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G Verheyen

Publications and source records attributed to G Verheyen.

At least 19 recordsLinked to original sources
PubMed2000

A European multicenter association study of HTR2A receptor polymorphism in bipolar affective disorder.

The available data on the role of 5-HT in a variety of behaviors support the hypothesis that a dysfunction in brain serotoninergic system activity contributes to vulnerability to major depression. The diversity in the electrophysiological actions of 5-HT in the central nervous system can now be categorized according to receptor subtypes and their respective effector mechanisms. In particular, the implication of central postsynaptic 5-HT2A receptor in affective disorders has been supported by findings consistent with the hypothesis of 5-HT2A receptor up-regulation in depression. For these reasons, the 5-HT2A receptor (HTR2A) gene can be considered as a candidate gene in bipolar affective disorder (BPAD). We tested the possible genetic contribution of the polymorphic DNA variation T102C in exon 1 of HTR2A (chromosome 13q14-21) gene in a large European multicentric case-control sample. Allele and genotype frequencies, as well as homo-heterozygote distributions were compared between the two groups of 309 bipolar affective disorder patients and 309 matched controls. No significant differences were observed in the allelic and genotypic (also for homo-heterozygote) distribution between BPAD and controls. These results indicate that, in our sample, the 5-HT2A receptor polymorphism studied is unlikely to play a major role in the genetic susceptibility to BPAD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:136-140, 2000.

Adult↗
PubMed2000

Linkage of mood disorders with D2, D3 and TH genes: a multicenter study.

BACKGROUND: It has been suggested that the dopaminergic system is involved in the pathophysiology of mood disorders. We conducted a multicenter study of families with mood disorders, to investigate a possible linkage with genes coding for dopamine receptor D2, dopamine receptor D3 and tyrosine hydroxylase (TH). METHODS: Twenty three mood disorder pedigrees collected within the framework of the European Collaborative Project on Affective Disorders were analyzed with parametric and non-parametric linkage methods. Various potential phenotypes were considered, from a narrow (only bipolar as affected) to a broad (bipolar+major depressive+schizoaffective disorders) definition of affection status. RESULTS: Parametric analyses excluded linkage for all the candidate genes, even though small positive LOD (Limit of Detection) scores were observed for TH in three families. Non-parametric analyses yielded negative results for all markers. CONCLUSION: The D2 and D3 dopamine receptors were, therefore, not a major liability factor for mood disorders in our sample, whereas TH may play a role in a subgroup of patients.

Bipolar Disorder↗
PubMed2000

Allelic distribution of CTG18.1 in Caucasian populations: association studies in bipolar disorder, schizophrenia, and ataxia.

CTG18.1 is a highly polymorphic and unstable CTG repeat within an intron of the SEF2-1 gene. We tested the CTG18.1 repeat length in affective disorder, schizophrenia, and nonspecific ataxia; these diseases all have shown clinical evidence for anticipation. There was no difference in the allele frequencies comparing the controls and disease groups. The most common allele contains 11 CAGs (35%) followed by alleles with 14-17 CAGs (35%). There was no difference in the distribution of the alleles in the cases vs controls for ataxia (P = 0.11), affective disorders (P = 0.21), or schizophrenia (P = 0.26). The frequency of unstable CTG18.1 alleles was approximately 3% in a population of N. European descent and is not related to the phenotypes tested.

Alleles↗
PubMed2000

Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in-situ hybridization in infertile men.

Spermatozoa from 32 infertile patients and 13 controls with normal semen parameters were analysed using dual and triple colour fluorescence in-situ hybridization (FISH) techniques, in order to investigate the rates of aneuploidy for chromosomes 13, 18, 21, X and Y. The patients were divided into three groups according to their karyotypes or the karyotypes of their offspring: 15 were infertile men with abnormal semen parameters and normal karyotypes (group 1), 13 were infertile men with abnormal karyotypes and normal or abnormal semen (group 2) and four were infertile men with abnormal semen and normal karyotypes but whose wives conceived a child (or a fetus) with a numerical chromosomal abnormality through an intracytoplasmic sperm injection cycle (group 3). Patients with abnormal semen parameters showed a significantly higher aneuploidy rate for the investigated chromosomes in their spermatozoa compared to controls (P < 0.005). Our data suggest the presence of a correlation between poor semen parameters and an increase in aneuploidy rate of chromosomes 13, 18, 21, X and Y in spermatozoa (r = -0.81071, P < 0.002); therefore the risk of a chromosomal aneuploidy in spermatozoa seems to be inversely correlated to sperm concentration and total progressive motility. Patients with abnormal karyotypes showed a higher incidence of diploidy and chromosomal aneuploidies compared to controls (P < 0.002). This strongly suggests the presence of an interchromosomal effect of the cytogenetic rearrangement. Men who fathered a child with an abnormal karyotype through intracytoplasmic sperm injection did not present a higher aneuploidy rate for the investigated chromosomes in spermatozoa compared to patients with infertility due to a similar male factor but showed higher incidence of chromosomal aneuploidy compared to normal controls.

