Obstetrical Outcomes of Amniocentesis or Chorionic Villus Sampling in Dichorionic Twin Pregnancies

BACKGROUND: Under certain situations, women with twin pregnancies may be counseled to undergo invasive prenatal diagnostic testing. Chorionic villus sampling and amniocentesis are the two generally performed invasive prenatal diagnostic tests. Studies comparing procedure-related fetal loss between first-trimester chorionic villus sampling and second-trimester amniocentesis in twin pregnancies are limited. This study aimed to evaluate the procedure-related fetal loss and the obstetrical outcomes of these two procedures, chorionic villus sampling and amniocentesis in twin pregnancies. METHODS: The data from dichorionic-diamniotic twin pregnancies on which first-trimester chorionic villus sampling (n = 54) or second-trimester amniocentesis (n = 170) was performed between December 2006 and January 2017 in a single center were retrospectively analyzed. The procedure-related fetal loss was classified as loss of one or all fetuses within 4 weeks of procedure, and overall fetal loss was classified as loss of one or all fetuses during the gestation. The groups were compared with respect to the procedure-related and obstetrical outcomes. RESULTS: The difference in proportion of procedure-related fetal loss rate (1.9% for chorionic villus sampling vs. 1.8% for amniocentesis; P = 1.000) and the overall fetal loss rate (7.4% for chorionic villus sampling vs. 4.7% for amniocentesis; P = 0.489) between the two groups was not significant. The mean gestational ages at delivery were not statistically significant. CONCLUSION: Both the overall fetal loss rate and the procedure-related fetal loss rate of chorionic villus sampling and amniocentesis in dichorionic twin pregnancies had no statistical significance. Both procedures can be safely used individually.

Higroma quístico retronucal como marcador de anomalías cromosómicas en el primer trimestre de la gestación / Retronuchal cystic hygroma in the first trimester of pregnancy as a marker of chromosomal abnormalities

Background: Nuchal cystic hygroma is the most frequently identified marker of chromosomal anomalies during first trimester screening. Objective: To determine the association of the nuchal cystic hygroma with chromosomal anomalies diagnosed with karyotyping done between the first and second trimesters of pregnancy. Design: Retrospective study. Setting: Instituto Latinoamericano de Salud Reproductiva (ILSAR), Lima, Peru. Patients. Fetuses with nuchal cystic hygroma. Methods: The data were obtained from the ILSAR database between August 2007 and May 2018, the cases diagnosed by ultrasound from week 11 to 13.6. Nuchal cystic hygroma was defined as the presence of septated liquid content in the nuchal axial section with a thickness above the 95th percentile value for increased nuchal translucency value for the crown-rump length. The karyotype was obtained between the first and second trimesters from material collected by chorionic villus sampling (BVS) or amniocentesis (AMC). Main outcome measures: Karyotyping results were compared between cases with cystic hygroma alone and cases with cystic hygroma in addition to another marker. Results: Out of 459 invasive procedures performed in fetuses with high risk for chromosomal anomalies based on the Fetal test database of Spain, there were 162 cases of chromosomal anomalies (35.3%), and 104 cases of nuchal cystic hygroma (22.7%). Nuchal cystic hygroma was associated with a higher frequency of chromosomal abnormalities, compared to fetuses without cystic hygroma (52.9% vs. 30.1%; p<0.001). Out of 61 cases of hygroma alone, 42.3% had chromosomal anomalies, and when the hygroma was associated with other markers (fetal hydrops, abnormal ductus venosus, heart disease), 65.1% had chromosomal abnormalities. There was a statistically significant difference (p=0.003) for the presence of monosomy X between the group with cystic hygroma alone and the group with hygroma and fetal hydrops. There was no difference in hygroma thickness between the groups with and without chromosomal abnormalities. Conclusions: Nuchal cystic hygroma is a risk marker with high predictive value for chromosomal abnormalities, and its identification during prenatal screening may be considered an indication to a diagnostic test. When cystic hygroma is associated to flow abnormalities of the ductus venosus or fetal hydrops, chromosomal abnormalities significantly increase. The hygroma associated with hydrops was primarily linked to monosomy X, while the hygroma associated with abnormal flow velocity waveforms of the ductus venosus was linked to trisomy 21.

