or valuation studies may help to overcome the decision problem. The present preference study is attached to two clinical studies (DIGTAT, ISRCT10363217; HYPITAT, ISRCT08132825) that evaluate induction of labour versus expectant management in term pregnancies with a mild risk profile. The purpose of the present study is to compare four methods of valuation/preference measurement. Methods: Multidimensional health state descriptions ('vignettes') defined by attributes and levels are presented to different response groups: laypersons, (ex-) patients, and medical experts. Valuations/ preferences are measured with the Visual Analogue Scale (VAS), Time Trade-Off (TTO), Willingness to Pay (WTP) and Discrete Choice Experiment (DCE) techniques. These methods are compared in terms of feasibility, reliability and validity. Anticipated results: By comparing the four techniques, we aim to answer (1) which of the techniques is most feasible, reliable and valid for use in multidimensional decision problems; (2) which of the techniques can be recommended for use in economic evaluations, and (3) do different response groups produce systematically different valuations, and if so, how can these be used to interpret preference results and to contribute to the development of clinical guidelines.

Progesterone for the prevention of preterm birth in women with multiple pregnancies: The AMPHIA trial (Article)

2007-06-19T00:00:00Z

Background: 15% of multiple pregnancies ends in a preterm delivery, which can lead to mortality and severe long term neonatal morbidity. At present, no generally accepted strategy for the prevention of preterm birth in multiple pregnancies exists. Prophylactic administration of 17-alpha hydroxyprogesterone caproate (17OHPC) has proven to be effective in the prevention of preterm birth in women with singleton pregnancies with a previous preterm delivery. At present, there are no data on the effectiveness of progesterone in the prevention of preterm birth in multiple pregnancies. Methods/Design: We aim to investigate the hypothesis that 17OHPC will reduce the incidence of the composite neonatal morbidity of neonates by reducing the early preterm birth rate in multiple pregnancies. Women with a multiple pregnancy at a gestational age between 15 and 20 weeks of gestation will be entered in a placebo-controlled, double blinded randomised study comparing weekly 250 mg 17OHPC intramuscular injections from 16-20 weeks up to 36 weeks of gestation versus placebo. At study entry, cervical length will be measured. The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 15% to 8%. Analysis will be by intention to treat. We will also analyse whether the treatment effect is dependent on cervical length. Discussion: This trial will provide evidence as to whether or not 17OHPC-treatment is an effective means of preventing bad neonatal outcome due to preterm birth in multiple pregnancies.

Predictive value and clinical impact of basal follicle-stimulating hormone in subfertile, ovulatory women (Article)

2007-06-01T00:00:00Z

Context: Basal FSH is a marker for ovarian reserve. Objectives: The objective of the study was to investigate the predictive value of basal FSH on spontaneous ongoing pregnancy in subfertile ovulatory women. Design: This was a prospective cohort study. Setting: The study was conducted in 19 fertility centers in The Netherlands. Participants: Subfertile ovulatory women without two-sided tubal pathology and in whom the man had normal sperm parameters (total motile count ≥ 3 × 106) participated in the study. Interventions: Interventions included a fertility work-up, including a basal FSH measurement on cycle d 3. Main Outcome Measures: Spontaneous ongoing pregnancy was measured. Results: We included 3519 consecutive couples of which 562 (16%) had a spontaneous ongoing pregnancy within 1 yr. Basal FSH levels of 8 IU/liter or higher were associated with a decreased probability of spontaneous ongoing pregnancy [hazard ratio (HR) 0.93/IU·liter (95% confidence interval [CI] 0.87-0.98)]. In a multivariable analysis, female age (HR 0.97/yr, 95% CI 0.95-0.99), cycle length (HR 0.96/d, 95% CI 0.93-1.0), and FSH levels 8 IU/liter or greater (HR 0.93/IU·liter, 95% CI 0.87-0.99) were strong negative predictors for spontaneous ongoing pregnancy. Addition of FSH to a prediction model based on female age, duration of subfertility, previous pregnancy, referral status, and semen analysis changed the probability to conceive spontaneously from 30% or greater to less than 30% in 97 of 3219 couples (3.0%). Conclusions: In ovulatory women, a basal FSH level of 8 IU/liter or higher is associated with decreasing fecundity, independent of female age and cycle length. Because the number of couples in whom the FSH level alters management decisions is low, we do not recommend routine testing of basal FSH in subfertile couples. Copyright

Author response to: Improving the existing diagnostic strategy by accounting for characteristics of the women in the diagnostic work up for postmenopausal bleeding [2] (Article)

2007-05-01T00:00:00Z

Pregnancy is predictable: A large-scale prospective external validation of the prediction of spontaneous pregnancy in subfertile couples (Article)

