Assisted reproduction: genetic aspects - risk of malformations - pre-treatment counselling.
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Congenital Abnormalities↗
Biomedical subjects
D Meschede
Publications and source records attributed to D Meschede.
Atom lithography with a holographic light mask.
In atom lithography with optical masks, deposition of an atomic beam on a given substrate is controlled by a standing light-wave field. The lateral intensity distribution of the light field is transferred to the substrate with nanometer scale. We have tailored a complex pattern of this intensity distribution through diffraction of a laser beam from a hologram that is stored in a photorefractive crystal. This method can be extended to superpose 1000 or more laser beams. The method is furthermore applicable during growth processes and thus allows full 3D structuring of suitable materials with periodic and non-periodic patterns at nanometer scales.
Journal Article↗
Deterministic delivery of a single atom.
We report the realization of a deterministic source of single atoms. A standing-wave dipole trap is loaded with one or any desired number of cold cesium atoms from a magneto-optical trap. By controlling the motion of the standing wave, we adiabatically transport the atom with submicrometer precision over macroscopic distances on the order of a centimeter. The displaced atom is observed directly in the dipole trap by fluorescence detection. The trapping field can also be accelerated to eject a single atom into free flight with well-defined velocities.
Journal Article↗
Low-level sex chromosome mosaicism in female partners of couples undergoing ICSI therapy does not significantly affect treatment outcome.
BACKGROUND: There is an increased rate of chromosomal anomalies, in particular low-level sex chromosome mosaicism, in the female partners of couples undergoing intracytoplasmic sperm injection (ICSI). METHODS: Among 811 consecutive couples presenting for pre-ICSI chromosome analysis, chromosomal abnormalities were detected in 54 individuals, of which 26 were low-level sex chromosome mosaicism in the females. Attention was focused on the treatment course and outcome of ICSI in 20 couples with low-level sex chromosome mosaicism in the females actually embarking on ICSI treatment (group I, n = 38 ICSI treatment cycles). Applying a case-control design, each of the 20 couples was matched according to female age and source of spermatozoa to couples without a chromosomal abnormality in either of the partners (group II, n = 38 ICSI treatment cycles). RESULTS: No significant differences were found between the groups in ovarian response, fertilization rate and number of embryos transferred. Pregnancy rates, as well as implantation and abortion rates did not differ significantly between the groups. CONCLUSIONS: The data suggest that low-level sex chromosome mosaicism in females has no major effect on the course and outcome of ICSI.
Abortion, Spontaneous↗
Single atoms in an optical dipole trap: towards a deterministic source of cold atoms
We describe a simple experimental technique which allows us to store a small and deterministic number of neutral atoms in an optical dipole trap. The desired atom number is prepared in a magneto-optical trap overlapped with a single focused Nd:YAG laser beam. Dipole trap loading efficiency of 100% and storage times of about one minute have been achieved. We have also prepared atoms in a certain hyperfine state and demonstrated the feasibility of a state-selective detection via resonance fluorescence at the level of a few neutral atoms. A spin relaxation time of the polarized sample of 4.2+/-0.7 s has been measured. Possible applications are briefly discussed.
Journal Article↗
The practical importance of pedigree analysis in women considering invasive prenatal diagnosis for advanced maternal age or abnormal serum screening tests.
Genetic counselling prior to prenatal diagnosis subserves several functions, one of them to put the planned prenatal test into the wider context of the personal and familial medical history. Even though considered a pivotal part of counselling, little is known about the informational yield and practical relevance of a comprehensive pre-test pedigree analysis. This is particularly true for patients who do not consider prenatal diagnosis for a specific heritable disorder with a high recurrence risk in the ongoing pregnancy, but for a moderate risk for conditions such as Down syndrome that mostly arise de novo. We analysed the informational yield of pedigree analysis for such patients through a retrospective analysis of 1356 consecutive genetic counselling sessions. All cases were referred for advanced maternal age or an abnormal result upon triple serum marker screening. 148 cases (10.9%) were classified as having a significant and previously unknown genetic or teratologic risk factor for the fetus that was uncovered through pedigree analysis. Of these cases, 55% could be recommended a specific prenatal test covering the previously unknown genetic risk factor.
