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Biomedical subjects

D D Braat

Publications and source records attributed to D D Braat.

At least 37 records · Page 2Linked to original sources
PubMed2000

Geographical distribution of publications in Human Reproduction and Fertility and Sterility in the 1990s.

Curious about the geographical distribution of publications in reproductive medicine, we compared the numbers of publications in Human Reproduction (HR) and Fertility and Sterility (F&S). The annual number of publications from the individual countries was obtained by searching the Medline database using the internet provider PubMed. The data were analysed and normalized to population size, gross domestic product (GDP) and total number of Medline publications. The 8511 publications of both journals in the 1990s came from 56 countries. The number of publications per year was increasing in HR and remained constant in F&S. In absolute numbers, the UK produced the most publications in HR (21%) and the USA in F&S (45%) as well as in both journals together (28%). Relatively, Israel was the most productive country per million inhabitants (8.4 +/- 2.1 publications/year), per billion US dollars GDP (0.85 +/- 0.21 publications/year) and per 1000 Medline publications (15 +/- 4 publications/year). Europe was the most productive world region in absolute numbers (54%) and Australia/New Zealand in relative numbers per million inhabitants and per 1000 billion US dollars GDP. Almost 87% of all publications in HR and F&S came from the 18 countries with a GDP per capita of >10 000 US dollars. In conclusion, the geographical distribution of publications in HR and F&S follows the pattern of the distribution of publications in general biomedical research. Most publications come from affluent countries. Although the USA and the UK appear to be the most productive countries in absolute numbers, smaller affluent countries like Israel and Belgium are more productive when the numbers are normalized to population or GDP.

Australia↗
PubMed2000

Obstetric outcome of singleton pregnancies after IVF: a matched control study in four Dutch university hospitals.

In singleton pregnancies after IVF a high rate of preterm deliveries and an increased rate of small-for-gestational age (SGA) children in comparison to the general parturient population have been reported. However, due to differences between IVF mothers and their peers who conceived naturally, careful selection of the control group is necessary to assess whether IVF pregnancies really carry increased risks of adverse outcome. In our study 307 IVF pregnancies were compared with 307 control pregnancies after elaborate matching for an extensive number of maternal characteristics, as well as for the hospital that provided the obstetric care. Four Dutch university hospitals contributed to the study. In cases with spontaneous onset of labour, gestational age at delivery was 3 days shorter in the IVF group (275 versus 278 days, P = 0.05). The proportion of SGA was higher in the IVF group (16.2 versus 7.9%, P < 0.001). The combination of these two results denotes a distinct difference between IVF and control pregnancies. Placental weight was comparable in both groups.

Abnormalities, Multiple↗
PubMed1999

Corticosteroids do not influence ovarian responsiveness to gonadotropins in patients with premature ovarian failure: a randomized, placebo-controlled trial.

OBJECTIVE: To determine the effect of corticosteroids on ovarian responsiveness to exogenous gonadotropins in patients with idiopathic premature ovarian failure (POF). DESIGN: Placebo-controlled, randomized, double-blind, multicenter study. SETTING: Two tertiary care academic centers for reproductive endocrinology and fertility and two general teaching hospitals. PATIENT(S): One hundred patients with idiopathic POF intended to enter the study. The study was discontinued after 36 patients failed to ovulate. INTERVENTION(S): Endocrine and immune parameters were tested on days 1 and 15. On day 1, subjects were randomized to receive either 9 mg of dexamethasone daily or placebo. From day 5 onward, 300 IU of hMG daily was added for 10 days in both groups. The dosage of dexamethasone was decreased stepwise in the second week and discontinued after day 15. Patients were monitored by transvaginal ultrasonography and by determining serum E2 levels. MAIN OUTCOME MEASURE(S): Ovulation rate. Fifty patients would have to be included in each study group to detect a statistically significant difference of 20% in the ovulation rate between the two groups with alpha = 0.05 and beta = 0.1 (one-tailed test). RESULT(S): No ovulation was recorded in the first 36 patients. Interim analysis showed that the 95% confidence intervals of an ovulation rate of 0 were 0-17% for the dexamethasone arm (n = 19) and 0-19% for the placebo arm (n = 17). Because the preset objective (a difference of 20%) would never be reached, the study was discontinued. CONCLUSION(S): Corticosteroids do not influence ovarian responsiveness to gonadotropins in patients with idiopathic POF.