Antecedentes. El higroma quístico retronucal es el marcador de anomalías cromosómicas identificado con mayor frecuencia en el tamizaje del primer trimestre. Objetivo. Evaluar la asociación del higroma quístico retronucal y anomalías cromosómicas diagnosticadas con el cariotipo, entre el primer y segundo trimestre del embarazo. Diseño. Estudio retrospectivo. Institución. Instituto Latinoamericano de Salud Reproductiva (ILSAR), Lima, Perú. Pacientes. Fetos con higroma quístico retronucal. Método. Estudio de fetos con higroma quístico retronucal, obtenidos de la base de datos de ILSAR, entre agosto del 2007 y mayo del 2018, diagnosticados por ecografía entre las 11 y 13,6 semanas. El higroma quístico retronucal se definió como la presencia de contenido líquido tabicado en el corte axial retronucal con un grosor mayor al percentil 95 del valor de translucencia nucal aumentada para la longitud corona-nalga. Se obtuvo el cariotipo entre el primer y segundo trimestre en material obtenido por biopsia de vellosidades coriales (BVC) o amniocentesis (AMC). Principales medidas de resultados. Los resultados del cariotipo fueron comparados entre los casos de higroma quístico solo y los casos que tuvieron higroma y adicionalmente otro marcador. Resultados. De un total de 459 procedimientos invasivos realizados en fetos con alto riesgo para anomalías cromosómicas en base al Fetal test de España, hubieron 162 casos de anomalías cromosómicas (35,3%) y se identificó 104 casos de higroma quístico retronucal (22s7%). El hallazgo de higroma quístico retronucal se asoció con mayor presencia de anomalías cromosómicas, comparado con los fetos sin higroma quístico (52,9% vs. 30,1%; p<0,001). De 61 casos de higroma solo, 42,3% tenían anomalía cromosómica, y cuando el higroma estaba asociado a otros marcadores (hidrops fetal, ductus venoso anormal, cardiopatía, ausencia de hueso nasal), hubo 65,1% de anomalías cromosómicas. Hubo diferencia estadística significativa (p=0,003) para la presencia de monosomía X, entre el grupo con higroma solo y el de higroma + hidrops fetal. No hubo diferencia en el grosor del higroma entre el grupo con y sin anomalía cromosómica. Conclusiones. El higroma quístico retronucal es un marcador de riesgo con alto valor predictivo para anomalías cromosómicas. Su identificación en el tamizaje prenatal podría ser indicación para recomendar una prueba diagnóstica. Cuando se asocia a anormalidad del flujo del ductus venoso o hidrops fetal, aumentan significativamente las anomalías cromosómicas. El higroma asociado con hidrops se vinculó mayoritariamente a la monosomía X, mientras que el higroma asociado con onda de velocidad de flujo-OVF de ductus venoso anormal a la trisomía 21.

Application of Next-Generation Sequencing in Detection of Mutation Gene in ZMPSTE24 in Prenatal Diagnosisa Chinese Pedigree with Pathological Chorioamniotic Membrane Separation / 中山大学学报(医学科学版)

[Objective] To describe a case of a rare,novel mutation causing recurrent chorioamniotic membrane separation in a Chinese family with combined next-generation sequencing (NGS) and Sanger sequencing.[Methods] For the affected fetus,potential mutation were detected by the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing.And the prenatal diagnosis were identified by Sanger sequencing.[Results] A frameshifting mutation c.1389_1390delAG (inherited from mother),and a missense mutationc.1006 G ＞ C (inherited from mother) have been identified in the affected fetus (the second pregnancy).The prenatal diagnosis of the third fetus turns out to be a carrier,the mutation was inherited from father.[Conclusions] We describe a novel mutation in gene ZMPSTE24,which was considered with mandibuloacral dysplasia with type B,and that may be the cousecoursecausing of recurrent chorioamniotic membrane separation.This rare mutation constitutes an additional heterogeneous defect causing chorioamniotic membrane separation.And the conbinedcombined next-generation sequencing (NGS) and Sanger sequencing allows high resolution characterization of novel mutions that are not readily detected by present methods.

Chorionic villus sampling

Chorionic villus sampling has gained importance as a tool for early cytogenetic diagnosis with a shift toward first trimester screening. First trimester screening using nuchal translucency and biomarkers is effective for screening. Chorionic villus sampling generally is performed at 10-12 weeks by either the transcervical or transabdominal approach. There are two methods of analysis; the direct method and the culture method. While the direct method may prevent maternal cell contamination, the culture method may be more representative of the true fetal karyotype. There is a concern for mosaicism which occurs in approximately 1% of cases, and mosaic results require genetic counseling and follow-up amniocentesis or fetal blood sampling. In terms of complications, procedure-related pregnancy loss rates may be the same as those for amniocentesis when undertaken in experienced centers. When the procedure is performed after 9 weeks gestation, the risk of limb reduction is not greater than the risk in the general population. At present, chorionic villus sampling is the gold standard method for early fetal karyotyping; however, we anticipate that improvements in noninvasive prenatal testing methods, such as cell free fetal DNA testing, will reduce the need for invasive procedures in the near future.

