Inm-4: Genetic Aspects of Male and Female Infertility

Genetic causes can be directly responsible for various clinical conditions of male and female infertility and genetic variability may affect the ability to reproduce. This review aims to summarize current research on genetic diagnosis and genetic causes of reproductive disorders. Chromosome abnormalities account for 60% of all spontaneous abortions, and the most common type, trisomy, is closely associated with advanced maternal age. Three percent of couples have a balanced chromosome abnormality. With regard to the chromosomal alterations, the predominating anomalies are those associated with the sex chromosomes. However, a wide range of structural autosomal anomalies has been identified such as Robertsonian and reciprocal translocations, inversions, duplications and deletions, which can be associated with infertility. Single-gene defects are most likely to be found among patients with hypogonadotropic hypogonadism, which may be due to defects in the Kallmann's syndrome (KAL) genes or the gonadotrophin-releasing hormone receptor genes in women. With premature ovarian failure there is an increased risk of having a pre-mutation of the FMR1 gene. Complex genetic inheritance may explain the variable familial links in polycystic ovary syndrome and endometriosis, but no definitive genetic pathways are as yet known. With recurrent miscarriage, genetic defects causing thrombophilias are 2-fold more likely. It is known that 10-15% of cases of azoospermia and severe oligozoospermia are genetically-based, represented mostly by Klinefelter’s syndrome (KS) and by the microdeletions of the Y chromosome. The microdeletions of the AZF region, the second most common cause of male infertility, determine a severe primitive testiculopathy with consequent azoospermia or severe oligozoospermia. Lastly, mutations in single genes can be directly responsible for male infertility, such as: CFTR (cystic fibrosis), KAL, AR and INSL3-RXFP2 (associated with anomalies in the descent of the testicles, as in cryptorchidism). The high frequency of genetic alterations in infertile couples demands appropriate and correct diagnosis of these patients in order to reduce the risk of transmitting genetic anomalies to the offspring. Moreover, understanding of the methods used for genetic diagnosis and research is becoming a standard requirement for the clinical practice of reproductive medicine.