Chapter 20
Unexplained Infertility

from the book How to Have a Baby: Overcoming Infertility
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.

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Unexplained infertility simply means we do not know why the couple is infertile - it is a confession of medical ignorance. Patients with unexplained infertility fall into two groups. One is the group who really have no infertility problem whatsoever, but are just plain "unlucky". The other is the group which do have a reason for their infertility - but the reason is so subtle, that with present-day medical technology, we cannot find it.

Infertility may be said to be 'unexplained' if the woman is ovulating regularly, has open fallopian tubes with no adhesions or endometriosis ; if the man has normal sperm production; and the postcoital test is positive. Intercourse must take place frequently, particularly around the time of ovulation, and the couple must have been trying to conceive for at least one year.

Using these criteria, about 10% of all infertile couples have unexplained infertility. However, the percentage of couples classified as having unexplained infertility will depend upon the thoroughness of testing; and the sophistication of medical technology.

The diagnosis is one of exclusion - that is, one which is made only after all the tests have been performed and their results found to be normal. This is why, the frequency of this diagnosis will depend upon how many tests are done by the clinic - the fewer the tests, the more frequent this diagnosis.

Possible causes of unexplained infertility

1. Tubal Abnormalities: It is possible that there may be a subtle defect in the mechanism by which the fimbria "pick up" the egg at ovulation; or the cilia in the tube may not function properly.
    
2. 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.
    
3. Trapped eggs: In some cases it would appear that eggs are produced, and mature correctly within the follicle which then goes on to become a corpus luteum without however first bursting to release the egg. The egg is therefore effectively 'trapped' inside the unbroken corpus luteum - called a luteinized unruptured follicle (LUF) syndrome.
    
4. Luteal phase abnormalities: The luteal phase is the part of the cycle that follows after the egg has been released from the ovary. It may be inadequate in one way - and this is called a luteal phase defect. 
   
   The corpus luteum produces the hormone called progesterone. Progesterone is essential for preparing the endometrium to receive the fertilized egg. 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. Another possibility is a defective endometrium that does not respond properly to the progesterone.
     
   Luteal phase defects can be investigated either by a properly timed endometrial biopsy; or by monitoring the progesterone output by taking a number of blood samples on different days after ovulation and measuring the progesterone level in them.
     
5. Immunological factors: The immune system can react against the man's sperm, and kill them, immobilize them or make them stick together. 
    
   Women can also develop an immune reaction to the coating of their own eggs, which can prevent sperm from attaching to them.
    
6. Infections: Certain infections have been shown to be responsible for some cases of unexplained infertility. For example, mycoplasma or chlamydia may be present in numbers that are not enough to show up in a clinical examination, but which nevertheless cause infertility. This is why some doctors use empiric therapy with antibiotics.
    
7. Inability of sperm to penetrate eggs: Some men have a completely normal sperm count, but their sperm cannot fertilise the egg. The only way to make this diagnosis is by IVF; if donor sperm can fertilize the eggs; but the husband's sperm fail to do so, then the diagnosis is confirmed.
    
8. Uterine factor: Some women have an abnormal endometrium ( uterine lining) which does not allow the embryo to implant . This is a subtle finding, which is often missed. It can be diagnosed by doing serial vaginal ultrasound scans, to assess the thickness and texture of the endometrium. In some infertile women, the endometrium remains persistently thin. This may be because of inadequate uterine blood flow, or poor estrogen receptors in the endometrial cells. This can be a difficult problem to treat, and therapy is usually empirical ( either low-dose aspirin or high doses of estrogen).
    
9. Psychological factors: Studies on infertile groups of men and women have produced contradictory findings about the importance of psychological factors in causing infertility. Emotional disturbances undoubtedly 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. This is an area which needs further investigation.

Has anything been missed?

Previous tests should be carefully reviewed to ensure that the diagnosis is in fact "unexplained" - and that no test has been omitted or missed. It may sometimes be necessary to repeat certain investigations. Thus, for example, if a previous Laparoscopy has been done by a single puncture and been reported as normal, it may be necessary to repeat the Laparoscopy with a double puncture, to look for early endometriosis.

How can unexplained infertility be treated?

Remember, you still have a fairly good chance of getting pregnant on your own without needing any treatment at all! If no abnormality is found, your chance of getting pregnant without treatment within 3 years is about 1 in 3. Taking treatment helps to increase the chances of your conceiving - and also makes it likelier that you will get pregnant sooner.

The treatment of luteal phase defects is as controversial as their diagnosis. They can be treated by using clomiphene which may help by augmenting the secretion of FSH and thus improving the quality of the follicle (and therefore the corpus luteum which develops from it). Direct treatment with progesterone can also help luteal phase abnormalities. The progesterone can be given either as injections or vaginal suppositories.

Many patients are worried that if we are not able to find the cause of the infertility, we will not be able to treat them. Fortunately, this is not true – today, our technology for treating infertility is far superior than our technology for making a diagnosis ! In any case, most infertile couples are not really interested in a diagnosis of what the problem is – they are much more interested in finding the solution to their problem - getting a baby ! Today, with assisted reproductive technology, the chance of treatment being successful is very good. Intrauterine insemination with superovulation is the simplest approach, and it helps because it increases the chances of the egg and sperm meeting; but some patients may also need IVF or ZIFT . IVF can be helpful, because it provides information about the sperm's fertilizing ability, and also allows the doctor to perform in the lab what is not happening in the bedroom ( whatever the reason for this ) ; ZIFT, on the other hand, has a higher pregnancy rate, and is very useful in these patients, since they have normal fallopian tubes.

by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.

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Professionals: InfertilityProfessionals.com
Professionals: InfertilityWebsites.com