Paracentric Inversions Found in Prenatal Diagnosis

PURPOSE: This study was designed to confirm whether the paracentric inversions of fetuses and parents may be harmless. MATERIALS AND METHODS: We report 10 cases (0.14%) with paracentric inversions among 7,181 prenatal cases observed during prenatal diagnosis performed at Cheil General Hospital between January 2009 and June 2013. We used cytogenetic GTL- and RBG-banding techniques. RESULTS: Of the 10 cases, nine cases were transmitted from each of the parents, and one case was de novo. Nine cases were phenotypically normal up to one month of age after birth. One case was lost to follow-up. We present prenatal diagnosis and follow-up examination of the fetuses with paracentric inversion. CONCLUSION: Based on our cases, most paracentric inversions are considered to be harmless. The precise identification of paracentric inversions might be clinically important and helpful for genetic counseling.

Análise dos resultados maternos e fetais dos procedimentos invasivos genéticos fetais: um estudo exploratório em Hospital Universitário / Analysis of fetal and maternal results from fetal genetic invasive procedures: an exploratory study at a University Hospital

OBJETIVO: Caracterizar as indicações das gestantes que procuraram o serviço de Medicina Fetal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo para realização de procedimentos invasivos diagnósticos e avaliar os resultados dos cariótipos fetais e de suas gestações. MÉTODOS: Estudo observacional retrospectivo das gestantes que realizaram biópsia de vilo corial (BVC), amniocentese e cordocentese no período de fevereiro de 2005 a dezembro de 2009. Não foram incluídos outros procedimentos diagnósticos ou procedimentos terapêuticos. O resultado da gestação foi obtido através de consulta de prontuário eletrônico e/ou físico e/ou contato telefônico. RESULTADOS: Foram realizados 713 procedimentos (113 BVC, 340 amniocenteses e 260 cordocenteses). A principal indicação para a realização dos procedimentos invasivos foi a presença de alterações estruturais nos fetos, seguido por valores aumentados da translucência nucal e pela idade materna avançada. O cariótipo fetal esteve alterado em 186 casos (26,1%). A trissomia do cromossomo 18 foi a aneuploidia mais comum, seguida pela trissomia do 21, a monossomia do X e a trissomia do cromossomo 13. Ocorreram 4,9% de abortamento, 25,7% de natimortos e 13% de neomortos. Oito gestantes optaram pela interrupção judicial, e 99% das gestantes cujos fetos não apresentavam malformação e que apresentavam cariótipo fetal normal tiveram nativivos.

OBJECTIVE: To characterize the indications of pregnant women who sought the Fetal Medicine Services of the Hospital das Clínicas, at the Medical School of the Universidade de São Paulo for performing invasive diagnostic procedures, and to evaluate the results of fetal karyotypes and their pregnancies. METHODS: A retrospective and observational study on pregnant women who underwent chorionic villus sampling (CVS), amniocentesis, and cordocentesis in the period from February, 2005 to December, 2009. Other diagnostic or therapeutic procedures were not included. The result of pregnancy was obtained by consulting patient electronic records, medical records, and/or telephone call. RESULTS: 713 procedures were performed (113 CVS, 340 amniocenteses, and 260 cordocenteses). The main indication for performing invasive procedures was the presence of structural changes in fetuses, followed by increased values of nuchal translucency, and advanced maternal age. Fetal karyotype was altered in 186 cases (26.1%). The 18 trisomy was the commonest aneuploidy followed by the 21 trisomy, X monosomy, and 13 trisomy. There were 4.9% cases of miscarriage, 25.7% cases of stillborn infants, and 13% cases of neonatal deaths. Eight pregnant women opted for legally induced abortion. 99% of pregnant women whose fetuses did not present abnormalities and presented normal fetal karyotype had infants who were born alive.

