Contents
Genetic causes of female infertility
About 5-8% of women of reproductive age suffer from infertility.
Karyotype abnormalities (chromosomal aberrations)
Chromosomal aberrations – these are changes in the number and/or structure of chromosomes. Chromosomal abnormalities in women, leading to reproductive disorders, can affect both sex chromosomes (gonosomal) and autosomes. These disorders can be regular (detected in all cells of the body) or mosaic (characterize a specific clone of cells). Often, chromosomal aberrations are detected only in oocytes. Even in healthy women with a normal karyotype, up to 20% of oocytes may have chromosomal abnormalities, most of which are structural rearrangements.
Gonosomal chromosomal abnormalities
include an increase in the number of X chromosomes (triple-X syndrome, 47,XXX; other poly-X aneuploidies 48, XXXX, etc.); reduction in the number of X chromosomes (Shereshevsky-Turner syndrome, 45,X0); X-autosomal translocations; gonadal dysgenesis with a clone of cells bearing the Y chromosome (mixed gonadal dysgenesis, 45,X0/46,XY; Swyer’s syndrome, gonadal dysgenesis with karyotype 46,XY; true hermaphroditism with a clone of cells bearing the Y chromosome; structural abnormalities of the X chromosomes (macro- and micro-deletions, inversions, translocations, ring chromosomes, isochromosomes).
Autosomal chromosomal abnormalities
include changes in the number and structure of non-sex chromosomes – inversions; translocations (Robertsonian, reciprocal); other structural abnormalities; partial deletions and duplications; trisomy (for example, Down syndrome).
Chromosomal heteromorphisms
Some common karyotype variants in the population (chromosomal heteromorphisms ) may be a risk factor for recurrent miscarriage (inversion of chromosome 9, Inv (9); increased/decreased pericentromeric constitutive heterochromatin; increased duplicated satellites of acrocentric chromosomes).
The increase in the number of chromosomal aberrations in oocytes increases with a woman’s age, especially after 35 years.
In couples with recurrent miscarriage, the frequency of chromosomal abnormalities in women is about 8%. In the case of spontaneous abortions, the frequency of chromosomal abnormalities in women is 3,5%; if spontaneous abortions are combined with stillbirths or congenital malformations, the incidence of karyotype abnormalities in women is 16,5%.
Gene mutations
Normal development and maintenance of reproductive function in women is controlled by about 2000 genes. Mutations in these genes can lead to diseases in which decreased fertility may be the main symptom or part of a broader symptom complex.
X-linked diseases:
- Fragile X syndrome (FRAXA)
- Kallmann syndrome
- Testicular feminization, full form
Autosomal diseases:
- Mutations in the gene encoding the FSH b-subunit and the genes encoding receptors for LH and FSH
- GnRH receptor insensitivity
- BPES syndrome (blepharophimosis, ptosis, inverted epicanthus)
- Denis-Dresch syndrome
- Frezier syndrome
- Cystic fibrosis
- Myotonic dystrophy
- Mucopolysaccharidoses (Mucopotysaccaridoses)
- Prader-Willi syndrome
- Insufficiency of steroidogenesis enzyme activity