Infertility may be defined in many ways. The commonest definition is the lack of a pregnancy after one year of unprotected regular intercourse, and in Europe and North America this is thought to affect 10%-15% of couples. Lack of pregnancy after two years of regular unprotected intercourse occurs in 5%-6% of couples. The cause of the infertility may be due to:-

1. Female factor

2. Male factor

3. Combined factors

4. Unexplained
   

Within each of these categories it is probably useful to consider patients as either sterile or sub-fertile. The number of truly sterile patients are very small and within the sub-fertile group there is always a chance of spontaneous pregnancy.

Female fertility may be due to problems in the function of the ovary, in which case periods may stop, or become irregular. Other problems may occur in the uterus, the fallopian tubes which connect the ovary to the uterus, or within the cervix. Checking a progesterone level on day 21 of the cycle is a useful starting point. If elevated this tends to suggest that normal ovulation is taking place i.e.eggs are being made and released normally. Other hormonal blood tests can be done to check the function of the ovary. These include FSH, LH, prolactin and thyroid hormones all of which may interfere with the ovary’s function. If there are mild abnormalities then further tests may need to be done such as test of pituitary function for the pituitary gland controls the function of the ovary. Scans may be needed such as ultrasound scan of the ovary, checking for conditions such as polycystic ovary disease, or pituitary scans. If the periods have stopped then these blood tests may give an indication as to whether early menopause has occurred.

If the female partner is having a normal menstrual cycle then abnormal ovarian function is less likely and obstruction of the fallopian tubes needs to be considered. This is more common in women who have previously used intra-uterine devices for contraception and those who had pelvic inflammatory disease, possibly secondary to sexually transmitted disease (STD). Pelvic inflammatory disease can be associated with low pelvic pain, sometimes in a cyclical nature at the time of periods (dysmenorrhoea). Tubal patency can be assessed either by "a hysterosalpingography" or by laparoscopy. Laparoscopy also enables the doctor to look at the uterus. Other ways of looking for the tubal patency are under investigation and development, e.g. hysteroscopy and falloposcopy.

If these initial tests are all normal then further investigations will be required. Initially it needs to be identified that a normally sized uterus is present. Other uterine abnormalities can be looked for including endometriosis and adhesions. However uterine abnormalities are more associated with recurrent miscarriages rather than difficulty in conception.

Examination of the mucus around the cervix may also be necessary, looking to see how much acid is within the mucus and to see if there is any infection in the mucus, as both of these may prevent movement of the sperm into the uterus. Penetration of sperm through the cervical mucus can be examined more carefully by obtaining a sample of mucus after sexual intercourse and looked at in the laboratory. Ability of sperm to penetrate through the mucus of the cervix is examined in this test.

Clearly it is important to determine that the male partner is not impotent. Thereafter it is necessary to look at the male partners testicular function and sperm function. Semen analysis involves looking at the number of sperm, the appearance of the sperm and the motility of the sperm. If the semen analysis is abnormal it is usually important to repeat it after 6-12 weeks as sperm function can vary and recover.

It may also be useful to perform blood tests to check for hormones like FSH and Testosterone and depending on the results further tests such as measuring prolactin may be required.

If the above tests do not identify a clear answer for male infertility then further investigations may be required. Testicular ultrasound may be useful to look for varicocele (which is a varicose vein around the testis which can cause infertility) or even tumours. Sending samples for bacterial analysis may be useful in identifying prostatitis which can be treated with antibiotics. Sometimes genetic tests may also be required.

Sperm function tests are increasingly being used. In these a sample of sperm are taken to the laboratory to see if they can penetrate the outer core of the human egg or to see if they are responsive to hormones such as progesterone. This is an area of increasing research.

Not infrequently both male and female partner may have causes of infertility. Beyond this it is clearly important to ensure that the couple are having regular unprotected intercourse. There is no evidence that prolonged abstinence increases the chances of pregnancy, although short periods of abstinence (around one week) may be useful for men with reduced sperm counts. The use of lubricants should in general be discouraged as this may have an adverse effect on sperms.

