Comparison of chorionic villus sampling and amniocentesis for fetal karyotyping at 10-13 weeks' gestation. Randomised trial to assess safety and fetal outcome of early and midtrimester amniocentesis. The Canadian Early and Mid-trimester Amniocentesis Trial (CEMAT) Group. Randomized trial comparing first-trimester transcervical chorionic villus sampling and second-trimester amniocentesis. Late first-trimester invasive prenatal diagnosis: results of an international randomized trial. [Randomized comparison of transabdominal, transcervical chorionic villi sampling and amniocentesis]. Transabdominal versus transcervical routes for chorionic villus sampling. The effect of ultrasonography on midtrimester genetic amniocentesis complications. First-trimester transcervical chorionic villus sampling by biopsy forceps versus mid-trimester amniocentesis: a randomized controlled trial project. Randomised study of risk of fetal loss related to early amniocentesis versus chorionic villus sampling. Randomized clinical trial of transabdominal versus transcervical chorionic villus sampling methods. Randomised controlled trial of genetic amniocentesis in 4606 low-risk women.
We did a prospective study of women with singleton viable pregnancies at 10-13 weeks' gestation who requested first-trimester fetal karyotyping because of advanced maternal age, parental anxiety, or family history of chromosomal abnormality. Women were counselled as to the available options of non-invasive screening or invasive testing by mid-trimester amniocentesis, early amniocentesis (EA), or chorionic villus sampling (CVS), or randomisation to EA or CVS at 10-13 weeks. EA was done in 731 patients (493 by choice and 238 by randomisation) and CVS in 570 (320 by choice and 250 by randomisation). Both procedures were done by transabdominal ultrasound-guided insertion of a 20-gauge needle. The rate of successful sampling was the same for both procedures (97.5%). Spontaneous loss (intrauterine or neonatal death) was significantly higher after EA (total group mean = 5.3%, 95% CI 3.8-7.2; randomised subgroup mean = 5.9%, 3.3-9.7) than after CVS (total group: mean = 2.3%, 1.2-3.9; randomised subgroup: mean = 1.2%, 0.3-3.5). The gestation at delivery and birthweight of the infants after EA and CVS were similar. In the EA group the incidence of talipes equinovarus (1.63%), was higher than in the CVS group (0.56%), but this difference was not significant. Most published reports on early amniocentesis are of cohort studies rather than randomised trials. This study was designed to assess the safety and cytogenetic accuracy of early amniocentesis in-contrast to midtrimester amniocentesis in a randomised multicentre setting.
                Pregnant women were randomly allocated early amniocentesis (between 11(+0) and 12(+6) gestational weeks(days)) or midtrimester (between 15(+0) and 16(+6) gestational weeks(days)) amniocentesis. A detailed fetal ultrasound examination was done between 15 and 20 gestational weeks in all women. All amniocenteses were done under continuous ultrasound guidance: 11 mL (early amniocentesis) or 20 mL (midtrimester amniocentesis) of amniotic fluid were removed for cytogenic analysis. No more than two needle insertions were done on the same day. All fetal losses (spontaneous or induced abortions) were counted as outcome events and post-procedural losses had cytogenic analysis. Maternal and fetal health were assessed at 20-22 weeks and 5 weeks after delivery. Logistic regression analysis was used to assess the significance of the differences between the early amniocentesis and midtrimester amniocentesis groups.
                4374 pregnant women took part in the study. 1916 (87.8%) of 2183 women in the early amniocentesis group had their amniocentesis before 13 gestational weeks. 1775 (81.2%) of 2185 women in the midtrimester group had their amniocentesis after 15 gestational weeks. There was a significant difference in total fetal losses for early amniocentesis compared with midtrimester amniocentesis (7.6% vs 5.9%; difference 1.7%, one-sided CI 2.98%, p = 0.012). There was a significant increase in talipes equinovarus in the early amniocentesis group compared with the midtrimester amniocentesis group (1.3% vs 0.1%, p = 0.0001). There was a significant difference in postprocedural amniotic-fluid leakage (early amniocentesis 3.5% vs midtrimester amniocentesis 1.7%, p = 0.0007).
