To be given the diagnosis of unexplained infertility can be very unsatisfactory. Many people feel that it is easier to cope with a definite reason for your inability to conceive.
Contrary to public opinion, and despite the ever-growing size of the human population, man is one of the least fertile of all animals. Studies have shown that the chances of a healthy couple conceiving in any one month, with frequent intercourse, are about 20-25%. World Health Organisation data suggest that 99% of those who are going to conceive without help will have done so within two years of trying. Yet there remains a group who, although they have no medical problems, are apparently unable to conceive. However, studies have shown that even in this group, over a period of seven years, 36% will eventually conceive, and over the same period, in a similar group who cannot conceive again after bearing one or more children, 79% will eventually conceive. Some infertility just reflects this inefficient human reproduction. One study of unexplained infertility of less than two years duration showed that 50% of these couples would conceive over the next two years, and suggested that the right treatment was to do nothing.
What is unexplained infertility?
Infertility may be said to be “unexplained” if the woman is ovulating regularly, has open fallopian tubes with no adhesions, fibrous growths or endometriosis and if the man has normal sperm production. Intercourse must take place frequently, at least twice a week, particularly around the time of ovulation, and the couple must have been trying to conceive for the previous two years at least.
Using these criteria, about 10% of all infertile couples have unexplained infertility according to the most often quoted figures. However, this proportion would probably be as low as 3% if thorough laparoscopic and other screenings were carried out. Some studies show unexplained infertility as representing 28% of their patients, so a great deal has to do with how thoroughly diagnostic tests are performed.
Possible causes of unexplained infertility 1. Anatomical abnormalities
It used to be thought that a retroverted uterus was a cause of infertility, but this is no longer taken to be the case. The position of the cervix is unlikely to be so abnormal that sperm are unable to reach it. It is possible that there may be failures in the mechanism in the mouth of the fallopian tubes which allows them to pick up the egg. Abnormal levels of hormones called prostaglandins, which are responsible for making the muscles contract, may interfere with the passage of the egg in the tube. High prostaglandin levels, however, are usually associated with endometriosis, and this condition is likely to be detected. Scar tissue, often associated with inflammation of the womb lining, or large multiple fibroids can interfere with the process of reproduction by making the womb unreceptive to a fertilised egg. Scar tissue can also result in damage to the fallopian tubes.
To aid accurate diagnosis of the cause of infertility, investigations should include vaginal ultrasound scans and hysteroscopy. Vaginal ultrasound will pick up abnormalities within the womb and abnormalities with the ovaries, which would otherwise be missed by a laparoscopy. If vaginal ultrasound is not available, a hysteroscopy should be performed at the same time as a laparoscopy so that any problems within the womb, which could cause infertility, may be excluded.
2. Abnormal development of the follicle and of ovulation
In some women the egg may be released from the follicle (bag) in which it develops before it is properly mature or it may not be released at all leading to formation of a cyst (see point 4).
3. Abnormal eggs
It would appear that a very small number of cases of unexplained infertility are due to the persistent production of abnormal eggs. These may have a deformed structure or chromosomal abnormalities.
4. Trapped eggs
In some cases it would appear that eggs are produced, and mature correctly within the follicle. This goes on to become a “corpus luteum” (the next stage of development) but without first bursting to releasing the egg. The egg is therefore effectively “trapped” inside the unbroken “corpus luteum”.
5. Luteal phase abnormalities
Perhaps the most important of all causes of “unexplained” infertility. This is where the part of the cycle that follows after the egg has been released from the ovary is abnormal in some way.
After releasing the egg, the bag which contained it within the ovary (the follicle) goes on to become the “corpus luteum” (yellow body). This is a gland which produces the hormone called progesterone. Progesterone is essential for preparing the lining of the womb to receive the fertilised egg, and for sustaining the embryo in its first seven weeks of life.