Adult↗
PubMed1999

Report of the chromosome 18 workshop.

At the first chromosome 18 workshop held at the 1997 World Congress on Psychiatric Genetics (WCPG) in Santa Fe, NM, several studies were presented that suggested the presence of a bipolar disorder (BP) as well as a schizophrenia (SZ) susceptibility locus on chromosome 18. Although the fact that several independent studies all pointed to a susceptibility locus (or loci) on chromosome 18, the observation that these studies identified nonoverlapping candidate regions was disappointing at least from the viewpoint of molecular genetics aiming at cloning the respective gene(s). Together, the data suggested four possible regions of considerable size that contained a susceptibility gene. At the 1998 WCPG chromosome 18 workshop in Bonn, Germany, less data were submitted and with the exception of a few studies, most data were nonsupportive or negative. Although some refinements were made to the previous candidate loci, overall the picture has not changed in that we are still confronted with the same four potential loci on chromosome 18 for BP and/or SZ, i.e., 18p11.2 and 18q12.1-q12.3 for BP and SZ, and 18q21-q22 and 18q23-qter for BP. So far, no other psychiatric phenotypes show evidence for a susceptibility locus on chromosome 18.

Bipolar Disorder↗
PubMed1999

Freezing of testicular tissue as a minced suspension preserves sperm quality better than whole-biopsy freezing when glycerol is used as cryoprotectant.

Frozen-thawed testicular spermatozoa have been used successfully for ICSI, especially in cases of obstructive azoospermia with normal spermatogenesis. Fewer attempts, however, have been made to check whether these rather immature spermatozoa, in a different environment with several other cell types present, have cryobiological requirements other than those of ejaculated spermatozoa. This is the reason why the freezing protocols and cryoprotectants (glycerol) used for freezing testicular tissue are based on experience with semen freezing. This study aimed to assess whether cryosurvival and/or motility was influenced by freezing of testicular tissue either as an intact biopsy or as a shredded tissue suspension, when glycerol was used as cryoprotectant. Freezing of testicular tissue as a suspension preserved motility (type B + C) significantly better than freezing of whole biopsies (9.2% vs. 4.0%). Similar observations have been made for vitality (39.3% vs. 25.4%). Centrifugation on 50% Percoll in order to remove the cryoprotectant resulted in a huge loss of spermatozoa (or late spermatids) and should therefore be especially avoided in cases of testicular failure. On the basis of these observations, mincing of the testicular biopsies before freezing may be advocated. Testicular spermatozoa seem to be better preserved when frozen in suspension, at least when slowly permeating glycerol is used as a cryoprotectant.

Biopsy↗
PubMed1999

No differences in outcome after intracytoplasmic sperm injection with fresh or with frozen-thawed epididymal spermatozoa.

This retrospective consecutive case series aimed at comparing the results of intracytoplasmic sperm injection (ICSI) with fresh and with frozen-thawed epididymal spermatozoa obtained after microsurgical epididymal sperm aspiration (MESA) in 162 couples. These couples were suffering from infertility because of congenital bilateral absence of the vas deferens (n = 109), failed microsurgical reversal for vasectomy or postinfectious epididymal obstruction (n = 44), irreparable epididymal obstruction (n = 4), ejaculatory duct obstruction (n = 2) or anejaculation (n = 3). Overall, 176 MESA procedures were performed in the husbands, followed by 275ICSI procedures with either fresh (n = 157) or frozen-thawed (n = 118) epididymal spermatozoa. No significant differences were observed in the parameters of spermatozoa used either freshly or frozen-thawed. In the fresh epididymal sperm group 59.4% of all the injected oocytes fertilized normally as compared to 56.2% of all injected oocytes in the frozen-thawed epididymal sperm group, and embryonic development was comparable between the two groups. A total of 245 transfers were performed: 145 after the use of fresh epididymal spermatozoa and 100 after the use of frozen-thawed spermatozoa. The overall pregnancy rate per ICSI cycle was significantly lower when frozen-thawed epididymal spermatozoa were used (26.3 versus 39.5%). However, no significant differences were found either in clinical and ongoing pregnancy rates or in implantation rates. There were no differences in pregnancy outcome. In patients suspected of having obstructive azoospermia with no work-up or an incomplete one, MESA is the preferred method for sperm recovery because a full scrotal exploration can be performed and, whenever indicated, a vasoepididymostomy may be performed concomitantly. Recovery of epididymal spermatozoa for cryopreservation during a diagnostic procedure is certainly a valid option in these patients since ICSI may be performed later or even in another centre using the frozen-thawed epididymal spermatozoa without jeopardizing the ICSI success rate.

