Biomedical subjects
E R te Velde
Publications and source records attributed to E R te Velde.
Developmental and endocrine aspects of normal ovarian aging.
Supplies of follicles are established during early fetal life and decrease exponentially thereafter by a process called atresia. Subfertility only starts at a mean age of about 30-31 years, when the remaining follicle reserve has become a fraction of its original number. Thereafter, a further decrease in both oocyte quantity and quality dictates the subsequent reproductive events including decrease of fertility, increased abortion rate, the end of fertility, the beginning of cycle irregularity and, when almost no follicles are left, the occurrence of menopause. The same remarkable variation of age at menopause almost certainly is also present for the preceding reproductive events. When quantity and quality of antral follicles drop below a critical threshold, there is a subsequent drop in inhibine B resulting in the selective FSH rise at a mean age of 37-38 years. This FSH rise explains the accelerated follicle depletion, the increased proportion of growing follicles reaching the selectable stage, the shortening of the follicular phase and the increased incidence of dizygotic twinning. The concurring decrease of oocyte quality is in line with the increased incidence of abortions and chromosomal aberrations after age 35.
General ageing and ovarian ageing.
The age related decrease in female fertility is associated with a decrease in follicle numbers and oocyte quality. Meiotic division errors, mitochondrial DNA mutations and ageing itself have been suggested to play a part in the age associated reduction in oocyte quality. During the past decades several hypothesis have been proposed, trying to explain the underlying mechanisms. However, none of them is yet conclusive. This review will consider the main hypotheses regarding the age related reduction in oocyte quality. This will be reviewed together with recent results of studies analysing a possible relationship between ageing and ovarian ageing. On the basis of our own results and those presented in the literature, it is concluded that ovarian ageing may only be related to specific aspects of general ageing.
Ovarian reserve tests in infertility practice and normal fertile women.
The decline in fecundity with the age of the woman is mainly attributed to the loss of follicles from the ovary and a decrease in oocyte quality. Evaluation of the aging status of the ovary in an individual woman has been hampered by a lack of knowledge with regard to the relative contribution of these two factors. Most if not all so called ovarian reserve tests (ORT) reflect indirectly the remaining follicle pool in the ovary. Direct a priori assessment of oocyte quality is not possible to date. In this section the predictive value of several ovarian reserve tests for the outcome of fertility treatment is listed and commented. In addition, the study of several of the ORTs in normal, fertile women is described. From the data presented dynamic testing of the ovarian function by the clomiphene citrate and GnRH agonist stimulation test, as well as static testing by the use of ultrasound based antral follicle counts seem to offer the highest clinical value. Studies performing direct comparison of these tests are needed, as well as analysis of the way these tests should direct decision making in infertility diagnosis and treatment.
Ovarian ageing and postponement of childbearing.
Explore the source record for details and available documents.
Age at menopause as a marker of reproductive ageing.
Ages of menopause and of the preceding reproductive events such as the beginning of subfertility and infertility, are likely to be dictated by the process of follicle depletion leading to loss of oocyte quantity and quality. To some extent this process is influenced by lifestyle factors like smoking, and possibly also by the use of oral contraceptives. Genetic factors and possibly also events during intrauterine life, probably play a more important role in the age-dependent decrease of female fertility.
Normal telomere lengths in young mothers of children with Down's syndrome.
Explore the source record for details and available documents.
Menstrual cycle length preceding menopause in relation to age at menopause.
OBJECTIVES: In one of the earlier hypotheses of the etiology of breast cancer (Korenman's 'oestrogen window' hypothesis (1981)), it was assumed that women with a later age at menopause have a longer period with irregular cycles preceding menopause than women with an early menopause. This assumption was tested in a prospective study. METHODS: Subjects were 628 women, born between 1932 and 1941, who had participated in a breast cancer screening project in Utrecht, The Netherlands (the DOM-project) in 1982-1985, and who were still menstruating at that time. The women had filled out a questionnaire and a menstrual calendar every 2 years to determine their age at menopause prospectively. The women had not used oral contraceptives or medicines for menopausal complaints and had reached natural menopause by 1992. The median of the mean menstrual cycle length per woman and the median of the standard deviation of the mean menstrual cycle length per woman were plotted against number of years prior to menopause in three categories of age at menopause (44-49; 50-54; 55-59). RESULTS: During the 9 years prior to menopause, women with a late age at menopause have a somewhat higher mean menstrual cycle length than women with a younger age at menopause (P = 0.0008). Cycle length variability in the 9 years prior to menopause is not statistically significantly different between the three categories of age at menopause (P = 0.16). CONCLUSIONS: The assumption that women with a late age at menopause have a longer period with irregular cycles than women with an earlier age at menopause was not corroborated by our results.
Crossover designs versus parallel studies in infertility research.
Explore the source record for details and available documents.
Crossover or parallel design in infertility trials? The discussion continues.
OBJECTIVE: To determine whether a crossover design results in a different estimate of treatment effect compared with a parallel design. DESIGN: With the aid of a computer program, data sets of subfertile patients were simulated under different assumptions. These patients were subjected to 2 treatments that were compared in either a parallel-design or a crossover-design trial. Results were analyzed using logistic regression. SETTING: University hospital. PATIENT(S): Simulated patients of a heterogeneous subfertile population. INTERVENTION(S): Two treatment modalities with a pregnancy rate of 10% and of 20% in the first cycle were offered for 6 cycles to simulated heterogeneous populations. MAIN OUTCOME MEASURE(S): After 1,000 simulations for each assumption, median pregnancy rates and odds ratios were compared between the crossover- and parallel-design trials. RESULT(S): No relevant difference in estimated treatment effect was found between the designs. The crossover design resulted in more pregnancies overall than the parallel design. CONCLUSION(S): In infertility research, parallel and crossover designs will lead to about the same results. Although the crossover design showed a slight tendency to overestimate the treatment effect of the most effective treatment, this overestimation is clinically not relevant and is small in relation to the random error. Because of its practical advantages and because more pregnancies are achieved, a crossover design should be the first choice in infertility research.
