Preimplantation diagnosis: A patient perspective

A new dimension in the prevention of birth defects will be achieved when genetic diseases can be routinely diagnosed in embryos prior to implantation. The impressions and attitudes towards preimplantation diagnosis were studied in prospective patients, women at high reproductive risk for a genetic disease. Their perspective highlighted not only the advantages and disadvantages of this new approach, but also those changes necessary in order for preimplantation diagnosis to become a useful and practical technique. The data presented are based on information obtained by a mailed questionnaire answered by 58 women. The main benefit of preimplantation diagnosis for these high-risk women would be the ability to undertake a pregnancy without having to be subjected to the physical and/or emotional trauma of elective termination. Their major concerns related to possible damage to the embryo following biopsy, the cost of the procedure, and the low success rate of completed pregnancies. Other issues to be addressed before preimplantation diagnosis could begin to compare favourably with existing forms of prenatal testing were that the methods of obtaining oocytes or embryos should be simple, well tolerated, highly efficient, and low in maternal risk, and that the genetic analysis of embryonic or extraembryonic cells should be unequivocally accurate.     

Estimating the risk of a fetal autosomal trisomy at mid-trimester using maternal serum alpha fetoprotein and age: A retrospective study of 142 pregnancies

Risks appropriate for mid-trimester prenatal screening for autosomal trisomies have been estimated from a combination of maternal age and maternal serum (MS) alpha-fetoprotein (AFP) levels at 16–20 weeks gestation. Published data on the frequency of Down's syndrome births relative to maternal age were modified to include the additional age-related frequency of trisomy 18 and trisomy 13 cases to provide an overall risk for an autosomal trisomy at midtrimester. MSAFP results from a retrospective study of 142 affected (114 trisomy 21, 19 trisomy 18, and 9 trisomy 13)and 113 000 unaffected pregnancies were converted to multiples of the appropriate gestational median (MOM). The AFP levels in the autosomal trisomy pregnancies were found to be significantly reduced at 0.72 MOM of the unaffected pregnancies. Risks (likelihood ratios) were derived from the overlapping log Gaussian distributions for affected and unaffected pregnancies and combined with maternal age risks to give the overall odds of an affected pregnancy. A mid-trimester cut-off risk of 1:280 gave an estimated 37 per cent detection rate for autosomal trisomies in the west of Scotland population for a follow-up (false-positive) rate of 6.6 per cent. These figures compare with a 30 per cent detection and 6.7 per cent false-positive rate if age 35 years and over is used as the sole criterion for selection of at-risk pregnancies.     

MATERNAL SERUM ALPHA-FETOPROTEIN SCREENING FOR OPEN NEURAL TUBE DEFECTS IN TWIN PREGNANCIES

Data on maternal serum alpha-fetoprotein (AFP) levels at 13–24 weeks' gestation in 46 twin pregnancies with open neural tube defects (22 with anencephaly, 24 with open spina bifida) and 169 unaffected twins were used to estimate the detection and false-positive rates associated with different cut-off levels. Using the conventional cut-off level of 2·5 multiples of the median (MoM) for unaffected singleton pregnancies of the same gestation and laboratory, the detection rate in twins was 99 per cent for anencephaly and 89 per cent for open spina bifida, with a false-positive rate of 30 per cent. Using a 5·0 MoM cut-off level to maintain a similar false-positive rate to that found among singleton pregnancies at 16–18 weeks' gestation (about 3 per cent), the detection rate was 83 per cent for anencephaly and 39 per cent for open spina bifida. Estimates are provided of the odds of having an affected twin pregnancy given a positive AFP result as well as the odds for individual women with a raised AFP level.     