Ten-year Clinical Study of Chorionic Villus Sampling

PURPOSE: We evaluated indications for chorionic villus sampling (CVS), the positive predictive value of CVS for fetal chromosomal abnormalities, and the fetal loss rate after CVS at CHA Medical Center. MATERIALS AND METHODS: We reviewed the medical records of 511 cases of CVS performed between 67 and 120 days of gestation for prenatal cytogenetic diagnosis from April 2000 to April 2010. Fetal karyotypes were obtained by direct and indirect culture methods. RESULTS: The most common indications for CVS were abnormal ultrasonic findings including increased nuchal translucency (294/635, 46.3%). The positive predictive value of abnormal karyotyping according to indication for CVS was highest in cases with abnormal parental karyotypes (14/21, 66.7%). Mosaicism revealed by CVS comprised 3.1% of the sample (16/509). Amniocentesis revealed two cases of true mosaicism and 11 cases of confined placental mosaicism. The fetal loss rate within 4 weeks of the procedure was 1.2% (6/511). CONCLUSION: If CVS is performed by an expert clinician, it is a feasible and reliable procedure for prenatal genetic diagnosis. When CVS indicates mosaicism, the finding should be confirmed by amniocentesis to distinguish true mosaicism from confined placental mosaicism.

Cytogenetic Analysis of Amniotic Fluid, CVS, and Abortus in a University Hospital for Ten Years / 임상검사와정도관리

BACKGROUND: This study was conducted to analyze, compare, and assess the indications, incidences, and types of chromosomal abnormalities in the amniotic fluid, chorionic villus sampling (CVS), and abortus and to compare these with those previously reported. METHODS: The study subjects included 1,995 cases of amniocentesis and 169 cases of abortus, 20 cases of CVS, 21 cases of cord blood, and 2 cases of cardiac-puncture fluid in the last ten years (June 1999 to May 2009). RESULTS: Among the indications, the maternal serum and triple/quad markers testing positive emerged the highest (57.5%). Other factors those were found were an advanced maternal age (over35) (19.5%) and abnormal ultrasonography findings (8.2%). The frequency of chromosomal abnormality in the amniotic fluid was 4.5%, wherein the numerical abnormality was 3.1% and the structural abnormality was 1.4%. Among the numerical abnormalities, trisomy of chromosome 21 emerged the highest (1.4%). The frequency of the chromosomal abnormality of CVS and abortus was 39.1%, the numerical abnormality was 23.7%, and the order of frequency for trisomy was obtained chromosomes 16, 22, and 21. In the sex ratio of the normal chromosomes, it was 1.1%, but it resulted in 0.5% in CVS. CONCLUSIONS: The results of this chromosomal study on amniotic fluid, CVS, and abortus could serve as useful data regarding the prenatal genetic abnormalities of fetuses and for genetic consultation.

Clinical analysis of chorionic villus sampling / 대한주산의학회잡지

OBJECTIVE: The aims of this study were 1) to evaluate the indications of chorionic villus sampling CVS) and the positive predictive value for fetal chromosomal abnormalities, 2) to evaluate the reliability of CVS at Asan Medical Center, 3) to find out the risk factors of procedure-related fetal loss, 4) to find out the risk factors of culture failure, and 5) to compare transabdominal with transvaginal approaches. METHODS: Medical records of the 429 out of 461 patients in whom the CVS for prenatal cytogenetic diagnosis were performed were reviewed retrospectively for the period of June 1998 to June 2006. RESULTS: (1) The most common indications of CVS were abnormal ultrasonic findings including increased nuchal translucency (153/429, 35.7%), a previous history of cytogenetically abnormal baby (125/429, 29.1%), old maternal age (100/429, 23.3%), family history of genetic disease (22/429, 5.1 %), and parental abnormal karyotype (11/429, 2.6%). (2) The positive predictive value of abnormal karyotyping according to the indication of CVS was highest in the cases showing abnormal USG findings, including increased fetal nuchal translucency (28.3%). (3) The trial success rate of CVS was 99.5%(427/429). Culture failure rate was 1.9%.(4) Of the 427 cases, normal karyotype was revealed in 349 cases (81.7%), abnormal karyotype in 66 cases (15.2%), maternal cell contamination in 6 cases (1.4%), and pseudomosaicism and confined placental mosaicism (CPM) in 6 cases (1.4%). (5) Procedure-related fetal loss rate was 1.6% (7/419). (6) The significant risk factor of fetal loss was presence of preprocedure vaginal bleeding. (7) The significant risk factor of culture failure was a small amount (less than 10 mg) of tissue. (8) The gestational age at procedure was significantly different between transabdominal and transvaginal methods. In the transabdominal approach group, the incidence of fundal location of placenta was significantly more common. CONCLUSION: If CVS is performed by an expert operator and at a good quality of genetic laboratory, CVS is a very safe and reliable procedure for prenatal genetic diagnosis.

