Chromosomes are of interest in fertility treatment because chromosome disorders occur in more than half of all first-trimester pregnancy losses. Many of these early miscarriages are due to the random occurrence of a chromosomal abnormality in the embryo.
In general, genetic diseases caused by chromosomal abnormalities are not inherited, but usually occur as random events during the formation of sperm, eggs and embryos.
Chromosomes are string-like structures that exist in all human cells and contain all genetic material, or genes. Each human cell has approximately 30,000 genes, which are made up of sequences of DNA (deoxyribonucleic acid), the strands of molecules that give every human unique physical traits.
Most human cells contain 23 pairs of chromosomes or 46 total. These include chromosomes 1 to 22 (the autosomes) and chromosomes X and Y (the sex chromosomes). However, sperm and eggs contain only 23 single chromosomes (one from each chromosome pair).
During fertilization, each parent contributes one chromosome of each pair to the embryo, producing a normal male (46,XY) or a normal female (46,XX).
Chromosomal abnormalities – variations from the normal male or normal female structure – may be either numerical or structural. The most common type of abnormality is known as aneuploidy, an abnormal number of chromosomes due to an extra or missing chromosome.
If either the father’s sperm or the mother’s egg harbors a gene mutation, a resulting embryo might carry a genetic disorder.
Single-gene diseases are usually inherited in one of several patterns depending on the location of the gene (for example, chromosomes 1-22 or X and Y) and whether one or two normal copies of the gene are needed for normal protein activity. There are five ways single-gene diseases are inherited:
Autosomal dominant diseases occur when someone carrying one mutated copy of a gene in each cell is affected by the disease. Each affected person usually has one affected parent. These tend to occur in every generation of an affected family.
For X-linked dominant genetic diseases, females are more frequently affected than males. Fathers cannot pass X-linked traits to sons (no male-to-male transmission).
Mitochondrial means that only females can pass on mitochondrial diseases to their children (maternal inheritance). Both males and females can be affected, and mitochondrial diseases can appear in every generation of a family.
Autosomal recessive diseases mean affected individuals must carry two mutated copies of a gene. Parents of affected children are usually unaffected and each carry a single copy of the mutated gene (known as carriers). These do not typically occur in every generation.
Multifactorial genetic diseases are caused by a combination of genetic, behavioral and environmental factors. Examples of these conditions include spina bifada, diabetes, and heart disease.
While multifactorial diseases can recur in families, some mutations can be acquired throughout an individual’s lifetime such as in cancer. All genes work in the context of environment and behavior. Alterations in behavior or the environment, such as diet, exercise, exposure to toxic agents, or medications can all have influences on genetic traits.
Treatment of these diseases is currently beyond the scope of fertility medicine.