Diagnostic tests

Semen analysis

A semen analysis informs us about the sperm count, motility and morphology.
In order to interpret the results of a semen analysis, we need to apply the normal values established by the WHO in 2009:

There is specific nomenclature for abnormal values:

• Hypospermia: less volumen than normal.
• Azoospermia: no sperm in the ejaculate.
• Cryptospermia: very few sperm in the ejaculate.
• Oligozoospermia: less than 15 mill/ml count.
• Asthenozoospermia: less motility than normal.
• Teratospermia: sperm count with good morphology, less than normal.

Karyotype

The karyotype is determined by a blood test and allows us to learn the chromosome count and structure. A normal male karyotype is 46XY.

Both the eggs and sperm contain half the chromosomes. An abnormality in a patient’s karyotype increases the risk of producing sperm with an abnormal genetic information. In such cases, embryos are produced with genetic problems resulting in unsuccessful pregnancies, sterility or recurrent miscarriages.

Therefore, it is advisable to perform a karyotype before undergoing an assisted reproduction treatment like In Vitro fertilisation (IVF).

With an abnormal male karyotype, we have two options available: genetic testing of the embryos by preimplantation genetic diagnosis (DGP) before transferring them or using donor sperm.

Genetic testing of sperm

The genetic testing of sperm is performed in the following cases:

• Severe male factor.
• Long-term sterility without diagnosis.
• Repeated failures with assisted reproduction techniques, such as In Vitro fertilisation (IVF) or egg donation.
• Recurrent miscarriages after natural pregnancies which have not been proven to have any other cause.

Meiosis Evaluation

What is meiosis?

Of the 46 chromosomes that our cells have, 23 come from the father and 23 from the mother. Eggs and sperm have half the chromosomes compared to the rest of the cells. This way, as a result of the union of an egg with a sperm, the embryo has 46 chromosomes. The process that reduces the number of the chromosomes to half is called meiosis. Meiosis only takes place during egg and sperm production.

Occasionally, errors occur during meiosis. These abnormalities imply a worse reproductive prognosis by increasing the amount of abnormal sperm, which does not mean that all of them are necessarily affected. Abnormal meiosis is generally associated with an abnormal semen analysis (especially with oligozoospermia), but it can also be in men with normal semen analysis.

How can I investigate meiosis problems?

FISH
Sperm normally have 23 chromosomes, even though they may have one extra chromosome or one less, or even have all 46 original chromosomes from the precursor cell. The FISH test examines a certain number of sperm chromosomes. A pathological result indicates that the percentage of abnormal sperm is more than the normal population. The great advantage of this test is that it is easy to perform since it is done directly on the sperm sample.

The limitation of this technique is that only a certain number of the sperm’s 23 chromosomes are examined, which could lead to a normal result for a man who actually has genetic abnormalities. For men with low sperm count, this technique might lead to no result at all due to the lack of material.

Testicular biopsy

The testicular biopsy allows us to directly examine the meiosis process. The procedure is simple and can be performed on an outpatient basis, under local anaesthesia. In this way, the chromosome division can be examined throughout the different phases of meiosis, which makes it much more specific and sensitive for diagnosing abnormalities than a FISH test. This is considered the conclusive test in genetic testing of the male factor.

What can be done if there are meiosis problems?

Even though we can diagnose men carrying meiosis abnormalities, we currently do not have the necessary means available to us to identify the normal sperm that we shall use in an assisted reproduction treatment, like In Vitro fertilisation (IVF). Given that it is impossible to select the sperm, the only viable option to improve the chances for pregnancy is to perform a genetic selection of the embryos, before their transfer by preimplantation genetic diagnosis (PGD) or by using donor sperm. Choosing one option or the other will depend on both the diagnostic test results and the reproductive clinical history of the patients.

Other genetic causes

Sperm DNA fragmentation

Sperm DNA can be broken into small fragments. The more fragments there are, the worse the reproductive prognosis. Sperm DNA fragmentation can be repaired in some cases by the egg. The better the egg quality, the greater its repairing capacity. Therefore, in treatments like egg donation where we dispose of many good-quality eggs, the repercussions of a high sperm DNA fragmentation will be less significant.

Fragmentation test is recommended in the following cases:

• Repeated failure of reproductive techniques
• Varicocele
• Urogenital infections
• Men over the age of 45
• Exposure to toxins or high temperatures

We have several techniques available to us to treat fragmentation:

• Eliminate the cause (fever treatment, varicocele surgery…).
• Drug therapy with antioxidants.
• IMSI: It allows sperm with less risk of fragmentation to be selected.

Y chromosome microdeletion

The Y chromosome is only present in men and is involved in the sperm production process. Abnormalities in certain fragments of this chromosome are associated with male sterility problems, especially in cases of azoospermia and oligozoospermia.

Cystic fibrosis CFTR gene mutations

CFTR gene mutations are associated with sterility problems and we find them related to cases of azoospermia and bilateral and unilateral absence of vas deferens.

Given it is a genetic mutation, it can be transmitted to the offspring, also handing down the problems these abnormalities cause. If the same mutation is also handed down by the mother, cystic fibrosis will be triggered.

To avoid problems stemming from this mutation, it is always recommended to investigate the couple carefully and perform preimplantation genetic diagnosis on the embryos during a cycle of In Vitro fertilisation (IVF) in order to transfer healthy embryos.

Varicocele

Definition and treatment

A varicocele is a venous dilation that drains the testicle. It can be associated with testicular discomfort, although it is not rare enough to be asymptomatic. The varicocele is also associated with an increased risk of DNA fragmentation.

The diagnosis is made by physical examination. A testicular Doppler ultrasound is a useful additional test since it detects abnormal blood flow in the veins, which is associated with the varicocele.

In low level or asymptomatic cases, it is very controversial that its treatment improves fertility. In severe cases, surgery is recommended.