About 25% of infertility is calculated to be directly due to the male partner, and another 15-25% probably also has a male contribution. How is male infertility diagnosed, what does it mean and what can be done about it?
[+] Physiology of the male reproductive system
Sperm are produced in long, densely packed tubes in the testis, called the seminiferous tubules. The ends of each tubule empty into an area called the "rete testis" and this leads on to the epididymis. The epididymis is a single, highly coiled tube in which the sperm undergo their final maturation. The epididymis connects with the vas deferens, which transports sperm (and which is cut and tied off in a vasectomy). To produce sperm, the testis must be 2 or 3ºC cooler than the core body temperature of 37ºC. The male reproductive tract is designed to keep sperm away from cells of the immune system that would otherwise recognise the sperm as 'foreign' and produce antibodies to them. This barrier may be breached if the testis is physically damaged or following vasectomy, sperm leak into the tissues around the cut end of the vas.
As well as producing sperm, the testis also make the male sex hormone testosterone. Testosterone levels rise at puberty, inducing development of the genitals, seminal vesicles and prostate, body hair, beard growth, and the muscle development associated with male physique.
Sperm and testosterone production are stimulated by two hormones from the pituitary gland at the base of the brain - luteinising hormone (LH) and follicle stimulating hormone (FSH), which are named after their functions in the female, not the male! The sperm, via a hormone called inhibin, and testosterone in turn exert negative feedback on LH and FSH secretion, so that the system is kept in balance.
At ejaculation, fluid from the epididymis (about 5% of the total volume), the prostate (30%) and the seminal vesicle (65%) are mixed. Components in the seminal vesicle fluid make the sperm coagulate; after 20 minutes or so enzymes once again make the fluid liquid.
The requirements of the male reproductive system are:
- to deliver semen near the cervix during intercourse
- to produce sufficient sperm:
- that are motile and able to “swim” through the woman’s cervical mucus into the uterus and fallopian tubes,
- that can undergo the changes in surface structure so that they can bind to an oocyte that can then penetrate the protective coating (zona pellucida) of the oocyte and, once inside the oocyte, deliver a set of normal chromosomes.
[+] Infertility tests
At present the range of tests that can evaluate sperm function is quite limited, apart from treatment by in vitro fertilisation, where sperm and oocytes are placed together in the laboratory to see whether fertilisation can occur.
In the physical examination the doctor looks at the size of the testes, the consistency of the testes and for the presence of a varicocele ("varicose" veins in the testicular blood vessels), and the development of the genitals and hair patterns (as a sign of adequate testosterone production).
Blood tests can measure FSH and testosterone. If FSH is high, then the pituitary gland is trying to stimulate sperm production, but the testes are not responding sufficiently and the usual balance is upset. If there are very few or no sperm in the ejaculate and there is not an obstructive reason for this then genetic testing is indicated. A karyotype to look at the chromosomes will pick up chromosome abnormalities that may cause male infertility. Recently it has been appreciated that some men with very few or no sperm have a tiny piece of the Y-chromosome missing. This is called a Y-chromosome micro-deletion and is an important test to be done if men who are azoospermic are considering sperm retrieval for IVF. About 1% of infertile men are born with a condition called congenital absence of the vas deferens. This is usually associated with a cystic fibrosis gene deletion so this test is done if the condition is suspected.
The semen analysis provides an estimate of how many sperm are being produced and some degree of prediction, from sperm movement and shape, of their ability to fertilise oocytes. The number of sperm in the ejaculate of fertile men covers a wide range (e.g. 20-400 million/ml) and there can be quite wide fluctuations from day to day, so that several semen analyses may be necessary to gain an accurate indication for a particular person. The number of days abstinence before ejaculation also influences the number of sperm, so a uniform period of 3 to 5 days is recommended before testing.
Sperm can also be tested for the presence of antibodies adhering to them; the antibodies can impair their ability to penetrate cervical mucus and prevent them from fertilising oocytes.
If it is not possible to be sure whether the lack of any sperm in the ejaculate is due to an obstruction then an exploratory testicular operation will help with diagnosis and potential treatment.
Although the male has only recently been acknowledged as playing such a big part in the cause of infertility, the good news is that rapid research in the area of male reproduction has brought about dramatic changes in the ability to treat couples with male factor infertility.
