Genetic Diseases

All healthy humans are born with 46 chromosomes that are part of every cell in the body. Chromosomes are divided into 22 matching pairs and one pair of sex chromosomes. These cell structures each carry the genetic material, or DNA, that makes every individual unique. 

You receive genes from both of your biological parents; half from your mother and half from your father. The genes determine which features you inherit, such as hair and eye colour, blood type, and other characteristics – like your father’s nose or your mother’s mouth. 

You also inherit, via genes, the risk of developing certain diseases. For example, haemophilia and Tay-Sachs disease are inherited diseases that can be passed on from parents to children. These diseases are due to defects in the chromosomes. Genetic problems with the embryo or fetus are responsible for a high percentage of pregnancy losses before 12 weeks.

The genetic causes of infertility are varied and include chromosomal abnormalities, single gene disorders and phenotypes with multifactorial inheritance. Some genetic factors influence males specifically, whereas others affect both males and females. For example, chromosome translocations affect both males and females, whereas Klinefelter syndrome and the subsequent infertility phenotype caused by it are specific to males.

Genetic diseases can generally be separated into two categories: inherited diseases and chromosomal abnormalities. Single-gene abnormalities cause serious issues with cell development and lead to fundamental problems with fertility. More common are chromosomal abnormalities, which involve random mutations and make it difficult to carry a child to term. 

Chromosome abnormalities

Chromosomally abnormal embryos have a low rate of implantation in the mother’s uterus, often leading to miscarriages. If an abnormal embryo does implant, the pregnancy may still result in miscarriage or the birth of a baby with physical problems, developmental delay, or mental retardation.

There are several kinds of chromosome abnormalities:

  • A missing piece of a chromosome (deletion)
  • An upside-down chromosome (inversion)
  • A change in the gene’s DNA sequence (mutation)
  • Too many or too few chromosomes (aneuploidy)
  • Chromosome pieces attached to the wrong chromosome (translocation)

Chromosome abnormalities occur when a chromosome, the carrier for genetic information that resides in the nucleus of the cell, is malformed or mutated. These abnormalities include missing or upside-down pieces of chromosomes, too few or too many chromosomes, pieces of chromosomes located in the wrong place, or DNA sequence changes. One of the most common abnormalities involves chromosome pieces that have been improperly attached, known as translocation. These chromosomal abnormalities are frequently caused by advanced maternal age in ways that are not entirely clear to scientists; Down syndrome is a common example of abnormal chromosome formation, involving an extra chromosome 21.  Oligospermia, a condition causing reduced sperm concentration in semen, has been linked to increased likelihood for Y chromosome microdeletions and other abnormalities. Another disorder that affects chromosome formation is non-obstructive azoospermia, a disorder that causes no sperm to be present in ejaculate. 

Inherited genetic diseases

More rare is the existence of an inherited genetic disease due to abnormal genes or mutations. Single-gene abnormalities are mutations caused by changes in the DNA sequence of a gene, which produce proteins that allow cells to work properly. Gene mutations alter the functioning of cells due to a lack of a protein. These rare genetic diseases include Tay Sachs, which causes fatty build-ups in tissues and nerve cells in the brain, or cystic fibrosis, which affects the mucous glands of vital organs. Carriers of these single-gene abnormalities may not have health issues themselves, but may be unable to conceive. 

Some of the more common genetic causes may include: 

  • A parental chromosome abnormality (such as Klinefelter syndrome, Turner syndrome, Y chromosome deletion or a structural rearrangement in chromosome material called a chromosome translocation) 
  • A parental genetic condition (such as cystic fibrosis, Fragile X syndrome, galactosaemia and sickle cell anaemia) 

Genetic Causes of Miscarriage

Fertile couples who experience repeated miscarriages should be evaluated for the presence of a chromosomal abnormality. The female or male partner may be a carrier of a balanced translocation or may be an aneuploid mosaic. Aneuploidy refers to an abnormal number of chromosomes. An extra or missing chromosome is a common cause of genetic birth defects. Aneuploidy occurs during cell division when the chromosomes do not separate properly between the two cells. Chromosome abnormalities occur in 1 of 160 live births, the most common being extra chromosomes 21 (Down Syndrome), 18 (Edwards Syndrome) and 13 (Patau Syndrome).

Chromosome abnormalities include aneuploidy and structural abnormalities. Aneuploidy is the most common chromosomal abnormality and it occurs in both eggs and sperm. Structural abnormalities in both eggs and sperm include translocations, inversions, and deletions. The transmission of a chromosome abnormality to an embryo can result in a low implantation rate, miscarriage, or the birth of a baby with a genetic disorder.


Aneuploidy and Advanced Maternal Age


Women 35 and older are at a higher risk of producing aneuploid embryos, which results in implantation failure, a higher risk of miscarriage or the birth of a child with a chromosome abnormality such as Down syndrome.

