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Egbert R te Velde

Publications and source records attributed to Egbert R te Velde.

At least 19 recordsLinked to original sources

The clomiphene citrate challenge test for the prediction of poor ovarian response and nonpregnancy in patients undergoing in vitro fertilization: a systematic review.

OBJECTIVE: To systematically review the value of the clomiphene citrate challenge test (CCCT) in the prediction of poor ovarian response and pregnancy in IVF. DESIGN: Systematic review. SETTING: All studies that evaluated the CCCT in the prediction of poor ovarian response or pregnancy after IVF. PATIENT(S): Infertility population undergoing an IVF treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Poor ovarian response, nonpregnancy. RESULT(S): From the literature we identified and analyzed 12 studies on the CCCT according to preset criteria. In predicting poor response, the sensitivity and specificity of the CCCT varied from 35% to 93% and 47% to 98%, respectively. In predicting nonpregnancy, the sensitivity and specificity varied from 13% to 66% and 73% to 97%, respectively. Because of heterogeneity among studies, a summary receiver operating characteristics (ROC) curve could not be estimated. Back-to-back comparison of the CCCT with basal FSH was possible in six studies. In predicting poor response, the sensitivity of the CCCT increased to some extent, whereas specificity did not increase or even diminished. In predicting nonpregnancy, the CCCT also showed an increase in sensitivity, counteracted by a decrease in specificity. CONCLUSION(S): Summary estimates of test accuracy for the CCCT in IVF are not possible, because of heterogeneity among individual studies. A subanalysis of studies comparing basal FSH and the full CCCT showed that the CCCT has hardly any additional value.

Adult↗

A high number of oocytes obtained after ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection is not associated with decreased pregnancy outcome.

OBJECTIVE: To investigate the possible negative effects of a strong ovarian response on oocyte quality. DESIGN: Retrospective study. SETTING: Tertiary academic center. PATIENT(S): A total of 1,894 women (IVF, n = 1,544; ICSI, n = 350) who underwent their first ovarian stimulation cycle during the period 1995-2002. INTERVENTION(S): Standardized controlled ovarian stimulation with urinary FSH or recombinant FSH after pituitary down-regulation, followed by IVF/intracytoplasmic sperm injection (ICSI) and ET. MAIN OUTCOME MEASURE(S): Fertilization rate, fraction of high-quality embryos, and implantation rate. RESULT(S): Using multivariate logistic regression, we analyzed the effect, expressed as an odds ratio (OR), of the number of oocytes obtained (i.e., ovarian response) on the outcome measures. No effect of the response on the ongoing implantation rate or fraction of high-quality embryos was observed. Both in IVF (OR = 0.81, 95% confidence interval [CI] 0.75-0.87) and in ICSI (OR = 0.88, 95% CI 0.76-1.00), a negative effect of increasing ovarian response was seen on the fertilization rate per oocyte obtained. However, no negative effect was observed on the fertilization rate per oocyte injected in ICSI (OR = 1.00, 95% CI 0.87-1.14). The fraction of immature oocytes rises from 3.9%, in women with < or = 3 oocytes, to 26% in women with > 20 oocytes. CONCLUSION(S): Oocytes from high responders contain a greater fraction of immature oocytes, but pregnancy outcome is not impaired.

Adult↗

FSH receptor genotype is associated with pregnancy but not with ovarian response in IVF.

Two very common single nucleotide polymorphisms at positions 307 and 680 in exon 10 of the FSH receptor gene have been associated with ovarian response in IVF. This observational study evaluated the role of the FSH receptor genotype in the prediction of poor response and clinical pregnancy in IVF in comparison with other markers, such as age, basal FSH, anti-Müllerian hormone and antral follicle count. In addition, the in-vitro cAMP response towards recombinant FSH in cultured granulosa cells of patients with different FSH receptor genotypes was determined. A total of 105 IVF patients undergoing ovarian stimulation in a long suppression protocol were included in the study. The ovarian response was comparable between patients with different FSH receptor genotypes. Patients with polymorphism Ser/Ser had implantation and pregnancy rates that were three times higher compared with patients with polymorphism Asn/Asn. FSH receptor genotype was not associated with a poor response in IVF, but showed a positive association with pregnancy, independent of age. There was no difference in cAMP production in cultured granulosa cells of patients with different FSH receptor genotypes (n=62). It is concluded that FSH receptor genotype is associated with pregnancy in IVF, but not with ovarian response.

