How Genetic Disorders Affect Infertility

Overview of genetic disorders and infertility

  • Abnormalities in the genetics of a male, female or both can cause infertility through implantation failure or miscarriage, as well as causing birth defects in a resulting child.
  • Three kinds of genetic abnormalities can affect the embryo: defects in chromosomal makeup resulting in such conditions as Down syndrome, single gene disorders like cystic fibrosis, and genomic imprinting disorders, for example Angelman syndrome.
  • In addition, specific genetic disorders in males can cause sperm abnormalities, and genetic disorders in females can cause ovulation problems, both resulting in infertility in the individual.
  • Preimplantation genetic testing evaluates embryos created through in vitro fertilization (IVF) for genetic disorders before transfer to the uterus in order to implant only a genetically healthy embryo(s).
  • Genetic counseling is available to provide information and support to couples so they can make an informed decision on genetic testing and determine the possibility of a genetic cause for infertility.

What are genetic disorders related to infertility?

Genes, which are made up of DNA, are an essential part of heredity. Genes come in pairs, with one inherited from the male and one from the female parent. Genes are the dominant elements in DNA that determine a human’s development, function and personal attributes such as hair and eye color. A genetic disorder results when genes are not properly formed, either before birth or through mutation after birth.

According to the American College of Obstetricians and Gynecologists, genetic disorders may be caused by problems with either genes or chromosomes, the latter of which are cellular structures that carry genes and also come in pairs. Genetic disorders can affect fertility in four ways:

  • Cause individual infertility in the male or female by affecting their reproductive systems.
  • A single gene disorder inherited by an embryo can cause implantation failure or miscarriage.
  • A chromosomal abnormality in the embryo can also result in failure to implant for pregnancy or miscarriage after implantation.

Genomic imprinting causes chemical changes in DNA or related materials, which when combined with a genetic mutation can result in miscarriage or disease in a resulting child.

A child born with a single gene disorder or a chromosomal abnormality may not survive or may have developmental difficulties or birth defects, depending on the disorder. Fertility specialists try to avoid the effects of gene disorders through evaluation prior to conception and embryo preimplantation genetic testing (PGT) after conception through IVF.

Chromosome problems cause more pregnancy/infertility problems than do single gene disorders. Together, these types of disorders are the reason why miscarriage occurs in about 20% of all pregnancies.

Another type of genetic disorder called genomic imprinting arises from abnormal chemical modification of parts of the DNA (nucleotides) that make up specific genes. This can result in changed proteins or messages that may cause miscarriage or a disease in a baby.

Genetic abnormalities that cause male or female infertility

Genetic disorders in males can cause sperm abnormalities that result in infertility. These include Kleinfelter syndrome, the cystic fibrosis gene mutation affecting only males, Noonan syndrome and others.

These genetic disorders can stop production of sperm (azoospermia), result in poor motility sperm (asthenozoospermia), or cause very poor-quality sperm (teratozoospermia). Genetic mutations can also result in the absence of the vas deferens that transports sperm.

We evaluate the man’s sperm with a semen analysis. There are several treatment options for male infertility, from lifestyle changes, micro-epididymal sperm aspiration to in vitro fertilization (IVF). Donor sperm may also be needed.

Genetic abnormalities in women can cause ovulation disruption and infertility. These include fragile X syndrome, Kallmann syndrome and others. Gene disorders can also result in malformations of the reproductive system that make conception difficult or impossible. Women with a family history of problems conceiving due to endometriosis or premature menopause that can be caused by genetic issues may also have trouble conceiving.

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Genetic evaluation

For couples who have a known family history of a genetic disorder, unsuccessful IVF transfers or recurring miscarriages, we may recommend a genetic evaluation. This is also appropriate for people of certain ethnic groups or races. Less than 5% of couples inherit a genetic disease.

Though rare, they do exist and can be tested with a chromosomal analysis of the parents’ blood, called a karyotype. Depending on the results of these screenings, couples may need to use donor eggs or sperm to achieve a healthy pregnancy.

Inherited single gene diseases

Single gene abnormalities are mutations created by shifts in the DNA sequence of a gene. Properly functioning genes produce protein that allows them to work efficiently, but without protein, the gene mutations modify the functioning of the cells.

Single gene diseases can be inherited and are often suggested by a family history of a genetic disease. During conception, either natural or by assisted reproductive technologies, the mother’s egg or father’s sperm can carry a single gene mutation and the embryo produced may acquire that genetic disorder. This can cause infertility by implantation failure or miscarriage. A resulting child is more likely to have a birth defect.

We can test an embryo created through IVF for single gene disorders such as:

  • Sickle cell anemia.
  • Cystic fibrosis.
  • BRCA1 and BRCA2 mutations that increase risk of breast or ovarian cancer in a female child.
  • Huntington’s disease.
  • Fragile-X syndrome.

Embryos with one of the above genetic issues will not be chosen for implantation.

