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Fertility testing |
Summary
Hormone testing is helpful in the investigation of infertility, but excessive testing is rarely valuable. The history of infertility and examination of both partners usually enables a simple approach to testing. Tests of ovulation rely on measuring serum progesterone seven days before an expected period. Measurement of serum testosterone is sufficient to exclude ovarian or adrenal tumours as a cause of hyperandrogenism, while prolactin and thyroid stimulating hormone may be valuable in women with irregular periods. Semen analysis is essential in the infertile male.
Key words: infertility, progesterone, testosterone.
(Aust Prescr 2002;25:38-40)
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Introduction
The general practitioner is usually the first person to see the 10-15% of couples who are concerned about their fertility. At some time in their lives, approximately half of these couples will seek medical advice. A third of these people will need to be referred to a specialist or assisted reproductive technology unit. In a third of infertility cases there is a female factor, in another third a male factor and in the remaining third there will be a combination of both, or no detected cause. The investigation by the general practitioner depends upon the couple's history, their ages and the findings on examination (Fig. 1). Patients who present with less than 12 months of infertility should have minimal testing unless a clear cause is found from clinical assessment. Selection of tests after this will depend on the potential cause of infertility indicated by the history and examination.
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Fig. 1 The investigation and management of the infertile couple by the family doctor
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Female infertility
A detailed history of the menstrual cycle often provides
a clue to problems such as anovulation or ovarian failure. A general examination
should be carried out, in addition to a pelvic examination, to look for problems
such as hypothyroidism or hirsutism.
Issues to consider when measuring female
hormones
The concentrations of most hormones fluctuate during the menstrual cycle, and
in the case of luteinising hormone (LH) and follicle stimulating hormone (FSH)
there is also a minute by minute pulsatile variation. Most hormones should be
measured in the first seven days of the cycle when there is little fluctuation
in their concentrations, but the pulsatile release of hormones such as LH may
lead to quite variable results between specimens. The measurement of hormones
such as prolactin can be significantly affected by stress and medication. Progesterone
and 17-hydroxyprogesterone vary substantially between the follicular and luteal
phase of the cycle. In the perimenopause, the concentrations of FSH can fluctuate
markedly as the ovarian sensitivity to gonadotrophins varies.
Tests for detection of ovulation
The most appropriate test for detecting ovulation is a serum progesterone concentration.
This is performed approximately seven days before the predicted date of a menstrual
period (day 1). The day can be calculated on the basis of a 14 day luteal phase
so if the menstrual cycle is 28 days, test on day 21. Test on day 23 of a 30
day cycle, and day 25 of a 32 day cycle.
A progesterone concentration above 20-25 nmol/L confirms ovulation occurred
in that cycle. Lower values mean either anovulation or inappropriate timing
of the blood test. A low concentration can be checked by taking two measurements
of progesterone a week apart in the next cycle or alternatively recalculating
the day of testing.
Urinary dip sticks for LH are also widely used for ovulation detection, but
are expensive, open to problems of interpretation and are only of value when
periods are regular. Blood or urinary LH tests are of no value in general practice.
Tests for hirsutism
The commonest cause of hair growth in women with abnormal
periods is polycystic ovary syndrome. The most appropriate test for hyperandrogenaemia
is a serum total testosterone. This will normally be below 2 nmol/L but can
vary from laboratory to laboratory and also during the menstrual cycle. Values
of testosterone above 10 nmol/L are suggestive of a testosterone producing tumour
of the ovary or adrenal. As testosterone is bound to sex hormone binding globulin,
an estimate of free androgen can be obtained by calculating the ratio of testosterone
to sex hormone binding globulin (the free androgen index). Direct measurement
of free testosterone is technically flawed and a useless test.
Tests for other androgens, such as androstenedione and dehydroepiandrosterone,
are of little value in general practice. The commonly used LH:FSH ratio is also
of little value although a raised LH with a normal FSH is helpful in the diagnosis
of polycystic ovary syndrome. Measurement of 17-hydroxyprogesterone is occasionally
helpful where late onset congenital adrenal hyperplasia (an inherited condition
affecting one of the enzymes in the adrenal gland) is suspected.
Many women with polycystic ovary syndrome will develop diabetes. When the syndrome
is diagnosed in an overweight patient, diabetes mellitus and hypertriglyceridaemia
should be excluded.
Tests for early menopause
The only test of any value where the diagnosis is uncertain is serum FSH. The
concentration may be raised above 20-30 IU/L, but this test should be repeated
on several occasions as the condition of ovarian failure fluctuates remarkably.
There is no place for measuring oestradiol or LH in this situation.
Tests for early pregnancy
Human chorionic gonadotrophin is the best test for early pregnancy. Values over
25 U/L in the blood or urine are usually diagnostic of pregnancy. Concentrations
below this are reported as equivocal or negative. If the result is equivocal
it can be repeated two days later and should have at least doubled in value.
While modern laboratory assays for human chorionic gonadotrophin are reliable,
urinary home pregnancy tests are often less satisfactory. There is usually a
1:1 relationship between concentrations of human chorionic gonadotrophin in
blood and urine. However, blood testing is more reliable and is positive 1-2
days earlier.
Tests for menstrual irregularity
Where abnormal periods are present, measurement of serum prolactin is of value.
Prolactin concentrations are increased by stress, hypothyroidism, dopamine depleting
drugs and microadenoma of the pituitary as well as by pregnancy and lactation.
When periods are irregular, measuring thyroid stimulating hormone is important
to exclude primary hypothyroidism. Routine measurement of FSH, LH and oestradiol
for infertility is of little value except in early menopause. Chromosome analysis
is needed in cases of primary amenorrhoea.
Male infertility
After a history and examination, semen analysis is the essential
test.
Semen analysis
Infertility in a couple requires analysis of a sample of semen. A semen specimen
should be produced, after three days abstinence from ejaculation, into a clean
wide-topped jar and delivered to the laboratory within 20 minutes. Previous
illness and some drugs (e.g. anabolic steroids, testosterone) can seriously
affect the amount and motility of the sperm.
Analysis required
The volume, concentration, motility and morphology of the seminal specimen are
measured. Sperm numbers should be above 20 x 106
per mL, their motility should be at least 50% and their morphology should be
above 20% normal. Morphology is poorly assessed by most laboratories other than
those routinely dealing with infertility, but it predicts the chances of fertility.
Single, double or triple defects necessitate the measurement of a second specimen
in a specialist laboratory and probable referral to a specialist.
Other tests
In patients with azoospermia, small testes and a high FSH, chromosome analysis
may be required to exclude conditions such as Klinefelter's syndrome (XXY).
Other disorders of semen analysis may require the measurement of FSH and LH
to show whether the defect is in the testis (high result) or in the hypothalamus
or pituitary (low result). Serum testosterone is normally well above 10 nmol/L
and low values may necessitate testosterone replacement or injection of human
chorionic gonadotrophin depending on the cause and desire for fertility. Occasionally,
microadenomas of the pituitary can present with high prolactin values and male
infertility. Sperm antibody testing is important in specialist practice but
not in primary care as a routine investigation.
Conclusion
Infertility is a condition initially best dealt with by the general practitioner. After history and examination, selective testing of hormones is helpful for making the diagnosis and for decisions regarding referral. Inappropriate hormone testing is expensive and a waste of resources.
Conflict of interest: none declared
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