Adult↗

Use of ovarian reserve tests for the prediction of ongoing pregnancy in couples with unexplained or mild male infertility.

The chance of infertile patients conceiving is related to factors like female age and duration of infertility. This prospective observational study evaluated whether the results of ovarian reserve tests, including the novel marker serum anti-Mullerian hormone (AMH), were of additional value in predicting ongoing pregnancy. Two hundred and twenty-two patients diagnosed with unexplained infertility or mild male factor (total motile count>10x10(6)) on the basis of the infertility work-up were prospectively included. Antral follicle count, AMH, inhibin B, FSH and oestradiol concentrations were determined during the early follicular phase. Outcome measures were treatment-dependent and treatment-independent ongoing pregnancy and time to ongoing pregnancy. There were 159 ongoing pregnancies, 52 of which occurred spontaneously. Pregnant patients were significantly younger than those who did not become pregnant (median age 32.4 versus 34.9 years, P<0.001) and FSH concentrations were higher in non-pregnant patients (median 6.8 versus 7.6 IU/l, P=0.04). Only age (hazard ratio 0.93, 95% CI 0.90-0.97) and whether or not the patient was undergoing treatment (hazard ratio 8.10, 95% CI 5.66-11.61) were significantly associated with time to ongoing pregnancy. Ovarian reserve tests, other than chronological age, seem of limited value in predicting (time to) ongoing pregnancy in patients with unexplained and mild male infertility.

Adult↗

Prospective validation of two models predicting pregnancy leading to live birth among untreated subfertile couples.

BACKGROUND: Models predicting clinical outcome need external validation before they can be applied safely in daily practice. This study aimed to validate two models for the prediction of the chance of treatment-independent pregnancy leading to live birth among subfertile couples. METHODS: The first model uses the woman's age, duration and type of subfertility, percentage of progressive sperm motility and referral status. The second model in addition uses the result of the post-coital test (PCT). For validation, these characteristics were collected prospectively in two University hospitals for 302 couples consulting for subfertility. The models' ability to distinguish between women who became pregnant and women who did not (discrimination) and the agreement between predicted and observed probabilities of treatment-independent pregnancy (calibration) were assessed. RESULTS: The discrimination of both models was slightly lower in the validation sample than in the original sample which provided the model. Calibration was good: the observed and predicted probabilities of treatment-independent pregnancy leading to live birth did not differ for both models. CONCLUSIONS: The chance of pregnancy leading to live birth was reliably estimated in the validation sample by both models. The use of PCT improved the discrimination of the models. These models can be useful in counselling subfertile couples.

Birth Rate↗

The antral follicle count is a better marker than basal follicle-stimulating hormone for the selection of older patients with acceptable pregnancy prospects after in vitro fertilization.

This observational study shows that the antral follicle count is a better predictor of ongoing pregnancy in IVF patients aged >38 years of age than is basal FSH. Patients aged <44 years with a normal antral follicle count still have acceptable pregnancy rates after IVF and therefore deserve treatment.

Adult↗

Serum antimullerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: a longitudinal study.