It is rare for the sperm problem to be due to a hormone deficiency but if so then drug treatment is usually helpful. An obstruction of the epididymis giving rise to no sperm in the ejaculate (azoospermia) can be corrected by microsurgery but now most couples choose sperm retrieval and IVF/ICSI because it is more successful. If the obstruction is due to vasectomy it is still often best dealt with by a microsurgical-vasectomy reversal but there are many factors to weigh up before this decision is made and so it is best to discuss all issues with a fertility expert first. In men with so-called non-obstructive azoospermia there are often little “nests” of tubules producing sperm that can be harvested for IVF and ICSI but the sperm production is not enough for the sperm to appear in the ejaculate.
Some men suffer from retrograde ejaculation into the bladder. If the concentration and acidity of the urine are controlled, then it is possible to recover sperm from urine and to use them for artificial insemination.
Varicoceles are essentially varicose veins within the blood vessels carrying blood away from the testis, and are more common in infertile men (30-40%) than in fertile men (10-15%). Whether removal of the affected veins helps is now doubted especially as the vein to the right testis is never affected and randomised controlled trials with operative correction of the varicocoele have not shown a treatment benefit.
Although over 90% of male infertility cannot be corrected, there are treatments with the available sperm that can significantly improve the fertility chances. This is especially so for those men with fewer than average sperm (oligospermia) or fewer sperm with the normal motility or normal physical appearance.
There has been interest in whether antioxidants help improve sperm production. Small studies have been conducted but more conclusive evidence is needed.
The position is slightly clearer on negative impacts of lifestyle on male fertility. Some studies suggest that alcohol and/or smoking tobacco can have a negative impact on fertility and the use of marijuana is more clearly associated with a negative impact. Environmental toxins may play a role but specfics have yet to be clarified, with lead and hebicides being the most likely culprits.
Recent data suggests an association between reduced sperm count and being overweight and/or having a sedentary lifestyle.
Some infertile men seem to have higher testicular temperatures than fertile men and, while habits that increase testicular temperature further may be unhelpful, there is little evidence to support actively trying to reduce testicular temperature.
Because of the relatively high spontaneous pregnancy rate with male infertility over long periods of time, you should be very cautious about attributing pregnancy outcomes to lifestyle changes.
Couples with male-based infertility usually have the most difficulty as the diagnosis is often difficult and the options many. Although "time" is often the best remedy, it is not easy to wait, as everyone likes "to do something".
[+] Microsurgery and sterilisation reversal
Women can sometimes have microsurgery to repair damage to the fallopian tubes and in men microsurgery to correct abnormalities in the epididymis. The surgery is called “micro” because the surgeon needs a microscope to define the extremely small structures operated on. Microsurgery should always be used to reverse male and female sterilisation.
The success of a vasectomy reversal is mainly dependent on the time from vasectomy to reversal – the shorter the gap, the better the outlook. However, nowadays there are many factors to be taken into account before deciding on which option to pursue, so it would be best for the couple to see a fertility specialist before undertaking vasectomy reversal. Female sterilisation reversal, unlike male sterilisation reversal, is not affected by the time interval but more by how the sterilisation was done. Nowadays most people seeking reversal have had clips or bands applied to their tubes laparoscopically so a microsurgical reversal should offer a good chance of success and is seriously worth considering as an option prior to IVF.
[+] Sperm freezing and storage
Long-term storage of sperm is almost always possible before various types of medical treatment that can damage sperm production, for example, chemotherapy, irradiation therapy or surgery (including vasectomy). How the sperm are later used depends on the number and quality of the sperm before freezing and how well they survive freezing and thawing. It is often wise to store two or three samples if possible.
[+] Surgical sperm recovery - MESA, PESA, TESA and TESE
These are jargon for various techniques to obtain sperm from the epididymis or testis from men who have no sperm in their ejaculate (azoospermia). If the cause of the azoospermia is an obstruction then the sperm retrieval procedure is usually simple and can be done under local anaesthetic with sperm being frozen for future use. If the cause is “non-obstructive” then the procedure will be more complex and best results are achieved with microsurgical techniques.
The testis and epididymis, and ways of retrieving sperm (image)
[+] Sperm microinjection (ICSI)
ICSI is a variation of IVF where, instead of the sperm and eggs being mixed in a test tube, a single sperm is injected into each mature egg. ICSI is used when sperm quality is too poor for conventional IVF to work. ICSI allows almost any man with sperm, either in his semen or in his testis, to try IVF.
[+] Intra-cytoplasmic Morphologically Selected Sperm Injection (IMSI)
IMSI is a process that uses advanced new technology incorporating 6000x magnification to detect abnormalities in sperm so only the best are selected and individually injected into the eggs. IMSI is indicated for couples where the male partner has significant known sperm problems, and also for those couples who have experienced recurrent unexplained implantation failure during IVF or miscarriage which could be due to sperm problems.