                Our study shows that early amniocentesis is associated with an increased risk of fetal loss and talipes equinovarus. Our results should be taken into consideration when invasive prenatal diagnosis is being offered. A total of 800 patients were randomized at the 9th to 11th week of pregnancy either for transcervical chorionic villus sampling (CVS) on the day of trial entry or for amniocentesis (AC) at the 16th week. The indication for fetal karyotyping was maternal age in 94 per cent of the cases; the mean maternal age was 39.2 years. An adequate sample was obtained in 98.3 per cent of the cases in the CVS group and in all cases in the AC group. Retesting was indicated in 3.3 per cent of the CVS cases. An abnormal karyotype was found in 6.1 per cent of the CV samples and in 4.5 per cent of the amniotic fluid samples. There was one false-positive chromosome result in both groups. Twelve (3.1 per cent) miscarriages occurred by the 22nd week of pregnancy in the CVS group in pregnancies intended to continue. No difference was seen between the groups for total fetal loss rates. The number of surviving infants in the CVS group was 92.2 per cent and in the AC group 91.7 per cent (rate difference 0.5 per cent (95 per cent confidence interval -3.3 to 4.3)). In our study, both the diagnostic accuracy and the risk of fetal loss were equal in the CVS and AC groups. To assess, in a randomized trial, the safety and accuracy of amniocentesis and transabdominal chorionic villus sampling (CVS) performed at 11-14 weeks of gestation, given that this time frame is increasingly relevant to early trisomy screening.
                We compared amniocentesis with CVS from 77 to 104 days of gestation in a randomized trial in a predominantly advanced maternal age population. Before randomization, the feasibility of both procedures was confirmed by ultrasonography, and experienced operators performed sampling under ultrasound guidance; conventional cytogenetic analysis was employed. The primary outcome measure was a composite of fetal loss plus preterm delivery before 28 weeks of gestation in cytogenetically normal pregnancies.
                We randomized 3,775 women into 2 groups (1,914 to CVS; 1,861 to amniocentesis), which were comparable at baseline. More than 99.6% had the assigned procedure, and 99.9% were followed through delivery. In contrast to previous thinking, in the cytogenetically normal cohort (n = 3,698), no difference in primary study outcome was observed: 2.1% (95% confidence interval 1.5, 2.8) for CVS and 2.3% (95% confidence interval, 1.7, 3.1) for amniocentesis. However, spontaneous losses before 20 weeks and procedure-related, indicated terminations combined were increased in the amniocentesis group (P =.07, relative risk 1.74). We found a 4-fold increase in the rate of talipes equinovarus after amniocentesis (P =.02) overall and in week 13 (P =.03, relative risk = 4.65), but data were insufficient to determine this risk in week 14.
                Amniocentesis at 13 weeks carries a significantly increased risk of talipes equinovarus compared with CVS and also suggests an increase in early, unintended pregnancy loss.
                I The transabdominal chorionic villus sampling method was compared with the transcervical route and second trimester amniocentesis in a 3-winged randomised trial. Examination of 45 epidemiological variables showed the three procedure groups to be comparable at enrollment. In 3079 women at low genetic risk, we compared transabdominal with transcervical chorionic villus sampling and amniocentesis. The total fetal loss was 10.9%, 6.3% and 6.4% in the transcervical, transabdominal chorionic villus sampling groups and the amniocentesis group, respectively (p < 0.001). The two CVS procedures were compared in 2882 low and high genetic risk women with cytogenetically normal fetuses. Rates of unintended post-procedure loss were 3.7% and 7.7% for transabdominal CVS and transcervical CVS, respectively (p < 0.001), difference in rates 4.0%, 95% C.I. +2.3% to +5.8%. By a priori ultrasound scanning, more transcervical than transabdominal procedures (p < 0.001) were considered to be inaccessible for sampling. Our data indicate that transabdominal allows freer access to the placental site than transcervical sampling and is easier to adapt to than transcervical CVS. Women run comparable risks with transabdominal CVS and amniocentesis. Given the results of our study, transabdominal procedures remain the first choice for prenatal diagnosis and, since in our hands transcervical sampling entails an increased fetal risk, we have abandoned transcervical CVS in our two study centres. nan Midtrimester amniocentesis for antenatal genetic diagnostic purposes is a relatively new procedure. The assumption that placental localization before amniocentesis will reduce the numbers of abortions, bloody taps, and missed taps has resulted in the routine use of diagnostic ultrasound for placental localization. This study consists of two groups undergoing midtrimester amniocentesis. The groups were distinguished by the use and absence of the use of ultrasound data prior to amniocentesis. Comparisons between the groups failed to support the contention that the routine use of ultrasound reduces the complications of midtrimester amniocentesis. Our findings support other published data concluding that the routine use of ultrasound does not help to reduce the number of midtrimester amniocentesis complications. Up to now, no data are available comparing amniocentesis and chorionic villus sampling (CVS) using biopsy forceps. A series of 1313 consecutive women referred to our unit before 12 weeks of pregnancy for fetal cytogenetic analysis because of advanced maternal age, were randomized into CVS with the use of transcervical biopsy forceps or mid-trimester amniocentesis. The diagnostic success rates of the two groups were 98 per cent and 100 per cent, and a second procedure was needed in 4.1 per cent (13/314) and in 0. 3 per cent (1/358), respectively. Follow-up was achieved in 98.7 per cent of the pregnancies. Postprocedure spontaneous fetal losses, until the first week after birth, in the 672 pregnancies that completed the trial accounted for 2.2 per cent (7/314) in the CVS group and 2.8 per cent (10/358) in the amniocentesis group. Although the trial was prematurely discontinued, and therefore the sample size was smaller than initially planned, the results indicate that transcervical CVS was as safe as mid-trimester amniocentesis.
