A lot of couples cannot have children. So, it is calculated that more than 48 million couples in the world are infertile. The mother’s age in the first gestation is important, but many times it is due by a genetic problem. Infertility is a clear example of complex disease with genetics base. The following is an explanation of genetic base of infertility in men and women.
INFERTILITY OR STERILITY?
You can think that infertility and sterility are synonymous, but they do not mean the same (Figure 1). However, infertility is the Anglo-Saxon word and the most used.
According to WHO, sterility is the difficulty getting a pregnancy after 1 year of frequent sexual relations near ovulation’s day and without protection. There are primary sterility and secondary sterility.
We talk to primary sterility when a woman is unable to become pregnant, while secondary sterility is when a woman in unable to become pregnant after having pregnancy history.
Infertility is when there is fecundation, but there are not implantation or an abort. There are primary infertility and secondary infertility too.
When a woman is unable to ever bear a child, due to the inability to carry a pregnancy to a live birth she would be classified as having primary infertility. However, when a woman is unable to carry a pregnancy to a live birth following either a previous pregnancy or a previous ability to carry a pregnancy to a live birth, she would be classified as having secondary infertility. Thus, women will suffer repetitive spontaneous miscarriages.
SOME INTERESTING FACTS
It is important to know that suffer a spontaneous aborts is normal in the reproductive history of a woman. It is estimated that 7 of 10 girls will suffer an abort during the first trimester.
Human species has not a high reproductive power, it is considered 25% the possibility of pregnancy in a sexual relation during the woman’s ovulation.
In addition, reproductive potential decreases when women are 35 years old. It is known that as of this age the reproductive potential drops and that after 40 years of age the possibility of pregnancy per month is less than 10%.
Approximately 1 of 6 couples in childbearing age is affected by sterility. This number represents 15-17% population.
GENETIC BASE OF MALE INFERTILITY
In men, up to 30% of infertility is associated with a direct genetic cause. A 50% of cases is indirect cause because the man is not just infertile, but he has other alterations and for this reason it is not classified like genetic anomaly. The remaining 20% has idiopathic origin, it means that is unknown cause (Figure 2).
There are three types of genetics causes:
PRE-TESTICULAR GENETIC CAUSES
These causes are associated before and during testicles developing:
- Alterations in testosterone synthesis.
- Alterations of the receptors of the hormones LH and FSH.
- Androgenic resistance syndromes: there is testicular feminization, it means the karyotype is masculine (46, XY), but the phenotype is feminine.
- Hypogonadism: testosterone deficiency with signs or symptoms associated, deficiency in sperm production or both. It could be because testicles are not functional or the affectation of hypothalamic-pituitary axis.
TESTICULAR GENETIC CAUSES
- Chromosomopathies: chromosomal abnormalities such as aneuploidies (abnormal number of chromosomes), chromosomal translocations (rearrangement of parts between nonhomologous chromosomes), inversions (a segment of a chromosome is reversed end to end) or trisomies.
- Meiotic abnormalities: abnormalities in germline .
- Microdeletions Yq: deletions of Y chromosome.
- Monogenic alterations: affecting a single gene.
- Gonadal dysgenesis: disorder of sexual development associated with anomalies in gonadal development, however having a male karyotype (46, XY), the external and internal genitalia are female.
POST-TESTICULAR GENETIC CAUSES
- Agenesis of vas deferens: absence of vas deferens, characteristic in cystic fibrosis.
- Sperm alterations.
- Autosomal dominant polycystic kidney: inherited disorder in which cysts form in the liver, pancreas and testes.
GENETIC BASE OF FEMALE INFERTILITY
Gene regulation of the formation and development of female sex cells (oogenesis) and ovarian follicle (folliculogenesis) is unmanageable and, in many cases, it is impossible to tell what the cause of infertility is.
Oocytes (female sex cells) need a suitable environment to grow and develop. The ovarian follicles surround the oocytes to provide them with this environment.
Even so, more or less we move with the same numbers as in men (Figure 2). 30% is for direct cause, where the genetic abnormality is known; 50% is due to indirect causes such as problems in the formation of hormones, and up to 20% for unknown reasons.
The genetic causes are divided into:
- Hypothalamic – pituitary axis
GENETIC CAUSES RELATED TO HYPOTHALAMIC-PITUITARY AXIS
Endocrine system is formed by a series of glands that release the hormones. In this system, hypothalamic-pituitary axis is very important (Figure 3).
The pituitary gland is a small gland less than 1cm in diameter. This gland is attached to the hypothalamus, which controls almost all of its secretion. The hypothalamus is at the base of the brain and is the receiving center for signals from many areas of the brain, as well as internal organs, so that painful or stressful emotional experiences cause changes in your attitude. Likewise, the hypothalamus controls the autonomic nervous system and regulates body temperature, hunger, thirst, sexual behavior and defensive reactions, such as fear or rage.
The hypothalamic-pituitary axis regulates virtually all aspects of the body’s growth, development, metabolism and homeostasis.
The genetic causes of infertility related to this axis may have:
- Hypothalamic origin: problems with the development of the gonads.
- Hypophyseal origin: hormones.
OVARIAN GENETIC CAUSES
They are related to the ovaries and follicles. Chromosomal abnormalities are very important, especially those affecting the X chromosome.
UTERINE GENETIC CAUSES
They are related to the development of the endometrium, implantation of the embryo … The affectation of these phenomena implies infertility.
- Foresta, C. et al. (2002). Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet; 10:303-312
- Hwang, K. et al.(2010). Mendelian genetics of male infertility. Ann N Y Acad Sci; 1214: E1-E17
- World Health Organization
- Reproducción Asistida ORG
- El Mundo
- Main picture: Mujer Bien