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Biomedical subjects

E R te Velde

Publications and source records attributed to E R te Velde.

At least 19 recordsLinked to original sources
PubMed2001

Morphometry of human ovaries in normal and growth-restricted fetuses.

According to the fetal origins hypothesis, normal growth and development of abdominal organs is disturbed by intra-uterine growth restriction, leading to diseases later in life. The aims of this study were to investigate the effect of growth restriction on the ovaries of human fetuses and to investigate the dynamics of follicular growth in normal fetuses. We selected 21 normal female fetuses (controls) and seven severely intra-uterine growth-restricted female fetuses (IUGR cases) from all autopsy records over a 10-year period. Ovarian volume was calculated and from histological sections the volume-percentage of follicles in the ovarian cortex, the maximum diameters of individual follicles and the distribution of the follicle classes and oogonia were determined. The volume of the ovaries increased significantly from 0.10 to 0.36 cm3 in the second half of gestation. The mean volume-percentage of ovarian follicles and the mean follicle diameter significantly increased with 0.48% and 0.52 microm per week, respectively. Class B/C (intermediary) follicles (72%) were predominantly present. Class B (primordial) follicles decreased from over 20% to less than 10% and class C (primary) increased from 6 to 19%. Class A (oogonia) were frequently present before 30 gestational weeks, but were rare after that age. For all studied parameters we did not find differences between IUGR cases and controls. Intra-uterine growth restriction does not seem to disturb ovarian development in the human fetus. In the second half of gestation the follicle pool increases by the growth of individual follicles, the transition of follicle to larger classes, and probably by increasing follicle numbers. As most follicles at term were class B/C and C, follicles up to class C are probably part of the resting stock.

Female↗
PubMed2001

Survival of human ovarian follicles from fetal to adult life: apoptosis, apoptosis-related proteins, and transcription factor GATA-4.

The majority of oocytes present in fetal ovaries are depleted before birth, and only about 400 will ovulate during the normal fertile life span. Studies on animals have shown that apoptosis is the mechanism behind oocyte depletion and follicular atresia. In the present study, we investigated the extent and localization of apoptosis in human fetal (aged 13-40 weeks) and adult ovaries. Furthermore, the expression of apoptosis-regulating proteins, bcl-2 and bax, and the relationship of transcription factor GATA-4 were studied. Apoptosis was found in ovarian follicles throughout fetal and adult life. During fetal development, apoptosis was localized mainly to primary oocytes and was highest between weeks 14-28, decreasing thereafter toward term. Expression of bcl-2 was observed only in the youngest fetal ovaries (weeks 13-14), and bax was present in the ovaries throughout the entire fetal period. In adult ovaries, apoptosis was detected in granulosa cells of secondary and antral follicles, and Bcl-2 and bax were expressed from primary follicles onwards. During fetal ovarian development, GATA-4 messenger RNA and protein were localized to the granulosa cells, with expression being highest in the youngest ovaries and decreasing somewhat toward term. The expression pattern of GATA-4 suggests that it may be involved in the mechanisms protecting granulosa cells from apoptosis from fetal to adult life. The results indicate that depletion of ovarian follicles in the human fetus occurs through intrinsic mechanisms of apoptosis in oocytes, and later in adult life the survival of growing follicles may be primarily determined by granulosa cell apoptosis.

Aging↗
PubMed2000

Timed intercourse versus intra-uterine insemination with or without ovarian hyperstimulation for subfertility in men.