Adrenal Cortex Hormones↗
PubMed1999

Retrieval, maturation, and fertilization of immature oocytes obtained from unstimulated patients with polycystic ovary syndrome.

PURPOSE: Our purpose was to determine whether immature oocytes could be retrieved under local anesthesia, whether these oocytes would mature and fertilize in vitro, and whether adequate endometrium development could be obtained after hormonal supplementation. METHODS: Ovum pick-up was performed under local anesthesia. Immature oocytes were cultured and inseminated. To prepare the endometrium, estradiolvalerate was administered in combination with micronized progesterone. RESULTS: Immature oocytes were obtained in all cases. Fifty-six percent (n = 30) of the oocytes developed into metaphase II (MII) after 48 hr of culture, and another 20% reached the MII stage by 72 hr. Normal fertilization was observed in only 10% of oocytes inseminated. No embryonic development occurred, and therefore embryo transfer was not performed in any of the patients. Endometrial microbiopsy was performed in all subjects and endometrial development was considered sufficient in eight patients. CONCLUSIONS: We collected immature oocytes from patients with polycystic ovary syndrome without general anesthesia. In vitro maturation of these oocytes seemed adequate but fertilization rates were poor. Sufficient endometrial quality was obtained after hormonal substitution.

Adult↗
PubMed1999

Familial idiopathic premature ovarian failure: an overrated and underestimated genetic disease?

The incidence of familial cases of premature ovarian failure varies from 4 to 31%. Recall bias may explain part of the variance. Thorough evaluation of alleged affected relatives showed a lower incidence than the original family history suggested. In the present study the incidence of familial cases was 12.7%. Pedigree studies on affected families showed a mode of inheritance suggestive of autosomal dominant sex-limited transmission or X-linked inheritance with incomplete penetrance. An adequate family history can distinguish between familial or sporadic premature ovarian failure. The risk of female relatives developing premature ovarian failure may be as high as 100% in familial premature ovarian failure, or as low as 1% in sporadic cases.

Adult↗
PubMed1999

Reproductive decisions of men with microdeletions of the Y chromosome: the role of genetic counselling.

Couples dealing with microdeletions of the Y chromosome have to make decisions about their reproductive future. Do they opt for intracytoplasmic sperm injection (ICSI), artificial insemination with donor insemination (AID) or no treatment? We analysed this decision in 28 couples and investigated the role of the counsellor and the counselling process on the final decision of the couple. Ten counsellors from six fertility clinics in The Netherlands and Belgium were interviewed about their genetic counselling of couples dealing with microdeletions. The answers to the questionnaire were converted to 11 dichotomous variables. Of the 1627 tested men in the six centres, 37 (2.3%) had a microdeletion in the AZFc region, a subregion of the AZF region on the Y chromosome important for normal spermatogenesis. The decisions of 28 of them could be analysed. Most couples chose ICSI (79%). The remaining couples chose donor insemination (7%) or refrained from treatment (14%). Several variables, including the counselling procedure, the counsellor and the available treatments in the fertility centre, influenced the decision of the couple. In conclusion, most couples dealing with microdeletions in the AZF region choose ICSI. Several aspects of the process of genetic counselling appear to be related to the final decision.

Adult↗
PubMed1998

The endocrinology of dizygotic twinning in the human.

Heredity, higher maternal age and increased parity are well defined conditions associated with dizygotic twinning. An endocrine model of excessive secretion of pituitary gonadotrophic hormones explains multiple ovulation as a result of multiple follicle growth. In hereditary conditions FSH levels are indeed clearly elevated because of increase in stimulating mechanisms that regulate pituitary gonadotropin secretion while in most non-hereditary conditions, overshoot FSH secretions occurs as a result of diminished ovarian feedback. Puberty is a condition in which the hypothalamic LHRH pulse generator is reinitiated and this is typically characterized by temporary overshoot LH and FSH secretion, probably due to not yet fully operational ovarian feedback. In adult females situations can be found that mimic this peripubertal event such as while recovering from hypothalamic amenorrhea. Under these circumstances more DZ twinning can be observed. Elevated FSH levels along with ageing in premenopausal women probably underlie the age related increased risk of dizygotic twinning. The apparent paradox in the combination of age related decline in fecundity and rise in twinning risk can be explained by incidental presence in the cohort of more than one follicle, containing vital oocytes under deficient feedback mechanisms that lead to high FSH.

