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E Van Assche

Publications and source records attributed to E Van Assche.

At least 19 recordsLinked to original sources
PubMed2026

Esketamine multi-omic biomarker evaluation in major depressive disorder (EMBER-MDD): concept, objectives and methodologies of a non-clinical investigator-initiated study.

Treatment resistance (TR) in major depressive disorder (MDD) affects a substantial minority of patients and is hard to recognize early, delaying intensified care. The Esketamine multi-omic biomarker evaluation in MDD (EMBER-MDD) is a non-interventional, investigator-initiated, in-vitro study within the EU Psych-STRATA programme, analyzing biospecimens collected in the randomized INTENSIFY study and the mirror OBS-TR cohort after participants complete treatment. EMBER-MDD aims to discover individual-omic and integrated multi-omic (hypothesis-free) biomarkers and signatures associated with TR risk, and molecular correlates of clinical response to esketamine nasal spray versus treatment as usual (TAU). Biomaterials will derive from approximately 420 adults with MDD (estimated n = 210 esketamine; n = 210 TAU) and include whole blood, RNA-stabilized whole blood, plasma and serum, sampled at baseline and, when feasible, during and after treatment (up to ~ 5,040 aliquots stored at - 80 °C). Genomics will use baseline DNA genotyping on Illumina Infinium GSA v3.0+MD arrays; epigenomics will profile genome-wide DNA methylation across time points using MethylationEPIC v2.0; transcriptomics will employ mRNA-seq (NovaSeq X/ X Plus); and proteomics/ metabolomics will be generated using high-throughput Olink and/ or Biocrates platforms. Each layer will undergo state-of-the-art preprocessing and analyses (e.g., GWAS/ PRS, EWAS, differential expression, WGCNA, pathway and network analyses), followed by integrative strategies including QTL mapping (meQTL/ eQTL/ pQTL/ mQTL) and intermediate-fusion machine learning with nested cross-validation, explainable AI (SHAP/ LIME) and treatment-effect modelling. All outputs are research-only and will not support individual efficacy, tolerability, or clinical decision-making. The study will deliver robust biosignatures and mechanistic hypotheses to guide future validation and inform stratified, molecularly guided intervention strategies in subsequent prospective trials. Trial registration number: 2023-506617-21-00 and 2025-178-f-S.

Humans↗
PubMed2005

Study of two markers of apoptosis and meiotic segregation in ejaculated sperm of chromosomal translocation carrier patients.

BACKGROUND: To try to explain the infertility of chromosomal translocation carrier patients, we compared the expression of two markers of apoptosis in the sperm of patients and of fertile donors, and we studied the meiotic segregation in the ejaculated sperm of these translocation carriers. METHODS: Twenty semen samples of translocation carriers, [reciprocal (n=14) and Robertsonian translocations (n=6)], were compared with the semen samples of donors (n=20). Different tests were applied: annexin V binding assay; terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL); and fluorescence in situ hybridization (FISH). RESULTS: The annexin V binding assay in sperm of patients with chromosomal translocation (n=17) showed a significantly increased proportion of sperm with externalized phosphatidylserine (PS) than in the control group (n=20, P<or=0.05). The rates of DNA fragmentation investigated by TUNEL reaction were higher in samples of translocation carriers (n=14) than in donors (n=20, P<0.0001). The measures by FISH technique showed that the proportions of balanced or normal gametes were predominant in the reciprocal translocation group (alternate: n=7; from 33.0 to 58.8%; adjacent I: n=7; from 4.6 to 43.8%) and in the Robertsonian translocation group (normal: n=5; from 76.0 to 88.5%). CONCLUSIONS: Our data show a predominant proportion of balanced gametes in sperm of chromosomal translocation carrier patients. Moreover, PS externalization and DNA fragmentation rates are significantly higher in ejaculated sperm of these patients than in donor sperm. These tests could be used to predict the outcome of ICSI for these patients.

Annexin A5↗
PubMed2005

Is chromosome analysis mandatory in the initial investigation of normovulatory women seeking infertility treatment?