BACKGROUND: Although intra-uterine insemination (IUI) is widely used, however its effectiveness remains a matter of debate. Although IUI is less invasive and expensive than IVF or GIFT, it should only be applied if the probability of conception is improved significantly as compared to the natural chance of conceiving. To increase the number of available oocytes at the site of fertilization, controlled ovarian hyperstimulation (COH) can be applied in conjunction with IUI. Uncontrolled studies suggest a beneficial effect of COH in combination with IUI, also when a male factor is present. To be able to draw firm conclusions whether IUI and/or COH improve the probability of conception, several comparisons should be performed in randomized controlled trials (RCTs). OBJECTIVES: To determine for male subfertility whether intrauterine insemination (IUI) improves the probability of conception compared with timed intercourse and whether the addition of controlled ovarian hyperstimulation influences the results. SEARCH STRATEGY: 1. The specialist database of the Cochrane Menstrual Disorders and Subfertility Group. 2. Medline search. 3. Embase search. 4. DDFU search. 5. BIOSIS search. 6. SCIsearch. 7. Manual searching of references mentioned in the obtained studies. 8. Personal communication and write letters to experts (14) in the field. 9. Abstracts of The American Society for Reproductive Medicine and European Society for Human Reproduction and Embryology Meetings. When important information is lacking from the original publications the authors will be contacted. SELECTION CRITERIA: Randomized controlled trials only. DATA COLLECTION AND ANALYSIS: Independently by the first 2 authors: 1. Trial design characteristics. 2. Baseline characteristics of participants. 3. Types of intervention. 4. Outcomes where pregnancy is the outcome of main interest. Number of multiple pregnancies and number of cycles with ovarian hyperstimulation syndrome (OHSS) are secondary outcomes. Analysis of agreement between the two observers was determined for the following items: inclusion or exclusion of a trial, method of randomization, definition of male subfertility, design of the trial, number of pregnancies and completed cycles. Sensitivity analysis is performed. MAIN RESULTS: Seventeen trials fulfilled the selection criteria for this review and were included. Four trials are pending. Crude agreement concerning inclusion or exclusion of trials occurred for 41 of 43 (95%) trials reviewed (kappa 0.90). The included trials comprised 3,662 completed cycles. In natural cycles intrauterine insemination (IUI) significantly improved the probability of conception compared with timed intercourse (TI) (combined odds ratio with 95% confidence intervals: 2.43, 1.54 - 3.83). In cycles with controlled ovarian hyperstimulation (COH) IUI significantly improved the probability of conception also compared with TI (combined odds ratio with 95% confidence intervals: 2.14, 1.30 - 3.51). Despite clinical heterogeneity, these results are based on strong evidence. Intrauterine insemination in cycles with COH improved the probability of conception compared with IUI in natural cycles but significance was not reached (combined odds ratio with 95% confidence intervals: 1.79, 0.98 - 3.25). Comparing IUI in COH-cycles with TI in natural cycles the first treatment modality significantly improved the probability of conception (combined odds ratio with 95% confidence intervals: 6.23, 2.35 - 16.52). REVIEWER'S CONCLUSIONS: Intra-uterine insemination offers couples with male subfertility benefit over timed intercourse, both in natural cycles and in cycles with COH. In the case of a severe semen defect (with more than 1 million motile sperm after semen preparation and no triple sperm defect) IUI in natural cycles should be the treatment of first choice. The value of COH need to be further investigated in RCTs. Mild ovarian hyperstimulation with gonadotrophins is advised in cases with less sever

Coitus↗
PubMed2000

Basal follicle-stimulating hormone levels are of limited value in predicting ongoing pregnancy rates after in vitro fertilization.

OBJECTIVE: To evaluate whether basal FSH (bFSH; measured on menstrual day 1-4) adds relevant clinical information to the prediction of ongoing pregnancy rates (OPRs) after IVF, once age and diagnostic characteristics have been taken into account. DESIGN: Retrospective. SETTING: Academic fertility center. PATIENT(S): 435 women undergoing their first IVF cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate. RESULT(S): The likelihood ratio of bFSH as a single prognosticator for treatment failure at a cutoff level of 15 IU/L was 3.87. The proportion of patients with such a bFSH level was 5%. Multivariate logistic regression analysis selected age, bFSH level, and infertility diagnosis as relevant predictors of ongoing pregnancy. When compared to a predictive model for OPRs based on age and infertility diagnosis, the inclusion of bFSH into this model helped to identify more patients (22 vs. 1) whose predicted OPR decreased from a low level (5%-12%) towards an extremely low level (<5%). CONCLUSION(S): An acceptable performance of bFSH as a single test to predict treatment failure is only obtained above a high cutoff level. Thus, the number of patients for whom bFSH provides relevant information is small. The predictive model including bFSH identified significantly more patients with an extremely poor prognosis than did the predictive model without bFSH. However, predictions based solely on age and infertility diagnosis usually were already poor in these patients. Measurement of bFSH adds little in only a few patients and is, therefore, debatable.

