Biomedical subjects

C W N Looman

Publications and source records attributed to C W N Looman.

14 recordsLinked to original sources

PubMed2005

Non-compliance with the re-excision guidelines for cutaneous melanoma in The Netherlands does not influence survival.

AIM: To evaluate causes and consequences of not adhering to the clinical practice guideline for cutaneous malignant melanoma. METHODS: We conducted a retrospective cohort study of the clinical records of 454 subjects whose pathological reports were obtained from a population-based cancer registry to assess determinants and effects of non-compliance of physicians with the excision policy and the related clinical practice guideline for patients with primary localized cutaneous malignant melanoma (CMM). A comparative analysis was performed of patients who did and did not undergo re-excision (compliance versus non-compliance with the guideline). Subjects diagnosed in 1988, 1993 and 1997, just 1 year after publication of the (adapted) guideline, were followed until death due to any cause or until July 1st 2003. RESULTS: Old age was the most important determinant of non-compliance. After adjusting for age at diagnosis, gender, subsite and Breslow thickness there was no significant difference in overall survival between the compliance group and the non-compliance group. CONCLUSIONS: Non-compliance to the guideline is more common in older patients and in patients with melanoma in the head and neck region. After adjusting for confounders, a significant effect of complying with the guidelines on overall survival could not be observed.

Age Factors↗

PubMed2005

Single and repeated GnRH agonist stimulation tests compared with basal markers of ovarian reserve in the prediction of outcome in IVF.

PURPOSE: To study the value of a single or repeated GnRH agonist stimulation test (GAST) in predicting outcome in IVF compared to basal ovarian reserve tests. METHODS: A total of 57 women was included. In a cycle prior to the IVF treatment, on day 3, an antral follicle count (AFC) was performed and blood taken for basal FSH, inhibin B and E2 measurements, followed by a subcutaneous injection of 100 microg triptorelin for the purpose of the GAST. Twenty-four hours later blood sampling was repeated. All the tests were repeated in a subsequent cycle. From the GAST E2 and inhibin B response were used as test parameters. The outcome measures were poor ovarian response and ongoing pregnancy. Group comparisons were done using the Mann-Whitney or chi-square test. Univariate and multivariate logistic regression was applied to assess which test revealed the highest predictive accuracy as expressed in the area under receiver-operating characteristic curve (ROC(AUC)). Clinical value was compared by calculating classical test characteristics for the best logistic models. RESULTS: All the basal and GAST variables were significantly different in the poor responders (n = 19) compared to normal responders (n = 38). In the univariate analysis on cycle 1 tests the AFC was the best predictor for poor ovarian response, while in cycle 2 the E2 response in the GAST performed best (ROC(AUC) of 0.91 for both). Multivariate analysis of the basal variables led to the selection of AFC and inhibin B in cycle 1, yielding a ROC(AUC) of 0.96. Mean E2 response was selected in a multivariate analysis of the repeated GAST variables (ROC(AUC) 0.91). At a specificity level of -0.90, several logistic models including GAST variables appeared to have a sensitivity (-0.80), positive predictive value (-0.82) and false positive rate (-0.18), comparable to a logistic model containing AFC and inhibin B. None of the test variables showed a significant relation with ongoing pregnancy. CONCLUSIONS: The GAST has a rather good ability to predict poor response in IVF. However, comparing the predictive accuracy and clinical value of the GAST with a day 3 AFC and inhibin B, it appeared that neither a single nor a repeated GAST performed better. In addition, the predictive ability towards ongoing pregnancy is poor. Therefore, the use of the GAST as a predictor of outcome in IVF should not be advocated.

Adult↗

PubMed2004

Expected poor responders on the basis of an antral follicle count do not benefit from a higher starting dose of gonadotrophins in IVF treatment: a randomized controlled trial.

BACKGROUND: The aim of this study was to evaluate the effect of doubling the starting dose of gonadotrophins on the ovarian response in IVF patients with a low antral follicle count (AFC). METHODS: Fifty-two patients with an AFC of <5 follicles of 2-5 mm diameter before starting their first IVF cycle participated in this randomized controlled trial. They were randomized by opening a sealed envelope, receiving either 150 IU (group I, n = 26) or 300 IU (group II, n = 26) of rFSH as a starting dose. The main outcome measures of the study were number of oocytes, poor response (<4 oocytes at retrieval or cancellation due to insufficient follicle growth) and ongoing pregnancy (12 weeks of gestation). RESULTS: The groups were comparable regarding patient characteristics and outcome of the IVF treatment. The median number of oocytes collected was 3 for both groups (P = 0.79). The difference in the mean number of oocytes was 0.3 oocytes in favour of group I (P=0.69). Sixty-five per cent of the patients in group I experienced a poor response and 62% in group II. The ongoing pregnancy rate was 8% in group I and 4% in group II (P = 0.55). CONCLUSIONS: Expected poor response patients, defined as patients with an AFC <5, are likely not to benefit from a higher starting dose of gonadotrophins in IVF.

