Genetic diagnostics in couples with infertility or recurrent miscarriages

Approximately 10-15% of all couples have an unfulfilled desire to have children, either due to failure to become pregnant or due to recurrent miscarriages. Detectable causes of a fertility disorder are found equally in men and women and in one third of couples both partners are involved. For 5-10% of female patients and 10-20% of male patients genetic causes can be detected with the currently established diagnostic analyses. An etiological clarification enables an informed prognosis and sometimes a specific treatment, which can indicate an increased risk for the occurrence of a fetal disease. A specific genetic clarification is therefore indicated, independent of any possibly planned reproductive medical treatment, in all couples who have been trying unsuccessfully to have a child for more than 1 year and in whom no other explanation for infertility has been identified. The genetic diagnostics of infertility usually include classical karyotyping in both partners to detect the possible presence of gonosomal or balanced structural chromosomal alterations. This is particularly indicated for both partners in the case of recurrent miscarriages. Depending on the hormonal findings, in women an attenuated congenital adrenal hypoplasia should be excluded and a premutation in the fragile X messenger ribonucleoprotein 1 gene (FMR1) should be ruled out if primary ovarian failure is suspected. The genetic diagnostics of men with azoospermia or severe oligospermia include in addition to karyotyping, testing for microdeletions in the azoospermia factor (AZF) regions as well as pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene as a possible cause of obstructive azoospermia, depending on the clinical parameters. Sequence analyses of specific genes can be considered in women and men with hypogonadotropic hypogonadism or men with a suspected monogenic disorder of spermatogenesis. According to the guidelines and national legal regulations, possible consequences as well as the significance for future children should be addressed in the context of genetic counseling before the genetic diagnostics as well as by the detection of a genetic cause of infertility.