Infertility ranks as the third major disease faced by humans, following tumors and cardiovascular diseases, affecting about 10% to 15% of couples of childbearing age. Besides common causes such as anatomical abnormalities, endocrine disorders, immune factors, infections, systemic diseases, and environmental factors, genetic issues also play a significant role in infertility. Common chromosomal diseases, monogenic diseases, and polygenic diseases are closely related to infertility.

Chromosomal Abnormalities

Chromosomal abnormalities are significant causes of recurrent miscarriages, intellectual disabilities in children, congenital deformities, growth retardation, and primary infertility. Spontaneous miscarriages, common in gynecology, are associated with chromosomal abnormalities in 50% to 60% of cases. Lethal chromosomal abnormalities are a primary cause of natural miscarriages and fetal defects, manifested by numerical or structural anomalies on one or more chromosomes. Over 80% of these abnormalities are numerical, and more than 5% are structural. With an increase in miscarriage incidents, the probability of chromosomal abnormalities rises, emphasizing the importance of genetic screening before pregnancy to guide further pregnancies. The older the parents, the higher the risk of birth defects in offspring. Thus, genetic screening, diagnosis, and counseling in reproductive and gynecological fields are crucial for preventing birth defects and hold significant social relevance.

Genetic Diseases Related to Fertility

Common genetic diseases related to fertility include chromosomal disorders, gene diseases (monogenic, polygenic, and mitochondrial diseases).

  1. Chromosomal Diseases

Diseases caused by numerical or structural chromosomal abnormalities are known as chromosomal diseases. Currently, over 3,000 chromosomal diseases have been reported, with more than 100 classified as common genetic diseases. Chromosomal abnormalities account for 50% to 60% of miscarriages, with a newborn chromosomal abnormality rate of 0.5% to 0.7%. The most common chromosomal disease is Trisomy 21, also known as Down syndrome, a leading cause of severe congenital intellectual disabilities. Other notable examples include Trisomy 18, Trisomy 13, and Fragile X Syndrome.

Chromosomal nondisjunction during meiosis leads to abnormal chromosomal numbers in reproductive cells, developing into monosomy or trisomy. Nondisjunction at the earliest stages of embryonic formation can result in monosomy and trisomy, while partial cell division during embryogenesis often leads to mosaicism. Chromosomal number abnormalities are significant causes of miscarriage or stillbirth. Nondisjunction of sex chromosomes results in structural and functional abnormalities of the reproductive system, leading to infertility. Abnormalities in the number of sex chromosomes (X and Y) are among the primary reasons for infertility today.

  1. Monogenic Diseases

Chromosomes serve as carriers of genetic material. Genetic diseases caused by mutations in a single gene or a pair of alleles on homologous chromosomes follow Mendelian inheritance patterns (laws of segregation, independent assortment, and recombination), thus referred to as Mendelian genetic diseases. Most known genetic diseases are monogenic, such as hemophilia, color blindness, and phenylketonuria. These diseases are categorized based on the chromosomal location and expression pattern of the pathogenic gene into autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and Y-linked genetic diseases.

  • Autosomal Dominant Diseases The pathogenic gene is located on an autosome and exhibits dominant inheritance. A mutation in any allele leads to the disease, with a 1/2 probability of transmission to offspring. Common diseases include osteogenesis imperfecta and retinoblastoma.
  • Autosomal Recessive Diseases The pathogenic gene is located on an autosome and exhibits recessive inheritance. Disease manifests in homozygous allelic states. If both parents carry the gene mutation, there is a 1/4 chance of disease in children, a 1/2 chance of carrying the gene without showing symptoms, and a 1/4 chance of being completely normal. Common diseases include albinism and phenylketonuria.
  • X-Linked Dominant Diseases The pathogenic gene is located on the X chromosome and exhibits dominant inheritance. Disease manifests if carried by either parent. If the parent carries the gene, all daughters or half the sons will inherit the disease. Common examples include Vitamin D-resistant rickets.
  • X-Linked Recessive Diseases The pathogenic gene is located on the X chromosome and exhibits recessive inheritance. Males carrying the gene will manifest the disease, and females will be carriers. Common examples include color blindness.
  • Y-Linked Diseases The pathogenic gene is located on the Y chromosome. If the father has the disease, all male offspring will inherit it, while female offspring will be unaffected. A common example is ear hair.

Additionally, even if parents carry normal genes, new pathogenic mutations on autosomes and sex chromosomes during gamete formation, known as De Novo mutations, can cause diseases in offspring and continue to be passed down. The probability of disease can be estimated based on the characteristics of the pathogenic mutations following Mendelian inheritance patterns, providing valuable information for genetic counseling.