BACKGROUND: There is no agreement about the frequency of chromosomal abnormalities (CAs) in the female partner of an infertile couple and therefore there is no evidence base for determining whether karyotype analysis is mandatory before the initiation of infertility treatment. The aim of this prospective study was to estimate the prevalence of karyotype abnormalities in normovulatory women attending an infertility clinic and compare it to that known to be present in the newborn female population. METHODS: Cytogenetic testing was performed in 1206 women with normal ovulatory cycle seeking infertility treatment. At least 15 GTG-banded metaphases were analysed in each case. In the case of a structural abnormality, fluorescent in situ hybridization (FISH) analysis and high resolution banding (HRB) were performed on a new blood sample to elucidate the aberration. When mosaicism was suspected, the number of analysed metaphases was increased to a total of 115 and an additional analysis of 200 metaphases was done on a second blood sample. RESULTS: A chromosomal abnormality was demonstrated in 0.58% (95% CI: 0.28-1.19) of cases which did not differ significantly from that reported in female newborns (0.79%; 95% CI: 0.68-0.94). Balanced reciprocal translocation was observed in 0.4% of patients (n = 5), paracentric inversion of chromosome X in 0.08% (n = 1) and gonosomal mosaicism in 0.08% (n = 1). However, chromosomal aberrations were less common among females with primary infertility compared to those with secondary infertility (0.25 versus 1.25%, P = 0.04). CONCLUSIONS: The present study suggests that routine cytogenetic analysis cannot be advocated in normovulatory infertile women. Nevertheless, the relatively higher frequency of abnormal karyotypes in women with secondary infertility indicates that this subgroup of patients might benefit from a routine karyotype analysis.

Adult↗
PubMed2004

Genetic counseling in carriers of reciprocal chromosomal translocations involving long arm of chromosome 16.

Families with balanced chromosomal changes ascertained by unbalanced progeny, miscarriages, or by chance are interested in their probability for unbalanced offspring and other unfavorable pregnancy outcomes. This is usually done based on the original data published by Stengel-Rutkowski et al. several decades ago. That data set has never been updated. It is particularly true for the subgroup with low number of observations, to which belong reciprocal chromosomal translocations (RCTs) with breakpoint in an interstitial segment of 16q. The 11 pedigrees from original data together with the new 18 pedigrees of RCT carriers at risk of single-segment imbalance detected among 100 pedigrees of RCT carriers with breakpoint position at 16q were used for re-evaluation of the probability estimation for unbalanced offspring at birth and at second trimester of prenatal diagnosis, published in 1988. The new probability rate for unbalanced offspring after 2 : 2 disjunction and adjacent-1 segregation for the total group of pedigrees was 4 +/- 3.9% (1/25). In addition, the probability estimate for unbalanced fetuses at second trimester of prenatal diagnosis was calculated as 2/11, i.e. 18.2 +/- 11.6%. The probability rates for miscarriages and stillbirths/early deaths were about 16 +/- 7.3% (4/25) and <2% (0/25), respectively. Considering different segment lengths of 16q, higher probability rate (0/8, i.e. <6.1%) for maternal RCT carriers at risk of distal 16q segment imbalance (shorter segment) was obtained in comparison with the rate (0/10, i.e. <4.8%) for RCT at risk of proximal segment imbalance (longer segment). It supports findings obtained from the original data for RCT with other chromosomes, where the probability for unbalanced offspring generally increased with decreasing length of the segments involved in RCT. Our results were applied for five new families with RCT involving 16q, namely three at risk of single-segment imbalance [t(8;16)(q24.3;q22)GTG, ish(wcp8+,wcp16+;wcp8-,wcp16+), t(11;16)(q25;q22)GTG, and t(11;16)(q25;q13)GTG] and two with RCT at risk of double-segment imbalance [t(16;19)(q13;q13.3)GTG, isht(16;19)(q13;q13.3) (D16Z3+,16QTEL013-D19S238E+,TEL19pR-; D16Z3-, D19S238E-,TEL19pR+), and t(16;20)(q11.1;q12)GTG, m ish,t(16;20)(wcp16+,wcp20+;wcp16+,wcp20+)]. They have been presented in details to illustrate how the available empiric data could be used in practice for genetic counseling.

Chromosomes, Human, Pair 16↗
PubMed2002

FISH analysis of chromosome X, Y and 18 abnormalities in testicular sperm from azoospermic patients.

