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Investigating infertility in primary care

How should assessment be carried out?
When should patients be referred?
What are the chances of successful treatment?

How should assessment be carried out?
When should patients be referred?
What are the chances of successful treatment?

Approximately 1 in 4 couples will see their GP for infertility problems.1 infertility is thus a very common condition with around 1 in 7 couples of reproductive age being diagnosed as infertile.

Assessment in primary care

Fertility is a couple issue. A detailed history should be taken, for both the woman and the man, including duration of infertility, any coital problems, previous conceptions, and frequency of intercourse, see table 1, attached.

For women this should include:
• a physical examination
• menstrual history (regular, irregular)
• general health, including BMI. Women should be advised that an abnormal BMI (>29 or <19) can adversely affect the chances of conception
• assessment of factors which can contribute to infertility e.g. previous sexually transmitted disease that may affect tubal patency. Smoking is also likely to reduce fertility.

Women intending to become pregnant should be informed that dietary supplementation with folic acid before conception and up to 12 weeks' gestation will reduce the risks of having a baby with neural tube defects. They should also be offered rubella screening so that those who are susceptible to rubella can be offered rubella vaccination.

For men, a physical examination should determine general health, testis size and record any obvious abnormalities of the reproductive system. Sperm dysfunction (i.e. sperm are present but malfunction) is the single most common cause of infertility and affects approximately 1 in 15 men.

Couples should be informed that sexual intercourse every 2-3 days optimises the chances of pregnancy. With regards to timing, postovulatory intercourse is not very effective. Preovulatory (within 4 days of ovulation) is likely to be more successful, with the optimum being 1 or 2 days before ovulation. However, there is a lot of variation. Too much emphasis on having intercourse to coincide with ovulation causes stress, and is not recommended by NICE.

The length of infertility and the woman's age are important predictive factors for the future chance of conception.

Investigations

Couples who have not conceived after one year of regular unprotected intercourse should be offered further clinical investigations. This should include assessment of ovulation and/or semen assessment.

The majority of women who have a regular menstrual cycle are likely to ovulate. While an irregular menstrual cycle does not prove anovulation it is an indicator that further tests should be done. A serum progesterone measurement should be taken on day 21, if the patient has a 28-day cycle, or later if the cycle is longer to confirm ovulation. Serum gonadotrophins (FSH, LH) should also be measured.

Serum prolactin should only be measured if galactorrhea is present or a pituitary tumour is suspected. Likewise, measurement of inhibin B, thyroid function tests (unless there are symptoms of thyroid disease) and endometrial biopsy are not recommended.

Tests for tubal patency should not be performed until the assessment of ovulation and the results of a semen analysis are known.

Where there is a history of predisposing factors, such as amenorrhoea, oligomenorrhoea, pelvic inflammatory disease (or undescended testis in the partner) or where a woman is aged 35 or over investigations should be offered earlier rather than waiting until the couple have had 12 months of unprotected intercourse.

If the semen analysis is grossly abnormal a repeat should be arranged as soon as possible. In some cases the semen analysis result is very helpful e.g. when there is azoospermia (no sperm) or when many motile sperm are present in the ejaculate (normal). However, the vast majority of men fall between these extremes and in these cases semen analysis is only moderately predictive of future fertility. Generally, the lower the semen parameters e.g. sperm concentration below 10 million per ml the lower the chance of conception but there are no hard and fast rules. An abnormality in all three of the main parameters (concentration, motility, morphology) is a clear indication of male factor infertility and the need for IVF or ICSI. The WHO provides guidelines as to what is regarded as a normal semen analysis (see table 2, attached) but these are very likely to be revised in late 2009 and the limits of normality will be significantly lower.3

Reassuring patients

One of the most significant factors affecting the chances of conception is the length of time the couple have been trying for a child. As fertility is always in the news, couples can become very anxious when they have only been trying for a very short period of time.

There is a comprehensive guideline from NICE on the assessment and treatment of fertility problems.2 This suggests that, unless there are confounding factors (see above), couples should not be referred for further investigation if they have been trying for a child for less than a year. In these cases, couples should be encouraged to keep trying. The NICE guideline states that overall half of couples will conceive within 6 months of trying, 85% within 12 months and 92% within 2 years.

In some cases, particularly when the woman is older (>35 years of age) earlier referral (<12 months) may be necessary. The chances of conception are very strongly dependent on the age of the woman, so early referral is important for older women and is very likely to increase the overall chances of conception. Older age in the man does have a negative influence on fertility but it is nowhere near as marked as the effect of the woman's age.

Referral

NICE recommends that people who experience fertility problems should be treated by a specialist team because this is likely to improve the effectiveness and efficiency of treatment and is known to improve patient satisfaction. Some couples may not have been trying for a child for long and should be encouraged to try longer before further investigations are instigated.

IVF/ICSI

In the UK, the mean live birth rate per cycle started for IVF and ICSI is 23%. It is generally recommended that patients should have three cycles of assisted conception to give themselves a reasonable chance of success (on average > 50% chance of having a baby). In order to reduce the number of multiple births from IVF/ICSI there has been a clear trend to replace fewer embryos. As such many patients particularly those with a high chance of pregnancy will only have one embryo replaced and have the remaining embryos cryopreserved.

IVF is generally used when there is tubal blockage and mild male factor infertility. ICSI should only be used when a clear male factor has been identified e.g. few sperm in the ejaculate, azoospermia, or failed IVF in previous cycles.

The national data (available as a patient's guide at www.hfea.gov.uk) shows the average success rates depend on female age with live birth rates in patients over 40 being very low. The use of donor gametes is a successful treatment although following legislative changes protecting anonymity gamete donors are in limited supply. There are variations in overall success rates of IVF/ICSI between different clinics (all are listed on the HFEA website) but overall these are not significant.

Useful information

The Human Fertilisation and Embryology Authority's website contains a host of information for both patients and healthcare professionals. Infertility and treatments are explained in clear detail as are success rates of treatment
www.hfea.gov.uk

Copies of the NICE guideline Fertility: assessment and treatment for people with fertility problems can be downloaded free of charge from the NICE website
www.nice.org.uk

Author

Professor Christopher LR Barratt
PhD
Professor of Reproductive Medicine University of Dundee Medical School

Key points Table 1: Examination and investigations Table 2: Semen analysis Investigating infertility in primary care

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