Adult↗

PubMed2004

Repeated clomiphene citrate challenge testing in the prediction of outcome in IVF: a comparison with basal markers for ovarian reserve.

BACKGROUND: The aim of this study was to investigate the predictive accuracy and clinical value of performing either a single or a repeated clomiphene citrate challenge test (CCCT) in predicting poor response in IVF, compared to that of currently used basal ovarian reserve markers. METHODS: Sixty-three patients undergoing their first IVF treatment were prospectively included. After measurement of basal markers on cycle day 3 (cd3) [FSH, inhibin B and antral follicle count (AFC)], a CCCT was performed. FSH and inhibin B levels were measured on day 10 (cd10). A second CCCT was performed after a washout period of one cycle. In all patients the tests were followed by an IVF treatment. Poor response (<4 oocytes or cancellation due to impaired (<3 follicles) or absent follicular growth) was used as primary outcome measure. RESULTS: Both the single as well as the repeated CCCT markers had a rather good discriminative potential for the prediction of poor response (area under the receiver operating characteristic curve (ROCAUC): FSH cd10=0.79, inhibin B cd10=0.79, mean FSH cd10=0.82 and mean inhibin B cd10=0.88). This compared well with the performance of the basal markers (FSH 0.82, inhibin B 0.72 and AFC 0.83). In a multivariate analysis on only the basal variables, FSH cd3 and AFC were selected (ROCAUC 0.89). Only stepwise forward analysis on the repeated CCCT variables revealed a better discriminating potential for the prediction of poor response (ROCAUC 0.92). At a specificity level of approximately 0.97, sensitivity and the positive predictive value were marginally improved in the CCCT models. CONCLUSIONS: Performing a CCCT (single or repeated) has a rather good ability to predict poor response in IVF. However, it appears that the predictive accuracy and clinical value of the CCCT is not clearly better than that of basal FSH in combination with an AFC. Therefore, the use of the CCCT as a predictor of outcome in IVF should not be advocated.

Adult↗

PubMed2004

The number of retrieved oocytes does not decrease during consecutive gonadotrophin-stimulated IVF cycles.

BACKGROUND: Our aim was to study whether there is a decreasing trend in the number of retrieved oocytes in women who had all undergone at least seven consecutive IVF cycles. METHODS: A nationwide retrospective cohort study was conducted among women whose first IVF cycle was stimulated with gonadotrophins in The Netherlands between 1983 and 1995. Among these eligible women, we identified all women who had received at least seven consecutive IVF cycles (n = 330). Poisson regression analysis was used to assess the trend in the number of retrieved oocytes over the first six IVF cycles. RESULTS: The unadjusted results showed a slight but non-significant decrease in the number of retrieved oocytes over six IVF cycles. The change in cycle 6 compared with cycle 1 was -0.06 oocytes (5.8% decrease) (P = 0.21). When adjusting for the number of ampoules and the stimulation protocol (fertility drug used combined with use of GnRH agonists), there was a considerable and highly significant decrease from cycle 1 to cycle 6 [change in cycle 6 compared with cycle 1: -0.19 oocytes (17.4% decrease), (P < 0.0001)]. However, when adjusting for age of the women, this decrease almost completely disappeared [change in cycle 6 compared with cycle 1: -0.05 oocytes (5% decrease), (P = 0.50)]. CONCLUSION: The results suggest that there is no decrease in the number of retrieved oocytes over subsequent cycles when simultaneously accounting for the increasing age of the women, differences in the number of ampoules of gonadotrophins used, type of stimulation protocol and year of IVF treatment.

Cohort Studies↗

PubMed2004

Use of stimulated serum estradiol measurements for the prediction of hyperresponse to ovarian stimulation in in vitro fertilization (IVF).