BACKGROUND: Sperm extracted from testicular biopsies of azoospermic men can successfully be used for ICSI. The concern exists that testicular sperm from azoospermic men suffering from severe testicular failure may have a higher frequency of aneuploidy, which may lead to an increased risk for chromosomally abnormal offspring. METHODS: Testicular sperm from patients showing spermatogenic failure (n = 17) and from patients with normal spermatogenesis (n = 26) were analysed by fluorescence in-situ hybridization (FISH). Numerical chromosomal abnormalities for chromosomes X, Y and 18 were evaluated by FISH in a total of 1697 testicular sperm derived from 43 azoospermic patients. RESULTS: No difference was observed between the frequency of chromosomal abnormalities in testicular sperm from patients with normal spermatogenesis (5.6%) and from patients with spermatogenic failure (8.2%). However, the frequency of aneuploidy for chromosome 18 was higher in the group of azoospermic patients with spermatogenic failure than in the group with normal spermatogenesis (3.2 versus 1.3%). Within the obstructive group, sex chromosome aneuploidy (4.5%) occurred more frequently than chromosome 18 aneuploidy (1.3%; P < 0.001). Among testicular sperm derived from patients with spermatogenic failure, sex chromosomal aneuploidy (5.8%) was similar to that for chromosome 18 (3.2%). CONCLUSIONS: So far, no difference in the total frequency of chromosomal abnormalities has been observed between patients with normal spermatogenesis and patients with severe testicular failure. However, aneuploidy for chromosome 18 was higher in the group with spermatogenic failure.

Adult↗
PubMed2001

Identification of human candidate genes for male infertility by digital differential display.

Evidence for the importance of genetic factors in male fertility is accumulating. In the literature and the Mendelian Cytogenetics Network database, 265 cases of infertile males with balanced reciprocal translocations have been described. The candidacy for infertility of 14 testis-expressed transcripts (TETs) were examined by comparing their chromosomal mapping position to the position of balanced reciprocal translocation breakpoints found in the 265 infertile males. The 14 TETs were selected by using digital differential display (electronic subtraction) to search for apparently testis-specific transcripts in the TIGR database. The testis specificity of the 14 TETs was further examined by reverse transcription-polymerase chain reaction (RT-PCR) on adult and fetal tissues showing that four TETs (TET1 to TET4) were testis-expressed only, six TETs (TET5 to TET10) appeared to be differentially expressed and the remaining four TETs (TET11 to TET14) were ubiquitously expressed. Interestingly, the two tesis expressed-only transcripts, TET1 and TET2, mapped to chromosomal regions where seven and six translocation breakpoints have been reported in infertile males respectively. Furthermore, one ubiquitously, but predominantly testis-expressed, transcript, TET11, mapped to 1p32-33, where 13 translocation breakpoints have been found in infertile males. Interestingly, the mouse mutation, skeletal fusions with sterility, sks, maps to the syntenic region in the mouse genome. Another transcript, TET7, was the human homologue of rat Tpx-1, which functions in the specific interaction of spermatogenic cells with Sertoli cells. TPX-1 maps to 6p21 where three cases of chromosomal breakpoints in infertile males have been reported. Finally, TET8 was a novel transcript which in the fetal stage is testis-specific, but in the adult is expressed in multiple tissues, including testis. We named this novel transcript fetal and adult testis-expressed transcript (FATE).

Chromosome Mapping↗
PubMed2000

Embryo implantation after biopsy of one or two cells from cleavage-stage embryos with a view to preimplantation genetic diagnosis.

Preimplantation genetic diagnosis (PGD) can be offered as an alternative to prenatal diagnosis (PND) to couples at risk of having a child with a genetic disease. The affected embryos are detected before implantation by fluorescent in situ hybridisation (FISH) for sexing (X-linked diseases) and chromosomal disorders (numerical and structural) or by polymerase chain reaction (PCR) for monogenic disorders (including some X-linked diseases). The accuracy and reliability of the diagnosis is increased by analysing two blastomeres of the embryo. However, the removal of two blastomeres might have an effect on the implantation capacity of the embryo. We have evaluated the implantation of embryos after the removal of one, two or three cells in 188 PGD cycles where a transfer was done. The patients were divided into five groups: a first group which received only embryos from which one cell had been removed, a second group which received only embryos from which two cells had been removed, a third group which received a mixture of embryos from which one and two cells had been taken, a fourth group where two and three cells had been removed, and a fifth group where three cells had been removed. The overall ongoing pregnancy rate per transfer was 26.1%, the overall implantation rate per transfer was 15.2% and the overall birth rate was 14.2%. Although pregnancy rates between the groups cannot be compared because the second group (two cells removed) contains more rapidly developing and therefore 'better quality' embryos, an ongoing pregnancy rate of 29.1% and an implantation rate of 18.6% per transferred embryo in this group is acceptable, and we therefore advise analysing two cells from a > or =7-cell stage embryo in order to render the diagnosis more accurate and reliable.