Prenatal diagnosis of thalassemia and hemoglobinopathies: 20 years experience at Siriraj Hospital.

Objective: To show the experience of prenatal diagnosis of Thalassemia and hemoglobinopathies in Siriraj Hospital. Methods: Hb Bart’s hydrops fetalis can be detected by DNA study from polymerase chain reaction (PCR) product in the first trimester of pregnancy either by chorionic villus sampling (CVS) or aminocentesis but in late pregnancy it can be detected unambiguous by ultrasonography at 18-20 weeks gestation, the suspected cases are confirmed by fetal blood sampling and Hb electrophoresis. Prenatal diagnosis (PND) for β-thalassemia diseases can be done at early pregnancy by direct visualization of the PCR products on electrophoresis or by dot blot analysis of amplified DNA with a set of HRP-labeled oligonucleotide probes complementary to the mutations. If the mutation is unknown. The couples have to wait for Hb analysis by HPLC or in vitro globins chain analysis from fetal blood in the second trimester. Results: The results of PND at Siriraj Hospital are summarized as Hb Bart’s Hydrops fetalis 228 cases, Homozygous Beta-Thalassemia 126 cases, and Beta Thalassemia/Hb E disease 550 cases. There are various methods of sampling namely chorionic villous sampling, amniocentesis, fetal blood sampling, ultrasound, or even combined method. There are minimal incidences of fetal loss 9 out 904 cases which comparatively give us one of the best center for prenatal diagnosis in Asia. Conclusion: Of the 904 pregnancies, the diagnosis were obtained in 891 pregnancies in which had 5 fetal loss from dead fetus in utero after fetal blood sampling in the second trimester. The other complication occurred after sampling failure.

Chorionic Villus Sampling: Clinical and Cytogenetic Study of the First 1,058 Cases in YUMC from 1984 to 2004 years / 대한산부인과학회지

OBJECTIVE: This study was performed to evaluate the feasibility, accuracy and safety of Chorionic Villus Sampling (CVS). METHODS: We analyzed the outcome of 1,058 cases of CVS performed for prenatal genetic diagnosis between 7 and 12 weeks of gestation in the outpatient prenatal genetic clinic in Yonsei University Medical Center (1,030 cases by trans-cervical method and 28 cases by trans-abdominal). Fetal Karyotyping was obtained by direct or indirect culture methods using Gimsa and Gimsa-Banding. RESULTS: Advanced maternal age was the most common indication for CVS (34.7%). The overall sampling success rate was 98% (1040/ 1,058), representing 92.5% in 7 to 8 weeks, 98.0% in 9 to 10 weeks, and 98.9% in 11 to 12weeks of gestation. The majority of cases (94.6%) required one or two aspirations. Cytogenetic analysis routinely included direct overnight and long-term culture methods, which revealed 27 chromosomal abnormalities (2.6%). Of 1,040 cases in which CVS were successful, 989 delivered normal baby, 23 resulted in fetal loss, 25 had therapeutic termination (24 with chromosome abnormalities and 1 with normal chromosome with huge myoma), and 3 with chromosome abnormalities were loss to follow up. The overall fetal loss rate was 2.2% (23/1,058). No congenital anomalies were found to be related to CVS in these series. CONCLUSION: When performed by experienced operators and cytogeneticists beyond 9 weeks of gestation, CVS is a feasible, accurate and safe method for prenatal genetic diagnosis capable of replacing genetic amniocentesis.

Clinical Analysis of Prenatal Cytogenetic Diagnoses: Four-year Experience at Asan Medical Center / 대한산부인과학회잡지

