genetic causes of male infertilitySperm production problems are the commonest cause of male infertility. Little is known about why the sperm produced in tubules in the testes fail to develop and function normally. Scientists believe that genetic variations are responsible in at least 40% of cases, particularly those involving the Y (or male) chromosome.
About 10% of men with zero or very low sperm counts have small pieces of the Y chromosome missing. The loss of this genetic information (called a deletion) leads to poor sperm production. Extensive analysis of the Y chromosome has identified three regions (termed AZFa, AZFb and AZFc) that contribute to different Y chromosome deletion types. There are six known deletion types, called AZFa, AZFb, AZFc, AZFbc, AZFabc and gr/gr deletions (Figure 1).
Figure 1: (A) Normal Y chromosome from a fertile man showing the three AZF regions (B) Different Y chromosome deletion types. Dotted lines indicate the deleted regions.
What causes Y chromosome deletions?
Y chromosome deletions are caused by an event called genetic recombination. Recombination occurs due to the presence of unstable DNA sequences on the Y chromosome. It is not known why some men are susceptible to Y chromosome deletions and others are not. Interestingly, the fathers and brothers of these men usually have normal sperm counts. Therefore, Y chromosome deletions are considered to be random events that occur during early embryonic development.
Who should be tested?
Given the relatively high frequency of Y chromosome deletions in infertile men, most andrology and infertility centres now provide Y chromosome testing as part of the routine investigation of men with poor sperm production due to unknown causes (sometimes called idiopathic infertility). Men with zero or very low sperm counts (less than 5 million/ml) are most likely to have deletions and therefore Y chromosome testing is recommended. There are three reasons to consider having this test:
1. To understand the reason for your infertility
For some couples, knowing that there is a genetic basis can help to resolve feelings about infertility.
2. To assist in predicting whether a son may have infertility
Each male child receives a Y chromosome from his father. Therefore, if the father has a Y chromosome deletion it will be transmitted to his son. It is likely that his son will also be subfertile.
3. To assist the clinician in making decisions about future reproductive treatment
Identifying a genetic basis for your infertility may allow the clinician to propose the best treatment option to achieve a successful pregnancy. If you carry a Y chromosome deletion, you may wish to discuss the following treatment options with your doctor:
- Deletions involving AZFa or AZFb have a poor prognosis for sperm retrieval even using testicular biopsy to try and retrieve sperm for fertilisation. Some couples may wish to consider using donor sperm as a back up if no sperm is retrieved.
- To avoid passing a Y chromosome deletion to their son, the couple may wish to consider the use of either donor sperm or preimplantation genetic diagnosis (PGD). PGD can be used to select female embryos for transfer. Females do not inherit a Y chromosome from their father.
What does the test involve?
The Y chromosome deletion testing offered by Monash IVF will detect the presence or absence of any of the six known Y chromosome deletions.
To perform this test, we require a 10ml blood sample. DNA will be extracted from the blood and tested for deletions using a procedure called multiplex Polymerase Chain Reaction (PCR). A report will normally be sent to your doctor within 2 weeks. Your doctor can then discuss the results with you.
What do the test results mean?
If we find a Y chromosome deletion, it strongly indicates a genetic cause for your infertility. Should you conceive either naturally or with the assistance of an IVF technique and have a son, there is a chance he may also have infertility problems.
If no deletion is found, it is still possible that you have a genetic cause for your infertility. It is very likely that new tests for genetic infertility will be developed. Monash IVF is continuing research into this important area and aim to provide the most comprehensive range of tests as soon as they become available.
Where is the service available?
This service is available at Monash Reproductive Pathology and Genetics (MRPG), the Pathology service associated with Monash IVF. MRPG is located at our Richmond and Clayton clinics in Victoria.
Cost
Please contact the Andrology Department at Monash IVF for information regarding the cost of Y chromosome testing. At present there is no Medicare rebate for these tests.
Quality Systems
The Y chromosome testing offered by Monash IVF is performed in accordance with the European Molecular Genetics Quality Network guidelines.
Our laboratories have been accredited to the highest standards of National Association of Testing Authorities (NATA). Through the application of our quality systems, we monitor and provide standards of excellence in quality service, care and advice.
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