PURPOSE: In ovarian stimulation an exaggerated ovarian response is often seen and is related to medical complications, such as ovarian hyperstimulation syndrome (OHSS), and increased patient discomfort. If it were possible to identify hyperresponders at an early stage of the stimulation phase, adaptation of the stimulation protocol would become feasible to minimize potential complications. Therefore, we studied the usefulness of measuring stimulated serum estradiol (E2) levels in predicting ovarian hyperresponse. METHODS: A total of 109 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospectively included. The E2 level was evaluated on day 3 and 5 of the stimulation phase. Two outcome measures were defined. The first was ovarian hyperresponse (collection of > or = 15 oocytes at retrieval and/or peak E2 > 10000 pmol/L, or cancellation due to > or = 30 follicles growing and/or peak E2 > 15000 pmol/L, or OHSS developed). The second outcome measure comprised a subgroup representing the more severe hyperresponders. named extreme-response (cancellation or OHSS developed). RESULTS: The data of 108 patients were analyzed. The predictive accuracy of E2 measured on stimulation day 3 towards ovarian hyperresponse was clearly lower than that of E2 measured on stimulation day 5 (area under the receiver operating characteristic curve (ROCAUC) 0.75 and 0.81, respectively). For extreme-response the predictive accuracy of E2 measured on stimulation day 3 or 5 was comparable (ROCAUC 0.81 and 0.82, respectively). For both outcome measures the stimulated E2 tests yielded only acceptable specificity with moderate sensitivity at higher cutoff levels. Prediction of extreme-response seemed slightly more effective due to a lower error rate. CONCLUSIONS: There is a significant predictive association between E2 levels measured on stimulation day 3 and 5 and both ovarian hyperresponse and extreme-response in IVF. However, the clinical value of stimulated E2 levels for the prediction of hyperresponse is low because of the modest sensitivity and the high false positive rate. For the prediction of extreme-response the clinical value of stimulated E2 levels is moderate.

Adult↗

PubMed2003

Age-related changes in the ultrastructure of the resting follicle pool in human ovaries.

Age-related decline of fertility in women is the result of the decline in both quantity and quality of the resting ovarian follicle pool. The aim of the present study was to determine whether the decline of follicle quality with age is reflected by ultrastructural changes in the resting follicle pool. Ovarian biopsy specimens were obtained by laparoscopy from seven healthy women aged 25-32 yr (young group) and from 11 healthy women aged 38-45 yr (advanced-age group). A total of 182 resting follicles from the young group were compared with 81 resting follicles from the advanced-age group for signs of age-related changes by transmission-electron microscopy. The ooplasmic fraction of vacuoles was increased (P = 0.02), and the fraction of mitochondria decreased (P = 0.005), in the advanced-age group. Also, the density of the mitochondrial matrix (P < 0.001) and the frequency of dilated smooth endoplasmic reticulum (SER; P = 0.001) and Golgi complex (P = 0.02) were increased with age. The frequencies of ruptured mitochondrial membranes (P = 0.001) and dilated SER (P = 0.003) were increased with age in the granulosa cells. Overall follicle-quality scores, which should reflect atretic changes, were not different for the young and advanced-age groups. In conclusion, in resting follicles, the morphological changes with age are different from the changes seen in quality decline by atresia. The morphological changes with age specifically involved the mitochondria, the SER, and the Golgi complex, and they may be the cause of atresia on initiation of follicular growth because of the substantial increase in metabolic requirements.

Adult↗

PubMed2003

[Mortality due to smoking in the Netherlands: 1.2 million tobacco-related deaths between 1950 and 2015].

OBJECTIVE: To quantify the medical consequences of the tobacco use in the Netherlands for the past 50 years and the near future. DESIGN: Theoretical study based on the national death records and published risks by cause of death of tobacco use. METHOD: Observed lung cancer mortality (1950-1999) was related to birth cohort and age by a statistical model (according to Peto), and then projected into the near future. The smoking intensity was defined as the difference between the expected lung-cancer mortality if no one smoked and the observed lung-cancer mortality. Using this smoking intensity and published risks for other smoking-related causes of death, the model provided estimates of smoking-related mortality by age, sex and cause of death. RESULTS: In 1999, 18% (women) and 32% (men) of all mortality before the age of 70 was attributable to smoking. If no one had smoked, Dutch life expectancy for men and women would have been 3 years and 1 year higher, respectively. Between 1950 and 1999, 13% of all deaths were caused by smoking, the large majority (> 90%) of which occurred among men. Between 2000 and 2015, slightly more deaths are to be attributed to smoking (14%), 62% of which will be among men. In 2015, women will have caught up with men in terms of absolute numbers of lung-cancer mortality. CONCLUSION: Around one quarter of premature deaths were caused by smoking. In the near future, women of the baby-boom generation will have reached middle age and the highest (relative) smoking-related risks. It is important that clinical practice takes this increased risk of disease into account among middle-aged women who smoke.

