Preconception and preimplantation diagnosis for cystic fibrosis

Preimplantation diagnosis provides couples at high genetic risk the possibility of avoiding genetic disease without the need for prenatal diagnosis and selective abortion of the affected pregnancy. Following extensive background work on the reliability of genetic diagnosis in a single cell, we offered on a research basis preimplantation diagnosis to five couples at risk for offspring with the delta-F508 mutation (the major mutation causing cystic fibrosis). There was no detrimental effect from polar body removal on either fertilization or preimplantation development. Genetic analysis, undertaken in 22 polar bodies and 15 corresponding blastomeres, identified 21 embryos of which ten were transferred.     

HUMAN CHORIONIC GONADOTROPHIN AND ALPHA-FETOPROTEIN LEVELS IN MATCHED SAMPLES OF AMNIOTIC FLUID,EXTRAEMBRYONIC COELOMIC FLUID,AND MATERNAL SERUM IN THE FIRST TRIMESTER OF PREGNANCY

Separately identified samples of amniotic fluid and extraembryonic coelomic fluid obtained by high resolution transvaginal ultrasound-guided amniocentesis from 32 women between 7 and 12 weeks of pregnancy were analysed for human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP). There was a highly significant difference between the hCG levels in amniotic fluid (median level 6.3 U/ml; range 1.6–310.0 U/ml) and those in extraembryonic coelomic fluid (median level 400.0U/ml; range 135.0–2250.0U/ml) (p<0.001; Mann-Whitney U/–test). The levels of AFP were very similar in amniotic fluid (median 26.0 kU/ml; range 10.0–116.5 kU/ml) and extraembryonic coelomic fluid (median level 24.1 kU/ml; range 12.4–94.4 kU/ml).     

Fetal skin biopsy in prenatal diagnosis of some genodermatoses

Various methods of obtaining fetal skin for prenatal diagnosis of certain autosomal-recessive congenital genodermatoses have been assessed. An attempt was made to obtain fetal skin by fetoscopy in 15 patients prior to pregnancy termination for a variety of medical reasons at 18–26 weeks. Specimens were obtained only in five cases (8 successful attempts out of 48). In twelve cases, of which five had a history of a child with junctional (Herlitz type) or dystrophic (Hallopeau-Siemens type) epidermolysis bullosa or non-bullous congenital ichthyosiform erythroderma at 16–25 weeks of pregnancy, fetal skin was obtained without fetoscopy under direct ultrasonic control. Specimens were obtained in all cases (33 successful attempts out of 39). In three cases, fetal pathology was diagnosed by the method of semi-thin and ultra-thin skin sections, and the respective pregnancies were terminated.     

The diagnostic potential of fetal renal biopsy

The feasibility of fetal renal biopsy has been investigated in order to assess the diagnostic value of the histological specimen. Two fetuses with a severe bilateral renal abnormality (multicystic dysplastic kidney, Meckel-Gruber syndrome with polycystic kidney) and one fetus with Down syndrome (no detectable structural anomaly) were sampled. Histological findings in the biopsy specimens of cases 1 and 2 were diagnostic of an early obstructive renal disease. In case 3 , the findings were consistent with normal development for gestational age of the kidney. Fetal renal biopsy is technically feasible; histological examination of the samples showed a good correlation with postnatal findings. Further studies of its diagnostic value are required.     

Prenatal sonographic detection of intra-abdominal extralobar pulmonary sequestration: Report of three cases and literature review

Three cases of intra-abdominal extralobar pulmonary sequestration detected antenatally by ultrasound are reported. One case was associated with a large left diaphragmatic hernia. Sonographically, all the cases were found in the left supra-renal region presenting as a well-defined echogenic mass with cystic hypoechoic areas. The condition should be considered in the differential diagnosis of all antenatally detected upper abdominal echogenic masses, particularly when associated with a diaphragmatic hernia. Postnatal ultrasound-guided fine needle aspiration biopsy in one case yielded respiratory type epithelium and this procedure could provide a reasonably confident diagnosis of the lesion.     

