Prenatal diagnosis in women of advanced maternal age

In this thesis several aspects of prenatal diagnosis in women of advanced maternal age were studied. The effects of the increasing number of elderly gravidas. the lowering of the maternal age at which prenatal diagnosis became accessible and the introduction of chorionic villus sampling, were evaluated. It appeared that the number of gravidas older than 36 years has been increasing in our region by 0.3% each year since 1984. The yearly increase of women who visited our centre for prenatal diagnosis because of advanced age was higher than 0.3% because also women of 36 and 37 years are entitled to prenatal testing since 1984. Chorionic villus sampling was introduced in our department at the end of 1983. In 1984 CVS was an established method of prenatal testing. Five years later 50% of the procedures for advanced maternal age and approximately 90% of the procedures for high genetic risks consisted of CVS. In the early years of CVS most procedures were performed transcervically. Since it appeared that the fetal loss rate was lowest when sampling took place after 12 weeks. transabdominal (TA) CVS in elderly gravidas became the procedure of choice. Notv.rithstanding the fact that CVS is performed later in pregnancy than in most other centres. many women make the first visit to our centre too late in pregnancy to be allowed a choice between amniocentesis and TACVS. We have come to the conclusion that our efforts to provide information about recent developments in prenatal diagnosis to both the medical profession ~d to the future parents must continue. Information to ethnic minorities needs special attention since most of these women have a limited knowledge of increased risks for chromosomally abnormal offspring and the availability to detect these abnormalities. Furthermore, most Muslim patients are unaware of the fact that in case of an abnormal result a first trimester abortion is allowed according to the Koran Termination of pregnancy in the first trimester is thought to be less traumatic than in the second trimester. This difference. however. was not expressed by the percentage of women who became pregnant again after a genetic termination of pregnancy. Both women who had undergone a mid-trimester abortion and women who had experienced a first trimester abortion became pregnant again in approximately 40% of cases. Women who lost a pregnancy after prenatal diagnosis had been performed. conceived in approximately 60% of cases. In de latter group there was also no difference between CVS and amniocentesis. Further psychological studies are needed to establish to what extent early termination of pregnancy is less traumatic than mid-trimester abortion. The difference in reproductive behaviour between those women who experienced a spontaneous abortion and those whose abortion was induced. suggests that it might be more traumatic to decide upon the abortion of a chromosomally abnormal fetus, than it is to experience the spontaneous loss of a fetus after prenatal diagnosis. The advantage of CVS in obtaining the result early in pregnancy seems more obvious for the vast majority of women with normal test results since they can be reassured 4-6 weeks earlier than after amniocentesis. Twin pregnancies in elderly gravidas create a special problem in prenatal diagnosis. When an abnonnal result is present the !win will most likely be discordant for the abnormality. The possibility and risks of selective feticide must be discussed with the parents before an invasive procedure is undertaken. The probability that both fetuses display a trisomy 21 is too low (e.g. 0.02% in a 40-year old woman ) to justify prenatal testing. Counselling older women with a twin pregnancy should therefore include assessment of the parental attitude towards a discordant twi

Retrospective study of trisomy 18 in chorionic villi with fluorescent in situ hybridization on archival direct preparations

Trisomy 18 in direct chorionic villus preparations needs further investigation since the chromosome abnormality may be confined to the placenta and may not represent the actual fetal karyotype. We performed, retrospectively, fluorescent in situ hybridization (FISH) with the chromosome 18 centromere probe (L1.84) on interphase nuclei of destained slides of all cases of full trisomy 18 (n=22) and mosaic trisomy 18 (n=8) detected among 7600 first-trimester chorionic villus samples during an 8-year period (1985–1992). More nuclei displaying three signals were encountered in cases of full and mosaic trisomy 18 confirmed in fetal tissue than in non-confirmed cases. FISH can be useful for the verification of trisomy 18 in direct chorionic villus preparations

Sonographically determined anomalies and outcome in 170 chromosomally abnormal fetuses

