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".

Keywords: genetic testing; next-generation sequencing; perinatal care; reproductive health; whole exome sequencing.

Figure 1

Reproductive journey vs. reproductive roulette: Genetic analysis can be implemented at any stage of the reproductive journey, starting from preconception to detect genetic carriers of frequent diseases, pre-implantation to ensure chromosomal and genetically normal embryos, prenatal diagnosis and lastly, for newborn screening of common and actionable diseases. The reproductive roulette is a term that aims to explain the unknown risk of having any form of genetic disease given the risk factors of the parents or purely by chance. The possibility of reducing this probability can be done by an adequate and directed genetic analysis or screening approaches.

Figure 1

Reproductive journey vs. reproductive roulette: Genetic analysis can be implemented at any stage of the reproductive journey, starting from preconception to detect genetic carriers of frequent diseases, pre-implantation to ensure chromosomal and genetically normal embryos, prenatal diagnosis and lastly, for newborn screening of common and actionable diseases. The reproductive roulette is a term that aims to explain the unknown risk of having any form of genetic disease given the risk factors of the parents or purely by chance. The possibility of reducing this probability can be done by an adequate and directed genetic analysis or screening approaches.

Figure 2

Classic genetic diagnostic (a) vs. Genomic diagnostic (b) flow-charts: Genomic Precision Diagnostic is an innovative approach that ultimately not only provides a precise diagnosis of a genetic alteration at every stage of the reproductive journey, it also alleviates the healthcare burden of a patient that has to go from specialist to specialist, increasing the degree of uncertainty and preoccupation. This can decrease the economic cost, psychological deterioration of the patient and the healthcare provider, and all in all, simplify the diagnosis for a more directed treatment and patient care, allowing the patient to be the center of the diagnostic axis.

Figure 2

Classic genetic diagnostic (a) vs. Genomic diagnostic (b) flow-charts: Genomic Precision Diagnostic is an innovative approach that ultimately not only provides a precise diagnosis of a genetic alteration at every stage of the reproductive journey, it also alleviates the healthcare burden of a patient that has to go from specialist to specialist, increasing the degree of uncertainty and preoccupation. This can decrease the economic cost, psychological deterioration of the patient and the healthcare provider, and all in all, simplify the diagnosis for a more directed treatment and patient care, allowing the patient to be the center of the diagnostic axis.

Figure 3

Closing the circle of the Reproductive Journey: Impact of the genomic diagnostic (dark blue) and screening (light blue) application along the different stages of the reproductive journey. Blue-gray arrows show new “access ways” to the reproductive journey driven by a precise diagnostic.