Chromosomal abnormalities that cause infertility

Chromosomal abnormalities can also cause embryos to have a low rate of implantation in the uterus and can lead to miscarriages. In the instance of an embryo with a chromosomal abnormality resulting in birth, the baby may not survive or may be born with a birth defect such as Down syndrome, Edwards syndrome, Patau syndrome or Klinefelter syndrome.

Generally, each embryonic cell has 46 chromosomes, that is, 23 from each parent. Chromosomal abnormalities can be carried by one or both of the soon-to-be-parents and then transferred on to the fetus. Among the many types of abnormalities that can develop, there are two main categories which are: numerical abnormalities and structural abnormalities.


Aneuploidy is a condition in which a person has one too few or one too many chromosomes in a normal pair. For instance, there is only one chromosome instead of a pair (monosomy), or there are three chromosomes present instead of two (trisomy). Down syndrome is the most common form of aneuploidy and is caused when abnormal cell division occurs and an extra copy of chromosome 21 is created. Thus, there are three copies instead of two. The result is trisomy 21, known as Down syndrome.

Chromosomal structural rearrangement

An example of a problem in the chromosome structure is an inversion or translocation. An inversion happens when a part of the chromosome is reversed end to end. Translocation occurs when a portion of one chromosome breaks off and attaches to another. This irregularity can disrupt implantation or lead to a miscarriage. Chromosomal inversion or translocation reduces the chances of a live birth.

We can perform genetic testing for these chromosomal abnormalities on embryos created through IVF.

Genomic imprinting

Genomic imprinting affects a gene’s expression, which is how instructions in DNA are carried out in the body, such as forming a protein that allows cells to respond to changes. Genomic imprinting doesn’t affect the DNA sequence but chemically modifies the DNA or the chromatin structure that helps DNA obtain its form. Imprinted genes are associated with neurological development and growth of the fetus and resulting child.

Research studies indicate that about 1% of the human genome is imprinted. This occurs during development of the male’s sperm and the female’s eggs. Genomic imprinting’s effects are a relatively new area of study in reproductive medicine, one that LLU Fertility Center stays abreast of.

Certain genetic factors are determined by whether the gene is inherited from the maternal chromosome or paternal chromosome. Our bodies tend to keep any one gene from maternal or paternal as active, and the other gene will become inactive due to epigenetic alterations, which are abnormal changes that take place after a gene is inherited. This aspect of genomic imprinting is normal.

However, the problem arises when a genetic mutation is present, which alters the DNA’s sequence. This is when disease can develop.

Prader-Willis syndrome is when a genomic imprinting occurs on chromosome 15 of the male. Angelman syndrome presents when the same deletion occurs on chromosome 15 of the female. Genomic imprinting can affect male fertility and can also lead to miscarriage and infertility in females, as well as other issues.

The above syndromes, as well as other genomic imprinting-associated disorders such as Beckwith-Wiedemann syndrome, can also adversely affect a child’s development.

Preimplantation genetic testing

Once embryos are produced through IVF and before implantation occurs, we can test them for a genetic disorder. Preimplantation genetic testing (PGT) screens embryos for single-gene and chromosomal abnormalities prior to transfer to the uterus during the IVF cycle.

The two main benefits offered by preimplantation genetic testing are:

  • Decreased risk of passing a genetic disease to a child.
  • Elevated chance of a successful pregnancy and birth from IVF treatment with a genetically normal embryo.

If ovulation inducing medications or hormone therapy are unsuccessful in restoring normal ovulation, a woman may be recommended to proceed with IVF. IVF involves a reproductive specialist removing a woman’s eggs directly from her ovaries, eliminating the need for ovulation altogether. The egg will be fertilized by her partner’s sperm in an IVF lab and the resulting embryo(s) will be implanted directly into her uterus.

Types of preimplantation genetic testing

PGT for aneuploidies (PGT-A), previously called preimplantation genetic screening (PGS), tests for multiple chromosome-related genetic issues in an embryo.

PGT for monogenic/single-gene disorders (PGT-M), previously called preimplantation genetic diagnosis (PGD),evaluates an embryo for a specific genetic disorder, e.g. muscular dystrophy, that the parents are suspected of carrying and may have passed to the embryo.

PGT for chromosomal structural rearrangements (PGT-SR) looks for specific inherited chromosome abnormalities in the embryo such as Robertsonian translocations.

Genetic counseling

Genetic counseling differs from genetic testing in that genetic counselors help couples determine what genetic tests are necessary and most helpful. This can be screening prior to conception or when a couple is considering PGT.

Genetic counselors are healthcare providers qualified to give couples information about genetic tests to make informed decisions. They are available to examine family histories to assist with determining a cause of infertility.

With their expertise, genetic counselors can be essential in working with providers to help answer questions and in some cases reveal the reason for infertility. Determining the genetic issue helps establish the most effective treatment, which improves the outlook to have a healthy baby.