Structural pathology and outcome were studied in 170 chromosomally abnormal fetuses. Numerical chromosomal abnormalities were established in 158 (93 per cent) cases, of which 110 (71 per cent) represented trisomies, 30 (18 per cent) Turner syndrome, and 18 (11 per cent) triploidy. Structural chromosomal abnormalities were diagnosed in 12 (7 per cent) cases. Gestational age at referral was significantly shorter for pregnancies with Turner syndrome than for the other chromosomal abnormalities. Referral before 20 weeks of gestation was mainly based on fetal structural pathology alone (92 per cent); after 20 weeks, patients were referred because of structural pathology combined with small for gestational age, oligohydramnios, or polyhydramnios. Referral as a result of suspected multiple organ pathology occurred in 73.5 per cent of pregnancies. An abnormal amniotic fluid volume was present in 59/170 (34.5 per cent) chromosomally affected pregnancies, i.e., oligohydramnios in 31 and polyhydramnios in 28 cases. Birth weight was below the tenth percentile in over half of the chromosomally abnormal fetuses, except for Turnersyndrome. Fetal outcome was poor, with a survival rate at 1 month of 30 per cent for trisomies which was mainly determined by trisomy 21 (14/18=77.5 per cent)

Increased incidence of cytogenetic abnormalities in chorionic villus samples from pregnancies established by in vitro fertilization and embryo transfer (IVF-ET)

We studied 201 pregnancies that were established by in vitro fertilization and embryo transfer (IVF–ET) and compared the frequency of cytogenetic abnormalities with that found in a large control population matched for indication group (advanced maternal age) and time of sampling. A total of 252 IVF–ET fetuses were cytogenetically analysed by either chorionic villus sampling (CVS; n = 80) or amniocentesis (n = 172). Eleven chromosome abnormalities were found in the CVS group (13·8 per cent); among them, a 45, X/46, X, dic(q11)/46, X, del(Y)(q11) mosaic that was found in an IVF pregnancy established by intracytoplasmic sperm injection (ICSI), four cases of trisomy 21, and three cases of trisomy 7 confined to the placenta. The results indicate a statistically significant three‐to five‐fold increase in both confined placental abnormalities (P<0·008) and true fetal chromosome anomalies (P<0·04). In the amniocentesis group, identical rates (1·7 per cent) of chromosome abnormalities were found in the IVF–ET and control groups. It is concluded that late first trimester, but not early second trimester, IVF–ET pregnancie

Prenatal diagnosis of Klippel—Trenaunay—Weber syndrome: a case report

At 20 weeks of gestation, a typical combination of a massive enlargement of the right fetal leg and multiple cystic lesions was detected at ultrasound examination. Color‐coded Doppler examination revealed no arteriovenous fistulae. These findings allowed an in utero diagnosis of the Klippel‐Trenaunay‐Weber syndrome, which was confirmed after subsequent termination of the pregnancy. The severe malformation involved the upper and lower right leg. No arteriovenous fistulae were found. Copyrigh

Prenatal diagnosis of mosaic tetrasomy 12p/trisomy 12p by fluorescent in situ hybridization in amniotic fluid cells: A case report of Pallister-Killian syndrome

A prenatally detected case of a rare mosaic tetrasomy 12p/trisomy 12p is reported, presenting as the well‐known accessory isochromosome 12p and a supernumerary single 12p marker in 17/24 and 6/24 clones of cultured amniotic fluid cells, respectively. The chromosomal nature of both marker chromosomes was investigated in cultured amniotic fluid cells by fluorescent in situ hybridization with various probes: the 12‐centromeric probes pa12H8 and D12Z3, a whole chromosome 12 paint, and the chromosome 12p‐specific paint M28. DNA analysis revealed a maternal origin of the extra 12p material. After counselling, the parents requested termination of pregnancy. Inspection and autopsy of the fetus revealed many of the dysmorphisms and internal structural abnormalities of the Pallister–Killian syndrome. Copyrigh

Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection

Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome aberrations including two cases of 47,XXY, four cases involving a 45,X cell line and three autosomal trisomies. Molecular analysis of the parental origin of the deleted or supernumerary chromosome was performed by using polymorphic microsatellite markers. Six cases involving a sex chromosome abnormality were found to be of paternal origin while the two trisomic cases that could be analysed were of maternal origin. Two cases involved the same infertile couple who had two consecutive ICSI pregnancies terminated because of a chromosome abnormality. The replaced embryos in both cases originated from a single batch of ICSI fertilized oocytes of which part was used to initiate the first pregnancy and part was cryopreserved and used to initiate the second pregnancy