Adult↗
PubMed1999

Occupationally related exposures and reduced semen quality: a case-control study.

OBJECTIVE: To determine whether there is an association between abnormal semen parameters and occupational exposures to organic solvents, metals, and pesticides. DESIGN: Case-control study using three case groups based on different cutoff values for semen parameters and one standard reference group. SETTING: University Hospital Utrecht and University Hospital Rotterdam, the Netherlands. PATIENT(S): Male partners of couples having their first consultation at the two infertility clinics (n = 899). INTERVENTION(S): Men provided at least one semen sample. Occupational exposure was assessed with use of job-specific questionnaires, a job exposure matrix, and measurements of metals and metabolites of solvents in urine. MAIN OUTCOME MEASURE(S): Standard clinical semen analyses were used to define case groups and controls. RESULT(S): An association between aromatic solvents and reduced semen quality was demonstrated, irrespective of the exposure assessment method used. The associations were stronger if the case definition was based on stricter cutoff values for semen parameters. Risk estimates were higher if the analysis was restricted to primary infertile men. Exposure to other pollutants at the workplace was not associated with impaired semen quality. CONCLUSION(S): The findings indicated an association between aromatic solvent exposure and impaired semen parameters.

Adult↗
PubMed1999

Antral follicle counts by transvaginal ultrasonography are related to age in women with proven natural fertility.

OBJECTIVE: To investigate the relation between reproductive age and ultrasound (US)-based follicle counts and the reproducibility of follicle counts in regularly cycling women with proven fertility. DESIGN: Prospective observational study. SETTING: Tertiary fertility center. PATIENT(S): Healthy female volunteers with proven fertility, recruited by advertisement in local newspapers. INTERVENTION(S): The number of antral follicles sized 2-10 mm and ovarian volume were estimated by transvaginal US in the early follicular phase of the menstrual cycle in 162 women. A subgroup of 81 women underwent transvaginal US at several times in three subsequent cycles. MAIN OUTCOME MEASURE(S): Antral follicle count and total ovarian volume. RESULT(S): Women aged 25-46 years (n = 162) were studied. The relation of age with the US indices was computed after natural log transformation. Antral follicle count showed the clearest correlation with age (R = -0.67). A biphasic linear model gave the best fit to the data. Before the age of 37 years, the antral follicle count showed a mean yearly decline of 4.8%, compared with 11.7% thereafter. The reproducibility of the antral follicle count in two subsequent cycles was moderate. CONCLUSION(S): The number of small antral follicles in both ovaries as measured by US is clearly related to reproductive age and could well reflect the size of the remaining primordial follicle pool.

Adult↗
PubMed1999

Diagnosis of subtle ovulation disorders in subfertile women with regular menstrual cycles: cost-effective clinical practice?

Serial monitoring by plasma progesterone measurement is advised in the literature for fertility work-up, to detect ovulation disturbances in women presenting with regular menstrual cycles. Three strategies to diagnose such 'subtle ovulation disorders' (SOD, defined as anovulation, inadequately timed ovulation or ovulation of a follicle of reduced size in regularly cycling women) were evaluated, in order to investigate costs of such a diagnosis. On the basis of a 'maximal', an 'ultrasound-only', and a 'preselection' strategy, total medical costs and costs including non-medical costs were calculated for each SOD diagnosis. A 'maximal' diagnostic strategy resulted in a total medical cost of ECU 9057 per diagnosis (including non-medical costs ECU 12,787); an 'ultrasound-only' strategy in ECU 4520 (ECU 6791) per diagnosis. By use of a 'preselection' strategy, 4.25% of the women were found to have an SOD, at a cost of ECU 3036 (ECU 6868) for each diagnosis. As the real significance of SOD diagnosis for the prognosis of the patient to become pregnant without treatment remains unclear, and as no randomized trials on treatment effectiveness have as yet been undertaken, it is questionable whether this approach is worthwhile.

Blood Chemical Analysis↗
PubMed1999

Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility.

