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At the heart of general practice since 1960

January 2007: Semen analysis is the cornerstone of investigation for male infertility

How do you interpret abnormal semen analysis?

What treatment options are effective?

Are there any health risks to children born through ICSI?

How do you interpret abnormal semen analysis?

What treatment options are effective?

Are there any health risks to children born through ICSI?

Around one in four couples will see their gp about infertility problems.1 Large epidemiological studies show that failure or difficulty in conceiving a child is a surprisingly common, worldwide problem with between one in six and one in seven couples classed as sub-fertile.2 Sperm dysfunction is the most common cause of infertility and affects one in fifteen men.3

Studies using semen assessment as the criteria for sub-fertility4 show that up to one in five 18-year-olds are classed as sub-fertile.5 Recent reports suggest that the incidence of male infertility is increasing.6

There are no drug treatments to enhance sperm function that have been shown to be effective in controlled trials, and in vitro fertilisation and intracytoplasmic sperm injection (IVF and ICSI; collectively termed ‘assisted conception') are the only treatment options. These approaches are expensive, invasive and availability is limited.

Assessment

A detailed history of the couple should be taken, including the duration of infertility, any coital problems and the frequency of intercourse. Information should be obtained from the man regarding previous conceptions, surgery likely to affect fertility, such as vasectomy, drug use, including illicit use, for example steroids for bodybuilding, and age.

A physical examination should be undertaken to determine general health, testis size and to record any obvious abnormalities of the reproductive system. If the couple have been trying to conceive for more than 12 months a semen analysis should be performed. If the result is abnormal a repeat analysis should be arranged as soon as possible as there is some variation between samples. In addition, severe illness and drugs that affect spermatogenesis will also adversely affect the semen analysis.

Advice for patients

One of the most significant factors affecting the chance of conception is the length of time that the couple have been trying to conceive. As fertility is often discussed in the media, couples can become anxious when they have only been trying for a short period of time.

There is a comprehensive guideline from NICE on the assessment and treatment of people with fertility problems.7 This suggests that, unless there are confounding factors, couples should not be referred for further investigation if they have been trying to conceive for less than 12 months. In these cases, couples should be encouraged to keep trying.

The NICE guideline states that, overall, 50 per cent of couples will conceive within six months of trying, 85 per cent within 12 months and 92 per cent within two years. Because the chances of conception depend strongly on the age of the woman, early referral is important in women over 35 years of age, and is likely to increase the overall chances of conception. The fertility of men does decline with age, but this process is not as rapid as in women.

Semen analysis

Semen analysis is the cornerstone of infertility investigation in male patients. On the basis of the result, couples are provided with prognostic and diagnostic information to assist in their management.

In some cases the semen analysis result is very helpful, for example in patients with azoospermia or when many motile sperm are present in the ejaculate. However, the majority of men fall between these extremes, and for these patients semen analysis is only moderately predictive of future fertility. Generally, the chance of conception is decreased with lower semen parameters (for example a sperm concentration below 10 million per ml), but this is not always the case (see table 1, attached).

One significant problem with semen analysis is the wide variation in standards. Several studies have shown that the same man can be categorised as either a semen donor or as sub-fertile depending on the laboratory used for analysis. This variation makes accurate diagnosis difficult. One way to obtain a high quality assessment is to use laboratories with Clinical Pathology Accreditation, but even then significant variations may occur. NICE recommends at least two semen analyses are performed, ideally three months apart.

Referral

The stage at which the couple are referred to a specialist (a consultant or the regional unit) depends on the diagnosis. As stated, some couples may not have been trying to conceive for long and should be encouraged to try longer before further investigations take place.

In most cases, when the results of a semen analysis are shown to be abnormal (according to the WHO criteria), advice and referral to a specialist is required. In a small number of cases men with sub-fertility should be referred directly to a urologist (for example in the case of vasectomy reversal or other surgery to repair the reproductive system).

Management

Currently NICE7 recommends the following management options:

Recommended treatments

•Men with hypogonadotrophic hypogonadism should be offered gonadotrophin drugs.

•Men with obstructive azoospermia should be offered surgical correction where appropriate.

•Men with ejaculatory failure can be offered treatment following further evaluation.

•Couples with mild male factor infertility (mild is defined as an abnormal semen analysis, not categorised as sub-fertile - see table 4, attached) should be offered intrauterine insemination (six cycles without ovarian stimulation). However, this recommendation is controversial as the success rates vary considerably.

Treatments not recommended

•Men with varicoceles should not be offered surgical treatment.

•Men with semen abnormalities should not be offered antioestrogens, gonadotrophins, androgens, bromocriptine or kinin-enhancing drugs.

•Steroid treatment should not be given to men with antisperm antibodies.

•Antibiotic treatment is not recommended for men with leukocytes in their semen unless a specific infection is identified.

In general, the only treatment option for the sub-fertile man is assisted conception.

IVF and ICSI

Generally, IVF and ICSI are successful in cases of male infertility. Usually it is recommended that patients should receive three cycles of assisted conception to give them a reasonable chance (on average over 50 per cent) of successful fertilisation. Most patients receive an average of one to two cycles, because of a variety of factors including cost, emotional support and NHS?funding. The majority of patients who are unsuccessful after three cycles decide not to continue treatment.

IVF is used when there is a mild male factor contributing to infertility, and ICSI when a clear male factor has been identified (such as few sperm in the ejaculate, azoospermia, or failed IVF in previous cycles).

The national data for the UK3 shows the average success rate is dependent on the woman's age. The national live birth rate is 20 per cent per treatment cycle started for IVF, and 23 per cent for ICSI. There are variations, depending on the cause of male sub-fertility. For example, men with non-obstructive azoospermia, when only a few sperm can be recovered from the testes, have a lower success rate than men with obstructive azoospermia.

Importantly, there are significant differences in overall success rates between clinics, and local options should be investigated to decide which clinic the couple should attend for the best chance of a healthy baby.

There are very few examples of male sterility where sperm can be isolated (either from the testes, epididymis or ejaculate) that do not achieve successful conception with ICSI. Thus, in men with clear male factor infertility, several cycles of ICSI should be performed before the couples consider alternative options, such as donor sperm.

Several long-term follow up studies have shown that there is a small increase in genitourinary abnormalities in male children born as a result of ICSI, but that the overall incidence is low.8

There has always been some concern that, because ICSI uses sperm that would not normally reach and fertilise the egg, there would be an increased risk of abnormalities. However, this concern is unfounded, as numerous studies have shown no obvious health problems in children conceived as a result of ICSI when compared with those conceived by IVF.

Because some forms of male fertility, such as microdeletions of the Y chromosome that affect the production of spermatozoa, are clearly genetic, there are concerns that these abnormalities will be inherited. In such cases the genetic abnormality can be passed on to the sons. As ICSI is a relatively new technique (the first children were born in 1992), the fertility of these boys remains unknown, but it is presumed that they will be sub-fertile. There is no evidence to date of an exacerbation of the fertility problem passed through the generations.

Key points Table 1: Initial advice to male patients Table 2: Occupational agents and their effects on male fertility Table 4: Fertile, intermediate and sub-fertile ranges for sperm measurements and corresponding odds ratios for infertility Table 3: Semen analysis Useful information

The HFEA site contains a patient guide to IVF and lists success rates of IVF clinics.
www.hfea.gov.uk

Author

Professor Christopher
L. R. Barratt
PhD
Professor in Reproductive Medicine, University of Birmingham, member of the Human Fertilisation Embryology Authority and the World Health Organization Male Fertility Task Force

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