As tests become more sophisticated the percentage of patients with unexplained infertility decreases. However there is still a significant number of patients in which a cause is not identified and this is likely to be due to subtle abnormalities which are beyond the scope of detection in modern scientific technology. However more than 30% of couples with unexplained infertility are likely to be pregnant within three years. The chances are greater in younger couples since female fertility starts to decrease at the age of 30.

Obesity (i.e. BMI greater than 30) significantly decreases the rate of fertility, and weight loss can have a dramatic effect on improving fertility. Patients with polycystic ovary syndrome may show improved ovarian function after treatment with Metformin or other newer insulin sensitising drugs.

a.  Ovulation Induction

Clomiphene is a commonly used medication. This is usually given in a dose of 50mg sometimes increasing to 100mg per day on day 2 to day 7 of the menstrual cycle. Clomiphene acts to stimulate ovulation (egg production). An alternative to this is to give pulse injections of Gonadotrophins (i.e. GnRH) or FSH to induce follicle development within the ovary. These hormones are normally secreted by the brain for the same purpose. Once follicles are developed another hormone called HCG is given by injection to promote ovulation. Occasionally with these techniques ovarian over-stimulation can occur and so careful follow-up is essential by the infertility expert gynaecologist. Alos the techniques sometimes result in more than one egg being released with the result of multiple pregnancies.

If the patient has high levels of prolactin then drugs such as Bromocriptine (or quinagolide or cabergoline) can be used to bring down prolactin levels which may result in normal ovulation and pregnancy. The cause of raised prolactin will need investigated.

b.    Tubal Infertility

For some patients with blocked fallopian tubes, surgical reconstruction is possible.

c.    Uterus Abnormalities

Endometriosis is often treated with drugs to help symptomatology but these drugs can cause infertility. Stopping these drugs will improve the chance of pregnancy. If the Endometriosis is severe then other forms of fertility treatment will be needed.

d.    Hormonal Abnormalities in the Male

If there are pituitary or hypothalamic problems with the male partner then he can get treated with pulsed injections of Gonadotrophins (i.e. GnRH) or HCG, which will help stimulate the testis to produce sperm.

a. Intrauterine insemination (IUI)

In this process sperm which have been previously isolated are placed within the uterus soon after ovulation. This is performed by using a catheter inserted via the vagina and can be useful in conditions where there is no evidence of tubal damage and where the male partner has no major infertility factor.

b.     Invitro Fertilisation (IVF)

In this process the ovaries are stimulated as described previously and under ultrasound guidance the eggs are removed from the ovary and are incubated for three to six hours and then inseminated with the sperm which have previously been collected. Two days later the fertilised egg will have started to grow and by this stage would be two to eight cells in size (i.e. early embryos). It is usual to withdraw several eggs at the time of collection (this is done under ultrasound guidance) and each egg would be fertilised with sperm resulting in several early embryos. Two to three of the embryos when they are at the stage of two to eight cells in size, would be transferred back to the uterus, in the hope that at least one of these will survive. Occasionally of course more than one does survive resulting in multiple pregnancy. IVF can be used for tubal abnormalities and many other forms of infertility.

c.     Gamete Intrafallopian Transfer (GIFT)

GIFT is a technique which can be used as an alternative to IVF. In this technique, after the eggs and sperm have been collected, instead of incubating them, they are placed around the region where the fallopian tube and the uterus meet. This is done using the laparoscope and usually a general anaesthetic is required. This means that the fertilisation can occur in the normal environment, without the need for very careful laboratory conditions. Again GIFT can be used for a number of different forms of infertility.

d.     Intracytroplasmic Sperm Injection (ICSI)

This technique is used for severe male infertility and in this process sperm are directly injected into the egg. The sperm are retrieved from the male partner, either from micro surgery of the tubes leading from the testicles to the penis or from needle biopsy or open biopsy of the testicle.

The treatment of infertility is a rapidly changing area with increasing success rates; although the overall success rates in general is only around 20%. Every couple will have differing problems and may require different treatments depending on the cause

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Ó NHS Tayside; 2006; version 1.0

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