Diagnosis and prenatal diagnosis of epidermolysis bullosa herpetiformis (Dowling-Meara) in a mother,two affected children,and an affected fetus

In utero skin biopsy was performed on a fetus at risk of an uncertain form of epidermolysis bullosa (EB). The mother had produced two affected offspring diagnosed variously as having junctional or dystrophic EB. The two offspring and the fetus were products of different fathers. The mother claimed to have no disease and on clinical examination was without blisters. Examination of the fetal skin biopsy by light and electron microscopy revealed separation of the epidermal sheet from the majority of the biopsy sample, although occasional remnants of basal cells remained associated with the basement membrane. Aggregations of keratin filaments were observed within basal cells of the detached epidermis and in the attached basal cell remnants. The diagnosis was thus suggested to be epidermolysis bullosa Dowling-Meara. Re-review of the clinical and laboratory data from the affected infants revealed a clinical and histological pattern consistent with this diagnosis. Further discussion with the mother revealed that her skin had blistered as a child and that she presently had hyperkeratotic palms and soles. This history is consistent with the autosomal dominantly inherited epidermolysis bullosa herpetiformis (Dowling-Meara). This is the first reported prenatal diagnosis of EB Dowling—Meara. The morphological criteria of intraepidermal blistering and clumped keratin filaments within basal and immediately suprabasal cells characteristic of an affected individual postnatally also identified an affected fetus. There is, however, insufficient experience to be certain that these findings will hold from region to region in the body or among all affected fetuses, and thus prenatal diagnosis on a morphological basis should still be made with caution.     

Maternal serum free β-human chorionic gonadotrophin levels in twin pregnancies: Implications for screening for down's syndrome

Free β-human chorionic gonadotrophin values are, on average, 1·90 times greater in twin pregnancies than in singleton pregnancies [95 per cent confidence interval (CI) 1·69–2·13]. This information can be used in screening for Down's syndrome, so that twin pregnancies can be interpreted in addition to singleton pregnancies.     

Prenatal diagnosis of the infantile type of neuronal ceroid lipofuscinosis by electron microscopic investigation of human chorionic villi

Chorionic villus biopsy specimens were studied electron microscopically in six pregnancies at risk of the infantile type of neuronal ceroid lipofuscinosis (INCL). The biopsy was performed in all cases in the first trimester of pregnancy (8–10 gestation weeks) by the transcervical route. In one case, the biopsy was repeated at 17 weeks by the transabdominal procedure. In two pregnancies, the endothelial cells and, to a lesser extent, the mesenchymal cells of the chorionic villi contained unit membrane-bound inclusions typical of INCL. In both cases, the pregnancy was terminated and in one of them identical inclusions were found in the brains and kidneys of the fetus at 20 weeks of gestational age. The children from the remaining four pregnancies are healthy and have shown no signs of the disease.     

Estimation of the weight of chorionic villus samples obtained from first trimester pregnancies by transcervical aspiration

Eight obstetricians experienced in chorionic villus sampling were asked to estimate the weight of samples of villi with and without a reference photograph. Referral to the photograph significantly improved the accuracy of their estimations.     

Sister chromatid exchanges in first-trimester chorionic villi after in vivo and in vitro exposure to diagnostic ultrasound

A study was done to evaluate the effects of diagnostic ultrasound on sister chromatid exchange (SCE) in first-trimester chorionic villi under controlled technical conditions. Chromosome analysis was performed by the direct method using spontaneous mitoses from the cytotrophoblast layer, and SCE visualization was accomplished by a 72 h treatment with 5-bromodeoxyuridine (BrdU) at a concentration of 10μg/ml. The slides were stained with ac ridine orange. Immediately before first-trimester chorionic villus sampling, a group of ten pregnant women was exposed to diagnostic ultrasound for 20min (in vivo exposure). This group of patients was compared with a control group who were not exposed. A mean value of SCE/cell frequency of 4·2 ± 0·2 was found in the exposed pregnancies, while a value of 3·7 ± 0·2 was observed in the control group. After in vitro exposure of chorionic villi obtained from elective abortions, the frequency of SCE/cell did not differ significantly among samples with different exposures (1,2, and 3 h) and controls. The positive control (mitomycin C) yielded a significant increase in SCE frequency.