We humans are a congregation of trillions of genes packed together in a set of 23 pairs of chromosomes within each cell. Worldwide about 48 million couples suffer from fertility issues, of these 25-30% have idiopathic causation, which is attributed to genetic etiology.
Genetic defects can be categorized as cytogenetic abnormalities, gene defects and epigenetic aberrations. These can present as numerical problems leading to syndromes such as Turner s in females, Klinefelter in males and Downs Syndrome.
Males have abnormal spermatogenesis leading to defective or low sperm count (Oligospermia) or no sperm production (Azoospermia). These may be due to Yq microdeletion or chromosomal aberrations (Inversion, translocation). These may be transmitted to male offspring, leading to fertility issues. Females with fibroids, endometriosis, premature ovarian insufficiency or failure, PCOD and Hypogonadotropic hypogonadism to name a few also have a familial predisposition suggesting a genetic basis. Some single gene mutations and sex chromosome alterations may also be having causation in the aforementioned conditions.
In females, it is polygenic and no single gene is attributed to the cause of the abnormality. Then there may be gene mutations such as CFTR to add to the list are de novo mutations, which are associated with severe male infertility.
Even though genetic causes vastly remain unexplained for a majority of patients still it is important to know about their association as this information is valuable in discussing and counselling about the prognosis of treatment, Risk of birth defects and childhood mental and developmental defects and transmission to offspring.
Because of the huge number of genes responsible for fertility, it is not possible and not relevant to test all of them. Next-generation sequencing, Karyotype analysis, Yq microdeletion and CFTR gene mutation are some of the known genetic tests.
Let me share a case history.
A young healthy couple in their early 30s, married for 1 year, came for preconception advice. On getting the baseline tests, it was revealed that the husband had azoospermia. Karyotype and Yq microdeletion from peripheral blood revealed that the husband had a numerical chromosomal abnormality that was assigned as Klinefelter Syndrome. It was a shocking revelation to them. The couple was counselled and they underwent IVF/ICSI with donor sperm and now have healthy twin babies. Apart from this they also underwent psychological and genetic counselling for acceptance of the condition and its further health implications. For another young couple, preconception investigations showed that both partners were carriers of the Thalassemia minor trait. This puts them at a 25% risk of having a Thalassemia Major baby. This is a life-threatening condition requiring blood transfusions. They were counselled to undergo IVF/ICSI followed by genetic testing of the embryos. The unaffected embryo was transferred into the womb of the mother. They had a successful pregnancy outcome after 9 months, even though the mother had to undergo extensive prenatal screening. Similarly, this is about a couple of African origins. They had their first child who had sickle cell anemia, a life-threatening condition that require bone marrow transplantation for survival. As both the parents were carriers of the trait, they underwent IVF/ICSI. Embryos formed were HLA matched with the samples collected from the first child and embryo transfer was done. This way the offspring will be able to donate a matched bone marrow for the first baby.