Aging↗
PubMed1998

Does intracytoplasmic sperm injection lead to a rise in the frequency of microdeletions in the AZFc region of the Y chromosome in future generations?

Microdeletions in the AZFc region of the Y chromosome are found in oligo- and azoospermic men. These mutations were genetically lethal before the intracytoplasmic sperm injection (ICSI) era but they can nowadays be transmitted to next generations via ICSI. We have tried to answer the question, 'Does ICSI lead to a significant rise in the frequency of these microdeletions in future generations?', by developing a mathematical model for Y-linked mutations with two variables (fitness and mutation frequency). To illustrate this model we have made estimates according to three imaginary scenarios. Using the assumptions described, the model predicted that the frequency of microdeletions in the AZFc region would increase in each generation until a plateau was reached. The higher the fitness, the higher the plateau and the later the plateau would be reached. Taking realistic estimates for fitness (0.5) and spontaneous mutation frequency (0.0001), the maximum increase in men with microdeletions would be twofold. This maximum would be already reached after five generations. However, if the fitness of these men were improved and approached 1.0, the mechanism of selection would disappear and finally all men would have the deletion in the AZFc region. Because of the assumptions in these scenarios, these estimates have limitations. The model presented shows that the rise in the frequency of men with microdeletions in the AZFc region in future generations would be limited as long as the fitness of these men remained limited.

Chromosome Deletion↗
PubMed1998

External validation of prognostic models for ongoing pregnancy after in-vitro fertilization.

This study aimed to validate prognostic models for predicting ongoing pregnancy after the first and second in-vitro fertilization cycles. Models were developed using data from the University Hospital, Nijmegen, 1991-1994 and tested using more recent data from the same centre and data from two other centres. Although the variables included in the models seemed plausible, the predictions of the models were unsatisfactory. The models did not discriminate between women who had achieved pregnancy and women who did not achieve pregnancy; neither could they indicate which women had a (very) low probability of ongoing pregnancy. Taking into account the success rate of a specific clinic or the success rate during a specific period did not show any advantage. The predictions were even inaccurate in the same hospital during another period. It is obvious that these prognostic models should not be used. This study shows the importance of validating prognostic models before their implementation in clinical practice.

Adult↗
PubMed1998

Surgical sperm retrieval and intracytoplasmic sperm injection as treatment of obstructive azoospermia.

Male genital tract obstructions may result from infections, previous inguinal and scrotal surgery (vasectomy) and congenital bilateral absence of the vas deferens (CBAVD). Microsurgery can sometimes be successful in treating the obstruction. In other cases and in cases of failed surgical intervention, the patient can be treated by microsurgical or percutaneous epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). We present the results of 39 ICSI procedures for obstructive azoospermia in 24 couples. The aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD in nine and genital infections in four. Sperm retrieval was accomplished via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was only applied when PESA failed to produce enough spermatozoa for simultaneous ICSI. In six patients, the ICSI procedure was performed with cryopreserved spermatozoa after an initial PESA procedure. Fertilization occurred in 47% of the metaphase II oocytes; embryo transfer was performed in 92% of procedures and resulted in a clinical pregnancy in 13/39 procedures. Ongoing pregnancy was achieved in 10/39 procedures. One pregnancy was terminated early after prenatal investigation showed a cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine pregnancies resulted in the live birth of 10 children, without any congenital abnormalities. Epididymal and testicular retrieved spermatozoa were successfully used for ICSI to treat obstructive azoospermia, and resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI procedures, a success rate of 25.6% per treatment cycle and of 27.7% per embryo transfer.

Embryo Transfer↗
PubMed1998

The effects of co-culture with human fibroblasts on human embryo development in vitro and implantation.