Cryopreservation↗
PubMed1999

Light and electron microscopic analysis of human testicular spermatozoa and spermatids from frozen and thawed testicular biopsies.

The morphological changes caused by freezing and thawing human testicular spermatozoa have been assessed here. Retrieval of testicular biopsies was carried out on six patients with obstructive azoospermia preparatory to intracytoplasmic sperm injection (ICSI). Light microscope analysis was carried out on testicular cells and ultrastructural analysis was carried out on spermatozoa and different spermatid stages before and after the freezing procedure. Upon examination under light microscopy, all germ cells presented increased vacuolization in their cytoplasm and shrinkage or swelling of the nuclei and cytoplasmic membranes. These altered structures were accentuated in the spermatocyte I cell which often presented disrupted membranes. The ultrastructural findings under transmission electron microscopy demonstrated that after freezing and thawing the major types of cryoinjury were the swelling and rupture of inner and outer acrosomal and plasma membranes. The acrosome material often appeared as dispersed material or as condensed spots or was even lost. Such damage was observed mainly at the spermatozoa and late spermatid stages. We conclude that the freezing and thawing of testicular biopsies causes similar morphological damage to testicular spermatozoa and frozen-thawed ejaculated spermatozoa. It is still unclear whether these changes in testicular spermatozoa after freezing and thawing may compromise its use in the ICSI procedure.

Adult↗
PubMed1999

Controlled comparison of conventional in-vitro fertilization and intracytoplasmic sperm injection in patients with asthenozoospermia.

A controlled comparison between conventional in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) has been carried out for patients with </=5% rapid progressive (type A) spermatozoa in their fresh semen. Twenty couples were allocated to the study. All semen samples fulfilled the minimum criteria to be allocated to the conventional IVF programme. The two pronuclear (2PN) fertilization rate per retrieved cumulus-oocyte complex was significantly higher after ICSI (63.4%) than after conventional IVF (22.9%), with complete fertilization failure after IVF in 10 out of the 20 cycles. Embryo quality was similar for both treatments. Sixteen patients received only ICSI embryos, two patients only IVF embryos and two patients received IVF and ICSI embryos. The ongoing clinical pregnancy rate was 45%, the implantation rate was 37%. Comparison of the characteristics of patients/cycles with and without 2PN fertilization revealed a higher proportion of progressively motile spermatozoa in the prepared sperm fraction for the group of patients with fertilization after conventional IVF. It can be concluded from this study that absence of or an extremely low proportion of rapid progressive motility in fresh semen indicates a high risk of complete fertilization failure with conventional IVF.

Embryo Implantation↗
PubMed1999

Seven years of intracytoplasmic sperm injection and follow-up of 1987 subsequent children.

Intracytoplasmic sperm injection (ICSI) with ejaculated, epididymal or testicular spermatozoa was first successful in 1992 and has since become the widely accepted treatment for couples with severe male-factor infertility. The outcome of several thousands of ICSI cycles in terms of fertilization, embryo cleavage and implantation is similar to that for conventional in-vitro fertilization in couples with tubal or idiopathic infertility. To evaluate the important issue of safety of the new technique of ICSI, a prospective follow-up study of 1987 children born after ICSI was carried out. The aim was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones. Parents' agreement to genetic counselling was obtained as well as prenatal diagnosis, followed by a physical examination of the children at 2 months, 1 year and 2 years. Between April 1991 and August 1997, 1699, 91 and 118 children were born after ICSI with ejaculated, epididymal and testicular spermatozoa respectively; 79 children were born from cryopreserved ICSI embryos. In all, 1082 karyotypes were determined by prenatal diagnosis, 18 of which were abnormal and de novo (1.66%) (nine each of autosomal and sex chromosomal aberrations), and 10 karyotypes (0.92%) were inherited structural aberrations. Of these, nine (eight balanced structural aberrations and one unbalanced trisomy 21) were transmitted from the father. Ten pregnancies were terminated after prenatal karyotyping or DNA testing. Forty-six major malformations (2.3%) were observed at birth. Seven malformations, observed by prenatal ultrasound, were terminated. Twenty-one (1.1 %) stillbirths, including four with major malformations, occurred later than 20 weeks of pregnancy. Mean gestational age at birth was 38.7 weeks for singletons, 36.0 weeks for twins and 32.0 weeks for triplets. No specifically higher incidence of malformations was found in any given subgroup.

