One of the first steps in in vitro fertilization (IVF) and other fertility procedures is the identification of the cause of infertility. Infertility can be caused by a variety of factors which could be present in either the man or woman, or both.

In many cases, straightforward diagnostic tests such as sperm count, and transvaginal ultrasound can directly point out the underlying cause of infertility. However, in some instances, the problem is much more complicated and could only be confirmed through genetic analysis.

One of the genetic analyses used to identify genetic causes of infertility is Karyotyping. What is Karyotyping? How does it work? Should you choose to undergo Karyotyping? This short article will answer these questions to help you learn more about genetic Karyotyping.

What is Karyotyping?

Karyotyping, also known as chromosome analysis, is a type of genetic testing that is used to examine the size, shape, and number of chromosomes in a human sample. Chromosomes are thread-like bundles of tightly packed DNA strands found in our cells. The chromosomes contain our genes, which ultimately determine our body functions and features, including fertility.¹

Humans have 23 pairs of chromosomes – 1 set comes from the mother and the other set is from the father. Chromosome pairs 1 to 22 are called autosomes. The 23^rd pair of chromosomes are the sex chromosomes, which could either be XX (for females) or XY (for males).²

During Karyotyping, the chromosomes are paired and arranged by size. Chromosome pair #1 is the biggest, while chromosome pair #22 is the smallest. The sex chromosomes are placed last in the karyotype. The X chromosome is noticeably larger than the Y chromosome. By organizing, labelling, and characterizing the chromosome pairs, the karyotype provides adequate information about a person’s complete set of chromosomes.³

Through Karyotyping, certain errors in the structure and number of chromosomes can easily be detected. For instance, a missing or extra chromosome in the karyotype suggests a genetic abnormality that could have serious health implications. Karyotypes can also reveal structural changes in the chromosomes, such as a duplications, deletions, inversions, or translocations.³

Since the chromosomes contain stacks of genes, abnormalities in the chromosomes signify genetic anomalies. These errors in the genes and abnormalities in chromosomes can cause serious infertility issues. For this reason, Karyotyping is a very useful tool in identifying the root cause of infertility in individuals undergoing IVF.

Who will benefit from Karyotyping during IVF?

Karyotyping is recommended for couples who are interested in intrauterine insemination (IUI) and IVF with intracytoplasmic sperm injection (ICSI).⁴ These procedures have an increased risk of passing on some genetic abnormalities to the offspring. Knowing your genetic profile will help you make an informed decision on whether you should undergo or forgo IUI or ICSI.

If you haven’t had any IVF cycles but is interested in doing so, Karyotyping would be very helpful if you experience any of the following scenarios:

• Inability to conceive for over a year.
• Gave birth to a stillborn baby.
• Absence of sperm or very low sperm count in the male partner.
• Primary ovarian insufficiency, also known as premature ovarian failure, in the female partner.

How does it work?

The process of Karyotyping starts with the of blood samples. Blood will be drawn from you and your partner. The blood samples will then be processed in the laboratory to extract the cells that will be grown in culture. When the cells reach a certain stage in cell division, the cells are stained and examined under a microscope. The cells are studied and a photograph of the complete set of chromosomes is taken. This photograph, known as the karyogram, presents the chromosomes arranged according to their size. The karyogram allows the fertility specialist to identify chromosomal abnormalities based on the chromosomes’ size and appearance.

Chromosomal abnormalities detected using Karyotyping in infertile couples

Several chromosomal abnormalities could be identified through Karyotyping, especially in the case of infertile couples. In both male and female infertile patients, higher frequency of chromosomal disorders has been recorded.⁵ The following are the main chromosomal abnormalities detected in infertile couples undergoing IVF treatment:

• Numerical abnormalities
• Humans have 46 chromosomes, grouped in pairs. Through Karyotyping, abnormalities in number could easily be identified.
• The most common numerical chromosomal abnormality in men is Klinefelter syndrome, which is found in 67% of abnormal karyotypes in males with azoospermia (absence of sperm in the semen). While normal males have a karyotype of XY, males with Klinefelter syndrome have an extra X chromosome in addition to their XY profile, resulting in a total of 47 chromosomes and a karyotype of XXY. The abnormal XXY cells fail to proceed to normal cell development, resulting in very low or absent sperm count, which then results in infertility.⁵
• Other numerical abnormalities that have been identified in infertile males include a karyotype of 47 chromosomes with an XYY profile and the presence of multiple chromosome fragments, also known as small supernumerary marker chromosomes.⁵
• Structural abnormalities

To function normally, chromosomes should have a normal structure, which includes the composition of fragments in each chromosomal arm. Karyotyping provides sufficient information about the structure of chromosomes.

Structural abnormalities could be in the form of repeating segments (duplication), missing fragments (deletion), unwarranted exchange of material between two chromosomes (translocation), segment that is placed in another location within the chromosome (inversion), and addition of fragment from another chromosome (addition).⁶ These aberrations can have serious effects on fertility. For instance, deletion of certain fragments in males could result in the alteration of testicular function, which could then lead to infertility. In females, inactivation of specific segments of the X chromosome could result in gonadal dysgenesis, a condition in which the ovaries fail to develop.⁵

What would be your net best step?

If your Karyotyping results turn out to be positive for a genetic problem, it is best to undergo genetic counseling. Through genetic counseling, your doctor will explain your results, identify your genetic risk, and layout your options based on your genetic risk. Your doctor may recommend one of the following procedures:

Preimplantation genetic diagnosis prior to embryo transfer.

Preimplantation genetic diagnosis (PGD) is a process in which a cell is extracted from one of the incubated embryos to check for certain genetic abnormalities. During PGD, healthy embryos without any genetic defects are selected for subsequent transfer into the uterus. With this procedure, there is a lower risk for early miscarriage and having a baby with a genetic disorder.

Regular IVF cycles instead of going through intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is a procedure wherein the doctor directly injects the sperm of the male partner into the cervix of the female for conception. The direct injection of sperm into the female reproductive tract bypasses the process of natural selection, which ensures that only the healthiest sperm could reach the female’s egg cell. For this reason, ICSI has a higher risk of passing on genetic defects to the baby.⁴ To prevent this, you may opt to undergo regular IVF cycles, although these do have lower success rates.

Consider a sperm, egg, or embryo donor.

Another option that you may consider is using the sperm, egg, or embryo from a donor. Donors typically undergo genetic analysis to screen for genetic diseases or abnormalities. Choosing a donor will allow you to have a baby that does not possess the genetic problem that you might have.

Your IVF Support

Going through Karyotyping and the IVF journey in general could be very confusing and overwhelming for aspiring parents. If you are thinking of going through IVF but do not know which IVF clinic you should go to, you can consult a trusted fertility consultant who will help you find the best IVF clinics in terms of technology, success rates, and affordability. Your fertility consultant can also provide online courses to help you understand the procedures, avoid common mistakes during IVF treatments, and optimize your fertility options. Contact a fertility consultant today and learn more about the IVF process, the best IVF clinics, and other assisted reproductive techniques.

References

• Medline Plus. (2022). Karyotype Genetic Test. https://medlineplus.gov/lab-tests/karyotype-genetic-test/.
• Yahaya, T. et al. (2021). Chromosomal abnormalities predisposing to infertility, testing, and management: a narrative review. Bull Natl Res Cent. 45(65):1-15.
• O’Connor, C. (2008). Karyotyping for Chromosomal Abnormalities. Nature Education. 1(1):27.
• Committee Opinion. (2016). Perinatal Risks Associated With Assisted Reproductive Technology. Obstet Gynecol, 128(3):e61-68.
• Chantot-Bastaraud, S., Ravel C., Siffroi, J. (2008). Underlying karyotype abnormalities in IVF/ICSI patients. Reproductive BioMedicine Online. 16(4):514-522.
• Ozkan, E., Lacerda, M. (2022). Genetics, Cytogenetic Testing and Conventional Karyotype. In: StatPearls. Treasure Island (FL): StatPearls Publishing.