OBJECTIVE: The aim of this study was to assess which of the basal ovarian reserve markers provides the best reflection of the changes occurring in ovarian function over time (i.e., reproductive aging). DESIGN: Prospective longitudinal study. SETTING: Healthy volunteers in an academic research center. PATIENT(S): Eighty-one women with normal reproductive performance during the course of their lives were longitudinally assessed. In this select group of women, becoming chronologically older was considered as a proxy variable for becoming older from a reproductive point of view. INTERVENTION(S): The women were assessed twice, with on average a 4-year interval (T(1) and T(2)). The number of antral follicles on ultrasound (AFC) and blood levels of antimullerian hormone (AMH), FSH, inhibin B, and E(2) were assessed. MAIN OUTCOME MEASURE(S): Longitudinal changes of the markers mentioned and the consistency of these parameters over time. RESULT(S): The mean ages at T(1) and T(2) were 39.6 and 43.6 years, respectively. Although AFC was strongly associated with age in a cross-sectional fashion, it did not change over time. The AMH, FSH, and inhibin B levels showed a significant change over time, in contrast to E(2) levels. The AMH and AFC were highly correlated with age both at T(1) and T(2), whereas FSH and inhibin B predominantly changed in women more than 40 years of age. To assess the consistency of these parameters over time, we investigated whether a woman's individual level above or below the mean of her age group at T(1) remained above or below the mean of her age group at T(2). Serum AMH concentrations showed the best consistency, with AFC as second best. The FSH and inhibin B showed only modest consistency, whereas E(2) showed no consistency at all. CONCLUSION(S): These results indicate that serum AMH represents the best endocrine marker to assess the age-related decline of reproductive capacity.

Adult↗

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↗

Linkage analysis of extremely discordant and concordant sibling pairs identifies quantitative trait loci influencing variation in human menopausal age.

Age at natural menopause may be used as parameter for evaluating the rate of ovarian aging. Environmental factors determine only a small part of the large variation in menopausal age. Studies have shown that genetic factors are likely to be involved in variation in menopausal age. To identify quantitative-trait loci for this trait, we performed a genomewide linkage study with age at natural menopause as a continuous quantitative phenotype in Dutch sister pairs, through use of a selective sampling scheme. A total of 165 families were ascertained using extreme selected sampling and were genotyped for 417 markers. Data were analyzed by Haseman-Elston regression and by an adjusted variance-components analysis. Subgroup analyses for early and late menopausal age were conducted by Haseman-Elston regression. In the adjusted variance-components analysis, 12 chromosomes had a LOD score of > or =1.0. Two chromosomal regions showed suggestive linkage: 9q21.3 (LOD score 2.6) and Xp21.3 (LOD score 3.1). Haseman-Elston regression showed rather similar locations of the peaks but yielded lower LOD scores. A permutation test to obtain empirical P values resulted in a significant peak on the X chromosome. To our knowledge, this is the first study to attempt to identify loci responsible for variability in menopausal age and in which several chromosomal regions were identified with suggestive and significant linkage. Although the finding of the region on the X chromosome comes as no surprise, because of its widespread involvement in premature ovarian failure, the definition of which particular gene is involved is of great interest. The region on chromosome 9 deserves further consideration. Both findings require independent confirmation.

Aging↗

Impact of repeated antral follicle counts on the prediction of poor ovarian response in women undergoing in vitro fertilization.

OBJECTIVE: To study the value of a single antral follicle count and the additional value of repeated counts in different cycles for the prediction of poor ovarian response in IVF. DESIGN: Prospective. SETTING: Tertiary fertility center. PATIENT(S): One hundred twenty women undergoing their first IVF cycle. INTERVENTION(S): Measurement of the number of antral follicles on cycle day 3 in two spontaneous cycles. Ovarian response. RESULT(S): A single antral follicle count is clearly predictive of poor ovarian response and there is good agreement between repeated measurements in subsequent cycles (area under the receiver operating characteristic curve [ROC(AUC)]; cycle 1: 0.87, cycle 2: 0.85). In a logistic regression analysis, information obtained after the second cycle contributed significantly to the prediction of poor response by the antral follicle count of the first cycle. The predictive accuracy of the highest of two counts (ROC(AUC) 0.89) was slightly better than that of each single count. The predictive model with the highest count yielded slightly higher values of specificity and positive predictive value. Sensitivity, negative predictive value, and error rates were slightly lower. CONCLUSION(S): A single antral follicle count is a good predictor of poor ovarian response in IVF. Although the impact of a second antral follicle count on ovarian response predictions in IVF is statistically significant, clinical relevance is very limited. Repeating an antral follicle count in a subsequent cycle is not recommended.

