The critical and expanding role of genetics in assisted reproduction

Abstract

With the progress of the human gene mapping initiative, it is expected that the entire genome will be mapped within two years. A significant use for these data will centre on testing for genetic disease. Professionals associated with assisted reproduction are presented with a very special subset of the population, namely, couples suffering from infertility. Infertility may occur in the male, the female or both partners and may be heritable. Infertility, subfertility or recurrent spontaneous miscarriage is associated with chromosomal or genetic anomalies, suggesting that basic developmental genetics should be a part of the education of the physician or clinical embryologist. A review of the most common infertility‐associated chromosomal and genetic diseases for which genetic testing has become routine in infertile parents and in the products of assisted reproduction through preimplantation genetic diagnosis (PGD) and prenatal testing follows. Less common genetic diseases that have compromising effects on reproduction and which are likely to be encountered by providers of assisted reproduction are also considered. Copyright © 2000 John Wiley & Sons, Ltd.

The Y Chromosome and Its Role in Testis Differentiation and Spermatogenesis

“…Most XX males are positive for SRY, although a few with probable mutations in regulators of the testis-determining pathway are SRY negative. 50 The euchromatin consists of approximately 59 megabases (Mb) of genetic information, but the majority of the Y chromosome is composed of heterochromatin (deletion interval 7). 51,52 Therefore, normally fertile males can exhibit a minute Y chromosome completely devoid of heterochromatin as long as the euchromatin (deletion intervals 1-6) is intact.…”

“…The correlation of azoospermia and cytological Yq deletions prompted several groups to focus on defining AZF. [50][51][52] These efforts have largely been centered around two methodologies: (1) producing deletion maps by testing phenotype-selected infertile men employing various panels of Y-linked sequence tagged site (STS) and (2) sequencing or mapping efforts involving cloning deletion breakpoints, exon trapping, chromosome "walking," and optical mapping. To date, more than 6000 patients have been tested for the presence of from 1 to 150 loci using Y-linked STS.…”

“…Functional regions are diagramed in the context of (1) the single-copy and/or testis-specific genes and (2) genes that are ubiquitously expressed and/or are copied on the Y or X chromosomes. 50,99 in terms of function related to gametogenesis as it applies to the patient seeking assisted reproduction and to the products of assisted reproduction.…”

CRISPR/Cas9 genome editing in human pluripotent stem cells: Harnessing human genetics in a dish

“…Preimplantation genetic diagnosis (PGD) is commonly used in fertility treatments to detect chromosomal abnormalities and disease‐associated mutations in IVF‐derived blastocysts (Kent‐First, ). The generation of genetically abnormal hESC lines from this therapeutically discarded pool of embryos represents an opportunity to model a number of inherited disorders.…”

Genetic testing experience of a private fertility clinic

“…In several studies involving a total of more than 5000 infertile males, 12 -27% of azoospermic males had a chromosomal defect, whereas, in oligospermic males, a chromosomal defect was observed in 2 -9% of affected males [2,5,6,8]. Though less attention has been paid to the female partner of couples seeking ICSI, up to half of the total anomalies are of maternal origin and will be found in 3-7% of the total [3,6,8].…”