Adult↗

PubMed2003

High coronary heart disease rates among Dutch women of the baby boom, born 1945-1959: age-cohort analysis and projection.

BACKGROUND: After a steep decline in older generations, coronary heart disease mortality is stagnating in female cohorts born after the Second World War. We analysed past trends and predicted future health care needs for coronary heart disease in the Dutch population. METHODS: A loglinear age-cohort model relates numbers of deaths and hospital admissions for coronary heart disease to sex, age, birth cohort and population size, and projects age-cohort changes over the future population. Population size, population forecasts and coronary heart disease mortality (period 1970-1999) are from vital statistics. Numbers of hospitalised acute coronary events are from the nationwide hospital register (period 1980-1999). RESULTS: Among men, the rate ratios of deaths and hospital admissions were, respectively, 0.21 (death) and 0.78 (survivors at discharge) in the cohorts born in the period 1948-1962 compared to the period 1918-1922. Among women, the same rate ratios were 0.41 and 1.89. The projection model predicts 22% less deaths from coronary heart disease and 22% more survivors of an infarction in 2015, among men. Among women, there will be 5% less deaths and 70% more survivors of an infarction, most of these being middle age members of the baby boom cohorts. CONCLUSIONS: Stagnating all-cause mortality is correlated with an upward trend in coronary heart disease risk in the female baby boomers. Heart health care needs among middle-aged women will increase sharply. These changes are correlated to high lung cancer mortality and high smoking rates in these cohorts.

Adult↗

PubMed2003

The number of antral follicles in normal women with proven fertility is the best reflection of reproductive age.

BACKGROUND: The purpose of this study was to compare the predictive capacity of several markers of reproductive age in normal women. METHODS: Healthy female volunteers (n = 162) aged 25-46 years with proven, normal fertility and regular menstrual cycles were recruited. In this selected group, chronological age was assumed to approximate reproductive age and, therefore, was taken as the proxy-variable for reproductive age. The number of antral follicles with 2-10 mm diameter, total ovarian volume, total follicular volume, mean follicular volume, and volume of either the smallest or largest ovary were estimated by transvaginal sonography of the ovaries. Serum levels of early follicular FSH, estradiol and inhibin B, as well as the response of estradiol and inhibin B to exogenous GnRH agonist administration (GAST), were also evaluated. RESULTS: Regression analysis revealed that the antral follicle number showed the highest correlation with age (r = -0.68, P = 0.001), and explained 46% of its variance. All other variables, except inhibin B, were moderately correlated with age. Responses of estradiol and inhibin B to the GnRH agonist were moderately correlated with age, but highly correlated with the number of antral follicles. CONCLUSIONS: It is concluded that the number of antral follicles has the closest association with chronological age in normal women with proven fertility. As stimulated estradiol and inhibin B clearly reflect the size of the antral follicle cohort, the GAST may be considered the second best single test to predict reproductive age.

Adult↗

PubMed2003

Do cycle disturbances explain the age-related decline of female fertility? Cycle characteristics of women aged over 40 years compared with a reference population of young women.

BACKGROUND: The cause of declining fertility with age, in women who still have regular menstrual cycles, is not clear. METHODS: Follicle development, endometrial growth and hormonal patterns were evaluated in cycles of older women (aged 41-46 years; n = 26) who previously were normally fertile, and these cycles were compared with a reference group of relatively young fertile women (aged 22-34 years; n = 35). RESULTS: Clearly abnormal cycles were found in only two women in the older age group, and in one woman in the younger group. The main differences between the age groups were a shorter follicular phase and cycle length in the older group, in combination with higher FSH levels in the late luteal and early follicular phase. In contrast to published data which suggest an "accelerated" follicle development in older women, sonographical and hormonal evidence was found of an "advanced" follicle growth, with an earlier start already during the luteal phase of the preceding cycle, and an advanced selection and ovulation of the dominant follicle. CONCLUSIONS: Such an earlier start of follicle growth in a possibly less favourable hormonal environment, as well as a limited oocyte pool, may contribute to a decreased follicle and oocyte quality, resulting in diminished fertility in ageing women.

Adult↗

PubMed2003

The use of fixed distance embryo transfer after IVF/ICSI equalizes the success rates among physicians.