Adult↗

High follicle-stimulating hormone levels should not necessarily lead to the exclusion of subfertile patients from treatment.

OBJECTIVE: To determine ongoing pregnancy rates in subfertile patients with elevated FSH levels and regular cycles and to assess whether or not it is justified to exclude such patients from treatment on the basis of elevated FSH levels alone. DESIGN: Retrospective follow-up study. SETTING: Tertiary fertility center. PATIENT(S): One hundred twenty-two patients with normal FSH levels <10.0 IU/L, 126 with FSH between 10.0 and 15.0 IU/L, and 53 with FSH levels >15.0 IU/L, all having regular cycles and belonging to a general subfertility population. INTERVENTION(S): Follow-up. MAIN OUTCOME MEASURE(S): Overall and treatment-independent and treatment-dependent ongoing pregnancy rates and time to ongoing pregnancy. RESULT(S): Overall ongoing pregnancy rates declined from 65% in the normal FSH group to 47%, and 28% in the respective elevated FSH groups. However, when adjusting for differences in age and whether or not treatment was applied, this declining trend became inconsistent for both treatment-independent and treatment-dependent ongoing pregnancy rates. Only when FSH levels exceeded 20 IU/L was a clear fall in ongoing pregnancy rate observed, independent of age. In a Cox regression analysis, FSH seemed significantly associated with the outcome time to overall ongoing pregnancy (odds ratio = 0.94, 95% confidence interval, 0.88-0.99), but after adjusting for age and being on treatment or not this significance disappeared (odds ratio = 0.97, 95% confidence interval, 0.91-1.01). CONCLUSION(S): The contribution of FSH in the initial evaluation of subfertile couples is restricted to counseling patients on the probability of having lower chances of conceiving. It does not seem justified to exclude patients with normal regular cycles from treatment on the basis of the FSH value alone.

Adult↗

Towards less confusing terminology in reproductive medicine: a proposal.

The use of the term 'infertility' and related terms in reproductive medicine is reviewed. Current terminology is found to be ambiguous, confusing, and misleading. We recommend that the fertility investigation report of a couple should consist of statements concerning description, diagnosis, and prognosis. The description concerns the duration of nonpregnancy before consulting the clinician. A system for prognostic grading is proposed. The fertility investigation report forms the basis for further action, including the possibility of waiting with treatment in case of almost normal or only slightly reduced fertility. The use of the terms 'infertility', 'subfertility', and 'fecundity' is not necessary, and it is recommended to avoid them.

Humans↗

Current smoking at menopause rather than duration determines the onset of natural menopause.

BACKGROUND: Smoking has frequently been associated with early menopause. However, studies of this association have been inconclusive with regard to duration and intensity of smoking. A major problem in analyzing the effect of smoking duration on menopausal age is that both exposure and outcome are age-dependent. METHODS: We calculated age-specific rates for categories of smoking duration and subsequently computed the rate ratios for occurrence of menopause. We were thus able to model the effect of smoking duration on 2 time scales without assumptions of linearity. We used data from a Dutch population-based cohort comprising 5544 women age 49-70 years who had experienced natural menopause. RESULTS: The rate ratio (RR) for occurrence of menopause was increased in women who smoked in the year of menopause (RR = 1.41; 95% confidence interval = 1.32-1.50). The rate ratio of former smokers was similar to women who never smoked (0.95; 0.89-1.02). Prolonged exposure of smoking did not materially affect the risk of menopause, although the daily number of cigarettes currently smoked could increase the risk. CONCLUSION: Perimenopausal smoking is apparently more important than smoking history in explaining an earlier age of onset of menopause among women who smoke.

