Screening For Chromosomal Abnormalities Research Articles

Distribution of nuchal translucency thickness in Japanese fetuses

To establish reference values for the nuchal translucency (NT) thickness in Japanese fetuses. Ultrasonographic measurements of the crown-rump length (CRL) and NT were performed from 11 to 13 + 6 weeks of gestation in consecutive Japanese fetuses examined during prenatal visits between February 2011 and January 2012. The median, 5th and 95th percentiles of the NT thickness with 5 mm intervals of the CRL were confirmed. A total of 970 cases were enrolled in the study. The median NT thickness for a CRL between 45 and 80 mm ranged from 1.2 mm to 1.9 mm, and the 95th percentile of these values ranged from 2.1 mm to 3.2 mm, respectively. The reference values for the NT thickness in Japanese fetuses were determined. These values should be useful for fetal biometry, morphological assessment and first trimester screening for chromosomal abnormalities in Japan.

OC20.01: The prefrontal space ratio in second and third trimester screening for chromosomal abnormalities

Results: In all women with atrophy and normal endometrium EI for endometrium was 0–2 points (72 women). In patients who had polyps, hypertrophy and cancer in the pathological result (34 women), EI was 3–4 points. The difference was significant (χ2 Pearson test; P < 0.0001). Conclusions: Elastography combined with conventional transvaginal ultrasonography is a helpful tool in differentiation of uterine bleeding in perimenopausal women and may decrease the number of unnecessary invasive procedures.

Oocyte and Embryo Selection in Assisted Reproductive Treatments: Methods Improving Outcome and Illuminating Aspects of Meiosis and Embryogenesis.

The introduction of in vitro fertilization (IVF) treatment over thirty years ago revolutionized the treatment of infertility and has led to the birth of more than five million babies worldwide. However, this remarkable success masks the fact that IVF treatment remains remarkably inefficient. It is still the case that most patients require more than one cycle of treatment to obtain a viable pregnancy and more than 80% of embryos transferred to the uterus fail to produce a birth. The poor success rate per embryo transferred is a consequence of the extreme variability in the competence of the oocytes and embryos produced during a typical IVF cycle, coupled with the inability of routine morphological evaluations to correctly identify the embryos having the greatest developmental potential. Innovations in genetic testing and embryo culture have recently become available, which may finally allow an accurate evaluation of embryo competence and offer the hope of significant improvements to IVF treatment. These new technologies are also shedding light on important aspects of human oogenesis and preimplantation development. Principal amongst the new methods for embryo selection are those that allow accurate screening for chromosome abnormalities. Aneuploidy is extremely common in human oocytes and embryos and is of great clinical significance, having responsibility for the majority of miscarriages and many instances of congenital abnormality and mental retardation. The application of comprehensive chromosome screening techniques has provided an insight into the frequency of aneuploidy affecting each chromosome. It has been confirmed that during female meiosis errors involving single chromatids are far more common than those affecting whole chromosomes. Lagging of chromosomes during anaphase and failure of chromosomes to migrate to the spindle both occur frequently, contributing to a preponderance of chromosome losses over gains in the polar bodies tested. It has long been known that female meiosis I is the source of most aneuploidies detected during pregnancy and that the incidence of abnormalities increases with advancing age. Data from the comprehensive chromosome screening of polar bodies confirms this to be true for younger patients. However, it is now clear that errors occurring in meiosis II increase more rapidly with advancing age than those derived from meiosis I, such that errors from the second meiotic division predominate for women over 40 years of age. Data from embryos has also provided an interesting insight into chromosome segregation during preimplantation development, confirming a remarkable level of genetic instability characterized by a high frequency of chromosomal malsegregation, mosaicism and chromosome breakage. Clinically, there is rapidly accumulating data showing that IVF outcomes (pregnancy and miscarriage rates) can be significantly improved by testing embryos for aneuploidy and transferring those found to be chromosomally normal, provided appropriate technologies are used.This lecture will review data from more than 2000 human oocytes and embryos tested in our laboratory, providing unique and sometimes unexpected information concerning the mechanisms leading to aneuploidy.