In a human in-vitro fertilization (IVF) programme, the effect of co-culture of embryos with human fibroblasts was evaluated with respect to pregnancy rate and embryo development. Patients were included in the study after giving informed written consent. The IVF treatments were randomly assigned by stratification of both age (<36 versus > or =36 years) and previous IVF attempts (yes versus no). After fertilization was established, the zygotes were transferred to a 4-well dish with or without fibroblasts and cultured for 2 days. On the third day after ovum pick-up (OPU), cell number and quality [5 (good) to 1 (poor)] of the embryos were scored and a maximum of three embryos was transferred. Supernumerary embryos of good quality were cryopreserved. The design of this study was a group sequential trial with the objective of detecting differences between pregnancy rates following IVF with conventional incubation or incubation in co-culture with fibroblasts. This design included one evaluation at half-way data collection. In the study, 148 patients had an OPU, of whom 77 were allocated to the co-culture group. There was no statistically significant difference in pregnancy rate, cell number and embryo quality between the two groups. The ongoing pregnancy rate per embryo transfer was 27% in co-culture and 30% in the conventional culture group. The implantation rates per transferred embryo were 17 and 18% respectively. Using a multivariate logistic regression model for the probability of ongoing pregnancies, the odds ratio of co-culture, adjusted for age and previous IVF attempts, was not statistically significant. In conclusion, co-culture with human fibroblasts does not contribute to an improvement of embryo quality nor to a higher pregnancy rate after IVF in an unselected group of patients.

Adult↗
PubMed1998

Screening male intracytoplasmic sperm injection candidates for mutations of the follicle stimulating hormone receptor gene.

Follicle stimulating hormone (FSH) is considered to be essential for spermatogenesis. Therefore, genetic abnormalities of FSH signalling on testicular Sertoli cells would be expected to affect sperm production negatively in males. Inactivating FSH receptor mutations have been reported earlier in both males and females. All affected males had elevated FSH serum concentrations and abnormal sperm parameters. We postulated that inactivating FSH receptor mutations might be a cause of oligozoospermia or azoospermia and reviewed the clinical data of 151 male intracytoplasmic sperm injection (ICSI) candidates with special attention to FSH serum concentrations. The exclusion criteria for mutation screening of the FSH receptor gene were: a history of operative sterilization or testicular malignancy, congenital abnormality other than cryptorchidism, and a chromosomal aberration or a Y-chromosome microdeletion. The inclusion criteria were: male (ICSI candidate) with azoospermia or oligoasthenoteratozoospermia (OAT) and elevated FSH serum concentrations. In total, 23 males with OAT and five males with azoospermia were tested for mutations of the coding sequences and the intron-exon boundaries of the FSH receptor gene by polymerase chain reaction (PCR) followed by single strand conformation polymorphism analysis (SSCP). Neutral polymorphisms were readily detected using this technique in both probands and controls. None of the 28 selected patients showed a pathogenic FSH receptor mutation. Mutations in the FSH receptor gene are not a common cause of infertility in ICSI candidates.

Cytoplasm↗
PubMed1998

Ovarian hyperstimulation syndrome: facts and fallacies.

Severe or critical ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian hyperstimulation for assisted reproduction techniques (ART). The syndrome is characterized by cystic enlargement of the ovaries and fluid shifts from the intravascular to the third space. The morbidity in OHSS is mainly determined by the hemodynamic changes caused by increased capillary permeability. The incidence of OHSS depends on definitions, risk factors, ovarian stimulation protocols, luteal support and conception. Currently, research on the pathogenesis of OHSS is focused on increased capillary permeability. Several theories are reviewed. Until the pathogenesis of OHSS becomes clear, treatment is restricted to supportive therapy. The various proposals for management of OHSS are discussed and, based on the available data, directions for the management of various grades of OHSS are summarized. However, prevention and early recognition are still the most important tools to handle OHSS. A flowchart with preventive measures for OHSS is presented derived from the available literature.

Algorithms↗
PubMed1997

[Pregnancy following oocyte donation].