The present prospective follow-up study was designed to identify whether clinical, endocrine, or ultrasound characteristics assessed by standardized initial screening of normogonadotropic oligo/amenorrheic infertile patients could predict conception in 160 women who reached ovulation after clomiphene citrate (CC) medication. Additional inclusion criteria were total motile sperm count of the partner above 1 million and a negative history for any tubal disease. Daily CC doses of 50 mg (increasing up to 150 mg in case of absent ovarian response) from cycle days 3-7 were used. First conception (defined as a positive urinary pregnancy test) was the end point for this study. A cumulative conception rate of 73% was reached within 9 CC-induced ovulatory cycles. Patients who did conceive presented more frequently with lower age (P < 0.0001) and amenorrhea (P < 0.05) upon initial screening. In a univariate analysis, patients with elevated initial serum LH concentrations (>7.0 IU/L) had a higher probability of conceiving (P < 0.01). In a multivariate analysis, age and cycle history (oligomenorrhea vs. amenorrhea) were identified as the only significant parameters for prediction of conception. These observations suggest that there is more to be gained from CC ovulation induction in younger women presenting with profound oligomenorrhea or amenorrhea. Screening characteristics involved in the prediction of ovulation after CC medication in normogonadotropic oligo/amenorrheic patients (body weight and hyperandrogenemia, as shown previously) are distinctly different from predictors of conception in ovulatory CC patients (age and the severity of cycle abnormality). This disparity suggests that the FSH threshold (magnitude of FSH required for stimulation of ongoing follicle growth and ovulation) and oocyte quality (chances for conception in ovulatory cycles) may be differentially regulated.

Adult↗
PubMed1999

Hormone patterns after induction of ovulation with clomiphene citrate: an age-related phenomenon.

Since the introduction of clomiphene citrate (CC), more than three decades ago, a discrepancy has been observed between ovulation and pregnancy rates for which as yet no explanation exists. To investigate if ovulation disorders or abnormal hormonal patterns occur more often in CC-stimulated seemingly ovulatory cycles, we performed hormonal and sonographic monitoring in first cycles of oligo- or amenorrheic patients who were stimulated with 50 mg CC, and compared the hormonal patterns to those in natural cycles of age-matched proven fertile women. Twenty-four first CC cycles were monitored. Twelve cycles appeared to be ovulatory, eleven showed no follicle development and one cycle exhibited the luteinized unruptured follicle (LUF) phenomenon. Ten ovulatory cycles were compared with 27 unstimulated control cycles. In four cycles stimulated by CC, a temporary decline in estradiol levels was apparent. In these cycles, estradiol reached a higher level on cycle day (CD) 7 or 8 compared to cycles without a decline. Such an estradiol decline was seen in only one control cycle. Furthermore, the estradiol levels on CD 7 or 8 appeared to be age-related. We conclude that the estradiol decline in CC-stimulated ovulatory cycles may be a consequence of a sharp rise after CC stimulation, and such a rise may be age-related and coincide with a diminished follicle quality. If this phenomenon is associated with a suboptimal cycle, and so contributes to the suboptimal pregnancy rates after ovulation-induction treatment with clomiphene citrate, is still unknown.

Adult↗
PubMed1998

[Exposure to pseudo-estrogens and the quality of sperm].

Some synthetic chemicals and natural compounds occurring in vegetables or animal food products mimic endogenous hormones, especially oestrogens, or may have a general action of disturbing hormonal status. It is assumed that intrauterine exposure to these compounds may have an adverse effect on development, differentiation and function of the genital organs of the male foetus. In a worldwide discussion a supposed drop in human sperm quality is related to foetal exposure to chemicals with oestrogen activity. Experimental animal evidence suggests that foetal exposure to compounds with oestrogenic activity may influence reproductive capabilities. In addition chemicals such as diethylstilbestrol (DES) in humans and dichlorodiphenyltrichloroethane (DDT) in wildlife influence the reproductive system. There is no conclusive evidence of decreasing semen quality in general.

Abnormalities, Drug-Induced↗
PubMed1998

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.

Aging↗
PubMed1998

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.

Aging↗