Reproductive decisions after fetal genetic counselling

A broad range of testing modalities for fetal genetic disease has been established. These include carrier screening for single-gene mutations, first-trimester and second-trimester screening for chromosome abnormalities and open neural-tube defects, prenatal diagnosis by means of chorionic villus sampling and amniocentesis, and preimplantation genetic diagnosis. Reproductive decisions before and after fetal genetic counselling represent the culmination of a dynamic interaction between prospective parents, obstetrician and genetic counsellor. The decision to undergo genetic testing before and after genetic counselling is influenced by a host of interrelated factors, including patient-partner and family relationships, patient-physician communication, societal mores, religious beliefs, and the media. Because of the complexity of personal and societal factors involved, it is not surprising that genetic counselling concerning reproductive decision-making must be individualised. A limited number of principles, guidelines and standards apply when counselling about testing for fetal genetic disease. These principles are that genetic counselling should be non-directive and unbiased and that parental decisions should be supported regardless of the reproductive choice. A critical responsibility of the obstetrician and genetic counsellor is to provide accurate and objective information about the implications, advantages, disadvantages and consequences of any genetic testing applied to prospective parents and their fetuses. These principles and responsibilities will be tested as newer technologies, such as array comparative genome hybridisation, non-invasive prenatal diagnosis and sequencing of the entire genome are introduced into the field of reproductive genetics and become routine practice.

Chromosomal abnormalities in azoospermic and non-azoospermic infertile men: numbers needed to be screened to prevent adverse pregnancy outcomes

How many infertile men who wish to conceive need to be screened for chromosomal abnormalities to prevent one miscarriage or the birth of one child with congenital anomalies (CAs)? In azoospermic men, the prevalence of chromosomal abnormalities is 15.2% and the number needed to be screened (NNS; minimum-maximum estimate) for a miscarriage is 80-88 and for a child with CAs is 790-3951. The prevalence of chromosomal abnormalities in non-azoospermic men is 2.3% and the NNS are 315-347 and 2543-12 723, respectively. Guidelines advise the screening of infertile men for chromosomal abnormalities to prevent miscarriages and children with congenital abnormalities, but no studies have been published on the effectiveness of this screening strategy. Retrospective cohort study of 1223 infertile men between 1994 and 2007. Men with azoospermia and men eligible for ICSI treatment visiting a university hospital fertility clinic in The Netherlands who underwent chromosomal analysis between 1994 and 2007 were identified retrospectively in a registry. Only cases of which at least one sperm analysis was available were included. Data were collected by chart review, with a follow-up of pregnancies and their outcomes until 2010. The chromosomal abnormalities were categorized according to their risk of unbalanced offspring, i.e. miscarriage and/or child with CAs. Multi-level analysis was used to estimate the impact of chromosomal abnormalities on the outcome of pregnancies in the different subgroups of our cohort. NNS for miscarriages and children with CAs were calculated based on data from our cohort and data published in the literature. A chromosomal abnormality was found in 12 of 79 men with azoospermia (15.2%) and in 26 of 1144 non-azoospermic men (2.3%). The chromosomal abnormalities were categorized based on the literature, into abnormalities with and abnormalities without increased risk for miscarriage and/or child with CAs. In our study group, there was no statistically significant difference between the subgroups with and without increased risk respectively, regarding the frequency of children born with CAs (1/20; 5.0% versus 1/14; 7.1%), miscarriage (9/20; 45.0% versus 2/14; 14.3%) or unaffected liveborn children (9/20; 45.0% versus 9/14; 64.3%). The prevalence of chromosomal abnormalities with a theoretically increased risk of unbalanced progeny was 1.0% in non-azoospermic men and 3.8% in men with azoospermia. For the calculation of the NNS, the risk of an adverse pregnancy outcome in our cohort was compared with the incidence ranges of miscarriage and children with CAs in the general population. The number of azoospermic men that needs to be screened to prevent one miscarriage (80-88) or one child with CAs (790-3951) was considerably lower compared with the NNS in the non-azoospermic group (315-347 and 2543-12 723, respectively). The prevalence of chromosomal abnormalities in infertile men is low, and although we included 1223 men, our conclusions are based on a small number (38) of abnormal karyotypes. As there are no large series on outcomes of pregnancies in infertile men with chromosomal abnormalities, our conclusions had to be partly based on assumptions derived from the literature. Based on the NNS calculated in our study, screening for chromosomal abnormalities is recommended in all azoospermic men. In non-azoospermic infertile men, screening might be limited to men with an additional risk factor (e.g. a history of recurrent miscarriage or a positive family history for recurrent miscarriage or children with CAs). The NNS can be used in future cost-effectiveness studies and the evaluation of current guidelines on karyotyping infertile men.