Chromosome Aberrations↗
PubMed1999

What is reflex sympathetic dystrophy?

In the literature there is no unanimity with respect to the diagnosis of reflex sympathetic dystrophy (RSD). Frequently, the diagnosis is established on mere clinical grounds. In our opinion, however, bone scintigraphy is of major importance for the diagnosis. Using this examination, true RSD can be clearly differentiated from other conditions which are incorrectly diagnosed and treated as RSD. If the bone scan is not suggestive of RSD, the clinical picture, radiological examination and vascular scan may lead to the correct diagnosis. This may be a pseudodystrophy, in which a hypovascularization is found right from the start, while in true RSD there is initially a hypervascularization. Other conditions which may be confused with RSD are causalgia, neurotic compulsive postures, hysterical conversion, malingering and even self-mutilation. In the spontaneous course of RSD three phases can be distinguished. Stage I is the warm or hypertrophic phase, stage II the cold or atrophic phase. Per definition the third phase corresponds to stabilization or, in rare instances, to healing. By means of the vascular scan the correct stage can be determined, and the results of treatment evaluated. Finally it should be noted that in children the condition is completely different from true RSD, as it concerns a pseudodystrophy or disuse-related dystrophy. This condition may also be seen in adults and adolescents, usually females. The bone scan is always negative. In this way bone scintigraphy constitutes the means to answer the question as to what RSD is and what it is not. An algorithm for the differential diagnosis is presented.

Adolescent↗
PubMed1998

Is there any need for diagnostic laparoscopy in couples undergoing intracytoplasmic sperm injection for severe male-factor infertility.

PURPOSE: Our purpose was to determine whether there is a need for a preliminary diagnostic laparoscopy in couples undergoing intracytoplasmic sperm injection (ICSI) because of severe male-factor infertility. METHODS: In this retrospective study, the results of diagnostic laparoscopy in 342 women with a normal fertility workup undergoing ICSI were evaluated and sperm parameters were correlated with the findings at laparoscopy. Subgroups of patients were defined according to sperm quality, which was expressed as total normal motile count [TNMC = volume (ml) x concentration (10(6)/ml) x percentage progressive motility/100 x percentage normal morphology/100]. RESULTS: When sperm morphology was evaluated according to Kruger's strict criteria, the probability of finding pathology on laparoscopy in the normal male group (16.7%) was statistically higher than that in the group with severely abnormal sperm (1.8%; P < 0.01). CONCLUSIONS: There is no need to perform a preliminary diagnostic laparoscopy in the female partner if a full workup is normal in couples with severe male-factor infertility willing to undergo ICSI.

Female↗
PubMed1998

Enzymatic digestion of testicular tissue may rescue the intracytoplasmic sperm injection cycle in some patients with non-obstructive azoospermia.

Recovery of testicular spermatozoa from azoospermic patients with testicular failure, followed by intracytoplasmic sperm injection (ICSI) is a recent advance in the treatment of male infertility. In most cases, free spermatozoa are recovered from testicular tissue after mechanical mincing of multiple biopsies. Testicular sperm retrieval, however, remains unsuccessful in 30-50% of male patients suffering from Sertoli cell-only syndrome and maturation arrest. In this study, a strategy was developed in order to maximize the chance of sperm retrieval in difficult cases of testicular failure. The ultimate step was the use of enzymatic procedures (collagenase type IV) to dissociate the testicular tissue completely. Testicular tissue of 41 patients for whom no spermatozoa were found after mechanical mincing of the testicular tissue was investigated. In 14 out of the 41 cases (34%), enough spermatozoa for ICSI were found after fine mincing of multiple biopsies and several hours' search in the cell suspension treated with the erythrocyte-lysing buffer (ELB). In 27 out of the 41 patients, no spermatozoa were found even after the use of ELB. In seven out of these 27 failures (26%), spermatozoa for ICSI were retrieved after enzymatic dissociation of the residual minced tissue pieces, thus making ICSI possible despite failure to find spermatozoa with conventional mincing. From this study, we may conclude that enzymatic digestion of testicular tissue is easy to perform, is not time-consuming and constitutes a successful method in reducing the sperm recovery failures in patients with non-obstructive azoospermia.

