Male factor infertility
Male Factor infertility is the cause in approximately 50% of couples who experience infertility. All couples undergoing infertility investigations should have a semen analysis completed, even in circumstances where an identified female problem has been diagnosed. Causes of infertility amongst men vary, but in general it is the result in failure to produce an ejaculate containing a sufficient quantity of normal functioning sperm, capable of travelling through the female reproductive tracts and fertilising an egg.
A semen analysis is usually carreied out by an embryologist at the laboratory of the clinic which you are currently attending. Repeat samples will usually be requested if an unsatisfactory result is returned or if you change clinic. Most clinics use a standard criteria for examining sperm, which is recommended by the WHO (World Health Organisation).
The criteria set out below has been kindly provided by the Glasgow Nuffield Hospital, and the guidelines they follow are regulated by the WHO.
A semen sample for testing can be produced either at home or at the clinic where you are being treated. If you produce the sample at home it is advised that you deliver it to the laboratory within one hour. You will also be asked to complete a form which will require specific information about the sample you have just produced.
- Any illnesses over the passed 3 months
- If you collected all of the sample, just the first part or just the last part
- No. days abstained from sex
- This information is important for the overall analysis of your sample. For example, sperm production and development takes approximately 3 months to complete. Therefore, any illnesses present within this 3 month period may have contributed to an abnormal sample being produced. In addition, the most concentrated part of the sperm is found in the first few ml supplied. If you collect the first part only, the semen would be very concentrated with sperm, but would give an inaccurate reading of the total concentration. The last few ml would be much less concentrated with sperm and again would provide an inaccurate reading. It is therefore important to try and collect as much of the sample as possible or be honest on your questionnaire.
The WHO specifies that a man should abstain from intercourse for between 2-7 days. Most clinics set out their own guidelines within this range.
Once the sample has been collected the embryologist will usually leave it for between 1-2 hours before they begin the analysis of a neat sample. There are usually 4 main criteria; Volume, Motility, Form & Antibodies. A minimum of 2ml Is required for testing.
The sample is placed onto a counting chamber, which is a small glass slide with a set depth and counting grid. This allows for the exact concentration to be measured. The WHO set out that a normal sample should contain a minimum of 20 million sperm per millilitre volume. Anything les than this is considered a low sperm count. No sperm present at all, is referred to as azoospemic, usually requiring investigation by a urologist.
Classed as the movement of the sperm.
There are usually 4 categories.
A) Moving Well.
C) Wiggling on the spot.
The WHO criteria for normal is at least one of the following:
25% of (A) or 50% of (A + B)
Refers to the morphology of A) Head. B) Mid-part. C) Tail.
The embryologist will score the sperm present on their general form.
Abnormal sperm heads may be classed as round, lumpy , elongated or more than one head present. Mid-parts may be lumpy, too long or large, too short or small. Tails may be too long, too short or again more than one present.
If there are antibodies present in semen this can cause the sperm to clump together and can prevent them from fertilising an egg. This can be an important factor for both natural conception and fertility treatment. If there is a very strong positive result for antibodies present in semen, then ICSI would be recommended over IVF due to the problems with fertilisation.
The following terms have been developed to describe conditions in which one or more of these factors is abnormal;
Aspermia - The patient produces no sperm.
Azoospermia - The patient produces semen containing no sperm.
Oligozoospermia or oligospermia - sperm concentration is low, less than 20 million per ml.
Asthenozoospermia or asthenospermia - less than 50% of the sperm are active.
Teatozoospermia or teratospermia - more than 70% of the sperm are abnormally shaped
Oligoasthen oteratozoospermia (sometimes referred to as OATS) - less than 20 million sperm pr ml with less than 50% being motile and more than 70% abnormally shaped.
Necrospermia - all sperm are dead.
Pyospermia or leucospermia - presence of large number of white blood cells in the semen, often associated with an infection.
What Causes Male Infertility?
Male infertility may be hormonal, genetic or physical:
In some cases insufficient levels of the hormones necessary for sperm production are present. In a few cases fertility may be improved by replacing or boosting hormone production. Unfortunately there are some hormone related causes of male infertility that are untreatable such as the condition in which the cells of the reproductive tract are insensitive to the hormones that stimulate sperm production and thus no sperm are produced.