Value of nasal bone and serological screening for the detection of fetal chromosomal disorders in second trimester

To assess the value of fetal chromosomal abnormality screening by a maternal serum test plus fetal nasal bone length in second trimester (parallel test). From January 2009 to December 2010, fetal nasal bone was measured at 19 - 22 weeks gestation in 6173 unselected cases. Karyotyping was performed in cases with a high risk for maternal serum test and/or abnormal fetal nasal bone length. All cases were followed-up postnatally. Nasal bone was assessed successfully in 5607 cases (90.83%). Normally it is increases with gestational age. The detection rate of chromosomal abnormality was 69.64% by maternal serum test, 79.76% by maternal serum test plus hypoplastic nasal bone and 83.93% by maternal serum test plus shortened nasal bone. Fetal nasal bone hypoplasia is closely correlated with chromosomal abnormality. And sonographic evaluation of nasal bone may be a useful tool for screening chromosomal abnormality. The combination of maternal serum test and fetal nasal bone length will boost the detection rate of chromosomal abnormality.

Early prenatal biochemical screening, present state, current problems and options

In Saint-Petersburg total biochemical screening for Down’s syndrome in 2-d trimester have been established since 1997. Also all pregnant women underwent ultrasound examinations for screening for chromosomal abnormalities. Results of introduction of 1-st trimester combined screening since 2006, its influence for detection rate, achievements and problems were discussed in our paper

First‐trimester screening for chromosomal abnormalities by integrated application of nuchal translucency, nasal bone, tricuspid regurgitation and ductus venosus flow combined with maternal serum free β‐hCG and PAPP‐A: a 5‐year prospective study

To investigate the performance of first-trimester screening for chromosomal abnormalities by integrated application of nuchal translucency thickness (NT), nasal bone (NB), tricuspid regurgitation (TR) and ductus venosus (DV) flow combined with maternal serum free β-human chorionic gonadotropin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at a one-stop clinic for assessment of risk (OSCAR). In total, 13,706 fetuses in 13,437 pregnancies were screened for chromosomal abnormalities during a period of 5 years. Maternal serum biochemical markers and maternal age were evaluated in combination with NT, NT + NB, NT + NB + TR, and NT + NB + TR + DV flow data in 8581, 242, 236 and 4647 fetuses, respectively. In total, 51 chromosomal abnormalities were identified in the study population, including 33 cases of trisomy 21, eight of trisomy 18, six of sex chromosome abnormality, one of triploidy and three of other unbalanced abnormalities. The detection rate and false-positive rate (FPR) for trisomy 21 were 93.8% and 4.84%, respectively, using biochemical markers and NT, and 100% and 3.4%, respectively, using biochemical markers, NT, NB, TR and DV flow. While risk assessment using combined biochemical markers and NT measurement has an acceptable screening performance, it can be improved by the integrated evaluation of secondary ultrasound markers of NB, TR and DV flow. This enhanced approach would decrease the FPR from 4.8 % to 3.4 %, leading to a lower number of unnecessary invasive diagnostic tests and subsequent complications, while maintaining the maximum level of detection rate. Pre- and post-test genetic counseling is of paramount importance in either approach.

