The Reproductive Journey in the Genomic Era: From Preconception to Childhood

Abstract

It is estimated that around 10–15% of the population have problems achieving a pregnancy. Assisted reproduction techniques implemented and enforced by personalized genomic medicine have paved the way for millions of infertile patients to become parents. Nevertheless, having a baby is just the first challenge to overcome in the reproductive journey, the most important is to obtain a healthy baby free of any genetic condition that can be prevented. Prevention of congenital anomalies throughout the lifespan of the patient must be a global health priority. Congenital disorders can be defined as structural or functional anomalies that occur during intrauterine life and can be identified prenatally, at birth, or sometimes may only be detected later during childhood. It is considered a frequent group of disorders, affecting 3–6% of the population, and one of the leading causes of morbidity and mortality. Congenital anomalies can represent up to 30–50% of infant mortality in developed countries. Genetics plays a substantial role in the pathogenesis of congenital anomalies. This becomes especially important in some ethnic communities or populations where the incidence and levels of consanguinity are higher. The impact of genetic disorders during childhood is high, representing 20–30% of all infant deaths and 11.1% of pediatric hospital admissions. With these data, obtaining a precise genetic diagnosis is one of the main aspects of a preventive medicine approach in developed countries. The field of reproductive health has changed dramatically from traditional non-molecular visual microscope-based techniques (i.e., fluorescence in situ hybridization (FISH) or G-banding karyotype), to the latest molecular high-throughput techniques such as next-generation sequencing (NGS). Genome-wide technologies are applied along the different stages of the reproductive health lifecycle from preconception carrier screening and pre-implantation genetic testing, to prenatal and postnatal testing. The aim of this paper is to assess the new horizon opened by technologies such as next-generation sequencing (NGS), in new strategies, as a genomic precision diagnostic tool to understand the mechanisms underlying genetic conditions during the “reproductive journey”.

Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice

“…Allelic abnormalities in the parental gametes or de novo genetic defects produced by the conceptus may subsequently worsen through post-translational disease processes, contributing to the MPF triad’s disease burden. Future whole exome sequencing and targeted high through-put next-generation genomic technologies before and following conception will more likely determine inherited genetic risks despite negative karyotypic and microarray screens ( 37 , 38 ). Future epigenetic biomarkers such as the methylome will assess biological maladaptation with increasing gestational ages ( 39 , 40 ) as diseases or adversities present or worsen during pregnancy.…”

Current Status of Genetic Counselling for Rare Diseases in Spain

“…First of all, when a child is born with a rare disease, the roles of the whole family are turned upside down because they now need to cope with a variety of symptoms together with many social, emotional and economical challenges [ 10 , 22 ]. Secondly, the unceasing visits to a long list of specialists not only affects the whole family psychologically and emotionally but also might, in some cases, be detrimental for the diagnosis [ 23 , 24 ]. Since not all specialists work within the same team/setting, clinical information from one specialty might not be correctly (or timely) communicated to others producing a delay in the diagnosis.…”

“…Also, prenatal genetic testing (either non-invasive as a screening method or invasive as a diagnostic tool) might allow early detection of genetic abnormalities. Finally, in neonatal care, newborn screening can also reduce diagnosis time for a genetic disease allowing rapid actions to be taken [ 18 , 24 ]. Thus, as methodology and genetic information become more complex and options in the reproductive field are increasing, other professionals, such as biologists, embryologists, clinical geneticists, genetic counsellors, and clinical laboratory geneticists need also to be involved from a clinical care perspective.…”

“…Several studies demonstrate the utility of whole-exome (WES) [ 61 , 62 ] or whole-genome (WGS) [ 63 , 64 ] sequencing, as well as including other omics, such as RNA-seq or methylation profiles, increasing the diagnostic yield particularly on undiagnosed individuals with a suspected genetic condition [ 65 , 66 ]. Nevertheless, the improvement in diagnostic efficiency comes with several shortcomings, such as cost and time/analysis load [ 24 , 67 ] that are expected to be solved in the near future as technology improves in efficiency. However, it is important to recognise diagnostic limitations for each technology and it is at this point at which genetic (or genomic) counsellors provide an added value.…”

Embryo Genetics

“…The first review introduces the reproductive journey in the genomic era, from preconception to childhood, leveraging NGS as a genomic precision diagnostic tool to understand the mechanisms underlying genetic conditions, which account for 20-30% of all infant deaths and more than 50% of clinical miscarriages [3]. Genome-wide technologies are applied at different stages of the reproductive health lifecycle from preconception carrier screening and preimplantation genetic testing, to prenatal and postnatal testing.…”