Biopsy↗
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

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

Clinical experience of sex determination by fluorescent in-situ hybridization for preimplantation genetic diagnosis.

In our centre we started using fluorescent in-situ hybridization (FISH) technique for sexing in couples with sex-linked diseases in May 1995. Probes specific for chromosomes X, Y and 18 were applied, allowing us to detect simultaneously both gender and ploidy status. The efficiency of the FISH procedure is 90.4% per biopsied blastomere or 95.2% per biopsied blastomere with a distinct nucleus visible at spreading. Up to December 1997, we treated 15 couples (20 treatment cycles) at risk for X-linked recessive disease and two couples with Yq deletion (two treatment cycles) with the aim of transferring only female embryos. In one cycle, no embryos suitable for biopsy were obtained and in five cycles no normal female embryos were available at diagnosis. In the remaining 16 cycles, transfer was possible and six pregnancies ensued: one miscarriage has occurred and six children have been born from the other five pregnancies. The implantation rate (fetal sacs) per transferred embryo was 20.8%. In 98 (61%) of the 161 diagnosed embryos, a diploid status was observed in one or in both biopsied blastomeres. In 10 out of the 161 (6.2%) embryos a heterogeneity among the two biopsied blastomeres was found: a diploid nucleus in one blastomere and a non-diploid pattern or binuclear status in the other. In the remaining 53 (32.9%) out of 161 diagnosed embryos, the biopsied blastomeres were abnormal. The embryos that were not transferred or frozen were further analysed. When two sex chromosomes and two autosomes were present in the biopsied blastomere, the sex determination of the biopsied blastomere was never in conflict with the sex determination in the rest of the embryo. Furthermore, if the biopsied cell was diagnosed as abnormal (triploid, aneuploid, chaotic) the embryo was indeed completely abnormal or at least mosaic. A FISH error could not be excluded in two embryos (1.2%); however, a wrong gender determination did not result from this.

Adult↗
PubMed1999

Preimplantation genetic diagnosis and sperm analysis by fluorescence in-situ hybridization for the most common reciprocal translocation t(11;22).

In this study we describe the pre-clinical development and clinical application of preimplantation genetic diagnosis (PGD) by fluorescence in-situ hybridization (FISH) for two non-related carriers (one male and one female) of the most common balanced reciprocal translocation: t(11;22)(q25;q12). For the couple with the female carrier, enumeration of the sex chromosomes in the embryos was also indicated (husband: 47,XXY karyotype). Four-colour FISH analysis was performed on six blastomeres from three embryos. No embryo transfer was possible because all the embryos were unbalanced. Three PGD cycles, with two-colour FISH, were carried out for the couple with the male translocation carrier. A total of 35 embryos were biopsied and diagnosed by FISH; nine out of the 35 embryos (25. 7%) were normal and seven of them were transferred (two embryos from the first and four from the third cycle), six out of 35 embryos (17%) were unbalanced, three out of 35 embryos (5.7%) were triploid or polyploid, 10 out of 35 embryos (28.6%) were mosaic and seven out of 35 embryos (20%) were chaotic. Diagnosis failed in 2.9% of the embryos. The spermatozoa of the male carrier were also analysed using three-colour FISH. Only 29.1% of the sperm cells seemed to be balanced or normal. By choosing probes lying on both sides of the breakpoints and by using a combination of sub-telomeric or locus-specific probes and centromeric probes, the use of three-colour FISH enabled detection of all the imbalances in sperm and/or cleavage-stage embryos in the patients. This may improve risk assessment and genetic counselling in the future for translocation carriers.

Blastocyst↗
PubMed1998

Obstetric outcome after prenatal diagnosis in pregnancies obtained after intracytoplasmic sperm injection.