Aged↗

Predicting poor ovarian response in IVF: use of repeat basal FSH measurement.

OBJECTIVE: To evaluate the additional value of a second basal follicle stimulating hormone (FSH) level, in a different cycle, in the prediction of poor response in in vitro fertilization (IVF) by a single basal FSH measurement. STUDY DESIGN: In 120 patients, basal FSH was determined prospectively in 2 spontaneous cycles. The additional value of a second basal FSH measurement in the prediction of poor ovarian response in IVF by a single basal FSH measurement was studied. RESULTS: Due to chance variation, the predictive accuracy of a poor response of the first and second basal FSH measurement differed (ROC(AUC) .84 and .74, respectively). In a multivariate analysis, the higher of the first and second basal FSH levels provided the best predictive accuracy (ROC(AUC) .85). In terms of clinical relevance, however, a predictive model with the highest basal FSH level provided only slightly more correct predictions of poor and normal ovarian response than did models based solely on a single basal FSH measurement. CONCLUSION: Using basal FSH, a substantial number of patients will be misdiagnosed with regard to their ovarian response potential in IVF, even if repeat measurement is performed.

Biomarkers↗

Women older than 40 years of age and those with elevated follicle-stimulating hormone levels differ in poor response rate and embryo quality in in vitro fertilization.

OBJECTIVE: To investigate whether IVF outcome of patients older than 40 years of age with basal FSH levels less than 15 IU/L differs from that in patients 40 years of age or younger with basal FSH levels of 15 IU/L or greater. DESIGN: Prospective observational study. SETTING: Tertiary academic fertility center. PATIENT(S): Women 41 years of age or older with basal FSH levels less than 15 IU/L (n = 50), and women 40 years of age or younger with elevated basal FSH levels (n = 36) undergoing their first IVF cycle. INTERVENTION(S): IVF treatment using a long suppression protocol with recombinant FSH at a fixed starting dose of 150 IU/L. MAIN OUTCOME MEASURE(S): Ovarian response, ongoing pregnancy rates, and implantation rates. RESULT(S): The high FSH group experienced more cycle cancellations due to absent follicular growth than did the high age group (31% vs. 8%). However, the high FSH group had better implantation rates per embryo (34% vs. 11%), higher ongoing rates per ET (40% vs.13%), and higher ongoing pregnancy rates per cycle (25% vs. 10%). In both groups, poor responders had lower pregnancy rates. CONCLUSION(S): The outcome of IVF differs between patients older than 40 years of age with normal FSH levels and relatively young patients with elevated FSH levels. This finding may have implications for the management of these patients.

Adult↗

Performance of basal follicle-stimulating hormone in the prediction of poor ovarian response and failure to become pregnant after in vitro fertilization: a meta-analysis.

OBJECTIVE: To assess the predictive performance and clinical value of basal FSH as a test for ovarian reserve in in vitro fertilization (IVF) patients. DESIGN: Meta-analysis. SETTING: Tertiary fertility center. PATIENT(S): Patients undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Poor ovarian response, nonpregnancy. RESULT(S): We located 21 studies that had reported on basal FSH and IVF outcome. No single study met high standards of methodological rigor; most studies are of moderate methodological quality only. The summary receiver operating characteristic curve indicated a moderate predictive performance for poor response, and a low predictive performance for nonpregnancy. Predictions with a substantial shift from pre-FSH-test probability to post-FSH test probability are only achieved at extreme cut-off levels for basal FSH. Sensitivity of such cut-off levels, for both the prediction of poor response and nonpregnancy, is limited. CONCLUSION(S): Clinical value of testing for basal FSH is restricted to a small minority of patients. Basal FSH should not be regarded as a useful routine test for the prediction of IVF outcome. The development of better tests to assess ovarian reserve remains of importance.

Female↗