First trimester prenatal screening among women pregnant after IVF/ICSI

Prenatal screening and diagnosis of chromosomal abnormalities especially Down's syndrome in IVF pregnancies are complicated by higher maternal age, a high multiple pregnancy rate, a high risk of a vanishing twin and an increased risk of chromosomal abnormalities, particularly in pregnancies after ICSI. The aim of the present systematic review was to evaluate the findings of first trimester screening for chromosomal abnormalities in IVF/ICSI singleton and twin pregnancies. A systematic MESH-term search in MEDLINE using PubMed and the Cochrane Library was performed until May 2011, with no earlier date limit. The electronic search retrieved 562 citations, 96 of which were evaluated in detail and 57 were then excluded for not meeting the selection criteria. A total of 61 articles were finally selected for review. Our analysis of the data shows that, for IVF/ICSI singletons, combined first trimester prenatal screening based on maternal age, nuchal translucency scan and biomarkers is appropriate. However, biomarkers seem to be altered, causing a higher false-positive rate, in IVF/ICSI singleton gestations. Correction factors have been developed and should be used when screening for Down's syndrome in singleton pregnancies. With regard to IVF/ICSI twin pregnancies, biomarker values seem to be dependent on chorionicity as well as gestational age. Whether the use of a correction factor for mode of conception in the risk calculations for Down's syndrome in twin pregnancies is valid has not been fully elucidated. In vanishing twin pregnancies with a second gestational sac with a dead fetus, first trimester screening should be based solely on the maternal age and the nuchal translucency scan as biomarkers are significantly altered in these cases. First trimester prenatal screening after IVF/ICSI treatment requires specific precautions in both singleton and twin pregnancies.

Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men

To investigate the frequency and type of both chromosomal abnormalities and Y chromosome microdeletions and analyze their association with defective spermatogenesis in Chinese infertile men. This is a single center study. Karyotyping using G-banding and screening for Y chromosome microdeletion by multiplex polymerase chain reaction(PCR)were performed in 200 controls and 1,333 infertile men, including 945 patients with non-obstructive azoospermia and 388 patients with severe oligozoospermia. Out of 1,333 infertile patients, 154(11.55%) presented chromosomal abnormalities. Of these, 139 of 945 (14.71%) were from the azoospermic and 15 of 388 (3.87%) from the severe oligozoospermic patient groups. The incidence of sex chromosomal abnormalities in men with azoospermia was 11.53% compared with 1.03% in men with severe oligozoospermia (P < 0.01). Also 144 of 1,333(10.80%) patients presented Y chromosome microdeletions. The incidence of azoospermia factor(AZF) microdeletion was 11.75% and 8.51% in patients with azoospermia and severe oligozoospermia respectively. Deletion of AZFc was the most common and deletions in AZFa or AZFab or AZFabc were found in azoospermic men. In addition, 34 patients had chromosomal abnormalities among the 144 patients with Y chromosome microdeletions. No chromosomal abnormality and microdeletion in AZF region were detected in controls. There was a high incidence (19.80%) of chromosomal abnormalities and Y chromosomal microdeletions in Chinese infertile males with azoospermia or severe oligozoospermia. These findings strongly suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.

First trimester screening for aneuploidies in successive pregnancies: correlations between markers

Screening for chromosomal abnormalities in the first trimester of pregnancy is based on maternal age, nuchal translucency (NT), and biochemical markers (pregnancy-associated plasma protein-A and free beta human chorionic gonadotrophin). We have assessed the influence of screenings and outcomes in previous pregnancies on screenings in subsequent pregnancies. Retrospective study of the correlation between the variables of first trimester combined screening for chromosome abnormalities in patients with subsequent pregnancies. Excluded were gestations with fetal aneuploidies. Between July 1999 and December 2009, there were 2291 women with more than 1 euploid pregnancy screened in the first trimester in our hospital. There was a moderate correlation for pregnancy-associated plasma protein-A (ρ = 0.530, p <0.001) and free beta human chorionic gonadotrophin (ρ = 0.439, p <0.001) between the first and second pregnancy. The trend continued in successive pregnancies. NT showed no correlations of clinical importance. With an overall false positive (FP) rate of 2.1% for the combined screening, the probability of having a recurrent FP in the second pregnancy was 4.3% (not significant). There are significant correlations between biochemical markers but not NT in successive pregnancies, leading to increased risk of recurrence of FP results. However, such increase is not statistically significant if the overall FP rate is very low.