Spontaneous conception in subfertile couples.
Explore the source record for details and available documents.
Controlled ovarian hyperstimulation and intrauterine insemination for treating male subfertility: a controlled study.
In this randomized crossover trial we investigated whether the use of controlled ovarian hyperstimulation with low-dose human menopausal gonadotrophin in couples with male subfertility leads to a higher probability of conception when intrauterine insemination (IUI) is applied. We also investigated whether the efficacy of IUI in natural or stimulated cycles was related to the severity of male subfertility. Seventy-four couples completed 308 treatment cycles. Thirteen pregnancies occurred after IUI in a natural cycle (pregnancy rate per completed cycle: 8.4%) and 21 after IUI in a stimulated cycle (pregnancy rate per completed cycle: 13.7%). The difference between the two treatment modalities was not statistically significant. The efficacy of IUI in stimulated cycles was related to the severity of the semen defect. In couples with a total motile sperm count < 10 x 10(6), ovarian stimulation did not improve treatment outcome, while it did in couples with a total motile sperm count > or = 10 x 10(6). Compared with the expected chance of conceiving spontaneously without treatment, both natural and stimulated cycles improved the probability of conception. We conclude that, for the group as a whole, ovarian stimulation did not improve the probability of conception. However, in couples with less severe semen defects, ovarian stimulation did improve the probability of conception.
Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.
The diagnostic criteria used to identify patients suffering from polycystic ovary syndrome remain controversial. The present prospective longitudinal follow-up study was designed to identify whether certain criteria assessed during standardized initial screening could predict the response to ovulation induction with clomiphene citrate (CC) in 201 patients presenting with oligomenorrhea or amenorrhea and infertility. Serum FSH levels were within the normal range (1-10 IU/L), and all patients underwent spontaneous or progestin-induced withdrawal bleeding. Initial CC doses were 50 mg daily for 5 days starting on cycle day 3. In the case of an absent response, doses were increased to 100 and 150 mg daily in subsequent cycles. First ovulation with CC was used as the end point. After a complete follow-up (in the case of a nonresponse, at least 3 treatment cycles with daily CC doses up to 150 mg), 156 patients (78%) ovulated. The free androgen index (FAI = testosterone/sex hormone-binding globulin ratio), body mass index (BMI), cycle history (oligomenorrhea vs. amenorrhea), serum androgen (testosterone and/or androstenedione) levels, and mean ovarian volume assessed by transvaginal sonography were all significantly different (P < 0.01) in responders from those in nonresponders. FAI was chosen to be the best predictor in univariate analysis. The area under the receiver operating characteristics curve in a multivariate prediction model including FAI, BMI, cycle history, and mean ovarian volume was 0.82. Patients whose ovaries are less likely to respond to stimulation by FSH due to CC treatment can be predicted on the basis of initial screening characteristics, such as FAI, BMI, cycle history (oligomenorrhea or amenorrhea), and mean ovarian volume. These observations may add to ongoing discussion regarding etiological factors involved in ovarian dysfunction in these patients and classification of normogonadotropic anovulatory infertile women.
Predictive value of serum inhibin-B for ART outcome?
Explore the source record for details and available documents.
Twins of mixed races: consequences for Dutch IVF laboratories.
Explore the source record for details and available documents.
Physical complaints and emotional stress related to routine diagnostic procedures of the fertility investigation.
The aim of this study was to map out the extent of the physical complaints and emotional stress due to diagnostic routines of the infertility work-up. To this end a questionnaire was sent to 96 consecutive couples visiting an infertility clinic of a university hospital. The results indicate that women often have physical complaints as a result of the hysterosalpingography (59%) and the diagnostic laparoscopy (47%) and mostly experience these diagnostic procedures as very stressful. Both the postcoital test and the semen analysis caused a moderate amount of stress. The other diagnostic procedures, including physical examination of both sexes, recording of the basal temperature and taking blood for hormonal determinations, were accompanied by fewer complaints and much less stress. It is concluded that the role of the hysterosalpingography and the diagnostic laparoscopy in the routine infertility work-up needs to be reconsidered in view of the burden they pose to the women involved.
Age-dependent decrease in embryo implantation rate after in vitro fertilization.
OBJECTIVE: To investigate the relation between the implantation rate per embryo after replacement in IVF-ET in relation to female age. DESIGN: Retrospective study using linear and biphasic models in a multivariate analysis. SETTING: Academic tertiary care institution. INTERVENTION(S): In vitro fertilization-ET and determination of gestational sacs at 6 to 7 weeks of pregnancy buy ultrasound. MAIN OUTCOME MEASURE(S): Implantation rate as defined by the number of gestational sacs per embryo replaced. RESULT(S): Woman's age and embryo morphology were strongly related to the implantation rate, indication for IVF-ET and cycle rank number also were related significantly but less strongly. A linear model was built describing the decrease in implantation rate with age, resulting in a decrease of approximately 7%. A biphasic model was tested also and performed significantly better, resulting in a yearly decrease of > 20% after 37 years of age. CONCLUSION(S): The most important independent factors related to the ability of embryos to implant are female age and embryo morphology. The best way to describe the relation with female age is biphasic model with a discontinuity at approximately 37 years of age.
[Role of andrology in the diagnosis and treatment of fertility disorders].
Explore the source record for details and available documents.