Five women, aged 31, 26, 31, 34, and 28 years, became pregnant after oocyte donation and in-vitro fertilization. One was a carrier of Leber's optical atrophy, three had had an early menopause (in two because of chromosomal abnormalities), and one had had bilateral ovarian extirpation because of a cystadenoma and endometriosis. Three developed (pre-)eclampsia during pregnancy and one had a serious fluxus post partum. One twin died in utero, the other children were healthy. In the Netherlands in-vitro fertilization (with or without egg-donation) takes place up to the age of about 40. Regarding the high incidence of obstetrical complications in women under 40, raising the age limit could lead to even more pregnancy problems. Candidates for oocyte donation should be informed about these risks, furthermore they should not deliver at home.

Adult↗
PubMed1997

Microdeletions of the Y chromosome and intracytoplasmic sperm injection: from gene to clinic.

Intracytoplasmic sperm injection (ICSI) is a successful treatment option for severe male infertility, although the aetiology of the disorder remains unclear in most cases. Recently, microdeletions in the AZF region of the Y chromosome have been detected in men with azoospermia or severe oligozoospermia. In this study we investigated the prevalence of microdeletions in the AZF region of the Y chromosome in a population of men undergoing ICSI, and looked for clinical characteristics of men with and without this deletion. Blood was drawn from 164 men, who were on the waiting list for ICSI treatment: 19 were azoospermic, 111 oligozoospermic and 34 normozoospermic (after previous total fertilization failure). A total of 100 men with proven fertility served as a control. Microdeletions in the AZFc region were present in seven of the 111 oligozoospermic men (6.3%). Compared with oligozoospermic men without microdeletions, men with microdeletions had a lower concentration of follicle stimulating hormone (FSH), a lower number of motile spermatozoa and a lower frequency of abnormal findings at andrological history or examination. No microdeletions were found in the azoospermic, normozoospermic and control groups. In conclusion, microdeletions in the AZFc region are relatively frequently found in men with severe unexplained oligozoospermia. In the ICSI era this finding has an important impact because this form of male infertility is now potentially hereditary. Therefore we recommend DNA screening (and genetic counselling) before ICSI, especially in men with normal FSH, severe oligozoospermia and no abnormal clinical andrological findings.

Case-Control Studies↗
PubMed1997

An artificially induced follicle stimulating hormone surge at the time of human chorionic gonadotrophin administration in controlled ovarian stimulation cycles has no effect on cumulus expansion, fertilization rate, embryo quality and implantation rate.

In the spontaneous menstrual cycle, the mid-cycle gonadotrophin surge causes maturation of the cumulus-oocyte complex, mucification of cumulus cells and expansion of the cumulus oophorus, resumption of meiosis and maturation of the cytoplasm of the oocyte. Whether this is an effect purely of luteinizing hormone (LH) or whether follicle stimulating hormone (FSH) also plays a role is unknown. The effect of an artificially induced FSH surge at the time of human chorionic gonadotrophin (HCG) injection on maturation of the cumulus-oocyte complex was investigated in a prospective randomized double-blind trial. Twelve patients underwent controlled ovarian hyperstimulation [long gonadotrophin-releasing hormone agonist (GnRHa)/human menopausal gonadotrophin (HMG) protocol] for in-vitro fertilization (IVF) treatment. At the time of HCG administration, six patients received a bolus injection of FSH (450 IU i.m.); the other six patients received a placebo. The peak plasma concentrations of FSH of the experimental group were compared with the peak values of FSH obtained at the mid-cycle gonadotrophin surge of the natural cycle of a group of 12 volunteers to validate the bolus injection of FSH. Maturation of the cumulus-oocyte complex was quantified by measuring the expansion of the cumulus, by the fertilization rate and the implantation rate. The quality of the embryos was scored according the average morphology score. The bolus injection of FSH mimicked the mid-cycle gonadotrophin surge. The mean peak value of FSH (12.9 IU/l) in the experimental group was fully comparable with the mean peak value of FSH (10.0 IU/l) of the mid-cycle gonadotrophin surge in the natural cycle. No effect of a bolus injection of FSH on the maturation of the cumulus-oocyte complex or any other outcome variable was found. It is not advantageous to combine the final HCG injection with a bolus injection of FSH in GnRHa/HMG stimulated cycles.

Adult↗