The most common genetic abnormality leading to infertility in the male is Klinefelters syndrome where instead of the normal XY male karyotype, the man has an extra x chromosome. The vast majority of these patients do not produce any sperm at all. This condition is untreatable and generally patients can only be offered donor sperm. Klinefelters Syndrome has other clinical features related to it such as above average height and in some cases reduced IQ.
In some situations oligozoospermia may be associated with genetic abnormalities as may some cases of azoospermia. The genetic abnormalities in these cases are likely to be defects on the y chromosome. If sperm are present, such cases can be treated using in vitro fertilisation or intracytoplasmic sperm injection. The preference of IVF over ICSI is usually determined by the clinic which you are attending. However, it is important to take into account the possibility that these genetic defects may be passed on, and any male children may also be subfertile.
Failure to produce any ejaculate may be the result of an obstruction in a tube called the vas deferens which carries the sperm from the testis to the ejaculate. This tube may be obstructed on one side or on both sides. In the majority of these cases this condition is the result of genetic mutation on Chromosome 7, which may also give rise to cystic fibrosis. These men may have sperm retrieved surgically and may achieve pregnancies using intracytoplasmic sperm injection. However, it is very important that these couples receive genetic counselling and genetic screening as their offspring may be at risk from cystic fibrosis. Some clinics offer screening for cystic fibrosis as standard when a male factor problem has been identified, but not all. If you are concerned about CF or have any examples of the condition in your family you would be advised to discuss this matter with your consultant before proceeding with treatment.
Other than congenital obstructions of the reproductive tract, obstructions may result from infection or from surgery or injury. If a man apparently has no sperm in his semen it is important to establish whether this is the result of an obstruction or whether he genuinely is not making sperm. A simple hormone test will usually give this information. If the obstruction occurs on one side only, then the sperm concentration may be reduced. If the obstruction is on both sides resulting in azoospermia, sperm can be retrieved surgically form the epididymis or directly from the testis. However, because the numbers of sperm retrieved are usually low and these sperm may be immature, successful treatment is only likely with intracytoplasmic sperm injection.
Unfortunately there are some problems that cannot be identified by semen analysis. Active sperm that are normally shaped may still be incapable of fertilising an egg as a result of a biochemical abnormality. The way in which sperm and eggs interact is complex. Sperm are highly specialised cells, they have a long tail which not only enables them to move towards the egg but by changing its motion provides the thrust that is necessary for the sperm to penetrate the outer coating that surrounds the egg, the zona pellucida. The head of the sperm consists of two components, the nucleus in which the genetic material is very tightly packed to protect it during its passage through the female tract, and the acrisomal cap. The acrisomal cap or acrisome contains enzymes that assist the sperm in its passage through the zona polucida. A reaction occurs, known as capacitation, when the sperm comes into contact with the egg that causes the loss of the acrosome, the release of these enzymes and the exposure of special sites on the sperm head that allow the sperm to bind to the membrane of the egg itself and subsequently to release the genetic material into the egg. This highly condensed genetic material must then decondense so that it is able to interact with the genetic material of the egg. Biochemical defects can occur that may prevent any one of these processes from taking place or form being completed and thus prevent fertilisation. These defects are very difficult to detect. There are tests that examine particular aspects of sperm function but it is important to remember that a positive result in any one of theses tests does not mean that sperm are fully functional in all respects. The potential for these biochemical defects means that a normal semen analysis does not guarantee fertility.
The treatment of male factor infertility using assisted conception was revolutionised in the late 1980’s in Belgium, with the development of intracytoplasmic sperm injection ICSI. This is a process whereby a single sperm is injected directly into the egg and can be carried out even when there are very few sperm present. ICSI, can be used very successfully with sperm that have been surgically retrieved form the testis or from the epididymis, by a procedure known as tesa or pesa, and with sperm that have very poor activity. This technique has superseded all other micromanipulation techniques and has become the treatment of choice where fertilisation fails with conventional IVF. On average 60 to 70% of eggs fertilise with ICSI, a similar rate to that achieved with IVF.
Some research suggests that there is a slightly raised incidence of sex chromosome abnormalities in children born as a result of ICSI. This is not however a result of the technique but rather a result of the presence of genetic defects in the fathers. Since ICSI is still a technique in its infancy with respect to future generations, evidence of inheritance of male factor infertility is still not available. The passing on of any genes involved in the pathway of male infertility is still only an incidence less than 3%. Couples who need treatment by ICSI should firstly be informed of the genetic implications.
This information is not meant as and should not replace any given medical advice