In this study we compared the pregnancy outcome of 576 pregnancies after prenatal diagnosis with that of 540 pregnancies without prenatal diagnosis in our microinjection programme. Amniocentesis was suggested for singleton pregnancies (n = 465) and chorionic villus sampling (CVS) was proposed for twin pregnancies (n = 111 pregnancies, 222 fetuses). A total of 365 patients with singleton pregnancies and 175 patients with twin pregnancies who did not undergo prenatal diagnosis were selected as controls. Compared with the controls, the odds ratios in the amniocentesis group for preterm delivery, low birthweight, very low birthweight and fetal loss were 0.97 [95% confidence interval (CI): 0.60-1.57], 1.27 (95% CI: 0.78-2.06), 1.57 (95% CI: 0.53-4.66) and 0.86 (95% CI: 0.32-2.37) respectively. Compared with the controls, the odds ratios in the CVS group for preterm delivery, low birthweight, very low birthweight and fetal loss were 0.89 (95% CI: 0.61-1.30), 1.03 (95% CI: 0.74-1.45), 0.79 (95% CI: 0.41-1.53) and 0.47 (95% CI: 0.17-1.30) respectively. We concluded that, in this series of intracytoplasmic sperm injection (ICSI) pregnancies, prenatal testing did not increase the preterm-delivery, the low-birthweight, or the very low-birthweight rates as compared with those of the controls. In the prenatal diagnosis group, the fetal loss rate was comparable to that of the control group. Larger prospective controlled studies are needed in order to inform patients reliably about the risks and the advantages of prenatal testing in ICSI pregnancies.

Adult↗
PubMed1998

Successful preimplantation genetic diagnosis is related to the number of available cumulus-oocyte complexes.

The inheritance pattern of monogenic inheritable disorders influences the proportion of unaffected embryos after preimplantation genetic diagnosis (PGD). We aimed to investigate the influence of the number of cumulus-oocyte complexes (COC) on the outcome after PGD. Eighty-four cycles of 47 couples were included in our analysis. All couples were at risk of transmitting autosomal recessive, autosomal dominant, X-linked single gene disorders or sexaneuploidies to their offspring. One PGD cycle was carried out for a Yq-deletion of the man. The correlation between the numbers of COC and biopsied embryos and between the numbers of COC and unaffected embryos was highly significant (P <0.05). A pregnancy occurred in 15 cycles and a minimum of six COC were needed to achieve a pregnancy. Thirteen pregnancies were observed in cycles with at least 9 COC. The transfer rate and number of transferred embryos per cycle in the subgroups with <9 COC and > or =9 COC were significantly higher in the latter. Although pregnancy rates did not differ significantly between the two subgroups (probably due to the low number of pregnancies), our data indicate that it is justifiable to cancel PGD cycles in which it is expected that <6 COC will be retrieved and that the couple should be informed about the poor prognosis if <9 COC are retrieved.

Cystic Fibrosis↗
PubMed1998

Clinical experience with preimplantation genetic diagnosis and intracytoplasmic sperm injection.

Preimplantation genetic diagnosis (PGD) is a novel procedure whose use may be considered to obtain a very early prenatal diagnosis for couples at risk for transmitting genetic diseases. Using the polymerase chain reaction (PCR) or fluorescence in-situ hybridization (FISH) the genotype or the sex of biopsied cleavage-stage embryos obtained after in-vitro fertilization can be determined and selected embryos can then be transferred. In-vitro fertilization with intracytoplasmic sperm injection is the method of choice to obtain embryos to be analysed through PCR to reduce contamination by residual sperm DNA. In our series of 61 PGD cycles for 29 couples at risk over a period of 4 years the ongoing pregnancy rate per cycle was 15%, per transfer 19% and per patient 31%. One of the six morphologically normal children born, who is still alive and doing well, weighed 850 g after birth at 25 weeks following a complicated triplet pregnancy. More experience is needed to correctly evaluate the efficiency and safety of this novel technique as well as to determine its place in the prevention of genetic disease.

Adult↗
PubMed1998

A follow-up study of children born after intracytoplasmic sperm injection (ICSI) with epididymal and testicular spermatozoa and after replacement of cryopreserved embryos obtained after ICSI.