Abnormalities, Drug-Induced↗
Seminal plasma characteristics as indicators of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in men with obstructive azoospermia.
OBJECTIVE: To determine the prognostic value of seminal plasma volume, pH, fructose, and alpha-glucosidase for the detection of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. DESIGN: Retrospective data analysis. SETTING: University infertility clinic (referral center). PATIENT(S): Fifty-nine men with obstructive azoospermia. INTERVENTION(S): Semen analysis including seminal plasma volume, pH, fructose, alpha-glucosidase, molecular genetic diagnosis of CFTR mutations and FSH measurement. MAIN OUTCOME MEASURE(S): Sensitivity and specificity of seminal plasma markers for the detection of CFTR mutations. RESULT(S): A CFTR mutation was detected in 26 of 59 patients with obstructive azoospermia. Patients carrying a mutation had significantly lower seminal plasma volume (mean +/- SEM: 1.5 +/- 1.4 mL vs. 2.8 +/- 2.2 mL), lower pH levels (25th percentile, median, 75th percentile: 6.5, 6.8, 7.5 vs. 7.7, 7. 9, 7.9) and lower fructose content (1.0, 1.1, 3.7 vs. 5.8, 20.0, 83. 0 micromol/ejaculate) than those without mutations. Diagnostic efficacy for detection of mutations was best (pH 81.4%, fructose 81. 8%) at a cutoff level for pH of 7.4 and fructose of 2 micromol/ejaculate. CONCLUSION(S): Seminal plasma markers provide an effective, noninvasive method to predict CFTR mutations in men with obstructive azoospermia.
Adolescent↗
Clustering of male infertility in the families of couples treated with intracytoplasmic sperm injection.
Intracytoplasmic sperm injection (ICSI) is an effective treatment modality for male factor infertility, but it could promote the transgenerational transmission of genetic defects causing gametogenic failure. Cytogenetic and molecular techniques permit the diagnosis of some infertility-causing genetic aberrations, but many more probably evade detection with currently available technology. The analysis of the recurrence pattern of infertility in infertile couples' families could define the importance of heritable factors in the pathogenesis of human infertility. We have subjected 621 consecutive infertile couples treated with ICSI in a single institution to a comprehensive genetic workup including documentation of the family history, karyotyping and various DNA tests. In all, 1302 fertile couples served as controls. Of the infertile couples 6.4% were shown to have a fertility problem with a definite genetic basis. Male, but not female fertility problems displayed a distinct pattern of familial aggregation. In addition, the infertile couples had fewer siblings than the fertile controls, a finding compatible with suboptimal fertility already among the infertile couples' parents. In summary, our data indicate that male factor infertility should be considered a potentially heritable condition. The recurrence risk for infertility in the offspring of couples treated with ICSI might be substantial.
Adult↗
Non-reproductive heritable disorders in infertile couples and their first degree relatives.
The genetic safety of intracytoplasmic sperm injection (ICSI) remains a matter of continuing debate. One source of concern is the limited knowledge about the general genetic constitution and background of patients who need sophisticated reproductive technology to procreate. It has been postulated that such individuals could be carriers of genetic lesions that might result in an increased prevalence of heritable disorders among their offspring. To investigate this issue, we determined the frequency of potentially heritable non-reproductive diseases in 621 infertile couples and their first degree relatives. A total of 1302 fertile couples who underwent genetic counselling prior to prenatal diagnosis served as controls. The infertile patients had a slightly higher prevalence of potentially heritable non-reproductive disorders ('significant genetic risk factors') than the controls (1. 9 versus 0.9%; P = 0.015). In contrast, such diseases were less prevalent in their families than in the fertile couples' families. Our data do not support the hypothesis that their familial genetic background predisposes children born after ICSI to malformations or other non-reproductive genetic diseases.
Adult↗
No evidence for uniparental disomy of the sex chromosomes in idiopathic male infertility.
