Reasons for Genetic Infertility and how to know at the earliest stage?

Dr. Indira Ganeshan

Genetic infertility means that there is some defect at the level of genes it may be abnormal genes, abnormalities in chromosomes, mutations and are heritable in nature.

There is something called epigenetic which means the changes are caused by modification of gene expression rather than alteration of the genetic code itself, it refers to external modifications to DNA that turns genes “on” or “off”, and it affects how the cells “read” genes.

What are Chromosomal Abnormalities?

· Deletion: a piece of chromosome is missing

· Inversion: the chromosome is upside down in this

· Mutation: some change in the gene’s DNA sequence

· Aneuploidy: change in number of chromosomes(extra or less)

· Translocation: piece of chromosome separated from its origin and attached to some other chromosome

Inherited Genetic Diseases

This occurs in less than 5% of couples, because of mutations or abnormal genes. This usually runs in the family and there is a clear family history. These are usually single gene abnormalities caused by the changes in the DNA sequence of a gene, and this causes alteration in the cellular function.

Cystic fibrosis, Tay Sachs is few examples of single gene disorder. Unlike inherited genetic diseases there is clear cut family history in the chromosomal abnormalities like translocation the parents are apparently normal and extra chromosome or less chromosome is transferred to embryos and thus increasing the chance of low implantation or miscarriage rate.

How can we diagnose these at the earliest??

If a couple is facing difficulty in conception, then a visit to the gynecologists ,who will take a detail history and some of the familial abnormalities will be discovered, once its discovered or if there is a strong suspicion then patient may benefit through IVF and followed by PGD/CHG

PGD-pre implantation genetic diagnosis, in this the couple goes through regular IVF and once the embryo is formed one cell from the embryo is taken out and is subjected to analysis and the defective embryos are identified and only healthy/ disease free embryos are transferred into the women.

If the couple is already pregnant then following screening tests may help in identification of genetic abnormalities:

First trimester:

Dual Marker-Blood test of mother, this is a blood test, measures beta hCG and proteins called PAPP-A(pregnancy associated plasma protein –A) if the level of these two are abnormally higher then this indicates an increased chances of Down Syndrome.

Ultrasound screening for nuchal translucency, this measures the space in the back of baby’s neck, and this if abnormal will indicate the increased risk of Down’s syndrome.

In women who are more than 35 years old the probability of Down syndrome is high and both these tests together provides high level of accuracy

CVS-Chorionic villi biopsy (1–12weeks)this is performed in first trimester and the couple who are in high risk of Down’s syndrome ,Tay-Sachs disease Fragile X syndrome are offered this test, where a sample of chorionic villi is removed from placenta through the cervix(transcervical) or per abdomen. The chorionic villi have the same chromosomes and genetic makeup as the fetus. This test is alternative to amniocentesis because it is performed much earlier between 10 week -12 weeks of pregnancy, thus allowing more time for the expectant parents to make decisions.

Second Trimester of Pregnancy

Triple Marker test at 16 weeks of pregnancy Blood is tested for

· b-hCG (beta subunit of human chorionic gonadotrophin)

  • AFP (serum alpha fetoprotein)
  • uEst (unconjugated estriol)

If couple is carrying a baby with Down’s syndrome, you will have higher levels of hCG, and lower levels of AFP and uEst in your blood

Level 2 ultrasound scan(18weeks-20weeks)

In this ultrasound is performed to detect structural abnormalities in the fetus , they may be able to find markers suggestive of Down syndrome, Spina bifida, anencephaly, congenital heart defects, cleft lip , cleft palate , gastro instinal and kidney malformation


Amniocentesis is a prenatal test in which a small amount of amniotic fluid is removed under ultrasound guidance with the help of fine needle per abdomen. This fluid is sent to genetic lab for analysis.Amniocentesis does not detect all birth defects, but is useful in high risk of Down Syndrome,Sickle cell disease,Cystic Fibrosis, Muscular Dystrophy,Tay Sachs.Amnicentesis can also detect Spina Bifida and Anencephaly