Several things can go wrong with progesterone production: the rise in output can be too slow, the level can be too low, or the length of time over which it is produced can be too short. Luteal phase defects can be investigated either by carefully examining samples from the lining of the womb (endometrial biopsy) or by monitoring the progesterone output by taking a number of blood samples on different days after ovulation so that the progesterone level in them can be measured. Defects in the luteal phase may also occur as a result of abnormal levels of the hormone, prolactin.
6. Immunological factors
The immune system, which is the body’s defence against the invasion of foreign particles and organisms such as bacteria and viruses, can in certain cases react against the man’s sperm; destroying them, or making them stick together. For further information see the factsheet on Mucus Hostility. Women can also develop an immune reaction to the coating of their own eggs, which can prevent sperm from attaching to them.
7. Inability of sperm to penetrate eggs
There is some evidence that some men’s sperm, although apparently adequate in every other way, are unable to get into the egg to fertilise it. There appears to be a correlation between infertility and the inability of sperm to penetrate the egg of a hamster from which the outer coating has been removed. This test, the “zona-free hamster egg test” is producing some interesting research results, but its implications are not clear at the moment. Sperm have an enzyme cap called an acrosome. Some sperm do not have this cap without which the acrosome reaction allowing the sperm to penetrate into the egg, cannot take place.
8. Psychological factors
Studies on infertile groups of men and women have produced contradictory findings about the importance of psychological factors in infertility. Psychosexual problems undoubtedly cause a small proportion of infertility cases, even in this “permissive” age: either through making a couple unable to consummate intercourse, or possibly through too infrequent intercourse.
Emotional disturbances, too, would appear to have some significance. This is only reasonable if you realise that the whole hormonal cycle, with its delicate adjustments, is controlled from the brain and therefore responds to the environment in the brain. Disturbances in the chemical balance within the brain will therefore affect both behaviour and the hormonal control mechanism. This is an area which needs further investigation.
Luteal phase abnormalities seem to be the result of problems with the two gonadotrophic hormones. Lower levels of the hormone FSH (follicle stimulating hormone) seem to be responsible for a smaller amount of progesterone being produced by the corpus luteum. Low luteinising hormone (LH) levels too, can be responsible for failure to develop an adequate secretion of progesterone. The ratio between LH and FSH appears to be critical to progesterone production.
For these reasons treatment with the drug, clomiphene may be useful in helping to restore adequate secretion of FSH and LH. Luteal phase abnormalities, abnormalities in the development of the follicle and in the timing of ovulation can thus be helped.
Direct treatment with progesterone can also help luteal phase abnormalities. The progesterone can be given either as injections or vaginal suppositories. Synthetic “progestin” should not be used as they have an anti-progesterone activity, and furthermore, they become broken down into male hormones within the body; this could adversely affect the developing embryo.
Women with luteal phase inadequacies produced by high prolactin levels can be successfully treated by use of the drug bromocriptine.
Psychosexual problems can be helped by professional counselling; there are several centres where this is available.
Immunological factors can be treated by the use of corticosteroid drugs such as Prednisolone. These suppress the immune response and are particularly effective if they are given in phase with the monthly cycle. They are, however, very powerful drugs and can have unwanted side-effects.
Cervical mucus quality can be improved by the use of oestrogens, administered either orally or as suppositories. Oestrogens, however, are better known as the contraceptive pill, and can therefore interfere with ovulation.
Of the other possible causes of “unexplained” infertility, not all are treatable with our current state of knowledge.
Undoubtedly as our knowledge increases and our techniques and treatments improve the diagnosis, “unexplained infertility” will become less and less frequent. No-one should expect that all these factors will automatically be taken into account when they are told that the reasons for their infertility are inexplicable. A little gentle prodding or some pertinent questions may be necessary!
Infertility Network UK Charter House 43 St Leonards Road Bexhill on Sea East Sussex TN40 1JA Telephone: 0800 008 7464 / 01424 732361
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