Uniparental disomy (UPD) is a rare genetic aberration characterized by the uni- rather than biparental inheritance of a pair of homologous chromosomes. Among the various adverse clinical effects that UPD can have in humans, abnormalities of the male reproductive system have been described in UPD of the chromosomes 7, 11, 14 and 15. Given the considerable rate of sex chromosomal aneuploidy in human gametes and zygotes, we postulated that paternal uniparental disomy of the sex chromosomes might be a cause of otherwise unexplained male infertility. With a set of highly polymorphic DNA markers the parental origin of the X chromosome in 41 men with severe idiopathic infertility was determined. In all patients the X chromosome was derived from the mother, indicating regular biparental inheritance of the sex chromosomes. We thus obtained no evidence that paternal uniparental disomy of the X and Y chromosomes is a mechanism underlying idiopathic male infertility.
Chromosome Aberrations↗
Submicroscopic deletion in 14q32.3 through a de novo tandem translocation between 14q and 21p.
We describe a male child with craniofacial anomalies, postnatal onset growth retardation, microcephaly, multiple minor anomalies, hearing loss, and moderate delay of mental and statomotor development. He carries a previously undescribed tandem translocation between the long arm of chromosome 14 and the short arm of chromosome 21 that arose de novo. As proven by fluorescence in situ hybridization a microdeletion not detectable with high-resolution G-banding occured in 14q32.3, the terminal band on the long arm of chromosome 14. The resulting phenotype includes most abnormalities encountered in patients with terminal 14q32.3 deletions but in addition includes some characteristics of the ring chromosome 14 syndrome.
Abnormalities, Multiple↗
Low rates of pregnancy termination for prenatally diagnosed Klinefelter syndrome and other sex chromosome polysomies.
Over the past 9 years we counseled 55 couples whose unborn child was found to carry a sex chromosome polysomy. We performed a survey of postcounseling parental decisions about continuation or termination of these pregnancies. Of the 55 embryos or fetuses, 23 had the karyotype 47,XXY, 10 had 47,XYY, and 12 had 47,XXX. In addition, there were 10 instances of true mosaicism, i.e. 47,XXY/46,XY (n = 5), 47,XYY/46,XY (n = 2), or 47,XXX/46,XX (n = 3). Mean gestational age (+/-standard deviation) at diagnosis was 18.3+/-3.0 weeks. After comprehensive genetic counseling 48 (87.3%) of these pregnancies were carried to term. In seven cases (12.7%) the parents elected a pregnancy termination. Two of 31 pregnancies (6.5%) primarily ascertained at our center were aborted, whereas amongst the 24 referred cases, 5 couples (20.8%) opted for a termination. The mean gestational age of the terminated pregnancies was 19.7 weeks. The overall termination rate of 12.7% appears low in comparison with literature data. Most reports from other institutions present termination rates between 32 and 66%. The reason for the low rate of induced abortions in our study cohort is not clear. Cultural differences in parental perception of sex chromosomal polysomies may be of importance, and peculiarities of genetic counseling at our institution could also play a role. Although counseling was nondirective, we did put emphasis on providing prospective parents with information from unbiased follow-up studies of children with Klinefelter syndrome and other sex chromosome polysomies.
Abortion, Induced↗
Genetic diseases of the seminal ducts.
Azoospermia due to an obstruction of the genital tract is one of numerous possible pathophysiologic mechanisms underlying male infertility. The blockage of the seminal ducts may be acquired or congenital. Only recently has the strong association between mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and various subtypes of obstructive azoospermia been elucidated. Most patients with congenital bilateral absence of the vas deferens or bilateral ejaculatory duct obstruction are carriers of such mutations. The relationship between abnormal CFTR alleles and unilateral absence of the vas deferens, isolated seminal vesicle anomalies, and Young syndrome is less well characterized and awaits further investigation.
Cystic Fibrosis↗
Prognostic value of male diagnostic profiles in intracytoplasmic sperm injection (ICSI).
Possible correlations between male hormone and semen parameters with pregnancy and oocyte fertilization rates following intracytoplasmic sperm injection (ICSI) were investigated. The study is based on 290 couples who underwent ICSI therapy for the first time. The parameters evaluated were male age, serum levels of follicle stimulating hormone (FSH) and testosterone, sperm concentration, sperm motility, normal sperm morphology, index of teratozoospermia (TZI) and sperm vitality. A marginal, barely significant association was found between the fertilization rate and serum FSH levels in the male partner (p = 0.046). There was no relevant association between male parameters and pregnancy rates. The study confirms that male hormonal and semen parameters are of low prognostic value for the outcome of ICSI.
