from the book How to Have a Baby:
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
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
- 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.
- 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.
- 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.
- 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.
- Immunological factors: The immune system can react against the
man's sperm, and kill them, immobilize them or make them stick
Women can also develop an immune reaction to the coating of their own eggs,
which can prevent sperm from attaching to them.
- 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.
- 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.
- 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).
- 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
by Dr. Aniruddha Malpani, MD and Dr. Anjali Malpani, MD.
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