All of a woman’s eggs are present at birth. Over time, the chromosomes within the egg are less likely to divide properly, resulting in cells with too many or too few chromosomes. Aneuploidy is also believed to be a major reason for the decrease of fertility with age. 

Male Factor Infertility


Approximately one-half of all infertility is caused by sperm abnormalities. Many sperm disorders are due to a chromosome abnormality such as aneuploidy or a structural chromosome abnormality. Men who carry a balanced translocation chromosome are at risk of producing sperm with a structural chromosome abnormality. Couples with infertility due to male factor should consider chromosome analysis of the male’s sperm prior to IVF.


Y Chromosome Deletions and Infertility


Y chromosome deletions are found in approximately 5 to 20 percent of males with a very low sperm count. These deletions appear to impair normal sperm development. While these deletions do not appear to cause any genetic disease, they appear to decrease the chance of men with a low sperm count to successfully fertilise eggs in a normal way.

Genetic diseases, most of which are either directly or indirectly associated with sperm abnormalities:

  • Cystic fibrosis. An inherited condition that typically involves the lungs and pancreas, but that can present also as a cause of infertility with or without mild sinus problems. Most men who have cystic fibrosis have obstructive azoospermia, because they were born without a vas deferens. This results in male infertility. 
  • Noonan syndrome. An inherited condition that can occur in either males or females. In males, this syndrome can cause abnormal gonadal (testicular) function.
  • Myotonic dystrophy. An inherited condition with progressive multisystem involvement, resulting in infertility (underdeveloped testes and abnormal sperm production) in some cases.
  • Hemochromatosis. An inherited condition affecting iron storage. Eighty percent of men with hemochromatosis have testicular dysfunction.
  • Sickle cell disease. An inherited condition affecting the normal production of haemoglobin.
  • Sex reversal syndrome. A male who has the sex chromosomes of a genetic female (XX, instead of XY), resulting in azoospermia and other characteristics.
  • Androgen receptor gene mutations. An inherited condition in which a man is genetically male (46,XY), but has infertility due to a defect in receptors for testosterone.
  • Chromosomal abnormalities. Men with an extra X sex chromosome, known as Klinefelter syndrome, often do not produce sperm or produce very low quantities of sperm.
  • Chromosome rearrangements. In some persons, there are the usual number of chromosomes (46) in the nucleus (centre) of cells, but rearrangements in the chromosome material, where a piece of a chromosome has exchanged places with another, has taken place. Men with either azoospermia or oligospermia have a higher frequency of chromosome rearrangements than is found in the general population.
  • Deletions in the Y chromosome. In some persons, there are the usual number of chromosomes (46) in the body cells, but small sections of the Y chromosome are missing or deleted. A small percentage of men with either azoospermia or oligospermia have deletions in the Y chromosome.

It is important to understand that men who have genetic problems that cause their infertility, such as a deletion in the Y chromosome, can pass this problem to their sons, who would also have infertility, if they elect to use their own sperm in achieving a pregnancy.

Preimplantation Genetic Diagnosis (PGD)

PGD is a screening process that enables us to test the embryos of a couple who carry a known genetic marker for a specific inherited disorder so that only healthy embryos are selected to be replaced/transferred to the woman’s uterus in order to attempt to achieve a pregnancy.

PGD testing has been a common practice for more than 20 years and is very successful in detecting genetic alterations in the embryos of couples known to be at risk of passing on an inherited disease to their children. Amongst infertile couples, PGD testing enables the identification of chromosomally normal embryos for transfer which improves IVF pregnancy rates. PGD is of great benefit to women with a history of miscarriage, failed IVF cycles and in those of an older maternal age. 

Previously, couples carrying the risk for transmitting genetic disorders were only able to diagnose the health of their unborn child after conception had occurred by amniocentesis. Subsequently, if the pregnancy is affected with the abnormality, couples are faced with the dilemma of having to decide whether they would terminate or continue with the pregnancy. For couples who carry the known risk for a serious inherited disorder, PGD offers an alternative to prenatal testing and pregnancy termination by screening embryos (fertilised eggs) before pregnancy is established.

PGD is performed using a high-powered microscope.  One or more cells are removed from the embryo and tested for the genetic trait of interest. The unaffected embryos are identified, separated from the affected embryos, and transferred into the uterus.  

Some of the single gene disorders indentified using PGD include: 

  • Cystic Fibrosis
  • Haemophilia
  • Huntington’s Disease
  • Marfan’s Disease
  • Muscular Dystrophy
  • Thalassemia
  • Tay Sachs
  • Spinal Muscular Atrophy
  • Sickle Cell Anaemia

Genetic Counselling

Genetic diseases are a complex topic, and the information here is meant only as an overview of the topic. If you and your partner believe you may be prone to genetic risks as parents, further research is warranted, as is the possibility of genetic counselling.

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