2007-02-01T00:00:00Z

Background: Prediction models for spontaneous pregnancy may be useful tools to select subfertile couples that have good fertility prospects and should therefore be counselled for expectant management. We assessed the accuracy of a recently published prediction model for spontaneous pregnancy in a large prospective validation study. Methods: In 38 centres, we studied a consecutive cohort of subfertile couples, referred for an infertility work-up. Patients had a regular menstrual cycle, patent tubes and a total motile sperm count (TMC) >3 × 106. After the infertility work-up had been completed, we used a prediction model to calculate the chance of a spontaneous ongoing pregnancy (www.freya.nl/probability.php). The primary end-point was time until the occurrence of a spontaneous ongoing pregnancy within 1 year. The performance of the pregnancy prediction model was assessed with calibration, which is the comparison of predicted and observed ongoing pregnancy rates for groups of patients and discrimination. Results: We included 3021 couples of whom 543 (18%) had a spontaneous ongoing pregnancy, 57 (2%) a non-successful pregnancy, 1316 (44%) started treatment, 825 (27%) neither started treatment nor became pregnant and 280 (9%) were lost to follow-up. Calibration of the prediction model was almost perfect. In the 977 couples (32%) with a calculated probability between 30 and 40%, the observed cumulative pregnancy rate at 12 months was 30%, and in 611 couples (20%) with a probability of ≥40%, this was 46%. The discriminative capacity was similar to the one in which the model was developed (c-statistic 0.59). Conclusions: As the chance of a spontaneous ongoing pregnancy among subfertile couples can be accurately calculated, this prediction model can be used as an essential tool for clinical decision-making and in counselling patients. The use of the prediction model may help to prevent unnecessary treatment.

Improving the existing diagnostic strategy by accounting for characteristics of the women in the diagnostic work up for postmenopausal bleeding (Article)

2007-01-01T00:00:00Z

Objectives: The aim of this study was to evaluate whether the efficiency of the current diagnostic work up following postmenopausal bleeding could be improved by diagnostic strategies that take into account characteristics of the women in addition to the currently recommended transvaginal measurement of endometrial thickness to determine for subsequent histological assessment. Design: Multicenter, prospective cohort study. Setting: A university hospital and seven teaching hospitals in the Netherlands. Sample: Consecutive women not using hormone replacement therapy, presenting with postmenopausal bleeding. Methods: Five hundred and forty women underwent transvaginal sonography, and in case of endometrial thickness (double layer) above 4 mm, subsequent endometrial sampling was performed. Presence of carcinoma was ruled out by the absence of abnormalities in histological specimen or by an uneventful follow up of at least 6 months. Main outcome measures: Probability of endometrial carcinoma was estimated by multivariable logistic regression models. For each diagnostic strategy, we calculated diagnostic accuracy (area under receiver operating characteristic curve [AUC]), negative predictive value (NPV) and the number of diagnostic procedures. Results: A strategy with transvaginal sonography alone with a fixed threshold incorrectly classified 0.7% of the women as nonmalignant (NPV: 99.3% [98.5-100%]), with 97% sensitivity and 56% specificity. A strategy integrating characteristics of the women with transvaginal sonography could result in less false reassurances (NPV: 99.6% [99.2-100%]), with only marginal decrease in diagnostic procedures, or a minor increase in false reassurances (NPV: 99.0% [98.3-100%]), with a substantial reduction (15-20%) in the procedures. AUCs associated with these strategies could improve from 0.76 (0.73-0.79) for transvaginal sonography alone to 0.90 (0.87-0.93) for the integrated strategy. Conclusion: Taking into account the characteristics of the women could increase the efficiency of the diagnostic work up for postmenopausal bleeding.

Should the post-coital test (PCT) be part of the routine fertility work-up? (Article)

2004-06-01T00:00:00Z

BACKGROUND: This study aimed to determine whether medical history and semen analysis can predict the result of the post-coital test (PCT). METHODS: A previously reported data set of Dutch patients collected between 1985 and 1993 was used. Our study was limited to just patients with an ovulatory cycle. Data were complete for medical history, semen analysis and PCT. We performed logistic regression analysis to evaluate whether these factors could predict the result of the PCT (PCT model). Furthermore, we evaluated the additional contribution of the PCT in the prediction of treatment-independent pregnancy (pregnancy model). RESULTS: Thirty-four percent (179 out of 522) had an abnormal PCT. The PCT model contained previous pregnancy [odds ratio (OR) 2.1; 95% confidence interval (CI) 1.3-3.5], semen volume (OR 0.88; 95% CI 0.77-0.99), sperm concentration (OR 0.96; 95% CI 0.94-0.97), sperm motility (OR 0.97; 95% CI 0.96-0.98) and sperm morphology (OR 2.7; 95% CI 1.2-6.8). The area under the ROC curve of the model was 0.81. In the pregnancy model, the result of the actual PCT could be replaced by the predicted result of the PCT model in about half of the couples, without compromising its predictive capacity. CONCLUSION: The medical history and semen analysis can predict the result of the PCT in approximately 50% of the subfertile couples with a regular cycle, without compromising its potential to predict pregnancy.

Prevalence of Asherman's syndrome after secondary removal of placental remnants or a repeat curettage for incomplete abortion (Article)

1998-01-01T00:00:00Z

This prospective study assesses the prevalence of intrauterine adhesions among women undergoing secondary removal of placental remnants after delivery, or a repeat curettage for incomplete abortions, and evaluates risk factors associated with the presence of intrauterine adhesions. In 50 women, undergoing either a secondary removal of placental remnants more than 24 h after delivery, or a repeat curettage for incomplete abortions, ambulatory hysteroscopy was performed 3 months after the intervention. Intrauterine adhesions were found in 20 of the women (40%): five patients had Asherman's syndrome grade I, six had grade II, six had grade III and three had grade IV. In women with menstrual disorders a statistically significant 12-fold increased risk for Asherman's syndrome grade II-IV was found. Previous abortion as well as infection during surgery were associated with a mildly but non-significant increased risk. Based on our findings, hysteroscopy is recommended only in those patients who develop menstrual disorders, either after secondary intervention for placental remnants after delivery or after a repeat curettage.