Tele-obstetric ultrasound: analysis of first-trimester ultrasound images transmitted in realtime

We evaluated the diagnostic quality of first-trimester ultrasound images transmitted in realtime using low-cost telecommunications. A prospective sample of fetal ultrasound images from 11 weeks to 13 weeks and six days of pregnancy was obtained from pregnant women over 18 years old. The examinations were transmitted in realtime to three independent examiners who carried out a qualitative assessment based on parameters established by the Fetal Medicine Foundation. All fetal structures could be viewed and the quality of images received by the examiners was considered normal. There were significant differences for crown-rump length and nuchal translucency in the transmitted images but the loss in definition was acceptable. Thus the quality of images transmitted via the Internet through the use of low-cost software appeared suitable for screening for chromosomal abnormalities in the first trimester of pregnancy.

Fetal hydrops and anemia as signs of Down syndrome

Before the 20th week of gestation, the most common cause of nonimmune hydrops fetalis is chromosomal abnormalities. Herein, we report a case of fetal hydrops, anemia, and intrauterine growth retardation that presented at 27 weeks of gestation with a negative chromosomal abnormality screening. Cordocentesis and karyotype analysis revealed fetal pancytopenia and Down syndrome. Down syndrome rarely presents with fetal hydrops and anemia. Therefore, when hydrops and anemia are diagnosed, especially in the second trimester of gestation, the possibility of Down syndrome should be kept in mind. In addition, if the pregnancy results in a live birth, the baby should be examined for transient abnormal myelopoiesis.

First trimester prediction of small‐ and large‐for‐gestation neonates by an integrated model incorporating ultrasound parameters, biochemical indices and maternal characteristics

To identify maternal/pregnancy characteristics, first trimester ultrasound parameters and biochemical indices which are significant independent predictors of small-for-gestational age (SGA) and large-for-gestational age (LGA) neonates. Retrospective cross-sectional study. Two fetal Medicine Units. 4 702 singleton pregnancies presenting for screening for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry at 11-14 weeks. Reference ranges for birthweight applied to our population were constructed by the Royston and Wright method. Multiple logistic regression was applied to develop first trimester prediction models for SGA and LGA. Birth of SGA or LGA neonate. Maternal height, parity, smoking, assisted conception, delta crown-rump length, delta nuchal translucency, free beta human chorionic gonadotrophin and pregnancy-associated plasma protein-A were significant independent predictors of SGA. Maternal weight and height, smoking, delta crown-rump length and delta nuchal translucency were significant independent predictors of LGA. Models for SGA (AUC=0.7296, CI: 0.69-0.76, p<0.0001) and LGA (AUC=0.6901, CI: 0.65-0.72, p<0.0001) were derived, applicable to routine obstetric population at low risk for these conditions. For 20% screen positive rate the modeling achieves sensitivities of about 55% for SGA and 48% for LGA neonates. Prediction for birthweight deviations is feasible using data available at the routine 11-14 weeks' examination. Delta CRL and delta nuchal translucency were significant independent predictors for both SGA and LGA.

OC02.05: Fetal echocardiography at 11–14 weeks by experienced obstetricians in a routine population during first trimester US screening for chromosomal abnormalities

OC02.05: Fetal echocardiography at 11–14 weeks by experienced obstetricians in a routine population during first trimester US screening for chromosomal abnormalities

OP18.02: Improving the detection rate in first trimester screening for chromosomal abnormalities: using a 1 in 300 vs. a 1 in 100 risk assessment cut‐off point

OP18.02: Improving the detection rate in first trimester screening for chromosomal abnormalities: using a 1 in 300 vs. a 1 in 100 risk assessment cut‐off point

P06.07: Effect of maternal age on patient choice for first trimester screening for chromosomal abnormalities on a private Fetal Medicine Unit in Brazil

Conclusions: The new NT mixture model challenges our classical approach of quality control. LHR-based quality control process is feasible at 11–14 weeks. The approach offers a sensitive approach to the quality of NT measurement and takes into account the mixture model of distribution. It could also be applied to biochemical markers as well as to the entire combined process of first trimester screening.

