When is unexplained infertility diagnosed?

Unexplained infertility is diagnosed when all traditional infertility tests have been found to be normal. Doctors will order tests and confirm the following scenarios:
1. The woman is ovulating regularly, and she has good quality eggs, ovarian reserve testing is negative.
2. The fallopian tubes are open, with no adhesions or endometriosis.
3. The man has normal sperm production; and the postcoital test, if it was done, is normal.

Most cases of unexplained infertility fall into 1 of 3 categories: Immunological factors, tubal anomalies, and abnormal eggs.

Intercourse must take place frequently, particularly before and around the time of ovulation, and the couple must have been trying to conceive for at least one year (6 months if the woman is over 35 years old). Using these criteria, about 10-20% 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 existing 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. And the better the tests, the more likely you are getting a diagnosis instead of being told it's "unexplained."

Most cases of unexplained infertility are caused by the following three conditions:

• Immunological factors (50 percent): 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.
• Tubal abnormalities and endometriosis (25 percent): 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.
• Abnormal eggs such as premature aging (25 percent): 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. 

Other reasons include:

• 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 first bursting to release the egg. The egg is therefore effectively trapped inside the unbroken corpus luteum. This is called luteinized unruptured follicle (LUF) syndrome. 

• Luteal phase abnormalities: The luteal phase is the part of the cycle that follows the release of the egg from the ovary. It may be inadequate in one way and this is called a luteal phase defect. The corpus luteum produces the hormone 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. 

• Infections: Infection by certain disease particles has been shown to be responsible for some cases of unexplained infertility. A disease particle called T-strain mycoplasma may be present in numbers too low to show up in a clinical examination, but that nevertheless causes infertility. 
• 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 fertilize it. The only way to make this diagnosis is by IVF. If donor sperm can fertilize the eggs; but the partner's sperm fails to do so, then the diagnosis is confirmed. 
• Psychological factors: Studies on infertile groups of men and women have produced contradictory findings of the importance of psychological factors in causing infertility. Emotional disturbances undoubtedly appear to have some significance. This is only reasonable if you realize 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. For example, if a previous laparoscopy has been done by a single puncture and reported as normal, it may be necessary to repeat the laparoscopy with a double puncture, to look for early endometriosis. 

Despite improvements in both diagnostic assessment and treatment of infertile couples, many couples still have no explanation for their infertility. Unexplained infertility is not an absolute condition but rather a relative inability to conceive, and many of these couples may conceive without treatment.

Chances of getting pregnant with unexplained infertility

One study showed that for couples with unexplained infertility of over three years' duration, the cumulative conception rate after 24 months of attempting conception without any treatment was 28%. This number was found to be reduced by 10% for each year that the woman is over 31.

How can unexplained infertility be treated?

The treatment options for unexplained infertility are several and the treatment results are promising. Expectant management can be recommended if the woman is under 28-30 years of age and the infertility duration is less than 2-3 years. In vitro fertilization (IVF) has revolutionized the treatment of infertile couples, as well as profoundly increasing the basic understanding of human reproduction. IVF can be used as both a diagnostic and a therapeutic tool in couples with unexplained infertility. The pregnancy rates with IVF are good, at 40% per treatment cycle. In addition, the outcome of pregnancies among women with unexplained infertility is generally comparable to that of spontaneous and other pregnancies using assisted reproductive technologies.

There is still 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 three years is about one in three.

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The first step in finding the right treatment is to find out if there is an actual cause for unexplained infertility. Taking treatment helps to increase the chances of conceiving, and also makes it likelier that you will get pregnant sooner. The treatment of luteal-phase defects is as controversial as the 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. Progesterone can be given either as injections or vaginal suppositories.

Today, with assisted-reproductive technology, the chance of successful treatment is very good. Intrauterine insemination with superovulation is the simplest approach since it increases the chances of the egg and sperm meeting, but some patients may also need GIFT and IVF. IVF can be helpful because it provides information about the sperm's fertilizing ability; GIFT, on the other hand, has a higher pregnancy rate and is applicable in these patients since they have normal fallopian tubes.