                Copyright 1999 John Wiley & Sons, Ltd. Several cohort studies have shown the feasibility of early amniocentesis (between 11 and 13 weeks of gestation) as an alternative to chorionic villus sampling (CVS) for karyotyping, but the only completed randomised study of fetal safety showed a significant fetal-loss risk related to first-trimester amniocentesis. We assessed fetal safety in early amniocentesis and CVS.
                We assessed early amniocentesis at 11-13 weeks gestational age compared with the fetal risk associated with CVS at 10-12 weeks. 1160 pregnant women were randomly assigned one procedure (581 early amniocentesis, 579 CVS) after a baseline ultrasound examination at 10 weeks' gestation and were followed up until birth. Total fetal loss and neonatal morbidity were the primary outcome measures. Sampling success and pregnancy complications were secondary outcomes. We used a filter to increase the cell yield in the early amniotic-fluid samples. CVS was transabdominal.
                We found a significantly increased occurrence of talipes equinovarus in the early amniocentesis group (p < 0.01), the risk of which was associated with sampling at the earliest gestational ages and with temporary leakage of amniotic fluid after sampling. Therefore, the trial was stopped early, which reduced the power of the safety study. 4.8% (27) of fetuses in the CVS group and 5.4% (30) in the early amniocentesis group were lost after randomisation (p = 0.66). More detailed survival analysis did not show any significant differences in fetal loss rates. Leakage of amniotic fluid after sampling occurred significantly more frequently after early amniocentesis than after CVS (p < 0.001), but we found no other major differences in pregnancy complications. Significantly more CVS than early amniocentesis procedures were repeated or failed to produce a karyotype (p < 0.01).
                Even though the numbers were small, we found an association between early amniocentesis and talipes equinovarus. We believe this association to be true, since it supports a trend in a similar randomised study. Our results show that early amniocentesis, when done with the filter technique, is associated with an abortion risk similar to CVS, although the limited size of our study population reduced the strength of this conclusion. The relative advantages and disadvantages of transabdominal (TA) and transcervical (TC) chorionic villus sampling (CVS) in terms of fetal risks and efficacy were evaluated in a clinical trial conducted on 1194 women randomized at 7-12 weeks' gestation. The results of the study indicate that, if any, the relative risk of fetal loss following either procedure is less than double that of the alternative technique when performed by a skilled operator. Overall, the fetal loss rate (spontaneous abortions following randomization, terminations of pregnancy, and perinatal deaths) is 16.5 and 15.5 per cent, respectively, among women allocated to TA- and TC-CVS. The two procedures are equally effective, although TA-CVS is associated with a significantly lower rate of repeat device insertions; on the other hand, a higher weight of chorionic tissue is obtained, on average, with TC-CVS. Bleeding is more common following TC-CVS, while peritoneal reaction developed only after TA-CVS. No diagnostic problems specifically related to one sampling technique were identified. Outcome of pregnancy after amniocentesis was studied in a randomised controlled trial of 4606 women, age-range 25-34 years, without known risk of genetic disease. Spontaneous abortion rate was 1.7% in the study group after amniocentesis and 0.7% in the control group after ultrasound (relative risk 2.3). In the study group, increased levels of maternal serum alpha-fetoprotein before amniocentesis, perforation of the placenta during amniocentesis, and withdrawal of discoloured amniotic fluid were associated with an increased risk of spontaneous abortion. In the first six weeks after amniocentesis/ultrasound scan, amniotic fluid leakage occurred more often in the study group but there was no difference in the rate of vaginal bleeding. Frequency of postural malformations in the infants in the two groups was the same. In the study group, respiratory distress syndrome was diagnosed more often (relative risk 2.1) and more babies were treated for pneumonia (relative risk 2.5).
Second trimester amniocentesis is safer than early amniocentesis or transcervical CVS, and is the procedure of choice for second trimester testing. Transabdominal CVS should be regarded as the procedure of first choice when testing is done before 15 weeks' gestation. Diagnostic accuracy of different methods could not be assessed adequately because of incomplete karyotype data in most studies.