BACKGROUND: It is suggested that the skill of the physician performing the embryo transfer may influence the outcome of the procedure. In this study we investigated the effects of a change in embryo transfer technique on the variability in success rates among physicians. METHODS: Retrospectively 4439 transfer cycles in which two different embryo transfer techniques were applied by seven physicians were studied. In the first 2210 cycles, transfers were performed using the 'clinical touch' method. In the following 2229 cycles, the so-called fixed distance technique was used. RESULTS: With the clinical touch method pregnancy rates differed greatly among providers, whereas after the introduction of the fixed distance technique these differences disappeared. Furthermore, the overall clinical pregnancy rate increased from 33.6 to 40.4% per transfer. Using smoothing spline curves we failed to detect a sudden rise in pregnancy rates at the time the transfer method was changed. CONCLUSIONS: The introduction of the fixed distance technique greatly reduced the variation in pregnancy rates among physicians. The overall increase in pregnancy rates after the introduction is likely to be related to the change in technique although definite proof is difficult. Both observations are suggested to be attributable to the atraumatic character of the fixed distance technique.

Embryo Transfer↗

PubMed2002

Quantitative transvaginal two- and three-dimensional sonography of the ovaries: reproducibility of antral follicle counts.

OBJECTIVE: To assess the intra- and interobserver reproducibilities in addition to the between-method reliability of antral follicle counts using two (2D)- and three (3D)-dimensional transvaginal sonography (TVS). METHODS: Two groups of women with regular menstrual cycles were studied. One group consisted of healthy volunteers with proven fertility and the other group consisted of patients visiting the general infertility clinic. In each woman, 2D or 3D TVS was performed in the early follicular phase (day 2, 3 or 4) of the menstrual cycle to measure the number of antral follicles (2-10 mm). RESULTS: Intraobserver reproducibility was calculated from follicle counts using 3D TVS in 41 women. The intraclass correlation coefficient was 0.99 and the 95% coverage interval of the difference (CID) was -3.2 to +3.2. Interobserver reproducibility was assessed from both 2D (n = 37) and 3D (n = 49) TVS-based follicle counts. An interclass correlation coefficient of 0.98 was found for both methods. The 95% CID was -5.0 to +4.1 for 2D and -5.6 to +5.7 for 3D measurements. The latter CID appeared to increase in the higher range of counts. Finally, the degree of agreement between 2D and 3D TVS counts (n = 76) was characterized by a 95% CID of -5.3 to +8.3. This coverage interval widened when higher numbers of follicles were counted. With the exception of the between-method analysis, kappa values indicated overall that follicle counts will hardly change from one category to another when repeatedly carried out. CONCLUSIONS: Determination of antral follicle numbers by both 2D and 3D TVS is adequate with regard to the intra- and interobserver reproducibility. The between-method reproducibility of follicle counts measured both by 2D and 3D ultrasound is moderate. When higher follicle counts are observed both interobserver and between-method reproducibilities tend to decline. If used in categorical classifications, ultrasound-based follicle counts appear to have a high level of agreement between and within observers.

Female↗

PubMed2002

Ultrastructure of the resting ovarian follicle pool in healthy young women.

In humans, follicle quantity and quality decline with age by atresia. In the present study we aimed to describe the quality of the follicle pool through an ultrastructural investigation of resting follicles in young healthy women. From ovarian biopsies of 7 women aged 25-32 yr, 182 small follicles were morphometrically assessed for various signs of atresia. Morphometric variables were analyzed by principal components analysis (PCA) to demonstrate correlations between variables and to construct an objective follicle score. One third of small follicles consisted of primordial follicles. Nucleus:cell ratios remained constant for oocytes and granulosa cells from primordial to primary follicles, suggesting that follicles up to primary stages belong to the resting pool. The distribution of follicle quality scores as derived from PCA showed that most follicles were of good quality and with little signs of atresia. Atresia in resting follicles appears to be a necrotic process, starting in the ooplasma. Early atresia was characterized by increasing numbers of multivesicular bodies and lipid droplets, dilation of smooth endoplasmic reticulum and Golgi, and irregular mitochondria with changed matrix density. In progressive atresia mitochondrial membranes ruptured, oocyte nuclear membranes were indented or ruptured, and the ooplasma showed extensive vacuolarization. The early involvement of mitochondria in this process suggests that damage is induced by oxygen radicals. PCA follicle quality scores can be reliably approximated using a reduced number of seven morphometric variables, which were selected by stepwise forward analysis. The algorithm to calculate these follicle scores is presented.

Adult↗