Infertility, defined as the inability to conceive after a year of unprotected intercourse, affects many individuals and couples. While various factors contribute, a notable percentage of cases have a genetic basis, influencing reproductive systems and impairing fertility.
Genetic Influences on Female Fertility
Genetic variations can impact female fertility, affecting ovarian function or the development of reproductive organs. One example is Turner Syndrome, a chromosomal condition characterized by the presence of only one X chromosome (45,X0 karyotype). This chromosomal anomaly leads to primary ovarian insufficiency, where the ovaries fail to develop or function, resulting in premature menopause and infertility.
Fragile X syndrome, caused by a mutation in the FMR1 gene, also affects female fertility, especially in carriers of pre-mutations. Women with an FMR1 pre-mutation may experience premature ovarian insufficiency (POI), leading to the cessation of ovarian function before age 40. This condition disrupts the menstrual cycle and egg production, making conception difficult.
Additionally, gene mutations can affect the development of the uterus or fallopian tubes. These can lead to structural abnormalities that impede conception or pregnancy.
Genetic Influences on Male Fertility
Male infertility also stems from genetic conditions that impair sperm production or transport. Klinefelter Syndrome, a chromosomal disorder, is a genetic cause of male infertility, characterized by an extra X chromosome (47,XXY karyotype). Individuals with Klinefelter Syndrome experience hypogonadism, which results in reduced testosterone production and impaired spermatogenesis, leading to low or absent sperm counts (azoospermia or severe oligospermia).
Deletions on the Y chromosome, in Azoospermia Factor (AZF) loci (AZFa, AZFb, AZFc), are another genetic cause of male infertility. These microdeletions affect genes for sperm production, leading to defects in spermatogenesis, ranging from a complete absence of sperm to low sperm counts.
Mutations in the CFTR gene, associated with cystic fibrosis, cause congenital bilateral absence of the vas deferens (CBAVD). This condition results in the absence of the tubes that transport sperm from the testes, leading to obstructive azoospermia even when sperm production is present.
How Genetic Infertility is Inherited
Genetic infertility can be inherited through several patterns. Autosomal dominant inheritance occurs when only one copy of an altered gene is sufficient to cause a condition, meaning an affected parent has a 50% chance of passing the gene to each child.
In contrast, autosomal recessive inheritance requires two copies of an altered gene, one from each parent, for the condition to manifest; parents are carriers and may not show symptoms.
X-linked inheritance involves genes located on the X chromosome. These conditions affect males more severely because they have only one X chromosome, while females have two.
Beyond inherited traits, de novo mutations also contribute to genetic infertility. These are new genetic changes occurring spontaneously in an individual’s DNA.
Identifying Genetic Causes of Infertility
Identifying the genetic causes of infertility involves diagnostic tests. Karyotyping analyzes the number and structure of chromosomes, helping to detect abnormalities such as Turner Syndrome (45,X0) or Klinefelter Syndrome (47,XXY). This test provides a visual map of an individual’s chromosomal makeup.
For men, Y-chromosome microdeletion testing identifies deletions in the AZF regions that impair sperm production. For women with suspected premature ovarian insufficiency, FMR1 gene testing identifies pre-mutations associated with Fragile X syndrome.
CFTR gene mutation analysis is performed for individuals with congenital bilateral absence of the vas deferens or a family history of cystic fibrosis. Genetic counseling helps determine which tests are appropriate based on clinical presentation and family history.
Navigating Infertility with Genetic Factors
When a genetic cause of infertility is identified, individuals and couples can explore various strategies and reproductive options. Genetic counseling becomes an important resource, providing detailed information about the specific genetic condition, its inheritance pattern, and risks for future offspring. Counselors can explain complex genetic concepts and help families understand the implications of their genetic findings.
Assisted reproductive technologies (ART) offer pathways for conception while addressing genetic concerns. Preimplantation genetic testing (PGT) is a specialized ART procedure that can be particularly relevant. PGT for aneuploidy (PGT-A) screens embryos for chromosomal abnormalities before implantation, helping to select embryos with the correct number of chromosomes. PGT for monogenic disorders (PGT-M) is used when a specific gene mutation is present in the parents, allowing for the selection of embryos unaffected by that genetic condition. These technologies provide options for individuals to reduce the risk of passing on genetic factors to their children.