The aim of this prospective follow-up study of children born after intracytoplasmic sperm injection (ICSI) was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones in order to evaluate the safety of this new technique. The study design included karyotyping of the parents and their agreement to genetic counselling and prenatal diagnosis and it was based on a physical examination of the child at the Centre for Medical Genetics at the ages of 2 months, 1 year and at 2 years, where major and minor malformations and psychomotor evolution are recorded. Here we describe the first 57 children born from 40 ICSI pregnancies with epididymal spermatozoa (group 1), the first 50 children born from 34 ICSI pregnancies with testicular spermatozoa (group 2) and the first 58 children born from 48 pregnancies after replacement of cryopreserved ICSI embryos (group 3). Parental karyotypes were obtained from only 72/246 (29%) parents and were all normal. Prenatal karyotypes were determined for a total of 70 samples (40%): 21 in group 1, 15 in group 2 and 34 in group 3. In this last group 2 abnormal 47,XXY karyotypes (5.8%) and no structural aberrations were found. This increase in de-novo sex-chromosomal aberrations has already been described with regard to the first 877 children born after ICSI carried out at our Centre and is probably linked directly to the characteristics of the infertile men treated rather than to the ICSI procedure itself. Major malformations, defined as those causing functional impairment or requiring surgical correction, were observed in four children: two born after ICSI with epididymal spermatozoa, one after ICSI with testicular spermatozoa and one after ICSI and cryopreservation. No particular malformation was disproportionally frequent. In the follow-up examinations at 2 months (107/161 or 66.5%) and at 1 year (37/161 or 22.9%), no additional anomalies were observed. Lost for follow-up rate at 2 months was 33.5%. These observations on a limited number of children do not suggest a higher incidence of diseases linked to imprinting, nor do they suggest a higher incidence of congenital malformations. These observations are still limited in number and should be further completed by others and by collaborative efforts. In the meanwhile patients should be told about the available data before any treatment: there appears to be some risk of transmitted chromosomal aberrations, of de-novo, mainly sex-chromosomal aberrations and of transmitting fertility problems to the offspring. Patients should also be reassured that until now there seems to be no higher incidence of congenital malformations in children born after ICSI with epididymal or testicular spermatozoa or after replacement of ICSI embryos.

Adult↗
PubMed1996

First trimester chorionic villus sampling in twin gestations.

First-trimester prenatal diagnosis was offered to 104 twin pregnancies mainly for advanced maternal age and cytogenetic evaluation of a new fertilization technique. Chorionic villus sampling (CVS) was performed transcervically (35%), transabdominally (23%), or by combination of these two techniques (42%). Although no placental biopsy failures occurred, two errors in fetal sexing were recorded due to non-selective placental sampling. In these two cases, both fetuses were sampled transcervically. Cytogenetic results were available for all fetuses; six of them showed an abnormal direct chromosomal pattern, but long-term villi culture analysis or additional amniocentesis (n = 1) reduced the number to four. Early fetal loss (3.4%) and perinatal mortality (6.3%) after CVS were comparable with a control group of 101 consecutive twin pregnancies without prenatal diagnosis (respectively 6.9% and 5.3%). Perinatal loss in the CVS group was associated in 10 of 12 fetuses with preterm premature rupture of the membranes and consequent preterm delivery. Mean gestational age at delivery, mean birthweight and the frequency of preterm delivery, and low birthweight infants were nearly identical in both groups. This study shows that CVS in the first trimester of pregnancy is an accurate and fast approach for prenatal diagnosis in twin gestations with an acceptable risk of adverse pregnancy outcome. However, a transcervical approach for both fetuses is not recommended.

Adult↗
PubMed1996

Cytogenetics of infertile men.

Chromosomally derived sterility has long been recognized. A review of the literature of somatic chromosome investigations in infertile males has shown that 13.7% of azoospermic males and 4.6% of oligozoospermic males have an abnormal karyotype. In the first group, sex chromosome abnormalities predominate (mainly 47,XXY), whereas in the latter, autosome anomalies (i.e. Robertsonian and reciprocal translocations) are the most frequent. A similar review on meiotic studies revealed that meiotic chromosome anomalies can explain male infertility in 4.3-40.4% of patients. Recently, fluorescent in-situ hybridization studies on spermatozoa from infertile men were published; it was suggested that both X-Y pairing and pairing of the autosomes were impaired, resulting in spermatogenic disruption. We investigated cytogenetically 694 infertile men with abnormal sperm parameters. More patients are needed for this research to investigate the relationship, if any, between the type of chromosome abnormality and its influence on the number, morphology and motility of spermatozoa. To be able to provide proper counselling for those couples whose male infertility can now be treated by intracytoplasmic sperm injection, it is suggested that clinical investigations should include mitotic and meiotic studies, an analysis of the chromosome content of individual spermatozoa and a DNA analysis of blood and spermatozoa to detect partially deleted Y chromosome material.

Chromosome Aberrations↗