First and early second-trimester diagnosis of fetal urinary tract anomalies using transvaginal sonography

Urinary tract anomalies are common. Prenatal diagnosis is important and enables either special obstetric management or termination of pregnancy and probably in the future, intrauterine intervention. Transvaginal sonography (TVS) allows visualization of the normal and anomalous fetal urinary tract at an early stage. One thousand nine hundred and forty women were examined via TVS at an early stage of pregnancy between 10 and 16 weeks from the last menstrual period (LMP) and 35 anomalies (1·8 per cent) were clearly identified: 29 cases of low urinary tract obstruction, 2 cases of multicystic dysplastic kidney, 2 cases of polycystic kidney (infantile type), 1 case of double collecting system, and 1 case of horseshoe kidney. Potter syndrome could be ruled out in three patients who had delivered fetuses suffering from this anomaly in previous pregnancies. The concise and early identification of anomalies makes TVS an important aid in the hands of the obstetrician, ultrasonographer, and neonatologist.     

Antenatal diagnosis and palliative treatment of non-immune hydrops fetalis secondary to fetal parvovirus B19 infection

Hydrops fetalis was diagnosed at 22 weeks. An ultrasound examination demonstrated cardiomegaly and a fetal blood specimen obtained by cordocentesis revealed thrombocytopenia, anaemia, and neutropenia. Fetal paracentesis yielded straw-coloured fluid with electrolytes indicative of a transudate. Non-enveloped icosahedral viral particles approximately 23 mm in diameter were visualized in the ascitic fluid by electron microscopy. Immune electron microscopy confirmed human parvovirus B19. Direct fetal digitalization led to a reduction in umbilical artery resistance, a decline in the abdominal circumference from 20·3 to 17·8 cm, and resolution of the ascites within 72 h. Despite this dramatic response to therapy, fetal death occurred on day 5 of treatment. The initial maternal serum was positive for anti-B19 IgM and IgG antibodies. Electron microscopy of fetal cardiac tissue obtained post-mortem revealed intranuclear viral particles typical of B19, confirming the antenatal diagnosis of myocarditis. This case demonstrates that direct viral identification is applicable to prenatal diagnosis. To our knowledge, this is the first reported case of the antenatal diagnosis and palliative treatment of fetal viral infection.     

Prenatal diagnosis of pelvic kidney

A 30-year-old woman had serial ultrasound scans from 28 weeks' gestation which revealed the presence of a cystic area in the fetal pelvis. The ‘cyst’ remained unchanged until delivery at 41 weeks. Fetal growth and amniotic fluid volume were normal throughout. A pelvic kidney was confirmed at birth. The differential diagnosis and antenatal management of this ‘cyst’ are discussed.     

Mosaicism of 46,XX/47,XX,+9/47,XX,+?mar in the same amniotic fluid with apparent loss of one cell line after delivery

A 46,XX; 47,XX,+9; 47,XX, + ?mar karyotype was detected in an amniotic fluid cell culture and confirmed in a subsequent fetal blood sample from a 40-year-old woman. After termination of the pregnancy, none of the 186 mitoses obtained from a second blood sample was trisomic for chromosome 9 (p<0.001). Selection against cells containing trisomy 9 is postulated to explain the disappearance of the lymphocyte clone.     

A rare case of de novo structural rearrangement of X chromosome diagnosed by amniocentesis

A dicentric X chromosome was found in a female fetus during cytogenetic studies performed on amniotic cells. Blood samples from the parents showed normal karyotypes and the pregnancy was terminated. The mechanism for the formation of this ‘de novo’ rearrangement is discussed.     

Iniencephaly is not uniformly fatal

Iniencephaly is an uncommon, but not rare, lesion involving a fusion between the posterior occipital bone and the cervical spine. Many cases are associated with other cranio-cervical abnormalities and anencephaly, and most are associated with other structural abnormalities. The prognosis is thought to be dismal. We describe a male infant, one of twins, who was diagnosed prenatally as having iniencephaly. The child was born without complication and has grown and thrived. This is the fourth patient with long-term survival with iniencephaly. We recommend that non-directive counselling be applied when presenting the findings of iniencephaly to parents.