Importance of Karyotyping in Infertility Screening

Karyotying is a technique to find chromosomal abnormalities such as Flinefeture, syndrome, Y chromosome microdeletions, Turner syndrome, sex reversal and other translocations in male and female infertility. 

Do You know?

  1. 15% of the world population suffer from infertility.
  2. 1 in 6 couples faces difficulties to reproduce. 
  3. Karyotype abnormalities are reported in 2 to 14% of male individuals. 

Karyotyping is a genetic technique, researchers use to rule out certain chromosomal defects such as structural and numerical aberrations. Many birth defects originate from chromosomal aberrations. 

Developmental delay, mental retardation, metabolic problems, reproductive failure & associated problems and heart defects are some of them. Note that these may occur for other reasons as well. 

Reproductive failure is when couples can’t reproduce and make babies or unable to conceive a pregnancy, usually are categorized into infertility. Put simply, when couples can’t make babies they are classified as “infertile”.

Many reasons cause infertility, genetic infertility is one of them. When classified even precisely, that infertility occurs only by alterations of chromosomes can rule out by karyotyping. 

Here is the article showing how the conventional and updated karyotyping technique is used to encounter and diagnose infertility in both males and females. 

Related article: Karyotyping Test Cost in- USA, UK and India.

What is infertility? 

Infertility is when a healthy couple can’t produce babies, as we explained. Scientifically it is defined as, 

“When a couple fails to achieve natural pregnancy after 12 months of reproduction.”

Globally 186 million peoples are living with infertility including males and females. Among infertile couples, male and female infertility are reported 30 to 40% and 40 to 50%, respectively. In the rest of the cases, both parents remain infertile. 

Numerous factors cause a different type of infertility, some of the reason are enlisted here: 

Reasons for infertility: 

In females, Fallopian tube blockage, cervical abnormalities, Uterine abnormalities, Pelvic adhesions, Ovulation and related disorders, Endometriosis, hormonal imbalance, Ovarian insufficiency and certain disease treatments cause infertility. 

In males, abnormal sperm structure, low sperm concentration, low-quality semen, low sperm delivery, overexposure to toxins, hormonal problems and other congenital gonadal abnormalities are common reasons for infertility. 

Besides, other factors are, 

  • Unhealthy food and lifestyle 
  • Stress 
  • Adverse environment and 
  • genetic factors 

Among all these, genetic factors not only directly cause infertility but also produce the above-listed conditions. 

For example, genes that are involved in sex differentiation, when mutated, can’t form primary and secondary sexual characters perfectly. 

Likewise, azoospermia occurs by deletion of the azoospermic region cause azoospermia in males. This article focuses on chromosomal aberrations for infertility and how karyotyping helps to diagnose it. 

Read more: The rarest case of 3p Mosaic Deletion Duplication Syndrome.

Chromosomal aberrations in infertility: 

Y chromosome microdeletion: 

Y chromosome microdeletion often occurs in males. The Y chromosome is a short acrocentric chromosome only present in males. It possesses information for maleness. 

Genes located on the Y chromosome regulates the process of spermatogenesis and production of secondary sexual phenotypes in males. 

The Y chromosome microdeletion occurs when some portion of the Y chromosome, especially, from the p arm, having an azoospermic region, gets deleted. 

The Region is classified into AZFa, AZFb and AZFc, the severity of azoospermia in patients depends on how much portion deletes. Y chromosome microdeletion is the common genetic infertility reported in males. 

Using conventional karyotyping and DNA-based amplification methods, scientists diagnose it. In karyotyping, the researcher studies the banding pattern of the Y chromosome while in PCR amplification, they amplified the region to know whether it is present or not. 

Note: azoospermia is a condition when no sperm count reported. 

Klinefelter syndrome:

Klinefelter syndrome is a rare chromosomal condition reported in males, having an additional X chromosome with a pair of sex chromosomes. Means, instead XY and two X along with the Y is reported; 46, XXY +X

Worldwide prevalence of the Klinefelter syndrome is 0.1 to 0.2% in newborns, however, KS is causing azoospermia in 67% of cases and in 11% of azoospermic patients Klinefelter syndrome is reported. 

Patients with Klinefelter syndrome are infertile usually having azoospermia reported. Some other common symptoms are: 

  • Elevated gonadotropin level
  • Low testosterone 
  • Azoospermia 
  • Low testicular volume 
  • Hypogonadism  

Mosaic KS is reported evidently too in which a mixed cell population of 46, XX/ 47, XXY are present. The severity of symptoms varies as well. Noteworthy, the 49, XXXXY syndrome is a variant of KS which is very rarely reported and has 49 chromosomes instead of 46.

The graphical representation of Klinefelter syndrome.
The graphical representation of Klinefelter syndrome.

47, XYY: 

47, XYY is yet another aneuploidy reported in males, however, not all patients with the 47, XYY have infertility problems. But It is reported in infertile male patients having mild to moderate mental retardation. 

Turner syndrome: 

Turner syndrome is again one of the rare chromosomal abnormalities in which only a single X chromosome is present in females. Cytologically it is denoted as, 45, XX/X0 -X. 

The prevalence of Tuner syndrome is 1 in 1500 to 1 in 2500 females worldwide. 

Though Turner syndrome isn’t directly associated with female infertility, females with the present condition are at a higher risk of having infertility problems. Females with full penetrance of Turner syndrome also can’t produce eggs or ovum.