Diseño de un simulador de cálculo de riesgo prenatal de anomalías cromosómicas para un programa de cribado combinado en el primer trimestre de gestación

Chromosomal abnormality screening programs require the use of computer software to calculate the prenatal risk in pregnancy. This software incorporates the different formulas and statistical parameters needed to calculate the risk in terms of probability. Here, we describe the application of a simulator for calculating the risk of chromosomal abnormalities in the first trimester of pregnancy, and the evaluation of the obtained performance by using different population statistical parameters.

Fetal cardiac evaluation at 11–14 weeks by experienced obstetricians in a low‐risk population

The aim of this study was to evaluate the detection rate of congenital heart diseases (CHD) in a low-risk population by performing cardiac evaluation during the first-trimester screening for chromosomal abnormalities. In this context, the role of four-chamber view, tricuspid regurgitation and abnormal ductus venosus flow in the screening for cardiac anomalies in a low-risk population was also investigated. The cardiac examination was performed by obstetricians with extensive experience in first- and second-trimester ultrasound (US). Follow-up US evaluations during the second and third trimesters were offered to all patients. In case of abnormal findings during routine assessment, fetal echocardiography was performed by a fetal cardiologist. Among the 4445 fetuses included in the study, 42 CHD were detected (39 diagnosed prenatally and 3 postnatally). In 27 cases, the fetal cardiologist confirmed the type of CHD diagnosed at US screening. In 1 case, the diagnosis was slightly different in the second trimester, and in 3 of the 26 correctly diagnosed in the first-trimester cases, the CHD developed and progressed in severity. A significant association of major CHD and US first-trimester markers was observed. First-trimester assessment of the fetal heart is feasible in a low-risk population when performed by experienced obstetricians. However, although most types of CHD can be diagnosed early in pregnancy, some may become apparent later in gestation.

BOOK REVIEW

Alan Cameron, Janet Brennand, Lena Crichton . Fetal Medicine for the MRCOG and Beyond, 2nd edn. 214 pages . RCOG press, London, UK, 2011. ISBN 978-1-906985-36-3. Price ∼60 €. The MRCOG and Beyond series is a collection of comprehensive guides on a range of the subspecialties in obstetrics and gynecology. Each guide gives a clear explanation of the foundations of the subject. The books are essential reading for all MRCOG trainees, but can be relevant for trainees and others elsewhere in the world. The second edition of Fetal Medicine for the MRCOG and Beyond has been updated to reflect the current clinical practice in an expanding and developing field of medicine. This updated edition provides a well-structured and easy-to-read 10 chapter overview written to assist not only MRCOG candidates for the Part Two examination, but also anyone working in fetal medicine who wants to update their knowledge at any stage in their career, including consultants, trainees and midwives. The first chapter gives a fairly comprehensive overview of the principal methods and programmes of chromosomal abnormality screening. In the second chapter, the invasive prenatal diagnostic techniques are well described, including a look into the future with the promising developments of non-invasive prenatal testing by the use of fetal cells isolated from the maternal circulation. Chapters 3 and 4 are devoted to the ultrasound examinations; the routine anomaly scan and a more detailed description of the scanning procedures for fetal structural abnormalities, including tables of risk factors and so on. The ultrasound images and photographs are generally of high quality, including the text and labelling. Chapter 5 is a well-updated chapter describing the current standards and future possibilities of invasive fetal therapy. This chapter briefly deals with complexity of decision making and ethical considerations. The later chapters of the book describe principles of fetal surveillance in intrauterine growth restriction and twin pregnancy, including Doppler evaluation of fetal blood flow patterns and laser therapy of twin–twin transfusion syndrome. I enjoyed the last part of the book, a comprehensive overview of intrauterine fetal infections, including the pitfalls of serology testing and the updated recommendations for treatment and mode of delivery of women with HIV. This book gives the reader a brief, up-to-date overview of the most fundamental areas of fetal medicine and is in no way to be regarded as an in-depth textbook covering all areas of the field. For the trainee, the book would be useful not only for the theoretical content, but also for the practical. For the specialist, the book gives an up-to-date review in the field of fetal medicine and the opportunity to discover how much he or she did not know.