Adult↗
Chromosome abnormalities in 447 couples undergoing intracytoplasmic sperm injection--prevalence, types, sex distribution and reproductive relevance.
Chromosomal abnormalities are thought to be a major contributor to the genetic risks of infertility treatment by intracytoplasmic sperm injection (ICSI). Apart from abnormalities arising de novo, abnormal karyotypes in pregnancies conceived through assisted reproductive technology may be directly derived from predisposing parental aberrations. In a prospective study we have analysed the chromosomes of 868 male and female patients prior to planned ICSI treatment. A total of 33 aberrant karyotypes was diagnosed, corresponding to an abnormality rate of 7.6% per couple or 3.8% per individual studied. Even though male factor infertility was twice as common as female factor infertility in this cohort, 24 of the chromosomal abnormalities were found among the women. Low-level mosaicism for numerical sex chromosome anomalies was diagnosed in 20 individuals, and one patient had the triple X karyotype. With respect to structural chromosomal anomalies, we found six reciprocal and three Robertsonian translocations, two paracentric inversions and one marker chromosome. Many of the aberrations that we diagnosed could be classified as carrying only a small to moderate reproductive risk. Given the high rate of abnormal karyotypes among the female subjects, we suggest that not only the males, but both partners should be routinely karyotyped prior to ICSI.
Adult↗
Three novel SRY mutations in XY gonadal dysgenesis and the enigma of XY gonadal dysgenesis cases without SRY mutations.
Mutations in the Y-located testis-determining gene SRY are one cause for XY sex reversal. We have previously identified four SRY mutations in a total of 45 sex-reversed females with XY gonadal dysgenesis (XY GD). In a new sample of 16 XY GD cases, three previously undescribed SRY mutations were identified. Two are point mutations that lead to amino acid substitutions in the HMG domain of SRY, M64R, and F67V. The third SRY mutation is a single base insertion 5' to the HMG box within codon 43, converting this lysine codon to a stop codon (K43X). A total of 33 SRY mutations have so far been described that account for only 10-15% of XY GD females. A further 10-15% of these cases result from deletion of SRY due to aberrant X/Y interchange. The etiology of the remaining 70-80% of XY GD cases is still enigmatic. Possible explanations for these XY sex-reversal cases are discussed.
Adolescent↗
Azoospermia and segmentation abnormalities of the cervicothoracic spine ('MURCS in the male').
The MURCS association is traditionally regarded as a disorder limited to the female sex. It has been hypothesized that men displaying the combination of azoospermia, segmentation abnormalities of the cervicothoracic spine and renal anomalies may have a male analogue of MURCS. Here we describe a patient with non-obstructive azoospermia and Klippel-Feil anomaly type II and suggest that this may represent another case of 'MURCS in the male'.
Abnormalities, Multiple↗
Strong preference for non-invasive prenatal diagnosis in women pregnant through intracytoplasmic sperm injection (ICSI)
Intracytoplasmic sperm injection (ICSI) is a new and most powerful technique to treat severe forms of human infertility. While the follow-up studies have not shown an increased malformation risk so far, the genetic implications of ICSI are still not fully understood. For this reason, many institutions routinely recommend or even enforce invasive prenatal tests after successful intracytoplasmic sperm injection. We have counselled 107 women pregnant through ICSI about prenatal diagnosis. Sixty-five had already received genetic counselling prior to the treatment (group 1), while 42 had not attended our clinic before (group 2). They were free to choose between invasive and non-invasive diagnosis or no prenatal tests at all. Fifty-four per cent of these patients had an indication for prenatal karyotyping or other invasive procedures independent of ICSI. Only 17 per cent of the total cohort made use of amniocentesis or fetal blood sampling, 82 per cent opted for non-invasive tests (ultrasound, serum screening), and one couple did not wish any prenatal studies. The preference for non-invasive procedures was stronger in group 1 (94 per cent) than in group 2 (65 per cent). We suggest that if patients pregnant through ICSI have the option to choose freely between invasive and non-invasive prenatal tests, they strongly favour the latter.
Adult↗