Sex reversal: 

Sex reversal is also the rarest genetic problem, in which a patient has the opposite sex instead of their natural one. For example, in the case of 46, XX male sex reversal, males have two X chromosomes present. A wide spectrum of phenotypic abnormalities related to sex differentiation and sex determination are associated with this condition.

46, XX male sex reversal: 

46, XX male sex reversal is more common than 46, XY sex reversal. Here males have two X chromosomes and lack the Y chromosomes. 

Phenotypically they have mixed gonads, however, dominant maleness if reported are occurred by translocation of some Y chromosome-bearing genes to the X chromosome. This happens because of translocation between the pseudo-autosomal region PAR.

46, XX male sex reversal patients are sterile and lacking testis hypotrophy. 

The present condition is a complex one and can rule out using karyotyping. Sex reversal patients who have mixed gonadal dysgenesis are mostly infertile. 

Related article: What is the Role of X and Y Chromosomes?

Balanced translocations: 

Translocation occurs when some portion of a chromosome deletes and incorporated into another location or chromosome. But the balanced translocation occurs when two equal-sized chromosomal parts translocate. 

Balanced translocations are hard to screen, however, are involved in many infertility conditions too. 

Mosaicism- 45, XO/ 46, XY males: 

Mosaic condition is reported when two different cell types with two different genetic compositions are present in a cell line. In patients with 45, XO/ 46, XY; two types of cells- one lacking a whole Y chromosome and another with 46 X and Y chromosomes; shows a varying degree of infertility problems. 

The symptoms of infertility depends on the ration of 45, XO to 46, XY cell types in the fetus. It is reported in male patients.

Mosaicism- 45, XO/ 46, XX in female: 

The present mosaic condition is known as mosaic Turner syndrome showing mild to moderate infertility problems in females. 

Prevalence of Chromosomal abnormality in infertility: 

Chromosomal abnormality Percentage of infertility 
47, XXY67%
46, XX sex reversal in male 10%
47, XYY8% (oligospermia)
Gonadal mosaicism 10%
Reciprocal translocation4%
Robertsonian translocation2%

Note that plenty of reasons are associated with female infertility and therefore it is difficult to rule out a single reason why it occurs. 

Studies also reported that chromosomal aberrations are more frequent in females, however, are clinically unknown, besides Turner syndrome. It is also reported that those aberrations affect female secondary sex characters more than primary. 

How infertility karyotype is performed? 

To find out chromosomal aberration in infertility, conventional karyotyping process is performed.

Blood samples from a couple are taken for evaluation and cells are cultured. 

A standard karyotyping and cell culture method is employed. Cells are stained and banded using GTG or Q banding technique are observed under the microscope. 

In another state-of-art technique known as SKY- spectral karyotyping, a specific region on chromosome is being targeted to rule out aberration. 

SKY requires prior sequence information to design colored probes specific to region being studied. 

Multiple probes bind on chromosomes, emit fluorescence and give a colored picture of chromosomes. You can learn more here: What is Spectral karyotyping?

When to go for karyotyping in case of infertility? 

Here is the scenario a couple should think for karyotyping without wasting much time, 

  • Unable to conceive a pregnancy after 12 months. 
  • Female having ovarian insufficient and abnormal periods 
  • Low semen volume and low sperm count 
  • Having a stillborn birth situation 
  • Consecutive miscarriages 
  • Planning to go for IUI, IVF or ICSN. 

Infertility literally means unable to get pregnant, and therefore we are not covering reasons and karyotyping for miscarriage. Because it is not infertility, females get pregnant but for some unknown reasons it can’t be sustained and that is a different topic. So we will cover it in some other topic. 

CFTR gene mutations are also responsible for inherited infertility in both males and females but technically speaking, CFTR gene mutations can’t be detected using karyotyping. 

Therefore it is also not discussed here as well. 

Origin of chromosomal aberration related to infertility: 

Broadly, genetic infertility can be categorized into genes involved in infertility and chromosomes involved in infertility. A wide spectral of gene mutations cause certain different infertility phenotypes.

However, chromosomal aberrations impose a small portion of genetic infertility. As we noted, Klinefelter syndrome, Turner syndrome and microdeletion are common. 

Chromosomal abnormalities are perhaps non-inherited certainly and so either of the above-listed conditions can’t be pass to offspring. In addition, a clear reason why it occur is still not known. 

few random process during meiosis cell division during sperm cell or egg cell differential leads to varied chromosomal aberrations. Those are known as non-disjunction event. 

The non-disjunction event occurs either at meiosis I or meiosis II and passes to fetus when fertilitized. People suffering from infertility have abnormal phenotypes associated with their fertility, however, other phenotypes remains normal otherwise. 

Chromosomal abnormality Azoospermia Oligozoospermia 
46, XX males 0.9%
Klinefelter syndrome 11%0.5%
Robertsonian translocation 0.2%1.5%


Infertility is common worldwide, but genetic factors aren’t the only reason and so chromosomal abnormalities too. 

Karyotyping is a primary technique used to investigate infertility in couples. However, in some other cases, FISH and microarray are employed as well. 

The microarray can screen thousands of copy number variations from 23 pairs. 

Though many different molecular genetic techniques and cytogenetic techniques are involved in recent times, the underlying cause of genetic infertility is still not clear. 

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