OBJECTIVE: To review and evaluate a total of 2,372 cases of prenatal cytogenetic diagnoses at Asan Medical Center from 1999 to 2002. METHODS: We reviewed the medical records of the patients in whom the procedure for prenatal cytogenetic diagnosis was performed. A total of 1780 cases of amniocentesis, 455 cases of cordocentesis, and 137 cases of chorionic villus sampling were analyzed. The cytogenetic results, indications for prenatal cytogenetic diagnoses, maternal ages, and the profiles of abnormal karyotypes were reviewed. We calculated the positive predictive value of each indication for abnormal fetal karyotypes and evaluated a factor that was the most sensitive marker for abnormal fetal karyotypes. RESULTS: Among the 2,372 cases of prenatal cytogenetic diagnoses, abnormal karyotypes were identified in a total of 158 cases (6.7%). The most frequent indication for prenatal cytogenetic diagnosis was abnormal maternal serum screening (33.9%), followed by ultrasonographic abnormality (22.9%) and old age (20.0%). No significant difference was found between mean maternal age with and without abnormal fetal karyotypes after excluding balanced rearrangements and polymorphisms (31.9 +/- 5.3 vs. 32.1 +/- 4.5 years). Among the 92 cases of abnormal fetal karyotypes after excluding balanced rearrangements and polymorphisms, the most frequent indication for prenatal cytogenetic diagnosis was ultrasonographic abnormality (58.7%), followed by abnormal maternal serum screening (10.9%). The positive predictive value of ultrasonographic abnormality for abnormal fetal karyotype was 9.9%. CONCLUSION: Among the several indications for prenatal cytogenetic diagnosis, ultrasonographic abnormality could be the most predictive marker for abnormal fetal karyotypes.

A Case of Limb Reduction Defect after Chorionic Villus Sampling at 9 Gestational Weeks / 대한산부인과학회잡지

Since it has been proposed that chorionic villus sampling could be an etiology of limb reduction defect, the relation between limb defect and chorionic villus sampling remains controversial. We experienced a case of limb reduction defect after chorionic villus sampling at 9 gestational weeks and report the case with brief review of literature.

DNA - based Prenatal Diagnosis of Epidermolytic Palmoplantar Keratoderma / 대한산부인과학회잡지

OBJECTIVE: The purpose of this investigation was to establish the prenatal diagnosis for identifying the risk for epidermolytic palmoplantar keratoderma(EPPK) of a fetus by sequence analysis of fetal genomic DNA from chorionic villi. METHODS: Chorionic villus sampling under transvaginal sonography at 12 weeks of gestation from a woman at risk for a child in a EPPK-affected family was perfomed. Polymerase chain reaction amplification of specific allele (PASA) assay was carried out for the detection of mutation(R162W in keratin 9 [K9] gene) previously identified in this family. Direct DNA sequencing analysis of K9 gene was accomplished to confirm the mutation. RESULTS: We had found the point mutation, R162W of K9 gene, in affected family members and confirmed by PASA assay. Affected family members were shown to have PCR products reactive with both the mutant and wildtype specific primers. Because we could not find any expected products after PASA assay with the primers la(+)/KSmt(-) of the fetal DNA, we predicted that the fetus did not inherited the mutant allele and that the fetus could be unaffected. After PASA assay, we analyzed DNA sequences of two family members to confirm the mutation. A C-to-T substitution at bp 545 was detected in the father, instead the fetus did not have any mutant band at that base pair. CONCLUSION: The PASA assay and direct DNA sequencing analysis of K9 gene through chorionic villi sampling and extraction of genomic DNA had validity to early prenatal diagnosis whether fetus was affected in EPPK or not.

Studies on the prenatal chromosomal analysis and the changes of maternal serum alpha-fetoprotein following chorionic villus sampling

Transcervical chorionic villus sampling (CVS) was performed in 174 patients between 7 & 12 menstrual weeks of pregnancy opting for prenatal diagnosis. Advanced maternal age was the most common indication for CVS (39.7%). The sampling success rate was 95.4% (166/174), representing 88.9% at 7 to 8 weeks, 98.9% at 9 to 10 weeks & 92.7% at 11 to 12 weeks gestation. In 139 of 174 patients (80%), successful sampling was accomplished in one or two catheter passages only. Four spontaneous fetal losses (2.3%) occurred. The cytogenetic analysis routinely used was the direct overnight & long-term culture methods which revealed 4 abnormalities (2.4%). To date, 90 of the women have been delivered & all infants are doing well and the remaining 65 pregnancies are continuing uneventually. Maternal serum alphafetoprotein (MSAFP) concentration was determined in 72 patients immediately before & after CVS. A significant increase of 20% or more, comparable to pre CVS levels, was noted immediately after sampling in 56 of 72 patients (77.8%). The increase in MSAFP concentration correlated with the amount of villi sampled (r = 0.498, p less than 0.001) & with the number of sampling attempts (p less than 0.05). Estimated CVS related fetomaternal hemorrhage (FMH) ranged from 0.005 to 0.1552 ml and in 5 of 72 patients (6.90%) 0.06 ml or more of FMH was noted. Two of the 5 patients had FMH of 0.1 ml or more.