A prospective study of the clinical utility of prenatal chromosomal microarray analysis in fetuses with ultrasound abnormalities and an exploration of a framework for reporting unclassified variants and risk factors.

PURPOSE: To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound. METHODS: Patients referred for prenatal diagnosis due to ultrasound anomalies underwent analysis by array comparative genomic hybridization as the first-tier diagnostic test. RESULTS: A total of 383 prenatal samples underwent analysis by array comparative genomic hybridization. Array analysis revealed causal imbalances in a total of 9.6% of patients (n = 37). Submicroscopic copy-number variations were detected in 2.6% of patients (n = 10/37), and arrays added valuable information over conventional karyotyping in 3.9% of patients (n = 15/37). We highlight a novel advantage of arrays; a 500-kb paternal insertional translocation is the likely driver of a de novo unbalanced translocation, thus improving recurrence risk calculation in this family. Variants of uncertain significance were revealed in 1.6% of patients (n = 6/383). CONCLUSION: We demonstrate the added value of chromosomal microarrays for prenatal diagnosis in the presence of ultrasound anomalies. We advocate reporting back only copy-number variations with known pathogenic significance. Although this approach might be considered opposite to the ideal of full reproductive autonomy of the parents, we argue why providing all information to parents may result in a false sense of autonomy.

First trimester screening for Down's syndrome after assisted reproductive technology: non-male factor infertility is associated with elevated free beta-human chorionic gonadotropin levels at 10-14 weeks of gestation.

We retrospectively compared the first trimester Down's syndrome serum screening markers free beta-hCG (fbetahCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11-14 weeks of gestation in 4,088 women with naturally conceived pregnancies and in women pregnant after ICSI (n = 163), IVF (n = 59) and frozen-thawed embryo transfer (n = 31), and we searched for a potential relationship between infertility cause and marker levels. We found lower serum PAPP-A levels in pregnancies after IVF and ICSI compared with spontaneously conceived pregnancies and non-male factor infertility was associated with elevated serum fbetahCG levels at 11-14 weeks of gestation.

Prenatal diagnosis of absent pulmonary valve syndrome in association with 22q11 deletion.

OBJECTIVE: To describe the prenatal sonographic appearances in cases of absent pulmonary valve syndrome and the importance of investigating the presence of 22q11 deletion. METHODS: We describe 2 cases, which were referred because of a suspicion of a cardiac malformation. In both cases, a large anechoic mass emerging from the right ventricle was visualized and identified as an aneurysmal dilatation of the pulmonary trunk with hypertrophy of the right ventricle. The diagnosis of tetralogy of Fallot with absent pulmonary valve syndrome and a secondary diverticular dilatation of the pulmonary artery was made. A review of the literature revealed another 18 cases of prenatal diagnosis of absent pulmonary valve syndrome with or without knowledge of chromosomal abnormalities. RESULTS: Pathologic examinations confirmed the diagnosis of absent pulmonary valve syndrome in both cases. Final results of fetal karyotyping revealed a 22q11 deletion in the first case. CONCLUSIONS: An abnormal 4-chamber view with an aneurysmal dilatation of the pulmonary trunk should suggest the diagnosis of this rare congenital anomaly. Perinatal death occurs in more than 60% of cases and is usually associated with hydrops fetalis, the presence of other malformations, or both. Even in the absence of extracardiac malformations, investigation for 22q11 deletion in cases of conotruncal cardiac abnormalities is recommended.