Adult↗
PubMed1998

Correlation between motility of testicular spermatozoa, testicular histology and the outcome of intracytoplasmic sperm injection.

The objective of the present study was to analyse the influence of motility on the results of intracytoplasmic sperm injection (ICSI) when testicular spermatozoa are used for microinjection and to correlate this with testicular histology. A total of 197 ICSI treatment cycles (167 couples) was analysed retrospectively in which testicular spermatozoa were used, because of complete azoospermia, for microinjection. Fertilization, embryo cleavage, transfer and pregnancy rates were evaluated and compared in relation to motility of testicular spermatozoa. In 170 cycles, histological diagnoses were compared with findings on motility. Injection of motile testicular spermatozoa (in 159 cycles) provided a higher normal fertilization rate than did injection of non-motile spermatozoa (in 14 cycles; 65 versus 45% respectively). Normal spermatogenesis was diagnosed in a significantly higher proportion and incomplete maturation arrest in a significantly lower proportion in the group of patients in which only motile spermatozoa were used for microinjection (65 and 10%), as compared to the group where exclusively non-motile spermatozoa were used (36 and 36%). Fertilization rate after ICSI was relatively high when non-motile testicular spermatozoa were used for microinjection, but use of motile testicular spermatozoa was associated with a still higher fertilization rate (except when histology of the testicular biopsy showed normal spermatogenesis), and therefore selection of motile testicular spermatozoa is always preferable for ICSI. Normal spermatogenesis predicts a greater probability, and maturation arrest a lower probability of recovering motile testicular spermatozoa.

Cytoplasm↗
PubMed1998

Simple and reliable identification of the human round spermatid by inverted phase-contrast microscopy.

Based on the results of animal studies, round spermatid injection (ROSI) has been introduced into the clinical practice of several in-vitro fertilization (IVF) centres. The efficiency of this procedure in terms of fertilization rates and pregnancy rates, however, remains very poor. An essential aspect which does not receive enough attention is the correct identification of this type of round cell within a heterogeneous population of testicular cells. A Nikon inverted microscope equipped with phase-contrast optics (DLL) provided a clear image which allowed reliable recognition of round spermatids in cell suspensions smeared at the glass bottom of the dish. Fluorescent in-situ hybridization confirmed the haploid status of the selected cells. However, exploration of several biopsies from patients with non-obstructive azoospermia showing no spermatozoa after extensive search did not reveal any round spermatids. This observation questions whether enough effort is spent on searching for mature spermatozoa or late spermatids. Experimental investigations should precede the introduction of ROSI into the clinical practice of any IVF centre.

Cell Size↗
PubMed1998

Results of intracytoplasmic sperm injection with ejaculated, fresh and frozen-thawed epididymal and testicular spermatozoa.

Over the past 5 years, intracytoplasmic sperm injection (ICSI) has been developed to alleviate severe long-standing andrological infertility in couples who could not be helped by standard in-vitro fertilization (IVF), or who could not undergo IVF because too few motile and morphologically normal spermatozoa were present in the ejaculate. ICSI can also be carried out with fresh and frozen-thawed epididymal spermatozoa from patients with obstructive azoospermia and with testicular spermatozoa from most patients with obstructive azoospermia and from some patients with non-obstructive azoospermia. This review reports the results of 5 years of ICSI practice (1991-1995) at the Brussels Free University Centre for Reproductive Medicine, including selection of patients, oocyte and spermatozoa for ICSI, ICSI procedures and its assessment. ICSI was performed in 97% of the 4688 planned treatment cycles. Ejaculated spermatozoa were used in 88% of the cycles, epididymal spermatozoa in 5% of the cycles and testicular spermatozoa in 7% of the cycles. ICSI was performed on 48393 metaphase II oocytes. Of these, 89.5% were morphologically intact, and 70.9% of the intact oocytes were normally fertilized; 64.9% of the two-pronuclear oocytes developed after a further 24 h of in-vitro culture into cleaved embryos, which were transferred or cryopreserved for subsequent use. After transfer of fresh embryos, the percentage of cycles with positive serum human chorionic gonadotrophin was 36.2% per transfer and the percentage of deliveries was 27.0% per transfer. The performance of ICSI with regard to damage, pronuclear status, embryo development and transfer was analysed separately for the four different types of spermatozoa used: fresh ejaculated, epididymal and testicular as well as frozen-thawed epididymal spermatozoa.

Cryopreservation↗